Prescription Drugs

CLINICAL PHARMACOLOGY Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation).

CLINICAL PHARMACOLOGY Combination oral contraceptives act by suppression of gonadotropins. Although the primary mechanism of this action is inhibition of ovulation, other alterations include changes in the cervical mucus (which increase the difficulty of sperm entry into the uterus) and the endometrium (which reduce the likelihood of implantation). Pharmacokinetics Absorption Ethinyl estradiol and norethindrone are rapidly absorbed with maximum plasma concentrations occurring within 2 hours after FEMCON Fe (norethindrone and ethinyl estradiol tablets) administration (see Table 1). Norethindrone appears to be completely absorbed following oral administration; however, it is subject to first-pass metabolism resulting in an absolute bioavailability of approximately 65%. Large intersubject variability is reflected in a 3- to 5-fold variation in norethindrone bioavailability. Ethinyl estradiol bioavailability is approximately 43% due to small-intestinal and hepatic first-pass metabolism. Table 1. Mean ±SD Pharmacokinetic Parameters Following Single Dose Administration of FEMCON Fe (norethindrone and ethinyl estradiol tablets) in Healthy Female Subjects Under Fasting Conditions. Norethindrone/Ethinyl Estradiol tmax (h) Cmax (pg/mL) AUC0-∞ (pg•h/mL) t½ (h) Norethindrone 0.4 mg 1.24 ± 0.40 a 4210.6 ± 1628.8 a 18034.9 ± 7852.9 b 8.6 ± 3.7 b Ethinyl Estradiol 35 µg 1.44 ± 0.33 b 131.4 ± 34.2 b 1065.8 ± 276.2 b 17.1 ± 4.4 b a n = 26 b n = 25 Cmax = maximum plasma concentration; tmax = time to reach Cmax; AUC = area under the curve; t½ - elimination half life. Effect of Food. Single-dose administration of FEMCON Fe tablets with food decreased the maximum norethindrone and ethinyl estradiol concentration by 53% and 47%, respectively; the extent of norethindrone and ethinyl estradiol absorption (AUC values) was not affected by food administration. Distribution Norethindrone is 36% bound to sex hormone-binding globulin (SHBG) and 61% bound to albumin. Ethinyl estradiol is not bound to SHBG but is highly (98.5%) bound to albumin. Volume of distribution of norethindrone and ethinyl estradiol ranges from 2 to 4 L/kg. Metabolism Norethindrone undergoes extensive biotransformation, primarily via reduction, followed by sulfate and glucuronide conjugation; less than 5% of a norethindrone dose is excreted unchanged; greater than 50% and 20-40% of a dose is excreted in urine and feces, respectively. The majority of metabolites in the circulation are sulfates, with glucuronides accounting for most of the urinary metabolites. Ethinyl estradiol is also extensively metabolized, both by oxidation and by conjugation with sulfate and glucuronide. Sulfates are the major circulating conjugates of ethinyl estradiol, and glucuronides predominate in urine. The primary oxidative metabolite is 2-hydroxy-ethinyl estradiol which is formed by the CYP3A4 isoform of cytochrome P450. Excretion Plasma clearance values for norethindrone and ethinyl estradiol are similar (approximately 0.4 L/hr/kg). Ethinyl estradiol and norethindrone are excreted in both urine and feces, primarily as metabolites. Ethinyl estradiol is excreted in urine and feces as glucuronides and sulfates, and about 28-43% undergoes enterohepatic circulation. The mean terminal elimination half-lives of norethindrone and ethinyl estradiol following single dose administration of FEMCON Fe (norethindrone and ethinyl estradiol tablets) are approximately 9 hours and 17 hours, respectively. Special Populations Race. The effect of race on the disposition of norethindrone and ethinyl estradiol after FEMCON Fe (norethindrone and ethinyl estradiol tablets) administration has not been evaluated. Renal Insufficiency. The effect of renal disease on the disposition of norethindrone and ethinyl estradiol after FEMCON Fe (norethindrone and ethinyl estradiol tablets) administration has not been evaluated. In premenopausal women with chronic renal failure undergoing peritoneal dialysis who received multiple doses of an oral contraceptive containing ethinyl estradiol and norethindrone, plasma ethinyl estradiol concentrations were higher and norethindrone concentrations were unchanged compared to concentrations in premenopausal women with normal renal function. Hepatic Insufficiency. The effect of hepatic disease on the disposition of norethindrone and ethinyl estradiol after FEMCON Fe (norethindrone and ethinyl estradiol tablets) administration has not been evaluated. However, ethinyl estradiol and norethindrone may be poorly metabolized in patients with impaired liver function. Drug-Drug Interactions See "Precautions" section-DRUG INTERACTIONS

Vyfemla™ (norethindrone and ethinyl estradiol ) Tablets, USP 28 - DAY REGIMEN Patients should be counseled that this product does not protect against HIV-infection (AIDS) and other sexually trans mitted diseases. DESCRIPTION Vyfemla™ (norethindrone and ethinyl estradiol tablets USP) provides a continuous regimen for oral contraception derived from 21 light peach tablets composed of norethindrone and ethinyl estradiol to be followed by 7 white tablets of inert ingredients. The structural formulas are: The light peach active Vyfemla (norethindrone and ethinyl estradiol tablets USP) contains 0.4 mg norethindrone and 0.035 mg ethinyl estradiol and contain the following inactive ingredients: FD&C yellow No. 6 (aluminum lake), lactose anhydrous, lactose monohydrate, magnesium stearate, povidone, and sodium starch glycolate. The white tablets in the 28 Day regimen contains only inert ingredients as follows croscarmellose sodium, lactose monohydrate, magnesium stearate and microcrystalline cellulose.

PHILITH™ (norethindrone and ethinyl estradiol) Tablets DESCRIPTION PHILITH™ 28-Day (norethindrone and ethinyl estradiol tablets, USP) provide a continuous regimen for oral contraception derived from 21 tan tablets composed of norethindrone and ethinyl estradiol to be followed by 7 white tablets of inert ingredients. The structural formulas are: NORETHINDRONE ETHINYL ESTRADIOL C20H26O2 Molecular Weight: 298.42 C20H24O2 Molecular Weight: 296.40 The tan active tablets each contain 0.4 mg norethindrone and 0.035 mg ethinyl estradiol, and contain the following inactive ingredients: titanium dioxide, macrogol/PEG 3350 NF, talc, polyvinyl alcohol, iron oxide yellow, iron oxide black, lecithin (soya), lactose monohydrate, magnesium stearate and pregelatinized starch. The white tablets in the 28-Day regimen contain only inert ingredients as follows: titanium dioxide, polydextrose, hypromellose, triacetin, macrogol/polyethylene glycol 8000, lactose monohydrate, magnesium stearate and pregelatinized corn starch.

OVCON®50 (norethindrone and ethinyl estradiol) Tablets, USP Patients should be counseled that this product does not protect against HIV-infection (AIDS) and other sexually transmitted diseases. DESCRIPTION OVCON® 50, 28-Day (norethindrone and ethinyl estradiol tablets, USP) provides a continuous regimen for oral contraception derived from 21 tablets composed of norethindrone and ethinyl estradiol to be followed by 7 green tablets of inert ingredients. The chemical name for norethindrone is 17-hydroxy-19-nor-17α­pregn-4-en-20-yn-3-one and for ethinyl estradiol the chemical name is 19-nor-17α-pregna-1,3,5(10)-trien­20-yne-3,17-diol. The structural formulas are: The active OVCON (norethindrone and ethinyl estradiol tablets) 50 tablets contain 1 mg norethindrone and 0.05 mg ethinyl estradiol. OVCON (norethindrone and ethinyl estradiol tablets) ® 50, 28-Day contains the following inactive ingredients: dibasic calcium phosphate, D&C Yellow No. 10 (aluminum lake), FD&C Blue No. 1 (aluminum lake), FD&C Yellow No. 6 (aluminum lake), lactose, magnesium stearate, povidone, sodium starch glycolate, starch (corn), and talc.

Necon® 1/35 (norethindrone and ethinyl estradiol) Tablets USP Necon® 0.5/35 (norethindrone and ethinyl estradiol) Tablets USP Necon® 10/11 (norethindrone and ethinyl estradiol) Tablets USP Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 (norethindrone and mestranol) Tablets USP Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. DESCRIPTION Each of the following products is a combination oral contraceptive containing the progestational compound norethindrone and the estrogenic compound ethinyl estradiol: Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) : Each dark yellow tablet contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include D&C Yellow No. 10 Aluminum Lake, microcrystalline cellulose, lactose (anhydrous), magnesium stearate, polacrilin potassium, and povidone. Each white tablet in the Necon (norethindrone and ethinyl estradiol tablets ) ® 1/35 package contains only inert ingredients, as follows: micro- crystalline cellulose, lactose (anhydrous), and magnesium stearate. Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35: Each light yellow tablet contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include D&C Yellow No. 10 Aluminum Lake, microcrystalline cellulose, lactose (anhydrous), magnesium stearate, polacrilin potassium, and povidone. Each white tablet in the Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35 package contains only inert ingredients as listed under white tablets in Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) . Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11: Each light yellow tablet (10) contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Each dark yellow tablet (11) contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Inactive ingredients include D&C Yellow No. 10 Aluminum Lake, microcrys- talline cellulose, lactose (anhydrous), magnesium stearate, polacrilin potassium, and povidone. Each white tablet in the Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 package contains only inert ingredients as listed under white tablets in Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) . Each of the following products is a combination oral contraceptive containing the progestational compound norethindrone and the estrogenic compound mestranol: Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50: Each light blue tablet contains 1 mg of norethindrone and 0.05 mg of mestranol. Inactive ingredients include FD&C Blue No. 1 Aluminum Lake, microcrystalline cellulose, lactose (anhydrous), magnesium stearate, polacrilin potassium, and povidone. Each white tablet in the Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 package contains only inert ingredients as listed under white tablets in Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) . The chemical name for norethindrone is 17- hydroxy-19-nor-17a-pregn-4-en-20-yn-3-one, for ethinyl estradiol is 19-nor-17a-pregna- 1,3,5(10)-trien-20-yn-3,17-diol, and for mestranol is 3-methoxy-19-nor-17a-pregna-1,3,5(10)- trien-20-yn-17-ol. The structural formulas are as follows:

Find Lowest Prices on FEMCON® Fe (norethindrone and ethinyl estradiol) Tablets, Chewable and Ferrous Fumarate Tablets 0.4mg/35mcg Ferrous fumarate tablets are not USP for dissolution and assay. Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. DESCRIPTION FEMCON® Fe (norethindrone and ethinyl estradiol tablets) provides a regimen for oral contraception derived from 21 white tablets composed of norethindrone and ethinyl estradiol followed by 7 brown ferrous fumarate (placebo) tablets. The chemical name for norethindrone is 17-hydroxy-19-nor-17a-pregn-4-en-20-yn-3-one and for ethinyl estradiol the chemical name is 19-nor-17a-pregna-1,3,5(10)-trien-20-yne-3,17-diol. The structural formulas are: The active white FEMCON Fe (norethindrone and ethinyl estradiol tablets) tablets contain 0.4 mg norethindrone and 0.035 mg ethinyl estradiol, and the following inactive ingredients: dibasic calcium phosphate, lactose, magnesium stearate, maltodextrin, povidone, sodium starch glycolate, spearmint flavor and sucralose. The brown tablets contain ferrous fumarate, microcrystalline cellulose, magnesium stereate, povidone, sodium starch glycolate, and compressible sugar. The ferrous fumarate tablets do not serve any therapeutic purpose.

INDICATIONS Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. TABLE 1 : LOWEST EXPECTED AND TYPICAL FAILURE RATES DURING THE FIRST YEAR OF CONTINUOUS USE OF A METHOD % of Women Experiencing an Accidental Pregnancy in the First Year of Continuous Use Method (No contraception) Lowest Expected* (85) Typical† (85) Oral contraceptives combined 0.1 3* progestin only 0.5 3* Diaphragm with spermicidal cream or jelly 6 18 Spermicides alone (foam, creams, jellies and vaginal suppositories) 3 21 Vaginal sponge nulliparous 6 18 multiparous 9 28 IUD 0.8 to 2.0 3§ Condom without spermicides 2 12 Periodic abstinence (all methods) 1 to 9 20 Injectable progestogen 0.3 to 0.4 0.3 to 0.4 Implants 6 capsules 0.04 0.04 2 rods 0.03 0.03 Female sterilization 0.2 0.4 Male sterilization 0.1 0.15 Reproduced with permission of the Population Council from J. Trussell, et al: Contraceptive failure in the United States: An update. Studies in Family Planning, 21(1), January-February 1990. *The authors' best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any reason other than pregnancy. †This term represents “typical” couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any reason other than pregnancy. ‡Combined typical rate for both combined and progestin only. §Combined typical rate for both medicated and nonmedicated IUD. DOSAGE AND ADMINISTRATION The following is a summary of the instructions given to the patient in the “HOW TO TAKE THE PILL” section of the DETAILED PATIENT PACKAGE LABELING. The patient is given instructions in five (5) categories: IMPORTANT POINTS TO REMEMBER: The patient is told (a) that she should take one pill every day at the same time, (b) many women have spotting or light bleeding or gastric distress during the first one to three cycles, (c) missing pills can also cause spotting or light bleeding, (d) she should use a back-up method for contraception if she has vomiting or diarrhea or takes some concomitant medications, and/or if she has trouble remembering the pill, (e) if she has any other questions, she should consult her physician. BEFORE SHE STARTS TAKING HER PILLS : She should decide what time of day she wishes to take the pill, check whether her pill pack has 28 pills, and note the order in which she should take the pills (diagrammatic drawings of the pill pack are included in the patient insert). WHEN SHE SHOULD START THE FIRST PACK: The Day-One start is listed as the first choice and the Sunday start (the Sunday after her period starts) is given as the second choice. If she uses the Sunday start she should use a back-up method in the first cycle if she has intercourse before she has taken seven pills. WHAT TO DO DURING THE CYCLE: The patient is advised to take one pill at the same time every day until the pack is empty. If she is on the 28 day regimen, she should start the next pack the day after the last inactive tablet and not wait any days between packs. WHAT TO DO IF SHE MISSES A PILL OR PILLS: The patient is given instructions about what she should do if she misses one, two or more than two pills at varying times in her cycle for both the Day-One and the Sunday start. The patient is warned that she may become pregnant if she has unprotected intercourse in the seven days after missing pills. To avoid this, she must use another birth control method such as condom, foam, or sponge in these seven days. HOW SUPPLIED Vyfemla (norethindrone and ethinyl estradiol tablets USP) is available in wallet (NDC 68180-875-11) containing 28 tablets packed in a pouch (NDC 68180-875-11). Such three pouches are packaged in a carton (NDC 68180-875-13). Each of the 21 light peach colored, round, flat face beveled edged tablets debossed with “LU” on one side and “I25” on the other side containing 0.4 mg norethindrone and 0.035 mg ethinyl estradiol. Each of the 7 white to off-white, round, biconvex tablets debossed with “LU” on one side and “U22” on other side containing inert ingredients. Store at 25°C (77°F); excursions permitted to 15 to 30°C (59 to 86°F). [See USP Controlled Room Temperature]. References are available upon request. Distributed by: Lupin Pharmaceuticals , Inc., Baltimore, Maryland 21202, United States. Manufactured by: Lupin Limited, Pithampur (M.P.) - 454 775, INDIA. Revised: Sep 2015

INDICATIONS Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. TABLE 1 LOWEST EXPECTED AND TYPICAL FAILURE RATES DURING THE FIRST YEAR OF CONTINUOUS USE OF A METHOD % of Women Experiencing an Accidental Pregnancy in the First Year of Continuous Use Method Lowest Expected* Typical** (No contraception) (85) (85) Oral contraceptives combined 0.1 3*** progestin only 0.5 3*** Diaphragm with spermicidal cream or jelly 6 18 Spermicides alone (foam, creams, jellies and vaginal suppositories) 3 21 Vaginal sponge nulliparous 6 18 multiparous 9 28 IUD 0.8-2.0 3# Condom without spermicides 2 12 Periodic abstinence (all methods) 1-9 20 Injectable progestogen 0.3-0.4 0.3-0.4 Implants 6 capsules 0.04 0.04 2 rods 0.03 0.03 Female sterilization 0.2 0.4 Male sterilization 0.1 0.15 Reproduced with permission of the Population Council from J. Trussell, et. al: Contraceptive failure in the United States: An update. Studies in Family Planning, 21(1), January-February 1990. *The authors’ best guess of the percentage of women expected to experience an accidental pregnancy among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any reason other than pregnancy. **This term represents “typical” couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any reason other than pregnancy. ***Combined typical rate for both combined and progestin only. #Combined typical rate for both medicated and nonmedicated IUD. DOSAGE AND ADMINISTRATION The following is a summary of the instructions given to the patient in the “ HOW TO TAKE THE PILL” section of the DETAILED PATIENT LABELING. The patient is given instructions in five (5) categories: IMPORTANT POINTS TO REMEMBER: The patient is told (a) that she should take one pill every day at the same time, (b) many women have spotting or light bleeding or gastric distress during the first one to three cycles, (c) missing pills can also cause spotting or light bleeding, (d) she should use a back-up method for contraception if she has vomiting or diarrhea or takes some concomitant medications, and/or if she has trouble remembering the pill, (e) if she has any other questions, she should consult her physician. BEFORE SHE STARTS TAKING HER PILLS: She should decide what time of day she wishes to take the pill, check whether her pill pack has 28 pills, and note the order in which she should take the pills (diagrammatic drawings of the pill pack are included in the patient insert). WHEN SHE SHOULD START THE FIRST PACK: The Day-One start is listed as the first choice and the Sunday start (the Sunday after her period starts) is given as the second choice. If she uses the Sunday start she should use a back-up method in the first cycle if she has intercourse before she has taken seven pills. WHAT TO DO DURING THE CYCLE: The patient is advised to take one pill at the same time every day until the pack is empty. If she is on the 28 day regimen, she should start the next pack the day after the last inactive tablet and not wait any days between packs. WHAT TO DO IF SHE MISSES A PILL OR PILLS: The patient is given instructions about what she should do if she misses one, two or more than two pills at varying times in her cycle for both the Day-One and the Sunday start. The patient is warned that she may become pregnant if she has unprotected intercourse in the seven days after missing pills. To avoid this, she must use another birth control method such as condom, foam, or sponge in these seven days. HOW SUPPLIED PHILITH™ 28-Day (norethindrone 0.4 mg and ethinyl estradiol 0.035 mg tablets, USP) are available in a compact blister card (NDC 16714-347-01). Each blister card contains 21 tan, biconvex round tablets debossed with “C35” on one side. Each 7 white, biconvex round tablets debossed with “P” on one side and “N” on the other side. PHILITH™ Tablets are available in the following: Carton of 1 NDC 16714-347-02 Carton of 3 NDC 16714-347-03 Carton of 6 NDC 16714-347-04 Store at controlled room temperature, 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP]. References are available upon request. Manufactured by: Novast Laboratories Ltd. Nantong, China 226009. Revised: Apr 2012

INDICATIONS Oral contraceptives are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptive products such as OVCON (norethindrone and ethinyl estradiol tablets) 50, 28-Day, which contain 50 mcg of estrogen, should not be used unless medically indicated. Oral contraceptives are highly effective. Table 1 lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. TABLE 1: LOWEST EXPECTED AND TYPICAL FAILURE RATES DURING THE FIRST YEAR OF CONTINUOUS USE OF A METHOD % of Women Experiencing an Accidental Pregnancy in the First Year of Continuous Use Method Lowest Expected* Typical** (No contraception) (85) (85) Oral contraceptives combined 0.1 3*** progestin only 0.5 3*** Diaphragm with spermicidal cream or jelly 6 18 Spermicides alone (foam, creams, jellies and vaginal suppositories) 3 21 Vaginal sponge nulliparous 6 18 multiparous 9 28 IUD 0.8-2.0 3# Condom without spermicides 2 12 Periodic abstinence (all methods) 1-9 20 Injectable progestogen 0.3-0.4 0.3-0.4 Implants 6 capsules 0.04 0.04 2 rods 0.03 0.03 Female sterilization 0.2 0.4 Male sterilization 0.1 0.15 Reproduced with permission of the Population Council from J. Trussell, et al: Contraceptive failure in the United States: An update. Studies in Family Planning, 21(1), January-February 1990. *The authors' men expected to experience an accidental pregnancybest guess of the percentage of wo among couples who initiate a method (not necessarily for the first time) and who use it consistently and correctly during the first year if they do not stop for any reason other than pregnancy. **This term represents "typical" couples who initiate use of a method (not necessarily for the first time), who experience an accidental pregnancy during the first year if they do not stop use for any reason other than pregnancy. ***Combined typical rate for both combined and progestin only. #Combined typical rate for both medicated and nonmedicated IUD. DOSAGE AND ADMINISTRATION The following is a summary of the instructions given to the patient in the "HOW TO TAKE THE PILL" section of the DETAILED PATIENT PACKAGE INSERT. The patient is given instructions in five (5) categories. IMPORTANT POINTS TO REMEMBER: The patient is told (a) that she should take one pill every day at the same time, (b) many women have spotting or light bleeding or gastric distress during the first one to three cycles, (c) missing pills can also cause spotting or light bleeding, (d) she should use a back-up method for contraception if she has vomiting or diarrhea or takes some concomitant medications, and/or if she has trouble remembering the pill, (e) if she has any other questions, she should consult her physician. BEFORE SHE STARTS TAKING HER PILLS: She should decide what time of day she wishes to take the pill, check whether her pill pack has 21 or 28 pills, and note the order in which she should take the pills (diagrammatic drawings of the pill pack are included in the patient insert). WHEN SHE SHOULD START THE FIRST PACK: The Day-One start is listed as the first choice and the Sunday start (the Sunday after her period starts) is given as the second choice. If she uses the Sunday start she should use a back-up method in the first cycle if she has intercourse before she has taken seven pills. WHAT TO DO DURING THE CYCLE: The patient is advised to take one pill at the same time every day until the pack is empty. If she is on a 21-day regimen, she should wait seven days to start the next pack. If she is on the 28-day regimen, she should start the next pack the day after the last inactive tablet and not wait any days between packs. WHAT TO DO IF SHE MISSES A PILL OR PILLS: The patient is given instructions about what she should do if she misses one, two or more than two pills at varying times in her cycle for both the Day-One and the Sunday start. The patient is warned that she may become pregnant if she has unprotected intercourse in the seven days. To avoid this, she must use another birth control method such as condom, foam, or sponge in these seven days. HOW SUPPLIED OVCON® 50 (norethindrone and ethinyl estradiol tablets, USP) is available in 28-day regimens. Each package contains 21 round, yellow tablets of 1.0 mg norethindrone and 0.05 mg ethinyl estradiol, imprinted with WC on one side and 585 on the other. Each capsule shaped, green tablet in the 28-day regimen contains inert ingredients and is imprinted with WC on one side and 850 on the other. OVCON (norethindrone and ethinyl estradiol tablets) ® 50, 28-Day N 0430-0585-14 Carton of 6 blister cards (dispensers) Store below 30º C (86º F). References are available upon request. Manufactured by: Warner Chilcott Company, Inc. Fajardo, PR 00738. Marketed by: Warner Chilcott (US), Inc. Rockaway, NJ 07866. 1-800-521-8813. Revised: July 2008. FDA rev date: 07/22/08

INDICATIONS Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) , Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35, Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11, and Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 are indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table I lists the typical accidental pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. TABLE I: PERCENTAGE OF WOMEN EXPERIENCING AN UNINTENDED PREGNANCY DURING THE FIRST YEAR OF TYPICAL USE AND THE FIRST YEAR OF PERFECT USE OF CONTRACEPTION AND THE PERCENTAGE CONTINUING USE AT THE END OF THE FIRST YEAR. UNITED STATES. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year3 Method (1) Typical Use1 (2) Perfect Use2 (3) (4) Chance4 - 85 85 Spermicides5 - 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-Thermal6 - 2 Post-Ovulation 1 Withdrawal 19 4 Cap7 - Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm7 - 20 6 56 Condom8 - Female (Reality) 21 5 56 Male 14 3 61 Pill 5 71 Progestin Only 0.5 Combined 0.1 IUD Progesterone T 2.0 1.5 81 Copper T380A 0.8 0.6 78 LNg 20 0.1 0.1 81 Depo-Provera 0.3 0.3 70 Norplant and Norplant -2 0.05 0.05 88 Female Sterilization 0.5 0.5 100 Male Sterilization 0.15 0.10 100 Adapted from Hatcher et al., 1998 Ref. # 1.Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason. 3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year. 4 The percents becoming pregnant in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% become pregnant within one year. This estimate was lowered slightly (to 85%) to represent the percent who would become pregnant within one year among women now relying on reversible methods of contraception if they abandoned contraception altogether. 5Foams, creams, gels, vaginal suppositories, and vaginal film. 6Cervical mucus (ovulation) method supplemented by calendar in the preovulatory and basal body temperature in the post-ovulatory phases. 7 With spermicidal cream or jelly. 8 Without spermicides. DOSAGE AND ADMINISTRATION To achieve maximum contraceptive effectiveness, Necon (norethindrone and ethinyl estradiol tablets ) ® Tablets must be taken exactly as directed and at intervals not exceeding 24 hours. 28-Day Regimen (Sunday Start) When taking Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) , Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35, Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 and Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50, the first tablet should be taken on the first Sunday after menstruation begins. If period begins on Sunday, the first tablet should be taken that day. Take one active tablet daily for 21 days followed by one white placebo tablet daily for 7 days. After 28 tablets have been taken, a new course is started the next day (Sunday). For the first cycle of a Sunday Start regimen, another method of contraception should be used until after the first 7 consecutive days of administration. If the patient misses one (1) active tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) active tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the dispenser. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. If the patient misses two (2) active tablets in the third week or misses three (3) or more active tablets in a row, the patient should continue taking one tablet every day until Sunday. On Sunday, the patient should throw out the rest of the dispenser and start a new dispenser that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. Complete instructions to facilitate patient counseling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section). 28-Day Regimen (Day 1 Start) The dosage of Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) , Necon (norethindrone and ethinyl estradiol tablets ) ®0.5/35, Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 and Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50, for the initial cycle of therapy is one active tablet administered daily from the 1st through the 21st day of the menstrual cycle, counting the first day of menstrual flow as "Day 1" followed by one white tablet daily for 7 days. Tablets are taken without interruption for 28 days. After 28 tablets have been taken, a new course is started the next day. If the patient misses one (1) active tablet in Weeks 1, 2, or 3, the tablet should be taken as soon as she remembers. If the patient misses two (2) active tablets in Week 1 or Week 2, the patient should take two (2) tablets the day she remembers and two (2) tablets the next day; and then continue taking one (1) tablet a day until she finishes the dispenser. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. If the patient misses two (2) active tablets in the third week or misses three (3) or more active tablets in a row, the patient should throw out the rest of the dispenser and start a new dispenser that same day. The patient should be instructed to use a back-up method of birth control if she has sex in the seven (7) days after missing pills. Complete instructions to facilitate patient coun- seling on proper pill usage may be found in the Detailed Patient Labeling ("How to Take the Pill" section). The use of Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) , Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35, Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 and Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 for contraception may be initiated 4 weeks postpartum in women who elect not to breast feed. When the tablets are administered during the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered. (See CONTRAINDICATIONS and WARNINGS concerning thromboembolic disease. See also PRECAUTIONS for "Nursing Mothers".) The possibil- ity of ovulation and conception prior to initiation of medication should be considered. (See Discussion of Dose-Related Risk of Vascular Disease from Oral Contraceptives.) Additional Instructions For All Dosing Regimens Breakthrough bleeding, spotting, and amenorrhea are frequent reasons for patients discontinuing oral contraceptives. In breakthrough bleeding, as in all cases of irregular bleeding from the vagina, nonfunctional causes should be borne in mind. In undiagnosed persistent or recurrent abnormal bleeding from the vagina, adequate diagnostic measures are indicated to rule out pregnancy or malignancy. If pathology has been excluded, time or a change to another formulation may solve the problem. Changing to an oral contraceptive with a higher estrogen content, while potentially useful in minimizing menstrual irregularity, should be done only if necessary since this may increase the risk of thromboembolic disease. Use of oral contraceptives in the event of a missed menstrual period: If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period and oral contraceptive use should be discontinued until pregnancy is ruled out. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. HOW SUPPLIED Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) : (Norethindrone and Ethinyl Estra- diol Tablets USP) Each dark yellow Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) tablet is round in shape, unscored, with a debossed WATSON on one side and 508 on the other side, and contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) is packaged in cartons of three tablet dispensers (NDC 52544-552-31) and in cartons of six tablet dispensers (NDC 52544-552-28). Each dispenser contains 21 dark yellow tablets and 7 white placebo tablets. (Placebo tablets have a debossed WATSON on one side and P on the other side.) Necon® 0.5/35: (Norethindrone and Ethinyl Estradiol Tablets USP) Each light yellow Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35 tablet is round in shape, unscored, with a debossed WATSON on one side and 507 on the other side, and contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35 is packaged in cartons of three tablet dispensers (NDC 52544-550-31) and in cartons of six tablet dispensers (NDC 52544-550-28). Each dispenser contains 21 light yellow tablets and 7 white placebo tablets (Placebo tablets have a debossed WATSON on one side and P on the other side.) Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11: (Norethindrone and Ethinyl Estra- diol Tablets USP) Each light yellow Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 tablet is round in shape, with a debossed WATSON on one side and 507 on the other side, and contains 0.5 mg of norethindrone and 0.035 mg of ethinyl estradiol. Each dark yellow Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 tablet is round in shape, with a debossed WATSON on one side and 508 on the other side, and contains 1 mg of norethindrone and 0.035 mg of ethinyl estradiol. Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 is packaged in cartons of three tablet dispensers (NDC 52544-554-31) and in cartons of six tablet dispensers (NDC 52544-554- 28). Each dispenser contains 10 light yellow tablets and 11 dark yellow tablets, and 7 white placebo tablets. (Placebo tablets have a debossed WATSON on one side and P on the other side.) Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50: (Norethindrone and Mestranol Tablets USP) Each light blue Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 tablet is round in shape, unscored, with a debossed WATSON on one side and 510 on the other side, and contains 1 mg of norethindrone and 0.05 mg of mestranol. Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 is packaged in cartons of three tablet dispensers (NDC 52544-556-31) and in cartons of six tablet dispensers (NDC 52544-556-28). Each dispenser contains 21 light blue tablets and 7 white placebo tablets. (Placebo tablets have a debossed WATSON on one side and P on the other side.) Store at 20°-25°C (68°-77°F). [See USP controlled room temperature.] Watson Pharma, Inc. A Subsidiary of Watson Pharmaceuticals, Inc. Corona, CA 92880, USA. Revised: September 2006. FDA Rev date: n/a

INDICATIONS FEMCON Fe (norethindrone and ethinyl estradiol tablets) is indicated for the prevention of pregnancy in women who elect to use this product as a method of contraception. Oral contraceptives are highly effective. Table 2 lists the typical unintended pregnancy rates for users of combination oral contraceptives and other methods of contraception. The efficacy of these contraceptive methods, except sterilization, the IUD, and implants, depends upon the reliability with which they are used. Correct and consistent use of methods can result in lower failure rates. TABLE 2: Percentage of women experiencing an unintended pregnancy during the first year of typical use and the first year of perfect use of contraception and the percentage continuing use at the end of the first year. United States. % of Women Experiencing an Unintended Pregnancy within the First Year of Use % of Women Continuing Use at One Year3 Method Typical Use1 Perfect Use2 (1) (2) (3) (4) Chance4 85 85 Spermicides5 26 6 40 Periodic abstinence 25 63 Calendar 9 Ovulation Method 3 Sympto-thermal6 2 Post-Ovulation 1 Cap7 Parous Women 40 26 42 Nulliparous Women 20 9 56 Sponge Parous Women 40 20 42 Nulliparous Women 20 9 56 Diaphragm7 20 6 56 Withdrawal 19 4 Condom8 Female (reality) 21 5 56 Male 14 3 61 Pill 5 71 Progestin only 0.5 Combined 0.1 IUD Progesterone T 2.0 1.5 81 Copper T 380A 0.8 0.6 78 LNg 20 0.1 0.1 81 Depo-Provera® 0.3 0.3 70 Norplant® and Norplant® 2 0.05 0.05 88 Female Sterilization 0.5 0.5 100 Male Sterilization 0.15 0.10 100 Emergency Contraceptive Pills: Treatment initiated within 72 hours after unprotected intercourse reduces risk of pregnancy by at least 75%9 Lactational Amenorrhea Method: LAM is a highly effective, temporary method of contraception10 Source: Trussell J, Stewart F, Contraceptive Efficacy. In Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, Contraceptive Technology: Seventeenth Revised Edition. New York, NY: Irvington Publishers, 1998. 1 Among typical couples who initiate use of a method (not necessarily for the first time), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason 2 Among couples who initiate use of a method (not necessarily for the first time) and who use it perfectly (both consistently and correctly), the percentage who experience an accidental pregnancy during the first year if they do not stop use for any other reason 3 Among couples attempting to avoid pregnancy, the percentage who continue to use a method for one year 4 The percentage of women becoming pregnant noted in columns (2) and (3) are based on data from populations where contraception is not used and from women who cease using contraception in order to become pregnant. Among such populations, about 89% became pregnant in one year. This estimate was lowered slightly (to 85%) to represent the percentage that would become pregnant within one year among women now relying on reversible methods of contraception if they abandon contraception altogether 5 Foams, creams, gels, vaginal suppositories and vaginal film 6 Cervical mucous (ovulation) method supplemented by calendar in the preovulatory and basal body temperature in the postovulatory phases 7 With spermicidal cream or jelly 8 Without spermicides 9 The treatment schedule is one dose within 72 hours after unprotected intercourse and a second dose 12 hours after the first dose. The Food and Drug Administration has declared the following brands of oral contraceptives to be safe and effective for emergency contraception: Ovral® (1 dose is 2 white pills), Alesse® (1 dose is 5 pink pills), Nordette® or Levlen® (1 dose is 2 light orange pills), Lo/Ovral® (1 dose is 4 white pills), Triphasil® or Tri-Levlen® (1 dose is 4 yellow pills) 10 However, to maintain effective protection against pregnancy, another method of contraception must be used as soon as menstruation resumes, the frequency or duration of breastfeeds is reduced, bottle feeds are introduced or the baby reaches six months of age DOSAGE AND ADMINISTRATION To achieve maximum contraceptive effectiveness, FEMCON Fe (norethindrone and ethinyl estradiol tablets) must be taken exactly as directed and at intervals not exceeding 24 hours. The dosage of FEMCON Fe (norethindrone and ethinyl estradiol tablets) is one white tablet daily for 21 consecutive days, followed by one brown tablet daily for 7 consecutive days. It is recommended that tablets be taken at the same time each day. The pill may be swallowed whole or chewed and swallowed. If the pill is chewed, the patient should drink a full glass (8 ounces) of liquid immediately after swallowing. During the first cycle of use, the patient is instructed to begin taking FEMCON Fe (norethindrone and ethinyl estradiol tablets) on either Day 1 or the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first tablet (white) is taken that day. One white tablet should be taken daily for 21 consecutive days followed by one brown tablet daily for 7 consecutive days. Withdrawal bleeding should usually occur within three days following discontinuation of white tablets and may not have finished before the next pack is started. During the first cycle with a Sunday start, contraceptive reliance should not be placed on FEMCON Fe (norethindrone and ethinyl estradiol tablets) until a white tablet has been taken daily for 7 consecutive days and a non-hormonal back-up method of birth control (such as condoms or spermicide) should be used during those 7 days. The possibility of ovulation and conception prior to initiation of medication should be considered. The patient begins her next and all subsequent 28-day courses of tablets on the same day of the week on which she began her first course, following the same schedule: 21 days on white tablets-7 days on brown tablets. If in any cycle the patient starts tablets later than the proper day, she should protect herself against pregnancy by using a non-hormonal back-up method of birth control until she has taken a white tablet daily for 7 consecutive days. When the patient is switching from a 21-day regimen of tablets, she should wait 7 days after her last tablet before she starts FEMCON Fe (norethindrone and ethinyl estradiol tablets) . She will probably experience withdrawal bleeding during that week. She should be sure that no more than 7 days pass after her previous 21-day regimen. When the patient is switching from a 28-day regimen of tablets, she should start her first pack of FEMCON Fe (norethindrone and ethinyl estradiol tablets) on the day after her last tablet. She should not wait any days between packs. The patient may switch any day from a progestin-only pill and should begin FEMCON Fe (norethindrone and ethinyl estradiol tablets) the next day. If switching from an implant or injection, the patient should start FEMCON Fe (norethindrone and ethinyl estradiol tablets) on the day of implant removal or, if using an injection, the day the next injection would be due. If spotting or breakthrough bleeding occurs, the patient is instructed to continue on the same regimen. This type of bleeding is usually transient and without significance; however, if the bleeding is persistent or prolonged, the patient is advised to consult her healthcare provider. Although pregnancy is unlikely if FEMCON Fe (norethindrone and ethinyl estradiol tablets) is taken according to directions, if withdrawal bleeding does not occur, the possibility of pregnancy must be considered. If the patient has not adhered to the prescribed schedule (missed one or more tablets or started taking them on a day later than she should have), the probability of pregnancy should be considered at the time of the first missed period and appropriate diagnostic measures taken. If the patient has adhered to the prescribed regimen and misses two consecutive periods, pregnancy should be ruled out. Hormonal contraceptives should be discontinued if pregnancy is confirmed. For additional patient instructions regarding missed pills, see the "WHAT TO DO IF YOU MISS PILLS" section in the DETAILED PATIENT LABELING. Any time the patient misses two or more white tablets, she should also use another method of non-hormonal back-up contraception until she has taken a white tablet daily for seven consecutive days. If the patient misses one or more brown tablets, she is still protected against pregnancy provided she begins taking white tablets again on the proper day. If breakthrough bleeding occurs following missed white tablets, it will usually be transient and of no consequence. The possibility of ovulation increases with each successive day that scheduled white tablets are missed. The risk of pregnancy increases with each active (white) tablet missed. FEMCON Fe (norethindrone and ethinyl estradiol tablets) may be initiated no earlier than day 28 postpartum in the nonlactating mother due to the increased risk for thromboembolism. When the tablets are administered in the postpartum period, the increased risk of thromboembolic disease associated with the postpartum period must be considered (see "CONTRAINDICATIONS," "WARNINGS," and "PRECAUTIONS" concerning thromboembolic disease). The patient should be advised to use a non-hormonal back-up method for the first 7 days of tablet-taking. However, if intercourse has already occurred, the possibility of ovulation and conception prior to initiation of medication should be considered. FEMCON Fe (norethindrone and ethinyl estradiol tablets) may be initiated after a first-trimester abortion; if the patient starts FEMCON Fe (norethindrone and ethinyl estradiol tablets) immediately, additional contraceptive measures are not needed. For additional patient instructions regarding complete dosing instructions, see the "HOW TO TAKE THE PILL" section in the DETAILED PATIENT LABELING. HOW SUPPLIED FEMCON® Fe (norethindrone and ethinyl estradiol tablets, chewable and ferrous fumarate tablets) is available only in a 28-day regimen. Each package contains 21 round, white tablets of 0.4 mg norethindrone and 0.035 mg ethinyl estradiol, imprinted with W|C on one side and 581 on the other. Each brown, round tablet contains 75 mg ferrous fumarate, imprinted with PD 622 on one side. FEMCON® Fe (norethindrone and ethinyl estradiol tablets) N 0430-0482-14 Carton of 5 Blister Cards of 28 Tablets Each Store at 25° C (77° F); excursions permitted to 15°- 30° C (59°- 86° F) [see USP Controlled Room Temperature] References are available upon request. Manufactured by: Warner Chilcott Company, Inc. Fajardo, PR 00738. Marketed by: Warner Chilcott (US), LLC, Rockaway, NJ 07866. 1-800-521-8813. Revised January 2008. FDA rev date: 1/9/2008

PATIENT INFORMATION BRIEF SUMMARY PATIENT PACKAGE INSERT This product (like all oral contraceptives ) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Oral contraceptives, also known as “birth control pills” or “the pill,” are taken to prevent pregnancy and when taken correctly, have a failure rate of about 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 3% per year when women who miss pills are included. Oral contraceptive use is associated with certain serious diseases that can be life-threatening or may cause temporary or permanent disability. The risks associated with taking oral contraceptives increase significantly if you: Smoke Have high blood pressure, diabetes, high cholesterol Have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors. You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding. Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. Most side effects of the pill are not serious. The most common side effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first three months of use. The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. However, you should know that the following medical conditions have been associated with or made worse by the pill: Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack or angina pectoris), or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer. High blood pressure, although blood pressure usually returns to normal when the pill is stopped. The symptoms associated with these serious side effects are discussed in the detailed leaflet given to you with your supply of pills. Notify your doctor or health care provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics may decrease oral contraceptive effectiveness. Studies to date of women taking the pill have not shown an increase in the incidence of cancer of the breast or cervix. There is, however, insufficient evidence to rule out the possibility that the pill may cause such cancers. Taking the pill provides some important noncontraceptive effects. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus. Be sure to discuss any medical condition you may have with your health care provider. Your health care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient labeling gives you further information which you should read and discuss with your health care professional. DOSAGE AND ADMINISTRATION HOW TO TAKE THE PILL: The instructions given in the COMBINATION DETAILED PATIENT LABELING AND BRIEF SUMMARY insert are included inside each compact dispenser. The instructions include the directions on starting the first pack on Day-One (first choice) of her period and the Sunday start (Sunday after period starts). The patient is advised that, if she used the Sunday start, she should use a back-up method in the first cycle if she has intercourse before she has taken seven pills. The patient is also instructed as to what she should do if she misses a pill or pills. The patient is warned that she may become pregnant if she misses a pill or pills and that she should use a back-up method of birth control in the event she has intercourse any time during the seven day period following the missed pill or pills. Instructions on how to use the blister card for the (28 Tablets) are included in the DETAILED PATIENT LABELING. DETAILED PATIENT LABELING This product (like all oral contraceptives ) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. INTRODUCTION: Any woman who considers using oral contraceptives (the “birth control pill” or the “pill”) should understand the benefits and risks of using this form of birth control. Although the oral contraceptives have important advantages over other methods of contraception, they have certain risks that no other method has and some of these risks may continue after you have stopped using the oral contraceptive. This brochure will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this brochure is not a replacement for a careful discussion between you and your health care professional. You should discuss the information provided in this brochure with him or her, both when you first start taking the pill and during your revisits. You should also follow your health care professional’s advice with regard to regular check-ups while you are on the pill. EFFECTIVENESS OF ORAL CONTRACEPTIVES: Oral contraceptives or “birth control pills” or “the pill” are used to prevent pregnancy and are more effective than other nonsurgical methods of birth control. The chance of becoming pregnant is less than 1% (1 pregnancy per 100 women per year of use) when the pills are used correctly and no pills are missed. Typical failure rates are actually 3% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle. In comparison, typical accidental pregnancy rates for other nonsurgical methods of birth control during the first year of use are as follows: IUD: 3% Diaphragm with spermicides: 18% Spermicides alone: 21% Vaginal Sponge: 18% to 28% Condom alone: 12% Periodic abstinence: 20% Injectable progestogen: 0.3% to 0.4% Implants: 0.03% to 0.04% No methods: 85% WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES: Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should not smoke. Some women should not use the pill. For example, you should not take the pill if you are pregnant or think you may be pregnant. You should also not use the pill if you have or have ever had any of the following conditions: A history of heart attack or stroke Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes A history of blood clots in the deep veins of your legs Chest pain (angina pectoris) Known or suspected breast cancer or cancer of the lining of the uterus Unexplained vaginal bleeding (until a diagnosis is reached by your doctor) Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill Liver tumor (benign or cancerous) Tell your health care professional if you have ever had any of these conditions. Your health care professional can recommend a safer method of birth control. OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES: Tell your health care professional if you have: Breast nodules, fibrocystic disease of the breast or an abnormal breast x-ray or mammogram Diabetes Elevated cholesterol or triglycerides High blood pressure Migraine or other headaches or epilepsy Mental depression Gallbladder, heart or kidney disease History of scanty or irregular menstrual periods Women with any of these conditions should be checked often by their health care professional if they choose to use oral contraceptives. Also, be sure to inform your doctor or health care professional if you smoke or are on any medications. RISKS OF TAKING ORAL CONTRACEPTIVES: Risk Of Developing Blood Clots: Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Either of these can cause death or disability. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision. If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness, or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your doctor about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breastfeeding. If you are breastfeeding, see the section on Breastfeeding in GENERAL PRECAUTIONS. Heart Attacks And Strokes : Oral contraceptives may increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or disability. Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease. Gallbladder Disease: Oral contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens. Liver Tumors: In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible, but not definite, association has been found with the pill and liver cancers in two studies, in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers in general are extremely rare and the chance of developing liver cancer from using the pill is thus even rarer. Cancer Of The Reproductive Organs: There is, at present, no confirmed evidence that oral contraceptives increase the risk of cancer of the reproductive organs and breasts in human studies. Several studies have found no overall increase in the risk of developing breast cancer. However, women who use oral contraceptives and have a strong family history of breast cancer, or who have breast nodules or abnormal mammograms, should be closely followed by their doctors. Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY: All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table. ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Method of control and outcome AGE 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 *Deaths are birth related. **Deaths are method related. It can be seen in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7- 26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was always lower than that associated with pregnancy for any age group, although over the age of 40, the risk increases to 32 deaths per 100,000 women, compared to 28 associated with pregnancy at that age. However, for pill users who smoke and are over the age of 35, the estimated number of deaths exceeds those for other methods of birth control. If a woman is over the age of 40 and smokes, her estimated risk of death is four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000 women) in that age group. The suggestion that women over 40 who don’t smoke should not take oral contraceptives is based on information from older high-dose pills and on less selective use of pills than is practiced today. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, nonsmoking women over 40 years of age may outweigh the possible risks. However, all women, especially older women, are cautioned to use the lowest dose pill that is effective. In the above table, the risk of death from any birth control method is less than the risk of childbirth, except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. You should discuss this information with your health care professional. WARNING SIGNALS: If any of these adverse conditions occur while you are taking oral contraceptives, call your doctor immediately: Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung) Pain in the calf (indicating a possible clot in the leg) Crushing chest pain or heaviness in the chest (indicating a possible heart attack) Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke) Sudden partial or complete loss of vision (indicating a possible clot in the eye) Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your doctor or health care provider to show you how to examine your breasts) Severe pain or tenderness in the stomach area (indicating a possibly ruptured liver tumor) Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression) Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems) Abnormal vaginal bleeding (see SIDE EFFECTS OF ORAL CONTRACEPTIVES, 1. Vaginal Bleeding below.) SIDE EFFECTS OF ORAL CONTRACEPTIVES: In addition to the risks and more serious side effects discussed above (see RISKS OF TAKING ORAL CONTRACEPTIVES, ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY and WARNING SIGNALS sections above), the following may also occur: Vaginal Bleeding: Irregular vaginal bleeding or spotting may occur while you are taking the pills. Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Irregular bleeding occurs most often during the first few months of oral contraceptive use, but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue taking your pills on schedule. If the bleeding occurs in more than one cycle or lasts for more than a few days, talk to your doctor or health care provider. Gastrointestinal Effects: The most frequent, unpleasant side effects are nausea and vomiting, stomach cramps, bloating, and a change in appetite. Contact Lenses : If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your doctor or health care provider. Fluid Retention: Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your doctor or health care professional. Melasma: A spotty darkening of the skin is possible, particularly of the face. Other Side Effects : Other side effects may include change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, and vaginal infections. If any of these side effects bother you, call your doctor or health care professional. GENERAL PRECAUTIONS: Missed Periods and Use of Oral Contraceptives Before or During Early Pregnancy: There may be times when you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss one menstrual period, continue taking your pills for the next cycle but be sure to inform your health care professional before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your health care professional immediately to determine whether you are pregnant. Do not continue to take oral contraceptives until you are sure you are not pregnant, but continue to use another method of contraception. There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects, when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these studies have not been confirmed. Nevertheless, oral contraceptives or any other drugs should not be used during pregnancy unless clearly necessary and prescribed by your doctor. You should check with your doctor about risks to your unborn child of any medication taken during pregnancy. While Breast feeding: If you are breastfeeding, consult your doctor before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breastfeeding. You should use another method of contraception since breastfeeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breastfeed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. Laboratory Tests : If you are scheduled for any laboratory tests, tell your doctor you are taking birth control pills. Certain blood tests may be affected by birth control pills. Drug Interactions : Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such as barbiturates (for example, phenobarbital) and phenytoin (Dilantin is one brand of this drug), phenylbutazone (Butazolidin is one brand) and possibly ampicillin and tetracyclines (several brand names). You may need to use an additional method of contraception when you take drugs which can make oral contraceptives less effective. HOW TO TAKE THE PILL IMPORTANT POINTS TO REMEMBER SEXUALLY TRANSMITTED DISEASES This product (like all oral contraceptives ) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as Chlamydia, genital herpes , genital warts , gonorrhea, hepatitis B, and syphilis . BEFORE YOU START TAKING YOUR PILLS: BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills. Anytime you are not sure what to do. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS. If you do feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your doctor or clinic. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. IF YOU HAVE VOMITING OR DIARRHEA, for any reasons, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well. Use a back-up method (such as condoms, foam or sponge) until you check with your doctor or clinic. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic. BEFORE YOU START TAKING YOUR PILLS DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. LOOK AT YOUR PILL PACK TO SEE IF IT HAS 28 PILLS: The 28 pill pack has 21 “active” tan pills (with hormones) to take for 3 weeks, followed by 1 week of reminder white pills (without hormones). Refer to the sample of the blister card below. ALSO FIND: where on the pack to start taking pills, in what order to take the pills (follow the arrows), and the week numbers as shown in the picture below. Example Only: BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms, foam or sponge) to use as a back-up in case you miss pills. An EXTRA, FULL PILL PACK. WHEN TO START THE FIRST PACK OF PILLS You have a choice of which day to start taking your first pack of pills. PHILITH™ (norethindrone and ethinyl estradiol tablets, USP): is available in a compact blister card which is designed for a Sunday Start. Day 1 Start is also provided. Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember. Pick the Days of the Week Sticker that starts with the first day of your period. When you have picked the right sticker, throw away the others and place the sticker on the blister card over the pre-printed days of the week and make sure it lines up with the pills. If your Physician has instructed you to use a “Sunday Start” method, then use the blister card which is set up for a Sunday start. DAY-1 START: Take the first “active” tan pill of the first pack during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: Take the first “active” tan pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms, foam, or the sponge are good back-up methods of birth control. WHAT TO DO DURING THE MONTH TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY. Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS: 28 pills: Start the next pack on the day after your last “reminder” pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS If you MISS 1 tan “active” pill: Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. You do not need to use a back-up birth control method if you have sex. If you MISS 2 tan “active” pills in a row in WEEK 1 OR WEEK 2 of your pack: Take 2 pills on the day you remember and 2 pills the next day. Then take 1 pill a day until you finish the pack. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam or sponge) as a back-up for those 7 days. If you MISS 2 tan “active” pills in a row in THE 3rd WEEK: If you are a Day-1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam or sponge) as a back-up for those 7 days. If you MISS 3 OR MORE tan “active” pills in a row (during the first 3 weeks): If you are a Day-1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam or sponge) as a back-up for those 7 days. A REMINDER FOR THOSE ON 28-DAY PACKS: If you forget any of the 7 white “reminder” pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE “ACTIVE” PILL EACH DAY until you can reach your doctor or clinic. GENERAL: Pregnancy Due to Pill Failure: The incidence of pill failure resulting in pregnancy is approximately 1% (i.e., one pregnancy per 100 women per year) if taken every day as directed, but more typical failure rates are about 3%. If failure does occur, the risk to the fetus is minimal. Pregnancy After Stopping the Pill: There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy. There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill. Other: a. Overdosage: Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your poison control center, health care professional, or nearest emergency room. KEEP THIS DRUG AND ALL DRUGS OUT OF THE REACH OF CHILDREN. b. General Medical Information: Your health care professional will take a medical and family history before prescribing oral contraceptives and examine you. The physical examination may be delayed to another time if you request it and the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once per year. Be sure to inform your health care professional if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your health care professional, because this is a time to determine if there are early signs of side effects of oral contraceptive use. Do not use the drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth control pills. NONCONTRACEPTIVE EFFECTS OF ORAL CONTRACEPTIVES: In addition to preventing pregnancy, use of oral contraceptives may provide certain benefits. They are: Menstrual cycles may become more regular Blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur Pain or other symptoms during menstruation may be encountered less frequently Ectopic (tubal) pregnancy may occur less frequently Noncancerous cysts or lumps in the breast may occur less frequently Acute pelvic inflammatory disease may occur less frequently Oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus. If you want more information about birth control pills, ask your doctor or pharmacist. They have a more technical leaflet called the Professional Labeling, which you may wish to read. To report SUSPECTED ADVERSE REACTIONS, contact Norths tar Rx LLC. Toll-Free at 1- 800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

PATIENT INFORMATION This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Oral contraceptives, also known as "birth control pills" or "the pill", are taken to prevent pregnancy and when taken correctly, have a failure rate of about 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 3% per year when women who miss pills are included. Oral contraceptive use is associated with certain serious diseases that can be life-threatening or may cause temporary or permanent disability. The risks associated with taking oral contraceptives increase significantly if you: Smoke Have high blood pressure, diabetes, high cholesterol Have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors. You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding. Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives are strongly advised not to smoke. Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first three months of use. The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. However, you should know that the following medical conditions have been associated with or made worse by the pill: Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack or angina pectoris), or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer. High blood pressure, although blood pressure usually returns to normal when the pill is stopped. The symptoms associated with these serious side effects are discussed in the Detailed Patient Package Insert given to you with your supply of pills. Notify your doctor or healthcare provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics may decrease oral contraceptive effectiveness. Studies to date of women taking the pill have not shown an increase in the incidence of cancer of the breast or cervix. There is, however, insufficient evidence to rule out the possibility that the pill may cause such cancers. Taking the pill provides some important noncontraceptive effects. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus. Be sure to discuss any medical condition you may have with your healthcare provider. Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The Detailed Patient Package Insert gives you further information which you should read and discuss with your healthcare professional. DOSAGE AND ADMINISTRATION HOW TO TAKE THE PILL IMPORTANT POINTS TO REMEMBER SEXUALLY-TRANSMITTED DISEASES This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as Chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. BEFORE YOU START TAKING YOUR PILLS: BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills. Anytime you are not sure what to do. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS. If you do feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well. Use a back-up method (such as condoms, foam, or sponge) until you check with your doctor or clinic. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic. BEFORE YOU START TAKING YOUR PILLS DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. LOOK AT YOUR PILL PACK: The 28-pill pack has 21 "active" yellow pills (with hormones) to take for 3 weeks, followed by 1 week of "reminder" green pills (without hormones). BE SURE TO HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms, foam, or sponge) to use as a back­ up in case you miss pills. AN EXTRA, FULL PILL PACK. Each of the 21 yellow pills contains norethindrone (1 mg) and ethinyl estradiol (0.05 mg). Each green pill in the 28-day regimen contains inert ingredients. WHEN TO START THE FIRST PACK OF PILLS You have a choice of which day to start taking your first pack of pills. Decide with your doctor or clinic which is the best day for you. Once you have decided which day you will begin taking your pills, immediately do the following: remove the Brief Summary from the cellophane pouch and look for the Day Label Sheet attached; peel the label from the sheet which has the start day printed on the left-hand side; affix the label to the blister card in the designated location. Take your pill daily in the order indicated by the week number in the illustration above. Pick a time of day which will be easy to remember. DAY 1 START: Take the first "active" yellow pill of the first pack during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: Take the first "active" yellow pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms, foam, or the sponge are good back-up methods of birth control. WHAT TO DO DURING THE MONTH TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY. Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS: 28 pills: Start the next pack on the day after your last "reminder" pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS If you MISS 1 yellow "active" pill: Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. You do not need to use a back-up birth control method if you have sex. If you MISS 2 yellow "active" pills in a row in WEEK 1 OR WEEK 2 of your pack: Take 2 pills on the day you remember and 2 pills the next day. Then take 1 pill a day until you finish the pack. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days. If you MISS 2 yellow "active" pills in a row in THE 3rd WEEK: If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days. If you MISS 3 OR MORE yellow "active" pills in a row (during the first 3 weeks): If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days. A REMINDER FOR THOSE ON 28-DAY PACKS: If you forget any of the 7 green "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE "ACTIVE" PILL EACH DAY until you can reach your doctor or clinic. This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infections (AIDS) and other sexually transmitted diseases DETAILED PATIENT PACKAGE INSERT This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. INTRODUCTION You should not use OVCON 50 (norethindrone and ethinyl estradiol tablets, USP), 28-Day, which contains higher doses of estrogen than other oral contraceptives, unless specifically recommended by your healthcare provider. Any woman who considers using oral contraceptives (the "birth control pill" or "the pill") should understand the benefits and risks of using this form of birth control. Although the oral contraceptives have important advantages over other methods of contraception, they have certain risks that no other method has and some of these risks may continue after you have stopped using the oral contraceptive. This booklet will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this booklet is not a replacement for a careful discussion between you and your healthcare professional. You should discuss the information provided in this booklet with him or her, both when you first start taking the pill and during your revisits. You should also follow your healthcare professional's advice with regard to regular check-ups while you are on the pill. EFFECTIVENESS OF ORAL CONTRACEPTIVES Oral contraceptives or "birth control pills" or "the pill" are usedto prevent pregnancy and are more effective than other nonsurgical methods of birth control. The chance of becoming pregnant is less than 1% (1 pregnancy per 100 women per year of use) when the pills are used correctly and no pills are missed. Typical failure rates are actually 3% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle. In comparison, typical accidental pregnancy rates for other nonsurgical methods of birth control during the first year of use are as follows: IUD: 3% Diaphragm with spermicides: 18% Spermicides alone: 21% Vaginal sponge: 18% to 28% Condom alone: 12% Periodic abstinence: 20% Injectable progestogen: 0.3% to 0.4% Implants: 0.03% to 0.04% No methods: 85%. WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should not smoke. Some women should not use the pill. For example, you should not take the pill if you are pregnant or think you may be pregnant. You should also not use the pill if you have or have ever had any of the following conditions: A history of heart attack or stroke Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes A history of blood clots in the deep veins of your legs Chest pain (angina pectoris) Known or suspected breast cancer or cancer of the lining of the uterus Unexplained vaginal bleeding (until a diagnosis is reached by your doctor) Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill Liver tumor (benign or cancerous) Tell your healthcare professional if you have ever had any of these conditions. Your healthcare professional can recommend a safer method of birth control. OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES Tell your healthcare professional if you have: Breast nodules, fibrocystic disease of the breast or an abnormal breast x-ray or mammogram Diabetes Elevated cholesterol or triglycerides High blood pressure Migraine or other headaches or epilepsy Mental depression Gallbladder, heart, or kidney disease History of scanty or irregular menstrual periods Women with any of these conditions should be checked often by their healthcare professional if they choose to use oral contraceptives. Also, be sure to inform your doctor or healthcare professional if you smoke or are on any medications. RISKS OF TAKING ORAL CONTRACEPTIVES 1. Risk of developing blood clots Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Either of these can cause death or disability. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision. If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness, or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your doctor about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breastfeeding. If you are breastfeeding see the section on breastfeeding in General Precautions. 2. Heart attacks and strokes Oral contraceptives may increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or disability. Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease. 3. Gallbladder disease Oral contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens. 4. Liver tumors In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible, but not definite, association has been found with the pill and liver cancers in two studies, in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers in general are extremely rare and the chance of developing liver cancer from using the pill is thus even rarer. 5. Cancer of the reproductive organs There is, at present, no confirmed evidence that oral contraceptives increase the risk of cancer of the reproductive organs and breasts in human studies. Several studies have found no overall increase in the risk of developing breast cancer. However, women who use oral contraceptives and have a strong family history of breast cancer, or who have breast nodules or abnormal mammograms, should be closely followed by their doctors. Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table. ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Age Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 *Deaths are birth related **Deaths are method related It can be seen in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7-26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was always lower than that associated with pregnancy for any age group, although over the age of 40, the risk increases to 32 deaths per 100,000 women, compared to 28 associated with pregnancy at that age. However, for pill users who smoke and are over the age of 35, the estimated number of deaths exceeds those for other methods of birth control. If a woman is over the age of 40 and smokes, her estimated risk of death is four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000 women) in that age group. The suggestion that women over 40 who don't smoke information from older high-dose pills and on less selective use of pills than is practiced today. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, nonsmoking women over 40 years of age may outweigh the possible risks. However, all women, especially older women, are cautioned to use the lowest dose pill that is effective. In the above table, the risk of death from any birth control method is less than the risk of childbirth, except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. You should discuss this information with your healthcare professional. WARNING SIGNALS If any of these adverse conditions occur while you are taking oral contraceptives, call your doctor immediately: Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung) Pain in the calf (indicating a possible clot in the leg) Crushing chest pain or heaviness in the chest (indicating a possible heart attack) Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke) Sudden partial or complete loss of vision (indicating a possible clot in the eye) Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your doctor or healthcare professional to show you how to examine your breasts) Severe pain or tenderness in the stomach area (indicating a possibly ruptured liver tumor) Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression) Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems) Abnormal vaginal bleeding (see SIDE EFFECTS OF ORAL CONTRACEPTIVES, 1. Vaginal bleeding.) SIDE EFFECTS OF ORAL CONTRACEPTIVES In addition to the risks and more serious side effects discussed above (see RISKS OF TAKING ORAL CONTRACEPTIVES, ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY and WARNING SIGNALS sections), the following may also occur: 1. Vaginal bleeding Irregular vaginal bleeding or spotting may occur while you are taking the pills. Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Irregular bleeding occurs most often during the first few months of oral contraceptive use, but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue taking your pills on schedule. If the bleeding occurs in more than one cycle or lasts for more than a few days, talk to your doctor or healthcare professional. 2. Gastrointestinal effects The most frequent, unpleasant side effects are nausea and vomiting, stomach cramps, bloating, and a change in appetite. 3. Contact lenses If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your doctor or healthcare professional. 4. Fluid retention Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your doctor or healthcare professional. 5. Melasma A spotty darkening of the skin is possible, particularly of the face. 6. Other side effects Other side effects may include change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, and vaginal infections. If any of these side effects bother you, call your doctor or healthcare professional. GENERAL PRECAUTIONS 1. Missed periods and use of oral contraceptives before or during early pregnancy There may be times when you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss one menstrual period, continue taking your pills for the next cycle but be sure to inform your healthcare professional before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your healthcare professional immediately to determine whether you are pregnant. Do not continue to take oral contraceptives until you are sure you are not pregnant, but continue to use another method of contraception. There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects, when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these studies have not been confirmed. Nevertheless, oral contraceptives or any other drugs should not be used during pregnancy unless clearly necessary and prescribed by your doctor. You should check with your doctor about risks to your unborn child of any medication taken during pregnancy. 2. While breastfeeding If you are breastfeeding, consult your doctor before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breastfeeding. You should use another method of contraception since breastfeeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breastfeed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 3. Laboratory tests If you are scheduled for any laboratory tests, tell your doctor you are taking birth control pills. Certain blood tests may be affected by birth control pills. 4. Drug interactions Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such as barbiturates (for example, phenobarbital) and phenytoin (Dilantin® is one brand of this drug), phenylbutazone (Butazolidin® is one brand) and possibly ampicillin and tetracyclines (several brand names). You may need to use an additional method of contraception when you take drugs which can make oral contraceptives less effective. DOSAGE AND ADMINISTRATION HOW TO TAKE THE PILL IMPORTANT POINTS TO REMEMBER SEXUALLY-TRANSMITTED DISEASES This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as Chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. BEFORE YOU START TAKING YOUR PILLS: BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills. Anytime you are not sure what to do. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS. If you do feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your doctor MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. IF YOU HAVE VOMITING OR DIARRHEA, for any reasons, or IF YOU TAKE SOME MEDICINES, including some antibiotics, your pills may not work as well. Use a back-up method (such as condoms, foam, or sponge) until you check with your doctor or clinic. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic. BEFORE YOU START TAKING YOUR PILLS 1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. 2. LOOK AT YOUR PILL PACK The 28-pill pack has 21 "active" yellow pills (with hormones) to take for 3 weeks, followed by 1 week of "reminder" green pills (without hormones). Each of the 21 yellow pills contains norethindrone (1 mg) and ethinyl estradiol (0.05 mg). Each green pill in the 28-day regimen contains inert ingredients. 3. BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms, foam, or sponge) to use as a back­ up in case you miss pills. AN EXTRA, FULL PILL PACK. WHEN TO START THE FIRST PACK OF PILLS You have a choice of which day to start taking your first pack of pills. Decide with your doctor or clinic which is the best day for you. Once you have decided which day you will begin taking your pills, immediately do the following: remove the Brief Summary from the cellophane pouch and look for the Day Label Sheet attached; peel the label from the sheet which has the start day printed on the left-hand side; affix the label to the blister card in the designated location. Take your pill daily in the order indicated by the week number in the illustration above. Pick a time of day which will be easy to remember. DAY 1 START: Take the first "active" yellow pill of the first pack during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: Take the first "active" yellow pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms, foam, or the sponge are good back-up methods of birth control. WHAT TO DO DURING THE MONTH TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY. Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. WHEN YOU FINISH A PACK OR SWITCH YOUR BRAND OF PILLS: 21 pills: Wait 7 days to start the next pack. You will probably have your period during that week. Be sure that no more than 7 days pass between 21-day packs. 28 pills: Start the next pack on the day after your last "reminder" pill. Do not wait any days between packs. WHAT TO DO IF YOU MISS PILLS If you MISS 1 yellow "active" pill: Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. You do not need to use a back-up birth control method if you have sex. If you MISS 2 yellow "active" pills in a row in WEEK 1 or WEEK 2 of your pack: Take 2 pills on the day you remember and 2 pills the next day. Then take 1 pill a day until you finish the pack. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days. If you MISS 2 yellow "active" pills in a row in THE 3rd WEEK: If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days. If you MISS 3 OR MORE yellow "active" pills in a row (during the first 3 weeks): If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up for those 7 days. A REMINDER FOR THOSE ON 28-DAY PACKS: If you forget any of the 7 green "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE "ACTIVE" PILL EACH DAY until you can reach your doctor or clinic. GENERAL 1. Pregnancy due to pill failure The incidence of pill failure resulting in pregnancy is approximately 1% (i.e., one pregnancy per 100 women per year) if taken every day as directed, but more typical failure rates are about 3%. If failure does occur, the risk to the fetus is minimal. 2. Pregnancy after stopping the pill There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy. There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill. 3. Other a. Overdosage Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your poison control center, healthcare professional, or nearest emergency room. KEEP THIS DRUG AND ALL DRUGS OUT OF THE REACH OF CHILDREN. b. General medical information Your healthcare professional will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year. Be sure to inform your healthcare professional if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your healthcare professional, because this is a time to determine if there are early signs of side effects of oral contraceptive use. Do not use this drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth control pills. NONCONTRACEPTIVE EFFECTS OF ORAL CONTRACEPTIVES In addition to preventing pregnancy, use of oral contraceptives may provide certain benefits. They are: Menstrual cycles may become more regular Blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur. Pain or other symptoms during menstruation may be encountered less frequently Ectopic (tubal) pregnancy may occur less frequently Noncancerous cysts or lumps in the breast may occur less frequently Acute pelvic inflammatory disease may occur less frequently Oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus. If you want more information about birth control pills, ask your doctor or pharmacist. They have a more technical leaflet called the Professional Labeling, which you may wish to read.

PATIENT INFORMATION Oral contraceptives, also known as "birth control pills" or "the pill," are taken to prevent pregnancy and when taken correctly, have a failure rate of less than 1% per year when used without missing any pills. The typical failure rate of large numbers of pill users is less than 3% per year when women who miss pills are included. For most women oral contraceptives are also free of serious or unpleasant side effects. However, forgetting to take pills considerably increases the chances of pregnancy. For the majority of women, oral contraceptives can be taken safely. But there are some women who are at high risk of developing certain serious diseases that can be fatal or may cause temporary or permanent disability. The risks associated with taking oral contraceptives increase significantly if you: smoke have high blood pressure, diabetes, high cholesterol have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors. Although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy, non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women. You should not take the pill if you suspect you are pregnant or have unexplained vaginal bleeding. Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives are strongly advised not to smoke. Most side effects of the pill are not serious. The most common such effects are nausea, vomiting, bleeding between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may subside within the first three months of use. The serious side effects of the pill occur very infrequently, especially if you are in good health and are young. However, you should know that the following medical conditions have been associated with or made worse by the pill: Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack or angina pectoris), or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences. Liver tumors, which may rupture and cause severe bleeding. A possible, but not definite association has also been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer High blood pressure, although blood pressure usually returns to normal when the pill is stopped. The symptoms associated with these serious side effects are discussed in the detailed leaflet given to you with your supply of pills. Notify your doctor or health care provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics may decrease oral contraceptive effectiveness. There is conflict among studies regarding breast cancer and oral contraceptive use. Some studies have reported an increase in the risk of developing breast cancer, particularly at a younger age. This increased risk appears to be related to duration of use. The majority of studies have found no overall increase in the risk of developing breast cancer. Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. There is insufficient evidence to rule out the possibility pills may cause such cancers. Taking the combination pill provides some important non-contraceptive benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus. Be sure to discuss any medical condition you may have with your health care provider. Your health care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. Your pharmacist should have given you the detailed patient information labeling which gives you further information which you should read and discuss with your health care provider This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. DETAILED PATIENT LABELING PLEASE NOTE: This labeling is revised from time to time as important new medical infor- mation becomes available. Therefore, please review this labeling carefully. The following oral contraceptive products contain a combination of estrogen and progesto- gen, the two kinds of female hormones: Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) Each dark yellow tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Each white tablet in Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) contains inert ingredients. Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35 Each light yellow tablet contains 0.5 mg norethindrone and 0.035 mg ethinyl estradiol. Each white tablet in Necon (norethindrone and ethinyl estradiol tablets ) ®0.5/35 contains inert ingredients. Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 Each light yellow tablet contains 0.5 mg norethindrone and 0.035 mg ethinyl estradiol. Each dark yellow tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Each white tablet in Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11 contains inert ingredients. Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 Each light blue tablet contains 1 mg norethindrone and 0.05 mg mestranol. Each white tablet in Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 contains inert ingredients. INTRODUCTION Any woman who considers using oral contracep- tives (the birth control pill or the pill) should understand the benefits and risks of using this form of birth control. This patient labeling will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use the pill properly so that it will be as effective as possible. However, this labeling is not a replace- ment for a careful discussion between you and your health care provider. You should discuss the information provided in this labeling with him or her, both when you first start taking the pill and during your revisits. You should also follow your health care provider's advice with regard to regular check-ups while you are on the pill. EFFECTIVENESS OF ORAL CONTRACEPTIVES Oral contraceptives or "birth control pills" or "the pill" are used to prevent pregnancy and are more effective than other nonsurgical methods of birth control. When they are taken correctly, the chance of becoming pregnant is less than 1% (1 pregnancy per 100 women per year of use) when used perfectly, without missing any pills. Typical failure rates are actually 3% per year. The chance of becoming pregnant increases with each missed pill during a menstrual cycle. In comparison, typical failure rates for other non- surgical methods of birth control during the first year of use are as follows: Implant: < 1% Injection: < 1% IUD: 1 to 2% Diaphragm with spermicides: 18% Spermicides alone: 21% Vaginal sponge: 18 to 36% Cervical Cap: 18 to 36% Condom alone (male): 12% Condom alone (female): 21% Periodic abstinence: 20% No methods: 85% WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives are strongly advised not to smoke. Some women should not use the pill. For exam- ple, you should not take the pill if you are pregnant or think you may be pregnant. You should also not use the pill if you have any of the following conditions: A history of heart attack or stroke Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes A history of blood clots in the deep veins of your legs Chest pain (angina pectoris) Known or suspected breast cancer or cancer of the lining of the uterus, cervix, or vagina Unexplained vaginal bleeding (until a diagnosis is reached by your doctor) Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill Liver tumor (benign or cancerous) Known or suspected pregnancy Tell your health care provider if you have ever had any of these conditions. Your health care provider can recommend a safer method of birth control. OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES Tell your health care provider if you have or have had: Breast nodules, fibrocystic disease of the breast, an abnormal breast x-ray or mammogram Diabetes Elevated cholesterol or triglycerides High blood pressure Migraine or other headaches or epilepsy Mental depression Gallbladder, heart or kidney disease History of scanty or irregular menstrual periods Women with any of these conditions should be checked often by their health care provider if they choose to use oral contraceptives. Also, be sure to inform your doctor or health care provider if you smoke or are on any medications. RISKS OF TAKING ORAL CONTRACEPTIVES 1. Risk of developing blood clots Blood clots and blockage of blood vessels are one of the most serious side effects of taking oral contraceptives and can cause death or serious disability. In particular, a clot in the legs can cause thrombophlebitis and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision. If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your doctor about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breast feeding or four weeks after a second trimester abortion. If you are breast feeding, you should wait until you have weaned your child before using the pill. (See also the section on Breast Feeding in General Precautions.) The risk of circulatory disease in oral contraceptive users may be higher in users of high-dose pills and may be greater with longer duration of oral contraceptive use. In addition, some of these increased risks may continue for a number of years after stopping oral contraceptives. The risk of abnormal blood clotting increases with age in both users and nonusers of oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages. For women aged 20 to 44, it is estimated that about 1 in 2,000 using oral contraceptives will be hospitalized each year because of abnormal clotting. Among nonusers in the same age group, about 1 in 20,000 would be hospitalized each year For oral contraceptive users in general, it has been esti- mated that in women between the ages of 15 and 34 the risk of death due to a circulatory disorder is about 1 in 12,000 per year, whereas for nonusers the rate is about 1 in 50,000 per year. In the age group 35 to 44, the risk is estimated to be about 1 in 2,500 per year for oral contraceptive users and about 1 in 10,000 per year for nonusers. 2. Heart attacks and strokes Oral contraceptives may increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or serious disability. Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increases the chances of developing and dying of heart disease. 3.Gallbladder disease Oral contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens. 4. Liver tumors In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible but not definite association has been found with the pill and liver cancers in two studies, in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers are rare. 5. Cancer of the reproductive organs and breasts There is conflict among studies regarding breast cancer and oral contraceptive use. Some studies have reported an increase in the risk of developing breast cancer, particularly at a younger age. This increased risk appears to be related to duration of use. The majority of studies have found no overall increase in the risk of developing breast cancer. Some studies have found an increase in the incidence of cancer of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. There is insufficient evidence to rule out the possibility that pills may cause such cancers. ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY All methods of birth control and pregnancy are associated with a risk of developing certain diseases that may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the follow- ing table. ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE. Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives non-smoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/ spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 * Deaths are birth-related ** Deaths are method-related Adapted from H.W. Ory, ref. #35 In the above table, the risk of death from any birth control method is less than the risk of childbirth, except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. It can be seen in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7-26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was always lower than that associated with pregnancy for any age group, although over the age of 40, the risk increases to 32 deaths per 100,000 women, compared to 28 associated with pregnancy at that age. However, for pill users who smoke and are over the age of 35, the estimated number of deaths exceeds those for other methods of birth control. If a woman is over the age of 40 and smokes, her estimated risk of death is four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000) in that age group. The suggestion that women over 40 who do not smoke should not take oral contraceptives is based on information from older, higher dose pills. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of low-dose oral contraceptive use by healthy, non-smoking women over 40 years of age may outweigh the possible risks. WARNING SIGNALS If any of these adverse effects occur while you are taking oral contraceptives, call your doctor immediately: Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung) Pain in the calf (indicating a possible clot in the leg) Crushing chest pain or heaviness in the chest (indicating a possible heart attack) Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke) Sudden partial or complete loss of vision (indicating a possible clot in the eye) Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your doctor or health care provider to show you how to examine your breasts) Severe pain or tenderness in the stomach area (indicating a possible ruptured liver tumor) Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression) Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems) SIDE EFFECTS OF ORAL CONTRACEPTIVES 1. Vaginal bleeding Irregular vaginal bleeding or spotting may occur while you are taking the pills. Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Irregular bleeding occurs most often during the first few months of oral contraceptive use, but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue taking your pills on schedule. If the bleeding occurs in more than one cycle or lasts for more than a few days, talk to your doctor or health care provider. 2. Contact lenses If you wear contact lenses and notice a change in vision or an inability to wear you lenses, contact your doctor or health care provider. 3. Fluid retention Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your doctor or health care provider. 4. Melasma A spotty darkening of the skin is possible, particularly of the face, which may persist. 5. Other side effects Other side effects may include nausea and vomiting, change in appetite, headache, nervousness, depression, dizziness, loss of scalp hair, rash, and vaginal infections. If any of these side effects bother you, call your doctor or health care provider GENERAL PRECAUTIONS 1. Missed periods and use of oral contraceptives before or during early pregnancy There may be times when you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss one menstrual period, continue taking your pills for the next cycle but be sure to inform your health care provider before doing so. If you have not taken the pills daily as instructed and missed a menstrual period, you may be pregnant. If you missed two consecutive menstrual periods and it is 45 days or more from the start of your last menstrual period, you may be pregnant. Check with your health care provider immediately to determine whether you are pregnant. Do not continue to take oral contraceptives until you are sure you are not pregnant, but continue to use another method of contraception. There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects, when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects, but these findings have not been seen in more recent studies. Nevertheless, oral contraceptives or any other drugs should not be used during pregnancy unless clearly necessary and prescribed by your doctor. You should check with your doctor about risks to your unborn child of any medication taken during pregnancy. 2. While breast feeding If you are breast feeding, consult your doctor before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been re- ported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contra- ceptives while breast feeding. You should use another method of contraception since breast feeding provides only partial protection from becoming pregnant and this partial protection decreases significantly as you breast feed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 3. Laboratory tests If you are scheduled for any laboratory tests, tell your doctor you are taking birth control pills. Certain blood tests may be affected by birth control pills. 4. Drug interactions Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such a barbiturates (for example, phenobarbital), anticonvulsants such as carbamazepine (Tegretol is one brand of this drug), phenytoin (Dilantin is one brand of this drug), phenylbutazone (Butazolidin is one brand), and possibly certain antibiotics. You may need to use additional contraception when you take drugs which can make oral contraceptives less effective. 5. Sexually transmitted diseases This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. HOW TO TAKE THE PILL IMPORTANT POINTS TO REMEMBER BEFORE YOU START TAKING THE PILLS: 1. BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills. Anytime you are not sure what to do. 2. THE RIGHT WAY TO TAKE THE PILL IS TO TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the dispenser late. The more pills you miss, the more likely you are to get pregnant. 3. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 DIS- PENSERS OF PILLS. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your doctor or clinic. 4. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. 5. IF YOU HAVE VOMITING OR DIARRHEA, for any reason, or IF YOU TAKE SOME MEDI- CINES, including some antibiotics, your pills may not work as well. Use a back-up method (such as condoms, foam, or sponge) until you check with your doctor or clinic. 6. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your doctor or clinic about how to make pill-taking easier or about using another method of birth control. 7. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your doctor or clinic. BEFORE YOU START TAKING YOUR PILLS 1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. 2. LOOK AT YOUR PILL DISPENSER TO SEE IF IT HAS 28 PILLS: The 28-pill dispenser has 21 "active" pills (with hormones) to take for 3 weeks. This is followed by 1 week of reminder white pills (without hormones). To remove a pill press down on it with the flat of your finger. The pill will drop through a hole in the bottom of the dispenser. Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11: There are 10 light yellow "active" pills and 11 dark yellow "active" pills. Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) : There are 21 dark yellow "active" pills. Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35: There are 21 light yellow "active" pills. Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50 : There are 21 light blue "active" pills. 3. ALSO FIND: 1) where on the dispenser to start taking pills, 2) in what order to take the pills CHECK ADDITIONAL INSTRUCTIONS FOR USING THIS DISPENSER IN THE BRIEF SUMMARY PATIENT PACKAGE INSERT. 4. BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms, foam or sponge) to use as a back-up in case you miss pills. AN EXTRA, FULL PILL DISPENSER. WHEN TO START THE FIRST DISPENSER OF PILLS: You have a choice of which day to start taking your first dispenser of pills. Decide with your doctor or clinic which is the best day for you. Pick a time of day which will be easy to remember. SUNDAY START: Necon (norethindrone and ethinyl estradiol tablets ) ®10/11: Take the first "active" light yellow pill of the first dispenser on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the dispenser the same day. Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) : Take the first "active" dark yellow pill of the first dispenser on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the dispenser the same day. Necon (norethindrone and ethinyl estradiol tablets ) ®0.5/35: Take the first "active" light yellow pill of the first dispenser on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the dispenser the same day. Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50: Take the first "active" light blue pill of the first dispenser on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the dispenser the same day. Use another method of birth control as back-up method if you have sex anytime from the Sunday you start your first dispenser until the next Sunday (7 days). Condoms, foam, or the sponge are good back-up methods of birth control. DAY 1 START: Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11: Take the first "active" light yellow pill of the first dispenser during the first 24 hours of your period. Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) : Take the first "active" dark yellow pill of the first dispenser during the first 24 hours of your period. Necon (norethindrone and ethinyl estradiol tablets ) ®0.5/35: Take the first "active" light yellow pill of the first dispenser during the first 24 hours of your period. Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50: Take the first "active" light blue pill of the first dispenser during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. WHAT TO DO DURING THE MONTH: 1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE DISPENSER IS EMPTY. Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. 2. WHEN YOU FINISH A DISPENSER OR SWITCH YOUR BRAND OF PILLS: Start the next dispenser on the day after your last "reminder" pill. Do not wait any days between dispensers. WHAT TO DO IF YOU MISS PILLS: Necon (norethindrone and ethinyl estradiol tablets ) ® 10/11: If you MISS 1 light yellow or dark yellow "active" pill: 1.Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. 2.You do not need to use a back-up birth control method if you have sex. If you MISS 2 light yellow or dark yellow "active" pills in a row in WEEK 1 or WEEK 2 of your dispenser: 1. Take 2 pills on the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the dispenser. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 2 dark yellow "active" pills in a row in THE 3RD WEEK: 1.If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dispenser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 3 OR MORE light yellow or dark yellow "active" pills in a row (during the first 3 weeks): 1. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dispenser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. Necon® 1/35 (norethindrone and ethinyl estradiol tablets ) : If you MISS 1 dark yellow "active" pill: 1.Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. 2.You do not need to use a back-up birth control method if you have sex. If you MISS 2 dark yellow "active" pills in a row in WEEK 1 or WEEK 2 of your dispenser: 1. Take 2 pills on the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the dispenser. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 2 dark yellow "active" pills in a row in THE 3RD WEEK: 1. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dis- penser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser that same day 2.You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3.You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 3 OR MORE dark yellow "active" pills in a row (during the first 3 weeks): 1. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dispenser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. Necon (norethindrone and ethinyl estradiol tablets ) ® 0.5/35: If you MISS 1 light yellow "active" pill: 1. Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. 2.You do not need to use a back-up birth control method if you have sex. If you MISS 2 light yellow "active" pills in a row in WEEK 1 or WEEK 2 of your dispenser: 1. Take 2 pills on the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the dispenser. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 2 light yellow "active" pills in a row in THE 3RD WEEK: 1 If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dis- penser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser that same day 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 3 OR MORE light yellow "active" pills in a row (during the first 3 weeks): 1. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dis- penser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. Necon (norethindrone and ethinyl estradiol tablets ) ® 1/50: If you MISS 1 light blue "active" pill: 1. Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. 2. You do not need to use a back-up birth control method if you have sex. If you MISS 2 light blue "active" pills in a row in WEEK 1 or WEEK 2 of your dispenser: 1. Take 2 pills on the day you remember and 2 pills the next day. 2. Then take 1 pill a day until you finish the dispenser. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 2 light blue "active" pills in a row in THE 3RD WEEK: 1. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dis- penser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser that same day 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. If you MISS 3 OR MORE light blue "active" pills in a row (during the first 3 weeks): 1. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the dis- penser and start a new dispenser of pills that same day. If you are a Day 1 Starter: THROW OUT the rest of the pill dispenser and start a new dispenser of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your doctor or clinic because you might be pregnant. 3. You MAY BECOME PREGNANT if you have sex in the 7 days after you miss pills. You MUST use another birth control method (such as condoms, foam, or sponge) as a back-up method for those 7 days. A REMINDER FOR THOSE ON 28-DAY DISPENSERS If you forget any of the 7 white "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the dispenser is empty. You do not need a back-up method. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE "ACTIVE" PILL EACH DAY until you can reach your doctor or clinic. PREGNANCY DUE TO PILL FAILURE The incidence of pill failure resulting in pregnancy is approximately one percent (i.e., one pregnancy per 100 women per year) if taken every day as directed, but more typical failure rates are about 3%. If failure does occur, the risk to the fetus is minimal. PREGNANCY AFTER STOPPING THE PILL There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy. There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill. OVERDOSAGE Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your health care provider or pharmacist. OTHER INFORMATION Your health care provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the health care provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year. Be sure to inform your health care provider if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your health care provider, because this is a time to determine if there are early signs of side effects of oral contraceptive use. Do not use the drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth control pills. HEALTH BENEFITS FROM ORAL CONTRACEPTIVES In addition to preventing pregnancy, use of combination oral contraceptives may provide certain benefits. They are: menstrual cycles may become more regular blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur pain or other symptoms during menstruation may be encountered less frequently ectopic (tubal) pregnancy may occur less frequently noncancerous cysts or lumps in the breast may occur less frequently acute pelvic inflammatory disease may occur less frequently oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus. If you want more information about birth control pills, ask your doctor or pharmacist. They have a more technical leaflet called the Professional Labeling, which you may wish to read. The Professional Labeling is also published in a book entitled Physicians' Desk Reference, available in many book stores and public libraries.

PATIENT INFORMATION PATIENT BRIEF SUMMARY This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Oral contraceptives, also known as "birth control pills" or "the pill", are taken to prevent pregnancy, and when taken correctly without missing any pills, have a failure rate of about 1% per year (1 pregnancy per 100 women per year of use). The typical failure rate of pill users is 5% per year (5 pregnancies per 100 women per year of use) when women who miss pills are included. For the majority of women, oral contraceptives can be taken safely. But for some women oral contraceptive use is associated with certain serious diseases that can be life-threatening or may cause temporary or permanent disability or death. The risks associated with taking oral contraceptives increase significantly if you: Smoke Have high blood pressure, diabetes, high cholesterol, or are obese Have or have had clotting disorders, heart attack, stroke, angina pectoris, cancer of the breast or sex organs, jaundice or malignant or benign liver tumors You should not take the pill if you are pregnant or have unexplained vaginal bleeding. Although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy, non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women. Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral contraceptive use. This risk increases with age and with the amount of smoking (15 or more cigarettes per day has been associated with a significantly increased risk) and is quite marked in women over 35 years of age. Women who use oral contraceptives should not smoke. Most side effects of the pill are not serious. The most common are nausea, vomiting, bleeding or spotting between menstrual periods, weight gain, breast tenderness, and difficulty wearing contact lenses. These side effects, especially nausea and vomiting, may decrease or subside within the first three months of use. The serious side effects of the pill occur very infrequently, especially if you are in good health and do not smoke. However, you should know that the following medical conditions have been associated with or made worse by the pill: Blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), stoppage or rupture of a blood vessel in the brain (stroke), blockage of blood vessels in the heart (heart attack or angina pectoris), or other organs of the body. As mentioned above, smoking increases the risk of heart attacks and strokes and subsequent serious medical consequences. Women with migraine also may be at increased risk of stroke when taking the pill. Liver tumors, which may rupture and cause severe bleeding. A possible but not definite association has been found with the pill and liver cancer. However, liver cancers are extremely rare. The chance of developing liver cancer from using the pill is thus even rarer. High blood pressure, although blood pressure usually returns to normal when the pill is stopped. The symptoms associated with these serious side effects are discussed in the detailed patient information leaflet given to you with your supply of pills. Notify your healthcare provider if you notice any unusual physical disturbances while taking the pill. In addition, drugs such as rifampin, as well as some anticonvulsants and some antibiotics, and herbal preparations containing St. John's Wort (hypericum perforatum), may decrease oral contraceptive effectiveness. Breast cancer has been diagnosed slightly more often in women who use the pill than in women of the same age who do not use the pill. This very small increase in the number of breast cancer diagnoses gradually disappears during the 10 years after stopping use of the pill. It is not known whether the difference is caused by the pill. It may be that women taking the pill are examined more often, so that breast cancer is more likely to be detected. You should have regular breast examinations by a healthcare provider and examine your own breasts monthly. Tell your healthcare provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use hormonal contraceptives because breast cancer is usually a hormone-sensitive tumor. Some studies have found an increase in the incidence of cancer or precancerous lesions of the cervix in women who use the pill. However, this finding may be related to factors other than the use of the pill. Taking the combination pill provides some important noncontraceptive health benefits. These include less painful menstruation, less menstrual blood loss and anemia, fewer pelvic infections, and fewer cancers of the ovary and the lining of the uterus. Be sure to discuss any medical condition you may have with your healthcare provider. Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year while taking oral contraceptives. The detailed patient information leaflet gives you further information which you should read and discuss with your healthcare provider. DOSAGE AND ADMINISTRATION HOW TO TAKE FEMCON Fe (norethindrone and ethinyl estradiol tablets) IMPORTANT POINTS TO REMEMBER BEFORE YOU START TAKING YOUR PILLS: BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills Anytime you are not sure what to do THE PILL MAY BE SWALLOWED WHOLE OR CHEWED AND SWALLOWED. IF THE PILL IS CHEWED, YOU SHOULD DRINK A FULL GLASS (8 OUNCES) OF LIQUID IMMEDIATELY AFTER SWALLOWING. TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS. If you have spotting or light bleeding or feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your healthcare provider. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. IF YOU HAVE VOMITING (within 3 to 4 hours after you take your pill), you should follow the instructions for WHAT TO DO IF YOU MISS PILLS. IF YOU HAVE DIARRHEA or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics, or the herbal supplement St. John's Wort, your pills may not work as well. Use a back-up method of birth control (such as condoms or spermicide) until you check with your healthcare provider. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your healthcare provider. BEFORE YOU START TAKING YOUR PILLS 1. DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. 2. LOOK AT YOUR PILL PACK: The pill pack has 21 "active" white pills (with hormones) to take for 3 weeks, followed by 7 "reminder" brown pills (without hormones) to take for 1 week. *For use of day labels, see WHEN TO START THE FIRST PACK OF PILLS. 3. ALSO FIND: where on the pack to start taking pills, in what order to take the pills (follow the arrows), and the week numbers as shown in the picture above. 4. BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicide) to use as a back-up in case you miss pills. AN EXTRA, FULL PILL PACK. WHEN TO START THE FIRST PACK OF PILLS You have 2 choices of which day to start taking your first pack of pills. (See DAY 1 START or SUNDAY START directions below.) Decide with your healthcare provider which is the best day for you. Once you have decided which day you will begin taking your pills, immediately do the following: remove the Brief Summary from inside the pouch and look for the attached day label sheet; peel the label from the sheet which has the start day printed on the left hand side; place the label on the blister card in the designated location. Take your pill daily in the order indicated by the arrows on the blister card illustration shown above. Pick a time of day which will be easy to remember and take your pill at the same time each day. DAY 1 START: Take the first "active" white pill of the first pack during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: Take the first "active" white pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms or spermicide are good back-up methods of birth control. WHAT TO DO DURING THE MONTH 1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY. Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. 2. WHEN YOU FINISH A PACK OF YOUR FEMCON Fe (norethindrone and ethinyl estradiol tablets) : Start the next pack on the day after your last brown "reminder" pill. Do not wait any days between packs. 3. WHEN YOU SWITCH FROM A DIFFERENT BRAND OF PILLS: If your previous brand had 21 pills, wait 7 days before starting FEMCON Fe (norethindrone and ethinyl estradiol tablets) . If your previous brand had 28 pills, start taking FEMCON Fe (norethindrone and ethinyl estradiol tablets) on the day after the last pill. WHAT TO DO IF YOU MISS PILLS The pill may not be as effective if you miss white "active" pills, and particularly if you miss the first few or the last few white "active" pills in a pack. If you MISS 1 white "active" pill: Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. You do not need to use a back-up birth control method if you have sex. If you MISS 2 white "active" pills in a row in WEEK 1 OR WEEK 2 of your pack: Take 2 pills on the day you remember and 2 pills the next day. Then take 1 pill a day until you finish the pack. You COULD BECOME PREGNANT if you have sex during the 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for those 7 days. If you MISS 2 white "active" pills in a row in THE 3rd WEEK: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant. 3. You COULD BECOME PREGNANT if you have sex during the 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for those 7 days. If you MISS 3 OR MORE white "active" pills in a row (during the first 3 weeks): 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant. 3. You COULD BECOME PREGNANT if you have sex on the days when you missed pills or during the first 7 days after restarting your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for the first 7 days after you restart your pills. If you forget any of the 7 brown "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method of birth control. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE "ACTIVE" (WHITE) PILL EACH DAY until you can reach your healthcare provider. DETAILED PATIENT PACKAGE INSERT This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against HIV infection (AIDS) and other sexually transmitted diseases. INTRODUCTION Any woman who considers using oral contraceptives (the "birth control pill" or "the pill") should understand the benefits and risks of using this form of birth control. Although oral contraceptives have important advantages over other methods of contraception, they have certain risks that no other method has, and some of these risks may continue after you have stopped using the oral contraceptive. This leaflet will give you much of the information you will need to make this decision and will also help you determine if you are at risk of developing any of the serious side effects of the pill. It will tell you how to use FEMCON Fe (norethindrone and ethinyl estradiol tablets) properly so that it will be as effective as possible. However, this booklet is not a replacement for a careful discussion between you and your healthcare provider. You should discuss the information provided in this booklet with your healthcare provider, both when you first start taking the pill and during your revisits. You should also follow your healthcare provider's advice with regard to regular check-ups while you are on FEMCON Fe (norethindrone and ethinyl estradiol tablets) . EFFECTIVENESS OF ORAL CONTRACEPTIVES Oral contraceptives or "birth control pill" or "the pill" are used to prevent pregnancy and are more effective than most other nonsurgical methods of birth control. The chance of becoming pregnant is approximately 1% per year (1 pregnancy per 100 women per year of use) when the pills are used correctly, and no pills are missed. Typical failure rates are 5% per year (5 pregnancies per 100 women per year of use) when women who miss pills are included. The chance of becoming pregnant increases with each missed pill during a menstrual cycle. In comparison, typical failure rates for other methods of birth control during the first year of use are as follows: No methods: 85% Vaginal sponge: 20 to 40% Cervical cap: 20 to 40% Spermicides alone: 26% Periodic abstinence: 25% Condom (female): 21% Diaphragm with spermicides: 20% Withdrawal: 19% Condom (male): 14% Female sterilization: 0.5% IUD: 0.1 to 2.0% Injectable progestogen: 0.3% Male sterilization: 0.15% Norplant® system: 0.05% WHO SHOULD NOT TAKE ORAL CONTRACEPTIVES Cigarette smoking increases the risk of serious adverse effects on the heart and blood vessels from oral contraceptive use. This risk increases with age and with the amount of smoking (15 or more cigarettes per day has been associated with a significantly increased risk) and is quite marked in women over 35 years of age. Women who use oral contraceptives should not smoke. Some women should not use the pill. You should not use the pill if you have or have ever had any of the following conditions: A history of heart attack or stroke A history of blood clots in the legs (thrombophlebitis), lungs (pulmonary embolism), or eyes A history of blood clots in the deep veins of your legs Chest pain (angina pectoris) Known or suspected breast cancer or cancer of the lining of the uterus, cervix, vagina, or certain hormonally-sensitive cancers Unexplained vaginal bleeding (until a diagnosis is reached by your healthcare provider) Yellowing of the whites of the eyes or of the skin (jaundice) during pregnancy or during previous use of the pill Liver tumor (benign or cancerous) Known or suspected pregnancy Heart valve or heart rhythm disorders that may be associated with formation of blood clots Diabetes affecting your circulation Uncontrolled high blood pressure Active liver disease with abnormal liver function tests Headache with neurological symptoms Allergy or hypersensitivity to any of the components of FEMCON Fe A need for surgery with prolonged bedrest Tell your healthcare provider if you have any of the above conditions. Your healthcare provider can recommend a safer method of birth control. OTHER CONSIDERATIONS BEFORE TAKING ORAL CONTRACEPTIVES Tell your healthcare provider if you or any family member has ever had: Breast nodules, fibrocystic disease of the breast or an abnormal breast x-ray or mammogram Diabetes Elevated cholesterol or triglycerides High blood pressure Migraine or other headaches or epilepsy Depression Gallbladder, liver, heart, or kidney disease History of scanty or irregular menstrual periods Women with any of these conditions should be checked often by their healthcare provider if they choose to use oral contraceptives. Also, be sure to inform your healthcare provider if you smoke or are on any medications. RISKS OF TAKING ORAL CONTRACEPTIVES 1. Risk of developing blood clots Blood clots and blockage of blood vessels are the most serious side effects of taking oral contraceptives and can cause death or serious disability. In particular, a clot in the legs can cause thrombophlebitis, and a clot that travels to the lungs can cause a sudden blocking of the vessel carrying blood to the lungs. Either of these can cause death or disability. Rarely, clots occur in the blood vessels of the eye and may cause blindness, double vision, or impaired vision. If you take oral contraceptives and need elective surgery, need to stay in bed for a prolonged illness or injury, or have recently delivered a baby, you may be at risk of developing blood clots. You should consult your healthcare provider about stopping oral contraceptives three to four weeks before surgery and not taking oral contraceptives for two weeks after surgery or during bed rest. You should also not take oral contraceptives soon after delivery of a baby. It is advisable to wait for at least four weeks after delivery if you are not breastfeeding. If you are breastfeeding, you should wait until you have weaned your child before using the pill (see the section on breastfeeding in GENERAL PRECAUTIONS). The risk of circulatory disease in oral contraceptive users may be higher in users of high-dose pills (containing 50 micrograms or higher of ethinyl estradiol) and may be greater with longer duration of oral contraceptive use. In addition, some of these increased risks may continue for a number of years after stopping oral contraceptives. The risk of abnormal blood clotting increases with age in both users and nonusers of oral contraceptives, but the increased risk from the oral contraceptive appears to be present at all ages. For women aged 20 to 44 it is estimated that about 1 in 2,000 using oral contraceptives will be hospitalized each year because of abnormal clotting. Among nonusers in the same age group, about 1 in 20,000 would be hospitalized each year. For oral contraceptive users in general, it has been estimated that in women between the ages of 15 and 34 the risk of death due to a circulatory disorder is about 1 in 12,000 per year, whereas for nonusers the rate is about 1 in 50,000 per year. In the age group 35 to 44, the risk is estimated to be about 1 in 2,500 per year for oral contraceptive users and about 1 in 10,000 per year for nonusers. 2. Heart attacks and strokes Oral contraceptives may increase the tendency to develop strokes (stoppage or rupture of blood vessels in the brain) and angina pectoris and heart attacks (blockage of blood vessels in the heart). Any of these conditions can cause death or disability. Smoking greatly increases the possibility of suffering heart attacks and strokes. Furthermore, smoking and the use of oral contraceptives greatly increase the chances of developing and dying of heart disease. Women with migraine (especially migraine with aura) who take oral contraceptives also may be at higher risk of stroke. 3. Gallbladder disease Oral contraceptive users probably have a greater risk than nonusers of having gallbladder disease, although this risk may be related to pills containing high doses of estrogens. 4. Liver tumors In rare cases, oral contraceptives can cause benign but dangerous liver tumors. These benign liver tumors can rupture and cause fatal internal bleeding. In addition, a possible, but not definite, association has been found with the pill and liver cancers in two studies, in which a few women who developed these very rare cancers were found to have used oral contraceptives for long periods. However, liver cancers in general are extremely rare, and the chance of developing liver cancer from using the pill is thus even rarer. 5. Cancer of the breast and reproductive organs Breast cancer has been diagnosed slightly more often in women who use the pill than in women of the same age who do not use the pill. This small increase in the number of breast cancer diagnoses gradually disappears during the 10 years after stopping use of the pill. It is not known whether the difference is caused by the pill. It may be that women taking the pill are examined more often, so that breast cancer is more likely to be detected. You should have regular breast examinations by a healthcare provider and examine your own breasts monthly. Tell your healthcare provider if you have a family history of breast cancer or if you have had breast nodules or an abnormal mammogram. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is usually a hormone-sensitive tumor. Some studies have found an increase in the incidence of cancer or precancerous lesions of the cervix in women who use oral contraceptives. However, this finding may be related to factors other than the use of oral contraceptives. There is insufficient evidence to rule out the possibility that the pill may cause such cancers. 6. Lipid metabolism and inflammation of the pancreas In patients with inherited defects of lipid metabolism, there have been reports of significant elevations of plasma triglycerides during estrogen therapy. This has led to pancreatitis in some cases. ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY All methods of birth control and pregnancy are associated with a risk of developing certain diseases which may lead to disability or death. An estimate of the number of deaths associated with different methods of birth control and pregnancy has been calculated and is shown in the following table. ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE AGE Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 *Deaths are birth related **Deaths are method related In the above table, the risk of death from any birth control method is less than the risk of childbirth, except for oral contraceptive users over the age of 35 who smoke and pill users over the age of 40 even if they do not smoke. It can be seen in the table that for women aged 15 to 39, the risk of death was highest with pregnancy (7-26 deaths per 100,000 women, depending on age). Among pill users who do not smoke, the risk of death was always lower than that associated with pregnancy for any age group, although over the age of 40, the risk increases to 32 deaths per 100,000 women, compared to 28 associated with pregnancy at that age. However, for pill users who smoke and are over the age of 35, the estimated number of deaths exceeds those for other methods of birth control. If a woman is over the age of 40 and smokes, her estimated risk of death is four times higher (117/100,000 women) than the estimated risk associated with pregnancy (28/100,000 women) in that age group. The suggestion that women over 40 who don't smoke should not take oral contraceptives is based on information from older high-dose pills. An Advisory Committee of the FDA discussed this issue in 1989 and recommended that the benefits of oral contraceptive use by healthy, nonsmoking women over 40 years of age may outweigh the possible risks. Older women, as all women who take oral contraceptives, should take an oral contraceptive which contains the least amount of estrogen and progestin that is compatible with the individual patient needs. WARNING SIGNALS If any of these adverse conditions occur while you are taking oral contraceptives, call your healthcare provider immediately: Sharp chest pain, coughing of blood, or sudden shortness of breath (indicating a possible clot in the lung) Pain in the calf (indicating a possible clot in the leg) Crushing chest pain or heaviness in the chest (indicating a possible heart attack) Sudden severe headache or vomiting, dizziness or fainting, disturbances of vision or speech, weakness, or numbness in an arm or leg (indicating a possible stroke) Sudden partial or complete loss of vision (indicating a possible clot in the eye) Breast lumps (indicating possible breast cancer or fibrocystic disease of the breast; ask your healthcare provider to show you how to examine your breasts) Severe pain or tenderness in the stomach area (possibly indicating a ruptured liver tumor) Difficulty in sleeping, weakness, lack of energy, fatigue, or change in mood (possibly indicating severe depression) Jaundice or a yellowing of the skin or eyeballs, accompanied frequently by fever, fatigue, loss of appetite, dark-colored urine, or light-colored bowel movements (indicating possible liver problems) SIDE EFFECTS OF ORAL CONTRACEPTIVES In addition to the risks and more serious side effects discussed above (see RISKS OF TAKING ORAL CONTRACEPTIVES, ESTIMATED RISK OF DEATH FROM A BIRTH CONTROL METHOD OR PREGNANCY and WARNING SIGNALS sections), the following may also occur: 1. Irregular vaginal bleeding Irregular vaginal bleeding or spotting may occur while you are taking FEMCON Fe (norethindrone and ethinyl estradiol tablets) . Irregular bleeding may vary from slight staining between menstrual periods to breakthrough bleeding which is a flow much like a regular period. Irregular bleeding occurs most often during the first few months of oral contraceptive use, but may also occur after you have been taking the pill for some time. Such bleeding may be temporary and usually does not indicate any serious problems. It is important to continue taking your pills on schedule. If the bleeding occurs in more than one cycle or lasts for more than a few days, talk to your healthcare provider. 2. Contact lenses If you wear contact lenses and notice a change in vision or an inability to wear your lenses, contact your healthcare provider. 3. Fluid retention Oral contraceptives may cause edema (fluid retention) with swelling of the fingers or ankles and may raise your blood pressure. If you experience fluid retention, contact your healthcare provider. 4. Melasma A spotty darkening of the skin is possible, particularly of the face. 5. Other side effects Other side effects may include nausea and vomiting, change in appetite, breast tenderness, headache, nervousness, depression, dizziness, loss of scalp hair, rash, vaginal infections, and allergic reactions. If any of these side effects bother you, call your healthcare provider. GENERAL PRECAUTIONS 1. Missed periods and use of oral contraceptives before or during early pregnancy There may be times when you may not menstruate regularly after you have completed taking a cycle of pills. If you have taken your pills regularly and miss one menstrual period, continue taking your pills for the next cycle but be sure to inform your healthcare provider. If you have not taken the pills daily as instructed and missed a menstrual period, or if you missed two consecutive menstrual periods, you may be pregnant. Check with your healthcare provider immediately to determine whether you are pregnant. Stop taking FEMCON Fe (norethindrone and ethinyl estradiol tablets) if you are pregnant. There is no conclusive evidence that oral contraceptive use is associated with an increase in birth defects when taken inadvertently during early pregnancy. Previously, a few studies had reported that oral contraceptives might be associated with birth defects but these studies have not been confirmed. Nevertheless, oral contraceptives should not be used during pregnancy. You should check with your healthcare provider about risks to your unbom child of any medication taken during pregnancy. 2. While breastfeeding If you are breastfeeding, consult your healthcare provider before starting oral contraceptives. Some of the drug will be passed on to the child in the milk. A few adverse effects on the child have been reported, including yellowing of the skin (jaundice) and breast enlargement. In addition, oral contraceptives may decrease the amount and quality of your milk. If possible, do not use oral contraceptives while breastfeeding. You should use another method of contraception since breastfeeding provides only partial protection from becoming pregnant, and this partial protection decreases significantly as you breastfeed for longer periods of time. You should consider starting oral contraceptives only after you have weaned your child completely. 3. Laboratory tests If you are scheduled for any laboratory tests, tell your healthcare provider you are taking birth control pills. Certain blood tests may be affected by birth control pills. 4. Drug interactions Certain drugs may interact with birth control pills to make them less effective in preventing pregnancy or cause an increase in breakthrough bleeding. Such drugs include rifampin, drugs used for epilepsy such as barbiturates (for example, phenobarbital), carbamazepine (Tegretol® is one brand of this drug), and phenytoin (Dilantin® is one brand of this drug), primidone (Mysoline®), topiramate (Topamax®), phenylbutazone (Butazolidin® is one brand), some drugs used for HIV such as ritonavir (Norvir®), modafinil (Provigil®) and possibly certain antibiotics (such as ampicillin and other penicillins, and tetracyclines), and herbal products containing St. John's Wort (hypericum perforatum). You may need to use a non-hormonal method of contraception during any cycle in which you take drugs that can make oral contraceptives less effective. Be sure to tell your healthcare provider if you are taking or start taking any other medications, including nonprescription products or herbal products while taking birth control pills. You may be at higher risk of a specific type of liver dysfunction if you take troleandomycin (Tao® capsules) and oral contraceptives at the same time. 5. Sexually transmitted diseases This product (like all oral contraceptives) is intended to prevent pregnancy. It does not protect against transmission of HIV (AIDS) and other sexually transmitted diseases such as Chlamydia, genital herpes, genital warts, gonorrhea, hepatitis B, and syphilis. HOW TO TAKE FEMCON Fe (norethindrone and ethinyl estradiol tablets) IMPORTANT POINTS TO REMEMBER BEFORE YOU START TAKING YOUR PILLS: BE SURE TO READ THESE DIRECTIONS: Before you start taking your pills Anytime you are not sure what to do THE PILL MAY BE SWALLOWED WHOLE OR CHEWED AND SWALLOWED. IF THE PILL IS CHEWED, YOU SHOULD DRINK A FULL GLASS (8 OUNCES) OF LIQUID IMMEDIATELY AFTER SWALLOWING. TAKE ONE PILL EVERY DAY AT THE SAME TIME. If you miss pills you could get pregnant. This includes starting the pack late. The more pills you miss, the more likely you are to get pregnant. MANY WOMEN HAVE SPOTTING OR LIGHT BLEEDING, OR MAY FEEL SICK TO THEIR STOMACH DURING THE FIRST 1-3 PACKS OF PILLS. If you have spotting or light bleeding or feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If it doesn't go away, check with your healthcare provider. MISSING PILLS CAN ALSO CAUSE SPOTTING OR LIGHT BLEEDING, even when you make up these missed pills. On the days you take 2 pills to make up for missed pills, you could also feel a little sick to your stomach. IF YOU HAVE VOMITING (within 3 to 4 hours after you take your pill), you should follow the instructions for WHAT TO DO IF YOU MISS PILLS. IF YOU HAVE DIARRHEA or IF YOU TAKE CERTAIN MEDICINES, including some antibiotics, or the herbal supplement St. John's Wort, your pills may not work as well. Use a back-up method of birth control (such as condoms or spermicide) until you check with your healthcare provider. IF YOU HAVE TROUBLE REMEMBERING TO TAKE THE PILL, talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control. IF YOU HAVE ANY QUESTIONS OR ARE UNSURE ABOUT THE INFORMATION IN THIS LEAFLET, call your healthcare provider. BEFORE YOU START TAKING YOUR PILLS DECIDE WHAT TIME OF DAY YOU WANT TO TAKE YOUR PILL. It is important to take it at about the same time every day. LOOK AT YOUR PILL PACK: The pill pack has 21 "active" white pills (with hormones) to take for 3 weeks, followed by 7 "reminder" brown pills (without hormones) to take for 1 week. *For use of day labels, see WHEN TO START THE FIRST PACK OF PILLS. 3. ALSO FIND: where on the pack to start taking pills, in what order to take the pills (follow the arrows), and the week numbers as shown in the picture above. 4. BE SURE YOU HAVE READY AT ALL TIMES: ANOTHER KIND OF BIRTH CONTROL (such as condoms or spermicide) to use as a back-up in case you miss pills. AN EXTRA, FULL PILL PACK. WHEN TO START THE FIRST PACK OF PILLS You have 2 choices of which day to start taking your first pack of pills. (See DAY 1 START or SUNDAY START directions below.) Decide with your healthcare provider which is the best day for you. Once you have decided which day you will begin taking your pills, immediately do the following: remove the Brief Summary from inside the pouch and look for the attached day label sheet; peel the label from the sheet which has the start day printed on the left hand side; place the label on the blister card in the designated location. Take your pill daily in the order indicated by the arrows on the blister card illustration shown above. Pick a time of day which will be easy to remember and take your pill at the same time each day. DAY 1 START: Take the first "active" white pill of the first pack during the first 24 hours of your period. You will not need to use a back-up method of birth control, since you are starting the pill at the beginning of your period. SUNDAY START: Take the first "active" white pill of the first pack on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the pack that same day. Use another method of birth control as a back-up method if you have sex anytime from the Sunday you start your first pack until the next Sunday (7 days). Condoms or spermicide are good back-up methods of birth control. WHAT TO DO DURING THE MONTH 1. TAKE ONE PILL AT THE SAME TIME EVERY DAY UNTIL THE PACK IS EMPTY Do not skip pills even if you are spotting or bleeding between monthly periods or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. 2. WHEN YOU FINISH A PACK OF YOUR FEMCON Fe (norethindrone and ethinyl estradiol tablets) : Start the next pack on the day after your last brown "reminder" pill. Do not wait any days between packs. 3. WHEN YOU SWITCH FROM A DIFFERENT BRAND OF PILLS: If your previous brand had 21 pills, wait 7 days before starting FEMCON Fe (norethindrone and ethinyl estradiol tablets) . If your previous brand had 28 pills, start taking FEMCON Fe (norethindrone and ethinyl estradiol tablets) on the day after the last pill. WHAT TO DO IF YOU MISS PILLS The pill may not be as effective if you miss white "active" pills, and particularly if you miss the first few or the last few white "active" pills in a pack. If you MISS 1 white "active" pill: Take it as soon as you remember. Take the next pill at your regular time. This means you may take 2 pills in 1 day. You do not need to use a back-up birth control method if you have sex. If you MISS 2 white "active" pills in a row in WEEK 1 OR WEEK 2 of your pack: Take 2 pills on the day you remember and 2 pills the next day. Then take 1 pill a day until you finish the pack. You COULD BECOME PREGNANT if you have sex during the 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for those 7 days. If you MISS 2 white "active" pills in a row in THE 3rd WEEK: 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant. 3. You COULD BECOME PREGNANT if you have sex during the 7 days after you restart your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for those 7 days. If you MISS 3 OR MORE white "active" pills in a row (during the first 3 weeks): 1. If you are a Day 1 Starter: THROW OUT the rest of the pill pack and start a new pack that same day. If you are a Sunday Starter: Keep taking 1 pill every day until Sunday. On Sunday, THROW OUT the rest of the pack and start a new pack of pills that same day. 2. You may not have your period this month but this is expected. However, if you miss your period 2 months in a row, call your healthcare provider because you might be pregnant. 3. You COULD BECOME PREGNANT if you have sex on the days when you missed pills or during the first 7 days after restarting your pills. You MUST use a non-hormonal birth control method (such as condoms or spermicide) as a back-up for the first 7 days after you restart your pills. If you forget any of the 7 brown "reminder" pills in Week 4: THROW AWAY the pills you missed. Keep taking 1 pill each day until the pack is empty. You do not need a back-up method of birth control. FINALLY, IF YOU ARE STILL NOT SURE WHAT TO DO ABOUT THE PILLS YOU HAVE MISSED: Use a BACK-UP METHOD anytime you have sex. KEEP TAKING ONE "ACTIVE" (WHITE) PILL EACH DAY until you can reach your healthcare provider. GENERAL 1. Pregnancy due to pill failure If taken every day as directed, the incidence of pill failure resulting in pregnancy is approximately 1% per year (one pregnancy per 100 women per year), but more typical failure rates are about 5% per year (5 pregnancies per 100 women per year). If pregnancy does occur, the risk to the fetus is minimal. 2. Pregnancy after stopping the pill There may be some delay in becoming pregnant after you stop using oral contraceptives, especially if you had irregular menstrual cycles before you used oral contraceptives. It may be advisable to postpone conception until you begin menstruating regularly once you have stopped taking the pill and desire pregnancy. There does not appear to be any increase in birth defects in newborn babies when pregnancy occurs soon after stopping the pill. 3. Overdosage Serious ill effects have not been reported following ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea and withdrawal bleeding in females. In case of overdosage, contact your healthcare provider or pharmacist. 4. Other information Your healthcare provider will take a medical and family history before prescribing oral contraceptives and will examine you. The physical examination may be delayed to another time if you request it and the healthcare provider believes that it is a good medical practice to postpone it. You should be reexamined at least once a year. Be sure to inform your healthcare provider if there is a family history of any of the conditions listed previously in this leaflet. Be sure to keep all appointments with your healthcare provider, because this is a time to determine if there are early signs of side effects of oral contraceptive use. Do not use this drug for any condition other than the one for which it was prescribed. This drug has been prescribed specifically for you; do not give it to others who may want birth control pills. HEALTH BENEFITS FROM ORAL CONTRACEPTIVES In addition to preventing pregnancy, use of oral contraceptives may provide certain benefits. They are: Menstrual cycles may become more regular Blood flow during menstruation may be lighter and less iron may be lost. Therefore, anemia due to iron deficiency is less likely to occur Pain or other symptoms during menstruation may be encountered less frequently Ovarian cysts may occur less frequently Ectopic (tubal) pregnancy may occur less frequently Noncancerous cysts or lumps in the breast may occur less frequently Acute pelvic inflammatory disease may occur less frequently Oral contraceptive use may provide some protection against developing two forms of cancer: cancer of the ovaries and cancer of the lining of the uterus If you want more information about birth control pills, ask your healthcare provider or pharmacist. They have a more technical leaflet called the Professional Labeling, which you may wish to read.

OVERDOSE Serious ill effects have not been reported following acute ingestion of large doses of oral contraceptives by young children. Overdosage may cause nausea, and withdrawal bleeding may occur in females. Non-Contraceptive Health Benefits The following non-contraceptive health benefits related to the use of combination oral contraceptives are supported by epidemiological studies which largely utilized oral contraceptive formulations containing estrogen doses exceeding 0.035 mg of ethinyl estradiol or 0.05 mg of mestranol (73-78). Effects on menses: increased menstrual cycle regularity decreased blood loss and decreased risk of iron-deficiency anemia decreased frequency of dysmenorrhea Effects related to inhibition of ovulation: decreased incidence of functional ovarian cysts decreased incidence of ectopic pregnancies Other effects: decreased incidence of fibroadenomas and fibrocystic disease of the breast decreased incidence of acute pelvic inflammatory disease decreased incidence of endometrial cancer decreased incidence of ovarian cancer CONTRAINDICATIONS Oral contraceptives should not be used in women who have the following conditions: Thrombophlebitis or thromboembolic disor- ders A past history of deep vein thrombophlebitis or thromboembolic disorders Cerebral vascular or coronary artery disease Known or suspected carcinoma of the breast Carcinoma of the endometrium or other known or suspected estrogen-dependent neoplasia Undiagnosed abnormal genital bleeding Cholestatic jaundice of pregnancy or jaundice with prior pill use Hepatic adenomas or carcinomas Known or suspected pregnancy REFERENCES 73. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development: Oral contraceptive use and the risk of ovarian cancer. JAMA 1983; 249: 1596- 1599. 74. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development: Combination oral contraceptive use and the risk of endometrial cancer. JAMA 1987; 257: 796-800. 75. Ory HW. Functional ovarian cysts and oral contraceptives: negative association confirmed surgically. JAMA 1974; 228: 68-69. 76. Ory HW, Cole P, MacMahon B, Hoover R. Oral contraceptives and reduced risk of benign breast disease. N Engl J Med 1976; 294: 419-422. 77. Ory HW. The noncontraceptive health benefits from oral contraceptive use. Fam Plann Perspect 1982; 14: 182-184. 78. Ory HW, Forrest JD, Lincoln R. Making choices: Evaluating the health risks and benefits of birth control methods. New York, The Alan Guttmacher Institute 1983; p.1.

SIDE EFFECTS To report SUSPECTED ADVERSE REACTIONS, contact Norths tar Rx LLC. Toll-Free at 1- 800-206-7821 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. An increased risk of the following serious adverse reactions has been associated with the use of oral contraceptives (see WARNINGS section): Thrombophlebitis Cerebral thrombosis Arterial thromboembolism Hypertension Pulmonary embolism Gallbladder disease Myocardial infarction Hepatic adenomas or benign liver tumors Cerebral hemorrhage There is evidence of an association between the following conditions and the use of oral contraceptives, although additional confirmatory studies are needed: Mesenteric thrombosis Retinal thrombosis The following adverse reactions have been reported in patients receiving oral contraceptives and are believed to be drug-related: Nausea Change in weight (increase or decrease) Vomiting Change in cervical ectropion and secretion Gastrointestinal symptoms Possible diminution in lactation when given (such as abdominal cramps and bloating) immediately postpartum Breakthrough bleeding Cholestatic jaundice Spotting Migraine Change in menstrual flow Rash (allergic) Amenorrhea Mental depression Temporary infertility after Reduced tolerance to carbohydrates discontinuation of treatment Vaginal candidiasis Edema Change in corneal curvature (steepening) Melasma which may persist Intolerance to contact lenses Breast changes: tenderness, enlargement, and secretion The following adverse reactions have been reported in users of oral contraceptives, and the association has been neither confirmed nor refuted: Premenstrual syndrome Erythema nodosum Cataracts Hemorrhagic eruption Changes in appetite Vaginitis Cystitis-like syndrome Porphyria Headache Impaired renal function Nervousness Hemolytic uremic syndrome Dizziness Budd-Chiari syndrome Hirsutism Acne Loss of scalp hair Changes in libido Erythema multiforme Colitis DRUG INTERACTIONS Reduced efficacy and increased incidence of breakthrough bleeding and menstrual irregularities have been associated with concomitant use of rifampin. A similar association, though less marked, has been suggested with barbiturates, phenylbutazone, phenytoin sodium, and possibly with griseofulvin, ampicillin, and tetracyclines.

WARNINGS Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. The use of oral contraceptives is associated with increased risk of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population*. For further information, the reader is referred to a text on epidemiological methods. *Adapted from Stadel BB: Oral contraceptives and cardiovascular disease. N Engl J Med, 1981;305:612-618, 672-677; with author's permission. Thromboembolic Disorders And Other Vascular Problems The physician should be alert to the earliest manifestations of thromboembolic thrombotic disorders as discussed below. Should any of these occur or be suspected the drug should be discontinued immediately. Myocardial Infarction An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older, with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Figure 1) among women who use oral contraceptives. FIGURE 1: CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMEN - YEARS BY AGE, SMOKING STATUS AND ORAL CONTRACEPTIVE USE Layde PM, Beral V: Further analyses of mortality in oral contraceptive users: Royal College of General Practitioners' oral contraception study. (Table 5) Lancet 1981; 1:541-546. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users [see section 9 in WARNINGS]. Such increases in risk factors have been associated with an increased risk of heart disease and the risk increases with the number of risk factors present. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped. A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four to six weeks after delivery in women who elect not to breastfeed. Cerebrovascular Diseases Oral contraceptives have been shown to increase both the relative and attributable risk of cerebrovascular events (thrombotic and hemorrhagic strokes); although, in general, the risk is greatest among older (greater than 35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and non-users, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes. In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. Dose-Related Risk Of Vascular Disease From Oral Contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/ progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on preparations containing 0.05 mg or less of estrogen. Persistence Of Risk There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40 to 49 years old who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least six years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens. Estimates Of Mortality From Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 2). TABLE 2 : ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Method of Control and Outcome AGE 15 to 19 20 to 24 25 to 29 30 to 34 35 to 39 40 to 44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker† 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker† 2.2 3.4 6.6 13.5 51.1 117.2 IUD† 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 Ory HW: Mortality associated with fertility and fertility control: 1983. Fam Plann Perspect 1983; 15:50-56. *Deaths are birth related. †Deaths are method related. These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risk. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's– but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed (Porter JB, Hunter J, Jick H, et al. Oral contraceptives and nonfatal vascular disease. Obstet Gynecol 1985;66:1-4 and Porter JB, Jick H, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32), the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risk may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective. Carcinoma Of The Reproductive Organs Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. The overwhelming evidence in the literature suggests that use of oral contraceptives is not associated with an increase in the risk of developing breast cancer, regardless of the age and parity of first use or with most of the marketed brands and doses. The Cancer and Steroid Hormone (CASH) study also showed no latent effect on the risk of breast cancer for at least a decade following long-term use. A few studies have shown a slightly increased relative risk of developing breast cancer, although the methodology of these studies, which included differences in examination of users and nonusers and differences in age at start of use, has been questioned. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. In spite of many studies of the relationship between oral contraceptive use and breast cancer and cervical cancers, a cause-and-effect relationship has not been established. Hepatic Neoplasia Benign hepatic adenomas are associated with oral contraceptive use, although their occurrence is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (greater than 8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. Oral Contraceptive Use Before Or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. Carbohydrate And Lipid Metabolic Effects Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier [see WARNINGS 1.a. 1.d.], changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. Elevated Blood Pressure An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users. Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Women with a history of oligomenorrhea or secondary amenorrhea or young women without regular cycles prior to taking oral contraceptives may again have irregular bleeding or amenorrhea after discontinuation of oral contraceptives. PRECAUTIONS Sexually-Trans Mitted Diseases Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually trans mitted diseases. Physical Examination And Follow-Up It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Lipid Disorders Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. Liver Function If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. Fluid Retention Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Emotional Disorders Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related. Contact Lenses Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Carcinogenesis See WARNINGS section. Pregnancy Pregnancy Category X See CONTRAINDICATIONS and WARNINGS sections. Nursing Mothers Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child. Vomiting And/Or Diarrhea Although a cause-and-effect relationship has not been clearly established, several cases of oral contraceptive failure have been reported in association with vomiting and/or diarrhea. If significant gastrointestinal disturbance occurs in any woman receiving contraceptive steroids, the use of a back-up method of contraception for the remainder of that cycle is recommended. Pediatric Use Safety and efficacy of Vyfemla (norethindrone and ethinyl estradiol tablets USP) have been established in women of reproductive age. Safety and efficacy are expected to be the same in postpubertal adolescents under the age of 16 years and in users ages 16 years and older. Use of this product before menarche is not indicated. Information For The Patient See patient labeling.

WARNINGS Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. The use of oral contraceptives is associated with increased risk of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population*. For further information, the reader is referred to a text on epidemiological methods. *Adapted from Stadel BB: Oral contraceptives and cardiovascular disease. N Engl J Med, 1981; 305: 612-618, 672-677; with author’s permission. Thromboembolic Disorders And Other Vascular Problems The physician should be alert to the earliest manifestations of thromboembolic thrombotic disorders as discussed below. Should any of these occur or be suspected the drug should be discontinued immediately. Myocardial Infarction An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older, with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Figure 1) among women who use oral contraceptives. Layde PM, Beral V: Further analyses of mortality in oral contraceptive users : Royal College of General Practitioners’ oral contraception study. (Table 5) Lancet 1981;1:54 1-54 6. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section WARNINGS). Such increases in risk factors have been associated with an increased risk of heart disease and the risk increases with the number of risk factors present. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped. A two- to four -fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four to six weeks after delivery in women who elect not to breastfeed. Cerebrovascular Diseases Oral contraceptives have been shown to increase both the relative and attributable risk of Oral contraceptives have been shown to increase both the relative and attributable risk of cerebrovascular events (thrombotic and hemorrhagic strokes); although, in general, the risk is greatest among older (>35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and non-users, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes. In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. Dose-Related Risk Of Vascular Disease From Oral Contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on preparations containing 0.05 mg or less of estrogen. Persistence Of Risk There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40-49 years old who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least six years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens. Estimates Of Mortality From Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 2). TABLE 2 ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Method of control and outcome AGE 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 *Deaths are birth related. **Deaths are method related. Ory HW: Mortality associated with fertility and fertility control: 1983. Fam Plann Perspect 1983; 15:50-56. These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risk. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970’s–but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed (Porter JB, Hunter J, Jick H, et al. Oral contraceptives and nonfatal vascular disease. Obstet Gynecol 1985;66:1-4 and Porter JB, Jick H, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32), the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risk may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective. Carcinoma Of The Reproductive Organs Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian and cervical cancer in women using oral contraceptives. The overwhelming evidence in the literature suggests that use of oral contraceptives is not associated with an increase in the risk of developing breast cancer, regardless of the age and parity of first use or with most of the marketed brands and doses. The Cancer and Steroid Hormone (CASH) study also showed no latent effect on the risk of breast cancer for at least a decade following long-term use. A few studies have shown a slightly increased relative risk of developing breast cancer, although the methodology of these studies, which included differences in examination of users and nonusers and differences in age at start of use, has been questioned. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. In spite of many studies of the relationship between oral contraceptive use and breast cancer and cervical cancers, a cause-and-effect relationship has not been established. Hepatic Neoplasia Benign hepatic adenomas are associated with oral contraceptive use, although their occurrence is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term (>8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. Oral Contraceptive Use Before Or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. Carbohydrate And Lipid Metabolic Effects Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS ), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. Elevated Blood Pressure An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent or severe requires discontinuation of oral contraceptives and evaluation of the cause. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Women with a history of oligomenorrhea or secondary amenorrhea or young women without regular cycles prior to taking oral contraceptives may again have irregular bleeding or amenorrhea after discontinuation of oral contraceptives. PRECAUTIONS Sexually-Transmitted Diseases Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases . Physical Examination And Follow-Up It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Lipid Disorders Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. Liver Function If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. Fluid Retention Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Emotional Disorders Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related. Contact Lenses Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Interactions With Laboratory Tests Certain endocrine and liver function tests and blood components may be affected by oral contraceptives: Increased prothrombin and factors VII, VIII, IX, and X; decreased antithrombin 3; increased norepinephrine-induced platelet aggregability. Increased thyroid-binding globulin (TBG) leading to increased circulating total thyroid hormone, as measured by protein-bound iodine (PBI), T4 by column or by radioimmunoassay. Free T3 resin uptake is decreased, reflecting the elevated TBG; free T4 concentration is unaltered. Other binding proteins may be elevated in serum. Sex-binding globulins are increased and result in elevated levels of total circulating sex steroids and corticoids; however, free or biologically active levels remain unchanged. Triglycerides may be increased. Glucose tolerance may be decreased. Serum folate levels may be depressed by oral contraceptive therapy. This may be of clinical significance if a woman becomes pregnant shortly after discontinuing oral contraceptives. Carcinogenesis See WARNINGS section. Pregnancy Pregnancy Category X: See CONTRAINDICATIONS and WARNINGS sections. Nursing Mothers Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child. Vomiting And/Or Diarrhea Although a cause-and-effect relationship has not been clearly established, several cases of oral contraceptive failure have been reported in association with vomiting and/or diarrhea. If significant gastrointestinal disturbance occurs in any woman receiving contraceptive steroids, the use of a back-up method of contraception for the remainder of that cycle is recommended. Pediatric Use Safety and efficacy of norethindrone and ethinyl estradiol tablets have been established in women of reproductive age. Safety and efficacy are expected to be the same in postpubertal adolescents under the age of 16 years and in users ages 16 years and older. Use of this product before menarche is not indicated. Information For Patient See PATIENT INFORMATION.

WARNINGS Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. The use of oral contraceptives is associated with increased risk of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia, and gallbladder disease, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population.* For further information, the reader is referred to a text on epidemiological methods. *Adapted from Stadel BB: Oral contraceptives and cardio-vascular disease. N Engl J Med, 1981;305:612­618, 672-677; with author's permission. Thromboembolic Disorders And Other Vascular Problems The physician should be alert to the earliest manifestations of thromboembolic thrombotic disorders as discussed below. Should any of these occur or be suspected the drug should be discontinued immediately. Myocardial Infarction An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older, with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Figure 1) among women who use oral contraceptives. FIGURE 1: CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMEN-YEARS BY AGE, SMOKING STATUS AND ORAL CONTRACEPTIVE USE Layde PM, Beral V: Further analyses of mortality in oral contraceptive users: Royal College of General Practitioners' oral contraception study. (Table 5) Lancet1981;1:541-546. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age, and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS). Such increases in risk factors have been associated with an increased risk of heart disease and the risk increases with the number of risk factors present. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped. A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four to six weeks after delivery in women who elect not to breastfeed. Cerebrovascular diseases Oral contraceptives have been shown to increase both the relative and attributable risk of cerebrovascular events (thrombotic and hemorrhagic strokes); although, in general, the risk is greatest among older ( > 35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes. In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. Dose-related risk of vascular disease from oral contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease. A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on preparations containing 0.05 mg or less of estrogen. Products containing 50 mcg estrogen should be used only when medically indicated. Persistence of risk There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40-49 years old who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens. Estimates Of Mortality From Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 2). TABLE 2: ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE Age Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 *Deaths are birth related **Deaths are method related Ory HW: Mortality associated with fertility and fertility control: 1983. Fam Plann Perspect 1983; 15:50-56. These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risk. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970s - but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed (Porter JB, Hunter J, Jick H, et al. Oral contraceptives and nonfatal vascular disease. Obstet Gynecol 1985;66:1-4 and Porter JB, Jick H, Walker AM. Mortality among oral contraceptive users. Obstet Gynecol 1987;70:29-32), the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risk may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose formulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective. Carcinoma Of The Reproductive Organs Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. The overwhelming evidence in the literature suggests that use of oral contraceptives is not associated with an increase in the risk of developing breast cancer, regardless of the age and parity of first use or with most of the marketed brands and doses. The Cancer and Steroid Hormone (CASH) study also showed no latent effect on the risk of breast cancer for at least a decade following long-term use. A few studies have shown a slightly increased relative risk of developing breast cancer, although the methodology of these studies, which included differences in examination of users and nonusers and differences in age at start of use, has been questioned. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. In spite of many studies of the relationship between oral contraceptive use and breast cancer and cervical cancers, a cause-and-effect relationship has not been established. Hepatic Neoplasia Benign hepatic adenomas are associated with oral contraceptive use, although their occurrence is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term ( > 8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. Oral Contraceptive Use Before Or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. Carbohydrate And Lipid Metabolic Effects Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. Elevated Blood Pressure An increase in blood pressure has been reported in women taking oral contraceptives and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users. Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Women with a history of oligomenorrhea or secondary amenorrhea or young women without regular cycles prior to taking oral contraceptives may again have irregular bleeding or amenorrhea after discontinuation of oral contraceptives. PRECAUTIONS Sexually - Transmitted Diseases Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Physcial Examination And Follow -Up It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Lipid Disorders Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. Liver Function If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. Fluid Retention Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Emotionl Disorders Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related. Contact Lenses Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Carcinogenesis See WARNINGS section. Pregnancy Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS sections. Nursing Mothers Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use oral contraceptives but to use other forms of contraception until she has completely weaned her child. Vomitting And/Or Diarrhea Although a cause-and-effect relationship has not been clearly established, several cases of oral contraceptive failure have been reported in association with vomiting and/or diarrhea. If significant gastrointestinal disturbance occurs in any woman receiving contraceptive steroids, the use of a back-up method of contraception for the remainder of that cycle is recommended. Pediatric Use Safety and efficacy of OVCON 50 (norethindrone and ethinyl estradiol tablets, USP) have been established in women of reproductive age. Safety and efficacy are expected to be the same in postpubertal adolescents under the age of 16 years and in users ages 16 years and older. Use of this product before menarche is not indicated. Information For The Patient See Patient Labeling.

WARNINGS Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with heavy smoking (15 or more cigarettes per day) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. The use of oral contraceptives is associated with increased risks of several serious conditions including myocardial infarction, thromboembolism, stroke, hepatic neoplasia and gallbladder disease, although the risk of serious morbidity and mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as hypertension, hyperlipidemias, obesity, and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population (adapted from refs. 2 and 3 with the author's permission). For further information, the reader is referred to a text on epidemiological methods. Thromboembolic Disorders And Other Vascular Problems Myocardial Infarction An increased risk of myocardial infarction has been associated with oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six (4-10). The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older with smoking accounting for the majority of excess cases (11). Mortality rates associated with circulatory disease have been shown to increase substantially in smokers, especially in those 35 years of age and older among women who use oral contraceptives. Table II. Circulatory Disease Mortality rates per 100,000 women years by age, smoking status, and oral contraceptive use Adapted from P.M. Layde and V. Beral, ref. #12. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age and obesity (13). In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism (14-18). Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS). Similar effects on risk factors have been associated with an increased risk of heart disease. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to nonusers to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease (2,3,19-24). Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization (25). The risk of thromboembolic disease associated with oral contraceptives is not related to length of use and disappears after pill use is stopped (2). A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives (9). The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions (26). If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four weeks after delivery in women who elect not to breast feed or four weeks after a second trimester abortion. Cerebrovascular disease Oral contraceptives have been shown to increase both the relative and attributable risks of cere- brovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older ( > 35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and nonusers, for both types of strokes, and smoking interacted to increase the risk of stroke (27-29). In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension (30). The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension (30). The attributable risk is also greater in older women (3). Dose-related risk of vascular disease with oral contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral contraceptives and the risk of vascular disease (31-33). A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents (14-16). A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the activity of progestogen used in the contraceptive. The activity and amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptives agents should be started on preparations containing 0.035 mg or less of estrogen. Persistence of risk of vascular disease There are two studies which have shown persistence of risk of vascular disease for everusers of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontinuing oral contraceptives persists for at least 9 years for women 40-49 years who had used oral contraceptives for five or more years, but this increased risk was not demonstrated in other age groups (8). In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small (34). However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens. Estimates Of Mortality From Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table III). These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risks. The study concluded that with the exception of oral contraceptive users 35 and older who smoke, and 40 or older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of an increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970's (35). Current clinical recommendation involves the use of lower estrogen dose formulations and a careful consideration of risk factors. In 1989, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the use of oral contraceptives in women 40 years of age and over. The Committee concluded that although cardiovascular disease risks may be increased with oral contraceptive use after age 40 in healthy non-smoking women (even with the newer low-dose formulations), there are also greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. The Committee recommended that the benefits of low-dose oral contraceptive use by healthy nonsmoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take an oral contraceptive which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and individual patient needs. Table III. Annual Number of Birth-related or Method-related deaths associated with control of fertility per 100,000 nonsterile women, by fer- tility control method according to age Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/ spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 * Deaths are birth-related ** Deaths are method-related Adapted from H.W. Ory, ref. #35. Carcinoma Of The Reproductive ORGANS AND BREASTS Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. While there are conflicting reports, most studies suggest that use of oral contraceptives is not associated with an overall increase in the risk of developing breast cancer. A meta-analysis of 54 studies reports that women who are currently using combined oral contraceptives or have used them in the past 10 years are at slightly increased risk of having breast cancer diagnosed although the additional cancers tend to be localized to the breast. There is no evidence of an increased risk of having breast cancer diagnosed 10 or more years after cessation of use. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia in some populations of women (45-48). However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. Hepatic Neoplasia Benign hepatic adenomas are associated with oral contraceptive use, although the incidence of benign tumors is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use especially with oral contraceptives of higher dose (49). Rupture of benign, hepatic adenomas may cause death through intraabdominal hemorrhage (50, 51). Studies have shown an increased risk of developing hepatocellular carcinoma in oral contraceptive users. However, these cancers are rare in the U.S., and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral con- traceptives. Oral contraceptives should be dis- continued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. Oral Contraceptive Use Before Or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy (56,57). The majority of recent studies also do not indicate a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned (55,56,58,59), when taken inadvertently during early pregnancy. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out before continuing oral contraceptive use. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued until pregnancy is ruled out. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral contraceptives and estrogens (60,61). More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal (62-64). The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. Carbohydrate And Lipid Metabolic Effects Oral contraceptives have been shown to cause a decrease in glucose tolerance in a significant percentage of users (17). This effect has been shown to be directly related to estrogen dose (65). Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents (17,66). However, in the non-diabetic woman, oral contraceptives appear to have no effect on fasting blood glucose (67). Because of these demonstrated effects, prediabetic and diabetic women in particular should be carefully monitored while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As dis- cussed earlier (see WARNINGS), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. Elevated Blood Pressure An increase in blood pressure has been reported in women taking oral contraceptives (68) and this increase is more likely in older oral contraceptive users (69) and with extended duration of use (61). Data from the Royal College of General Practitioners (12) and subsequent randomized trials have shown that the incidence of hypertension increases with increasing progestational activity. Women with a history of hypertension or hypertension-related diseases, or renal disease (70) should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued. For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension between former and never users (68-71). Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. Non-hormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy in the event of breakthrough bleeding, as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Some women may encounter post-pill amenorrhea or oligomenorrhea, especially when such a condition was preexistent. Ectopic Pregnancy Ectopic as well as intrauterine pregnancy may occur in contraceptive failures. However, in progestogen-only oral contraceptive failures, the ratio of ectopic to intrauterine pregnancies is higher than in women who are not receiving oral contraceptives, since the drugs are more effective in preventing intrauterine than ectopic pregnancies. PRECAUTIONS Physical Examination And Follow-Up It is good medical practice for all women to have annual history and physical examinations, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen, and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent, or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. Lipid Disorders Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. Liver Function If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. Fluid Retention Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. Emotional Disorders Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Contact Lenses Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. Carcinogenesis See WARNINGS section. Pregnancy Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS sections. Nursing Mothers Small amounts of oral contraceptive steroids have been identified in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, combination oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use combination oral contraceptives but to use other forms of contraception until she has completely weaned her child. Sexually Transmitted Diseases Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. Pediatric Use Safety and efficacy of NECON (norethindrone and ethinyl estradiol tablets ) Tablets has been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 16 and for users 16 years and older. Use of this product before menarche is not indicated. Information For Patient See Patient Labeling. REFERENCES 1. Source: Trussell J. Contraceptive Efficacy Table from Hatcher RA, Trussell J, Stewart F, Cates W, Stewart GK, Kowal D, Guest F, In Con- traceptive Technology: Seventeenth Revised Edition. New York, NY: Irvington Publishers, 1998. 2. Stadel BV, Oral contraceptives and car- diovascular disease. (Pt. 1). N Engl J Med 1981; 305:612-618. 3. Stadel BV, Oral contraceptives and cardiovascular disease. (Pt. 2). N Engl J Med 1981; 305:672-677. 4. Adam SA, Thorogood M. Oral contraception and myocardial infarction revisited: the effects of new preparations and prescribing patterns. Br J Obstet Gynaecol 1981; 88:838-845. 5. Mann JI, Inman WH. Oral contraceptives and death from myocardial infarction. Br Med J 1975; 2(5965): 245-248. 6. Mann JI, Vessey MP, Thorogood M, Doll R. Myocardial infarction in young women with special reference to oral contraceptive practice. Br Med J 1975; 2(5956): 241-245. 7. Royal College of General Practitioners' Oral Contraception Study: Further analyses of mortality in oral contraceptive users. Lancet 1981; 1:541-546. 8. Stone D, Shapiro S, Kaufman DW, Rosenberg L, Miettinen OS, Stolley PD. Risk of myocardial infarction in relation to current and discontinued use of oral contracep- tives. N Engl J Med 1981;305:420-424. 9. Vessey MP. Female hormones and vascular disease-an epidemiological overview. Br J Fam Plann 1980; 6(Supplement): 1-12. 10. Russell-Briefel RG, Ezzati TM, Fulwood R, Perlman JA, Murphy RS. Cardiovascular risk status and oral contracep- tive use, United States 1976-1980. Prevent Med 1986; 15:352-362. 11. Goldbaum GM, Kendrick JS, Hogelin GC, Gentry EM. The relative impact of smoking and oral contraceptive use on women in the United States. JAMA 1987; 258:1339- 1342. 12. Layde PM, Beral V Further analyses of mortality in oral contraceptive users; Royal College of General Practitioners' Oral Contraception Study. (Table 5) Lancet 1981; 1:541-546. 13. Knopp RH. Arteriosclerosis risk: the roles of oral contraceptives and postmenopausal estrogens. J Reprod Med 1986; 31(9) (Supplement) :913- 921. 14. Krauss RM, Roy S, Mishell DR, Casagrande J, Pike MC. Effects of two low-dose oral contraceptives on serum lipids and lipoproteins: Differential changes in high-density lipoproteins subclasses. Am J Obstet 1983; 145;446-452. 15. Wahl P, Walden C, Knopp R, Hoover J, Wallace R, Heiss G, Rifkind B. Effect of estrogen/progestin potency on lipid/lipopro- tein cholesterol. N Engl J Med 1983; 308:862- 867. 16. Wynn V, Niththyananthan R. The effect of progestin in combined oral contraceptives on serum lipids with special reference to high density lipoproteins. Am J Obstet Gynecol 1982; 142: 766-771. 17. Wynn V, Godsland I. Effects of oral contraceptives on carbohydrate metabo- lism. J Reprod Med 1986; 31 (9) (Supplement) :892-897. 18. LaRosa JC. Atherosclerotic risk factors in cardiovascular disease. J Reprod Med 1986; 31 (9) (Supplement): 906-912. 19. Inman WH, Vessey MP. Investigation of death from pul- monary, coronary, and cerebral thrombosis and embolism in women of child-bearing age. Br Med J 1968; 2(5599): 193-199. 20. Maguire MG, Tonascia J, Sartwell PE, Stolley PD, Tockman MS. Increased risk of thrombosis due to oral con- traceptives: a further report. Am J Epidemiol 1979; 110(2):188-195. 21. Petitti DB, Wingerd J, Pellegrin F, Ramacharan S. Risk of vascular disease in women: smoking, oral contraceptives, noncontraceptive estrogens, and other factors. JAMA 1979; 242: 1150-1154. 22. Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. Br Med J 1968;2(5599) :199-205. 23. Vessey MP, Doll R. Investigation of relation between use of oral contraceptives and thromboembolic disease. A further report. Br Med J 1969; 2 (5658): 651-657. 24. Porter JB, Hunter JR, Danielson DA, Jick H, Stergachis A. Oral contraceptives and non-fatal vascular disease-recent experience. Obstet Gyneco 1982; 59 (3):299-302. 25. Vessey M, Doll R, Peto R, Johnson B, Wiggins P. A long- term follow-up study of women using different methods of contraception: an interim report. J Biosocial Sci 1976; 8: 375-427. 26. Royal College of General Practitioners: Oral Contraceptives, venous thrombosis, and varicose veins. J Royal Coll Gen Pract 1978;28: 393-399. 27. Collaborative Group for the Study of Stroke in Young Women: Oral contraception and increased risk of cerebral ischemia or thrombosis. N Engl J Med 1973; 288: 871-878. 28. Petitti DB, Wingerd J. Use of oral contraceptives, cigarette smoking, and risk of subarachnoid hemorrhage. Lancet 1978; 2: 234-236. 29. Inman WH. Oral contra- ceptives and fatal subarachnoid hemorrhage. Br Med J 1979; 2 (6203): 1468-1470. 30. Collaborative Group for the Study of Stroke in Young Women: Oral Contraceptives and stroke in young women: associated risk factors. JAMA 1975; 231: 718- 722. 31. Inman WH, Vessey MP, West- erholm B, Engelund A. Thromboembolic disease and the steroidal content of oral contraceptives. A report to the Committee on Safety of Drugs. Br Med J 1970; 2: 203-209. 32. Meade TW, Green- berg G, Thompson SG. Progestogens and cardiovascular reactions associated with oral con- traceptives and a comparison of the safety of 50- and 35-mcg oestrogen preparations. Br Med J 1980; 280 (6224): 1157-1161. 33. Kay CR. Progestogens and arterial disease-evidence from the Royal College of General Practitioners' Study. Am J Obstet Gynecol 1982; 142: 762-765. 34. Royal College of General Practitioners: Incidence of arterial disease among oral contraceptive users. J Royal Coll Gen Pract 1983; 33: 75- 82. 35. Ory HW. Mortality associated with fertility and fertility control: 1983. Family Planning Perspectives 1983; 15: 50-56. 36. The Cancer and Steroid Hormone Study of the Centers for Disease Control and the National Institute of Child Health and Human Development: Oral contraceptive use and the risk of breast cancer. N Engl J Med 1986; 315: 405-411. 37. Pike MC, Henderson BE, Krailo MD, Duke A, Roy S. Breast cancer in young women and use of oral contraceptives: possible modifying effect of formula- tion and age at use. Lancet 1983; 2: 926-929. 38. Paul C, Skegg DG, Spears GFS, Kaldor JM. Oral contraceptives and breast cancer: A national study. Br Med J 1986; 293: 723-725. 39. Miller DR, Rosenberg L, Kaufman DW, Schottenfeld D, Stolley PD, Shapiro S. Breast cancer risk in relation to early oral contraceptive use. Obstet Gynecol 1986; 68: 863-868. 40. Olson H, Olson KL, Moller TR, Ranstam J, Holm P. Oral contraceptive use and breast cancer in young women in Sweden (letter). Lancet 1985; 2: 748-749. 41. McPherson K, Vessey M, Neil A, Doll R, Jones L, Roberts M. Early contraceptive use and breast cancer: Results of another casecontrol study. Br J Cancer 1987; 56: 653-660. 42. Huggins GR, Zucker PF Oral contraceptives and neoplasia; 1987 update. Fertil Steril 1987; 47: 733-761. 43. McPherson K, Drife JO. The pill and breast cancer: why the uncertainty? Br Med J 1986; 293: 709-710. 44. Shapiro S. Oral contraceptives-time to take stock. N Engl J Med 1987; 315: 450-451. 45. Ory H, Naib Z, Conger SB, Hatcher RA, Tyler CW. Contraceptive choice and prevalence of cervical dysplasia and carcinoma in situ. Am J Obstet Gynecol 1976; 124: 573-577. 46. Vessey MP, Lawless M, McPherson K, Yeates D. Neoplasia of the cervix uteri and contraception: a possible adverse effect of the pill. Lancet 1983; 2: 930. 47. Brinton LA, Huggins GR, Lehman HF, Malli K, Savitz DA, Trapido E, Rosenthal J, Hoover R. Long term use of oral contraceptives and risk of invasive cervical cancer. Int J Cancer 1986; 38: 339-344. 48. WHO Collaborative Study of Neoplasia and Steroid Contraceptives: Invasive cervical cancer and combined oral contraceptives. Br Med J 1985; 290: 961-965. 49. Rooks JB, Ory HW, Ishak KG, Strauss LT, Greenspan JR, Hill AP, Tyler CW. Epidemiology of hepatocellular adenoma; the role of oral contraceptive use. JAMA 1979; 242: 644-648. 50. Bein NN, Goldsmith HS. Recurrent massive hemorrhage from benign hepatic tumors secondary to oral contraceptives. Br J Surg 1977; 64: 433-435. 51. Klatskin G. Hepatic tumors: possible relationship to use of oral contraceptives. Gastroenterology 1977; 73: 386- 394. 52. Henderson BE, Preston- Martin S, Edmondson HA, Peters RL, Pike MC. Hepatocellular carcinoma and oral contraceptives. Br J Cancer 1983; 48: 437-440. 53. Neuberger J, Forman D, Doll R, Williams R. Oral contraceptives and hepatocellular carcinoma. Br Med J 1986; 292: 1355-1357. 54. Forman D, Vincent TJ, Doll R. Cancer of the liver and oral contraceptives. Br Med J 1986; 292: 1357-1361. 55. Harlap S, Eldor J. Births following oral contraceptive failures. Obstet Gynecol 1980; 55: 447-452. 56. Savolainen E, Saksela E, Saxen L. Teratogenic hazards of oral contraceptives analyzed in a national malformation register. Am J Obstet Gynecol 1981; 140: 521-524. 57. Janerich DT, Piper JM, Glebatis DM. Oral contraceptives and birth defects. Am J Epidemiol 1980; 112: 73-79. 58. Ferencz C, Matanoski GM, Wilson PD, Rubin JD, Neill CA, Gutberlet R. Maternal hormone therapy and congenital heart disease. Teratology 1980; 21: 225-239. 59. Rothman KJ, Fyler DC, Goldblatt A, Kreidberg MB. Exogenous hormones and other drug exposures of children with congenital heart disease. Am J Epidemiol 1979; 109: 433-439. 60. Boston Collaborative Drug Surveillance Program: Oral contraceptives and venous thromboembolic disease, surgically confirmed gallbladder disease, and breast tumors. Lancet 1973; 1:1399-1404. 61. Royal College of General Practitioners: Oral contraceptives and health. New York, Pittman 1974. 62. Layde PM, Vessey MP, Yeates D. Risk of gallbladder disease: a cohort study of young women attending family planning clinics. J Epidemiol Community Health 1982; 36: 274-278. 63. Rome Group for Epidemiology and Prevention of Cholelithiasis (GREPCO): Preva- lence of gallstone disease in an Italian adult female population. Am J Epidemiol 1984; 119: 796-805. 64. Storm BL, Tamragouri RT, Morse ML, Lazar EL, West SL, Stolley PD, Jones JK. Oral contraceptives and other risk factors for gallbladder disease. Clin Pharmacol Ther 1986; 39: 335- 341. 65. Wynn V, Adams PW, Godsland IF, Melrose J, Niththyananthan R, Oakley NW, Seedj A. Comparison of effects of different combined oral contraceptive formulations on carbohydrate and lipid metabolism. Lancet 1979; 1: 1045- 1049. 66. Wynn V Effect of progesterone and progestins on carbohydrate metabolism. In: Progesterone and Progestin. Bardin CW, Milgrom E, Mauvis-Jarvis P. eds. New York, Raven Press 1983; pp. 395-410. 67. Perlman JA, Roussell-Briefel RG, Ezzati TM, Lieberknecht G. Oral glucose tolerance and the potency of oral contraceptive progestogens. J Chronic Dis 1985; 38: 857-864. 68. Royal College of General Prac- titioners' Oral Contraception Study: Effect on hypertension and benign breast disease of progestogen component in combined oral con- traceptives. Lancet 1977; 1: 624. 69. Fisch IR, Frank J. Oral contraceptives and blood pressure. JAMA 1977; 237: 2499-2503. 70. Laragh AJ. Oral contraceptive induced hypertension - nine years later. Am J Obstet Gynecol 1976; 126: 141-147. 71. Ramcharan S, Peritz E, Pellegrin FA, Williams WT Incidence of hypertension in the Walnut Creek Contraceptive Drug Study cohort: In: Pharmacology of steroid contraceptive drugs. Garattini S, Berendes HW. eds. New York, Raven Press 1977; pp. 277-288, (Monographs of the Mario Negri Institute for Pharmacological Research Milan.) 79. Schlesselman J, Stadel BV, Murrary P, Lai S. Breast cancer in relation to early use of oral contraceptives. JAMA 1988; 259: 1828-1833. 80. Hennekens CH, Speizer FE, Lipnick RJ, Rosner B, Bain C, Belanger C, Stampfer MJ, Willett W, Peto R. A case-control study of oral contraceptive use and breast cancer. JNCI 1984; 72: 39-42. 81. La Vecchia C, Decarli A, Fasoli M, Franceschi S, Gentile A, Negri E, Parazzini F, Tognoni G. Oral contraceptives and cancers of the breast and of the female genital tract. Interim results from a case-control study. Br J Cancer 1986; 54: 311- 317. 82. Meirik O, Lund E, Adami H, Bergstrom R, Christoffersen T, Bergsjo P. Oral contraceptive use and breast cancer in young women. A Joint National Casecontrol study in Sweden and Norway. Lancet 1986; II: 650-654. 83. Kay CR, Hannaford PC. Breast cancer and the pill - A further report from the Royal College of General Practitioners' oral contraception study. Br J Cancer 1988; 58: 675-680. 84. Stadel BV, Lai S, Schlesselman JJ, Murray P. Oral contraceptives and premenopausal breast cancer in nulliparous women. Contraception 1988; 38: 287-299. 85. Miller DR, Rosenberg L, Kaufman DW, Stolley P, Warshauer ME, Shapiro S. Breast cancer before age 45 and oral contraceptive use: New Findings. Am J Epidemiol 1989; 129: 269-280. 86. The UK National Case-Control Study Group, Oral contraceptive use and breast cancer risk in young women. Lancet 1989; 1: 973-982. 87. Sch- lesselman JJ. Cancer of the breast and reproductive tract in relation to use of oral contraceptives. Contraception 1989; 40: 1-38. 88. Vessey MP, McPherson K, Villard-Mackintosh L, Yeates D. Oral contraceptives and breast cancer: latest findings in a large cohort study. Br J Cancer 1989; 59: 613-617. 89. Jick SS, Walker AM, Stergachis A, Jick H. Oral contraceptives and breast cancer. Br J Cancer 1989; 59: 618-621.

WARNINGS Cigarette smoking increases the risk of serious cardiovascular side effects from oral contraceptive use. This risk increases with age and with the extent of smoking (in epidemiologic studies, 15 or more cigarettes per day was associated with a significantly increased risk) and is quite marked in women over 35 years of age. Women who use oral contraceptives should be strongly advised not to smoke. The use of oral contraceptives is associated with increased risk of several serious conditions including venous and arterial thrombotic and thromboembolic events (such as myocardial infarction, thromboembolism, and stroke), hepatic neoplasia, gallbladder disease, and hypertension, although the risk of serious morbidity or mortality is very small in healthy women without underlying risk factors. The risk of morbidity and mortality increases significantly in the presence of other underlying risk factors such as certain inherited thrombophilias, hypertension, hyperlipidemias, obesity and diabetes. Practitioners prescribing oral contraceptives should be familiar with the following information relating to these risks. The information contained in this package insert is principally based on studies carried out in patients who used oral contraceptives with higher formulations of estrogens and progestogens than those in common use today. The effect of long-term use of the oral contraceptives with lower formulations of both estrogens and progestogens remains to be determined. Throughout this labeling, epidemiological studies reported are of two types: retrospective or case control studies and prospective or cohort studies. Case control studies provide a measure of the relative risk of a disease, namely, a ratio of the incidence of a disease among oral contraceptive users to that among nonusers. The relative risk does not provide information on the actual clinical occurrence of a disease. Cohort studies provide a measure of attributable risk, which is the difference in the incidence of disease between oral contraceptive users and nonusers. The attributable risk does provide information about the actual occurrence of a disease in the population. For further information, the reader is referred to a text on epidemiological methods. 1. Thromboembolic Disorders And Other Vascular Problems a. Myocardial Infarction An increased risk of myocardial infarction has been attributed to oral contraceptive use. This risk is primarily in smokers or women with other underlying risk factors for coronary artery disease such as hypertension, hypercholesterolemia, morbid obesity, and diabetes. The relative risk of heart attack for current oral contraceptive users has been estimated to be two to six. The risk is very low under the age of 30. Smoking in combination with oral contraceptive use has been shown to contribute substantially to the incidence of myocardial infarctions in women in their mid-thirties or older, with smoking accounting for the majority of excess cases. Mortality rates associated with circulatory disease have been shown to increase substantially in smokers over the age of 35 and nonsmokers over the age of 40 (Figure 1) among women who use oral contraceptives. FIGURE 1: CIRCULATORY DISEASE MORTALITY RATES PER 100,000 WOMEN-YEARS BY AGE. SMOKING STATUS AND ORAL CONTRACEPTIVE USE Layde PM, Beral V. Lancet 1981;1:541-546. Oral contraceptives may compound the effects of well-known risk factors, such as hypertension, diabetes, hyperlipidemias, age, and obesity. In particular, some progestogens are known to decrease HDL cholesterol and cause glucose intolerance, while estrogens may create a state of hyperinsulinism. Oral contraceptives have been shown to increase blood pressure among users (see section 9 in WARNINGS). Such increases in risk factors have been associated with an increased risk of heart disease and the risk increases with the number of risk factors present. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. b. Thromboembolism An increased risk of thromboembolic and thrombotic disease associated with the use of oral contraceptives is well established. Case control studies have found the relative risk of users compared to non-users to be 3 for the first episode of superficial venous thrombosis, 4 to 11 for deep vein thrombosis or pulmonary embolism, and 1.5 to 6 for women with predisposing conditions for venous thromboembolic disease. Cohort studies have shown the relative risk to be somewhat lower, about 3 for new cases and about 4.5 for new cases requiring hospitalization. The approximate incidence of deep-vein thrombosis and pulmonary embolism in users of low dose ( < 50 µg ethinyl estradiol) combination oral contraceptives is up to 4 per 10,000 woman-years compared to 0.5-3 per 10,000 woman-years for non-users. However, the incidence is substantially less than that associated with pregnancy (6 per 10,000 woman-years). The risk of thromboembolic disease due to oral contraceptives is not related to length of use and disappears after pill use is stopped. A two- to four-fold increase in relative risk of postoperative thromboembolic complications has been reported with the use of oral contraceptives. The relative risk of venous thrombosis in women who have predisposing conditions is twice that of women without such medical conditions. If feasible, oral contraceptives should be discontinued at least four weeks prior to and for two weeks after elective surgery of a type associated with an increase in risk of thromboembolism and during and following prolonged immobilization. Since the immediate postpartum period is also associated with an increased risk of thromboembolism, oral contraceptives should be started no earlier than four to six weeks after delivery in women who elect not to breastfeed. c. Cerebrovascular diseases Oral contraceptives have been shown to increase both the relative and attributable risk of cerebrovascular events (thrombotic and hemorrhagic strokes) although, in general, the risk is greatest among older ( > 35 years), hypertensive women who also smoke. Hypertension was found to be a risk factor for both users and nonusers, for both types of strokes, while smoking interacted to increase the risk for hemorrhagic strokes. In a large study, the relative risk of thrombotic strokes has been shown to range from 3 for normotensive users to 14 for users with severe hypertension. The relative risk of hemorrhagic stroke is reported to be 1.2 for nonsmokers who used oral contraceptives, 2.6 for smokers who did not use oral contraceptives, 7.6 for smokers who used oral contraceptives, 1.8 for normotensive users and 25.7 for users with severe hypertension. The attributable risk is also greater in older women. Oral contraceptives also increase the risk for stroke in women with other underlying risk factors such as certain inherited or acquired thrombophilias, hyperlipidemias, and obesity. Women with migraine (particularly migraine with aura) who take combination oral contraceptives may be at an increased risk of stroke. d. Dose-related risk of vascular disease from oral contraceptives A positive association has been observed between the amount of estrogen and progestogen in oral con- traceptives and the risk of vascular disease. A decline in serum high density lipoproteins (HDL) has been reported with many progestational agents. A decline in serum high density lipoproteins has been associated with an increased incidence of ischemic heart disease. Because estrogens increase HDL cholesterol, the net effect of an oral contraceptive depends on a balance achieved between doses of estrogen and progestogen and the nature and absolute amount of progestogens used in the contraceptive. The amount of both hormones should be considered in the choice of an oral contraceptive. Minimizing exposure to estrogen and progestogen is in keeping with good principles of therapeutics. For any particular estrogen/progestogen combination, the dosage regimen prescribed should be one which contains the least amount of estrogen and progestogen that is compatible with a low failure rate and the needs of the individual patient. New acceptors of oral contraceptive agents should be started on prepara- tions containing the lowest estrogen content which is judged appropriate for the individual patient. e. Persistence of risk of vascular disease There are two studies which have shown persistence of risk of vascular disease for ever-users of oral contraceptives. In a study in the United States, the risk of developing myocardial infarction after discontin- uing oral contraceptives persists for at least 9 years for women 40-49 years old who had used oral con- traceptives for five or more years but this increased risk was not demonstrated in other age groups. In another study in Great Britain, the risk of developing cerebrovascular disease persisted for at least 6 years after discontinuation of oral contraceptives, although excess risk was very small. However, both studies were performed with oral contraceptive formulations containing 50 micrograms or higher of estrogens. 2. Estimates Of Mortality From Contraceptive Use One study gathered data from a variety of sources which have estimated the mortality rate associated with different methods of contraception at different ages (Table 3). TABLE 3: ANNUAL NUMBER OF BIRTH-RELATED OR METHOD-RELATED DEATHS ASSOCIATED WITH CONTROL OF FERTILITY PER 100,000 NONSTERILE WOMEN, BY FERTILITY CONTROL METHOD ACCORDING TO AGE AGE Method of control and outcome 15-19 20-24 25-29 30-34 35-39 40-44 No fertility control methods* 7.0 7.4 9.1 14.8 25.7 28.2 Oral contraceptives nonsmoker** 0.3 0.5 0.9 1.9 13.8 31.6 Oral contraceptives smoker** 2.2 3.4 6.6 13.5 51.1 117.2 IUD** 0.8 0.8 1.0 1.0 1.4 1.4 Condom* 1.1 1.6 0.7 0.2 0.3 0.4 Diaphragm/spermicide* 1.9 1.2 1.2 1.3 2.2 2.8 Periodic abstinence* 2.5 1.6 1.6 1.7 2.9 3.6 *Deaths are birth related **Deaths are method related Ory HW. Family Planning Perspectives 1983; 15:57-63. These estimates include the combined risk of death associated with contraceptive methods plus the risk attributable to pregnancy in the event of method failure. Each method of contraception has its specific benefits and risk. The study concluded that with the exception of oral contraceptive users 35 and older who smoke and 40 and older who do not smoke, mortality associated with all methods of birth control is low and below that associated with childbirth. The observation of a possible increase in risk of mortality with age for oral contraceptive users is based on data gathered in the 1970s but not reported until 1983. However, current clinical practice involves the use of lower estrogen dose formulations combined with careful restriction of oral contraceptive use to women who do not have the various risk factors listed in this labeling. Because of these changes in practice and, also, because of some limited new data which suggest that the risk of cardiovascular disease with the use of oral contraceptives may now be less than previously observed, the Fertility and Maternal Health Drugs Advisory Committee was asked to review the topic in 1989. The Committee concluded that although cardiovascular disease risk may be increased with oral contraceptive use after age 40 in healthy nonsmoking women (even with the newer low-dose for- mulations), there are greater potential health risks associated with pregnancy in older women and with the alternative surgical and medical procedures which may be necessary if such women do not have access to effective and acceptable means of contraception. Therefore, the Committee recommended that the benefits of oral contraceptive use by healthy non- smoking women over 40 may outweigh the possible risks. Of course, older women, as all women who take oral contraceptives, should take the lowest possible dose formulation that is effective. 3. Carcinoma Of The Reproductive Organs And Breasts Numerous epidemiological studies have been performed on the incidence of breast, endometrial, ovarian, and cervical cancer in women using oral contraceptives. Although the risk of breast cancer may be slight- ly increased among current users of oral contraceptives (RR = 1.24), this excess risk decreases over time after oral contraceptive discontinuation and by 10 years after cessation the increased risk disappears. The risk does not increase with duration of use, and no relationships have been found with dose or type of steroid. The patterns of risk are also similar regardless of a woman's reproductive history or her family breast cancer history. The subgroup for whom risk has been found to be significantly elevated is women who first used oral contraceptives before age 20, but because breast cancer is so rare at these young ages, the number of cases attributable to this early oral contraceptive use is extremely small. Breast cancers diagnosed in current or previous oral contraceptive users tend to be less advanced clinically than in never-users. Women who currently have or have had breast cancer should not use oral contraceptives because breast cancer is a hormone-sensitive tumor. Some studies suggest that oral contraceptive use has been associated with an increase in the risk of cervical intraepithelial neoplasia or invasive cervical cancer in some populations of women. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. In spite of many studies of the relationship between oral contraceptive use and breast cancer and cervical cancers, a cause-and-effect relationship has not been established. 4. Hepatic Neoplasia Benign hepatic adenomas are associated with oral contraceptive use, although their occurrence is rare in the United States. Indirect calculations have estimated the attributable risk to be in the range of 3.3 cases/100,000 for users, a risk that increases after four or more years of use. Rupture of hepatic ade- nomas may cause death through intra-abdominal hemorrhage. Studies from Britain have shown an increased risk of developing hepatocellular carcinoma in long-term ( > 8 years) oral contraceptive users. However, these cancers are extremely rare in the U.S. and the attributable risk (the excess incidence) of liver cancers in oral contraceptive users approaches less than one per million users. 5. Ocular Lesions There have been clinical case reports of retinal thrombosis associated with the use of oral contraceptives that may lead to partial or complete loss of vision. Oral contraceptives should be discontinued if there is unexplained partial or complete loss of vision; onset of proptosis or diplopia; papilledema; or retinal vascular lesions. Appropriate diagnostic and therapeutic measures should be undertaken immediately. 6. Oral Contraceptive Use Before Or During Early Pregnancy Extensive epidemiological studies have revealed no increased risk of birth defects in women who have used oral contraceptives prior to pregnancy. Studies also do not suggest a teratogenic effect, particularly in so far as cardiac anomalies and limb reduction defects are concerned, when taken inadvertently during early pregnancy (see "CONTRAINDICATIONS" section). The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy. Oral contraceptives should not be used during pregnancy to treat threatened or habitual abortion. It is recommended that for any patient who has missed two consecutive periods, pregnancy should be ruled out. If the patient has not adhered to the prescribed schedule, the possibility of pregnancy should be considered at the time of the first missed period. Oral contraceptive use should be discontinued if pregnancy is confirmed. 7. Gallbladder Disease Earlier studies have reported an increased lifetime relative risk of gallbladder surgery in users of oral con- traceptives and estrogens. More recent studies, however, have shown that the relative risk of developing gallbladder disease among oral contraceptive users may be minimal. The recent findings of minimal risk may be related to the use of oral contraceptive formulations containing lower hormonal doses of estrogens and progestogens. 8. Carbohydrate And Lipid Metabolic Effects Oral contraceptives have been shown to cause glucose intolerance in a significant percentage of users. Oral contraceptives containing greater than 75 micrograms of estrogens cause hyperinsulinism, while lower doses of estrogen cause less glucose intolerance. Progestogens increase insulin secretion and create insulin resistance, this effect varying with different progestational agents. However, in the nondiabetic woman, oral contraceptives appear to have no effect on fasting blood glucose. Because of these demonstrated effects, prediabetic and diabetic women should be carefully observed while taking oral contraceptives. A small proportion of women will have persistent hypertriglyceridemia while on the pill. As discussed earlier (see WARNINGS 1.a. and 1.d.), changes in serum triglycerides and lipoprotein levels have been reported in oral contraceptive users. 9. Elevated Blood Pressure Women with significant hypertension should not be started on hormonal contraceptives. An increase in blood pressure has been reported in women taking oral contraceptives, and this increase is more likely in older oral contraceptive users and with continued use. Data from the Royal College of General Practitioners and subsequent randomized trials have shown that the incidence of hypertension increases with increasing concentrations of progestogens. Women with a history of hypertension or hypertension-related diseases, or renal disease should be encouraged to use another method of contraception. If women elect to use oral contraceptives, they should be monitored closely and if significant elevation of blood pressure occurs, oral contraceptives should be discontinued (see CONTRAINDICATIONS section). For most women, elevated blood pressure will return to normal after stopping oral contraceptives, and there is no difference in the occurrence of hypertension among ever- and never-users. 10. Headache The onset or exacerbation of migraine or development of headache with a new pattern which is recurrent, persistent, or severe requires discontinuation of oral contraceptives and evaluation of the cause (see WARNINGS 1.c.). 11. Bleeding Irregularities Breakthrough bleeding and spotting are sometimes encountered in patients on oral contraceptives, especially during the first three months of use. If bleeding persists or recurs, nonhormonal causes should be considered and adequate diagnostic measures taken to rule out malignancy or pregnancy as in the case of any abnormal vaginal bleeding. If pathology has been excluded, time or a change to another formulation may solve the problem. In the event of amenorrhea, pregnancy should be ruled out. Some women may encounter post-pill amenorrhea or oligomenorrhea (possibly with anovulation), especially when such a condition was preexistent. 12. Ectopic Pregnancy Ectopic as well as intrauterine pregnancy may occur in contraceptive failures. PRECAUTIONS 1. Sexually Transmitted Diseases Patients should be counseled that this product does not protect against HIV infection (AIDS) and other sexually transmitted diseases. 2. Physical Examination and Follow-up A periodic personal and family medical history and complete physical examination are appropriate for all women, including women using oral contraceptives. The physical examination, however, may be deferred until after initiation of oral contraceptives if requested by the woman and judged appropriate by the clinician. The physical examination should include special reference to blood pressure, breasts, abdomen and pelvic organs, including cervical cytology, and relevant laboratory tests. In case of undiagnosed, persistent or recurrent abnormal vaginal bleeding, appropriate measures should be conducted to rule out malignancy. Women with a strong family history of breast cancer or who have breast nodules should be monitored with particular care. 3. Lipid Disorders Women who are being treated for hyperlipidemias should be followed closely if they elect to use oral contraceptives. Some progestogens may elevate LDL levels and may render the control of hyperlipidemias more difficult. (See WARNINGS 1.d.). In patients with familial defects of lipoprotein metabolism receiving estrogen-containing preparations, there have been case reports of significant elevations of plasma triglycerides leading to pancreatitis. 4. Liver function If jaundice develops in any woman receiving such drugs, the medication should be discontinued. Steroid hormones may be poorly metabolized in patients with impaired liver function. 5. Fluid Retention Oral contraceptives may cause some degree of fluid retention. They should be prescribed with caution, and only with careful monitoring, in patients with conditions which might be aggravated by fluid retention. 6. Emotional Disorders Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. Patients becoming significantly depressed while taking oral contraceptives should stop the medication and use an alternate method of contraception in an attempt to determine whether the symptom is drug related. Women with a history of depression should be carefully observed and the drug discontinued if depression recurs to a serious degree. 7. Contact Lenses Contact lens wearers who develop visual changes or changes in lens tolerance should be assessed by an ophthalmologist. 10. Carcinogenesis See WARNINGS section. 11. Pregnancy Pregnancy Category X. See CONTRAINDICATIONS and WARNINGS sections. 12. Nursing Mothers Small amounts of oral contraceptive steroids and/or metabolites have been identifed in the milk of nursing mothers and a few adverse effects on the child have been reported, including jaundice and breast enlargement. In addition, combination oral contraceptives given in the postpartum period may interfere with lactation by decreasing the quantity and quality of breast milk. If possible, the nursing mother should be advised not to use combination oral contraceptives but to use other forms of contraception until she has completely weaned her child. 13. Pediatric Use Safety and efficacy of FEMCON Fe (norethindrone and ethinyl estradiol tablets) have been established in women of reproductive age. Safety and efficacy are expected to be the same in postpubertal adolescents under the age of 16 years and in users ages 16 years and older. Use of this product before menarche is not indicated. 14. Geriatric Use This product has not been studied in women over 65 years of age and is not indicated in this population. Information for the Patient See Patient Labeling printed below