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CLINICAL PHARMACOLOGY Mechanism Of Action COCs lower the risk of becoming pregnant primarily by suppressing ovulation. Other possible mechanisms may include cervical mucus changes that inhibit sperm penetration and endometrial changes that reduce the likelihood of implantation. Pharmacodynamics No specific pharmacodynamic studies were conducted with SEASONALE. Pharmacokinetics Absorption No specific investigation of the absolute bioavailability of SEASONALE in humans has been conducted. However, literature indicates that levonorgestrel is rapidly and completely absorbed after oral administration (bioavailability nearly 100%) and is not subject to first-pass metabolism. EE is rapidly and almost completely absorbed from the gastrointestinal tract but, due to first-pass metabolism in gut mucosa and liver, the bioavailability of EE is approximately 43%. Following continuous dosing with once-daily administration of SEASONALE tablets, plasma concentrations of levonorgestrel and EE reached steady-state within 7 days. The mean plasma pharmacokinetic parameters for SEASONALE under fasting conditions in normal healthy women following once-daily administration of one levonorgestrel/EE combination tablet for 10 days are summarized in Table 5. Table 5: Mean ±SD Pharmacokinetic Parameters Under Fasting Conditions in Healthy Women Following 10 Days Administration of One Tablet of SEASONALE (n=44) Analyte AUC0-24 Cmax Cmin Cavga Tmax Levonorgestrel 54.6 ± 16.5 ng*hr/mL 5.0 ± 1.5 ng/mL 1.6 ± 0.5 ng/mL 2.3 ± 0.7 ng/mL 1.4 ± 0.7 hours Ethinyl estradiol 935.5 ± 346.9 pg*hr/mL 106.1 ± 41.2 pg/mL 18.5 ± 9.4 pg/mL 38.9 ± 14.4 pg/mL 1.6 ± 0.6 hours a Cavg = AUC0-24/24 Food Effect The effect of food on the rate and the extent of levonorgestrel and EE absorption following oral administration of SEASONALE has not been evaluated. Distribution The apparent volume of distribution of levonorgestrel and EE are reported to be approximately 1.8 L/kg and 4.3 L/kg, respectively. Levonorgestrel is about 97.5 -99% protein-bound, principally to sex hormone binding globulin (SHBG) and, to a lesser extent, serum albumin. EE is about 95 -97% bound to serum albumin. EE does not bind to SHBG, but induces SHBG synthesis, which leads to decreased levonorgestrel clearance. Following repeated daily dosing of levonorgestrel/EE oral contraceptives, levonorgestrel plasma concentrations accumulate more than predicted based on single-dose pharmacokinetics, due in part, to increased SHBG levels that are induced by EE, and a possible reduction in hepatic metabolic capacity. Metabolism Following absorption, levonorgestrel is conjugated at the 17β-OH position to form sulfate and to a lesser extent, glucuronide conjugates in plasma. Significant amounts of conjugated and unconjugated 3α,5β-tetrahydrolevonorgestrel are also present in plasma, along with much smaller amounts of 3α,5α-tetrahydrolevonorgestrel and 16β-hydroxylevonorgestrel. Levonorgestrel and its phase I metabolites are excreted primarily as glucuronide conjugates. Metabolic clearance rates may differ among individuals by several-fold, and this may account in part for the wide variation observed in levonorgestrel concentrations among users. First-pass metabolism of EE involves formation of EE-3-sulfate in the gut wall, followed by 2-hydroxylation of a portion of the remaining untransformed EE by hepatic cytochrome P-450 3A4 (CYP3A4). Levels of CYP3A4 vary widely among individuals and can explain the variation in rates of EE hydroxylation. Hydroxylation at the 4-, 6-, and 16-positions may also occur, although to a much lesser extent than 2-hydroxylation. The various hydroxylated metabolites are subject to further methylation and/or conjugation. Excretion About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates. The terminal elimination half-life for levonorgestrel after a single dose of SEASONALE was about 30 hours. EE is excreted in the urine and feces as glucuronide and sulfate conjugates, and it undergoes enterohepatic recirculation. The terminal elimination half-life of EE after a single dose of SEASONALE was found to be about 15 hours. Clinical Studies In a 12-month, multicenter, randomized, open-label clinical trial, 456 women aged 18-40 were studied to assess the safety and efficacy of SEASONALE, completing 809 91-day cycles of exposure. The racial demographic of those enrolled was: Caucasian (77%), African-American (11%), Hispanic (7%), Asian (2%), and Other (3%). There were no exclusions for body mass index (BMI) or weight. The weight range of those women treated was 84 to 304 pounds, with a mean weight of 157 pounds and a median weight of 147 pounds. Among the women in the trial, 63% were current or recent hormonal contraceptive users, 29% were prior users (who had used hormonal contraceptives in the past but not in the 6 months prior to enrollment), and 8% were new starts. The pregnancy rate (Pearl Index [PI]) in the 397 women aged 18-35 years was 1.98 pregnancies per 100 women-years of use (95% CI: 0.54 to 5.03), based on 4 pregnancies that occurred after the onset of treatment and within 14 days after the last combination pill. Cycles in which conception did not occur, but which included the use of back-up contraception, were not included in the calculation of the PI.

Find Lowest Prices on Seasonique (levonorgestrel/ethinyl estradioland ethinyl estradiol) Tablets for Oral Use WARNING: CIGARETTE SMOKING AND SERIOUS CARDIOVASCULAR EVENTS Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives (COC) use. This risk increases with age, particularly in women over 35 years of age, and with the number of cigarettes smoked. For this reason, COCs should not be used by women who are over 35 years of age and smoke. [See CONTRAINDICATIONS.] DESCRIPTION Seasonique (levonorgestrel, ethinyl estradiol) (levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets) is an extended-cycle oral contraceptive consisting of 84 light blue-green tablets each containing 0.15 mg of levonorgestrel, a synthetic progestogen and 0.03 mg of ethinyl estradiol, and 7 yellow tablets containing 0.01 mg of ethinyl estradiol. The structural formulas for the active components are: Levonorgestrel is chemically 18,19-Dinorpregn-4-en-20-yn-3-one, 13-ethyl-17-hydroxy-, (17a)-, (-)-. Ethinyl Estradiol is 19-Norpregna-1,3,5(10)-trien-20-yne-3,17-diol, (17a)-. Each light blue-green tablet contains the following inactive ingredients: anhydrous lactose, D&C yellow no. 10 aluminum lake, FD&C blue no. 1 aluminum lake, FD&C yellow no. 6/Sunset yellow aluminum lake, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, titanium dioxide and triacetin. Each yellow tablet contains the following inactive ingredients: anhydrous lactose, D&C yellow no. 10 aluminum lake, FD&C yellow no. 6/Sunset yellow aluminum lake, hypromellose, magnesium stearate, microcrystalline cellulose, polacrilin potassium, polyethylene glycol, polysorbate 80 and titanium dioxide.

INDICATIONS Seasonique (levonorgestrel, ethinyl estradiol) ® (levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets) is indicated for use by women to prevent pregnancy. DOSAGE AND ADMINISTRATION Take one tablet by mouth at the same time every day. The dosage of Seasonique (levonorgestrel, ethinyl estradiol) is one light blue-green tablet containing levonorgestrel and ethinyl estradiol daily for 84 consecutive days, followed by one yellow ethinyl estradiol tablet for 7 days. To achieve maximum contraceptive effectiveness, Seasonique (levonorgestrel, ethinyl estradiol) must be taken exactly as directed and at intervals not exceeding 24 hours. Instruct the patient to begin taking Seasonique (levonorgestrel, ethinyl estradiol) on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, the first light blue-green tablet is taken that day. One light blue-green tablet should be taken daily for 84 consecutive days, followed by one yellow tablet for 7 consecutive days. A non-hormonal back-up method of contraception (such as condoms or spermicide) should be used until a light blue-green tablet has been taken daily for 7 consecutive days. A scheduled period should occur during the 7 days that the yellow tablets are taken. Begin the next and all subsequent 91-day cycles without interruption on the same day of the week (Sunday) on which the patient began her first dose of Seasonique (levonorgestrel, ethinyl estradiol) , following the same schedule: 84 days taking a light blue-green tablet followed by 7 days taking a yellow tablet. If the patient does not immediately start her next pill pack, she should protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a light blue-green tablet daily for 7 consecutive days. If unscheduled spotting or bleeding occurs, instruct the patient to continue on the same regimen. If the bleeding is persistent or prolonged, advise the patient to consult her healthcare provider. For patient instructions regarding missed pills, see FDA-Approved Patient Labeling. For postpartum women who are not breastfeeding, start Seasonique (levonorgestrel, ethinyl estradiol) no earlier than four to six weeks postpartum due to increased risk of thromboembolism. If the patient starts on Seasonique (levonorgestrel, ethinyl estradiol) postpartum and has not yet had a period, evaluate for possible pregnancy, and instruct her to use an additional method of contraception until she has taken a light blue-green tablet for 7 consecutive days. HOW SUPPLIED Dosage Forms And Strengths Seasonique (levonorgestrel, ethinyl estradiol) tablets (levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets) are available in Extended-Cycle Tablet Dispensers, each containing a 13-week supply of tablets: 84 light blue-green tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol, and 7 yellow tablets each containing 0.01 mg of ethinyl estradiol. The light blue-green tablets are round, film-coated, biconvex, unscored tablets debossed with stylized b on one side and 555 on the other side. The yellow tablets are round, biconvex, film-coated, unscored tablets debossed with stylized b on one side and 556 on the other side. Storage And Handling How Supplied Seasonique (levonorgestrel, ethinyl estradiol) tablets (levonorgestrel/ethinyl estradiol tablets and ethinyl estradiol tablets) are available in Extended-Cycle Tablet Dispensers (NDC 51285-087-87), each containing a 13-week supply of tablets: 84 light blue-green tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol, and 7 yellow tablets each containing 0.01 mg of ethinyl estradiol. The light blue-green tablets are round, film-coated, biconvex, unscored tablets debossed with stylized b on one side and 555 on the other side. The yellow tablets are round, biconvex, film-coated, unscored tablets debossed with stylized b on one side and 556 on the other side. Box of 2 Extended-Cycle Tablet Dispensers NDC 51285-087-87 Storage Conditions Store at 20° to 25° C (68° to 77° F) [See USP Controlled Room Temperature]. DURAMED PHARMACEUTICALS, INC., Subsidiary of Barr Pharmaceuticals, Inc. Pomona, New York 10970. Revised July 2010

INDICATIONS SEASONALE® (levonorgestrel and ethinyl estradiol tablets) is indicated for use by females of reproductive potential to prevent pregnancy. DOSAGE AND ADMINISTRATION How To Start SEASONALE SEASONALE is dispensed in an Extended-Cycle Tablet Dispenser [see HOW SUPPLIED/Storage and Handling]. SEASONALE should be started on a Sunday (see Table 1). For the first cycle of a Sunday Start regimen, an additional method of contraception should be used until after the first 7 consecutive days of administration. Instruct patients to take SEASONALE once a day by mouth at the same time every day for 91 days. To achieve maximum contraceptive effectiveness, SEASONALE should be taken exactly as directed and at intervals not exceeding 24 hours. For patient instructions regarding missed pills, see FDA-approved patient labeling. How To Take SEASONALE Table 1: Instructions for Administration of SEASONALE Starting COCs in women not currently using hormonal contraception (Sunday Start) Important: Consider the possibility of ovulation and conception prior to initiation of this product. Tablet Color: SEASONALE active tablets are pink (Day 1 to Day 84). SEASONALE inactive tablets are white (Day 85 to Day 91). Sunday Start: For each 91-day course, take in the following order: Take the first pink tablet (0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol) on the first Sunday after the onset of menstruation. If menstruation begins on a Sunday, take the tablet on that day. Due to the potential risk of becoming pregnant, use additional non-hormonal contraception (such as condoms or spermicide) for the first 7 days of treatment. Take subsequent pink tablets once daily at the same time each day for a total of 84 days. Take one white tablet (inert) daily for the following 7 days and at the same time of day that active tablets were taken. A scheduled period should occur during the 7 days that the white tablets are taken. Begin the next and all subsequent 91-day courses of SEASONALE without interruption on the same day of the week (i.e., Sunday) on which the patient began her first dose. Follow the same schedule as the initial 91-day course: a pink tablet once a day for 84 days, and a white tablet once a day for 7 days. If the patient does not immediately start her next pill pack, instruct her to protect herself from pregnancy by using a non-hormonal back-up method of contraception until she has taken a pink tablet daily for 7 consecutive days. Switching to SEASONALE from another oral contraceptive Start on the same day that a new pack of the previous oral contraceptive would have started. Switching from another contraceptive method to SEASONALE Start SEASONALE: Transdermal patch On the day when the next application would have been scheduled. Vaginal ring On the day when the next insertion would have been scheduled. Injection On the day when the next injection would have been scheduled. Intrauterine contraceptive (IUD) On the day of removal. If the IUD is not removed on first day of the patient’s menstrual cycle, additional non-hormonal contraception (such as condoms or spermicide) is needed for the first seven days of the first 91-day course. Implant On the day of removal. Complete instructions to facilitate patient counseling on proper tablet usage are located in the FDA-approved patient labeling. Starting SEASONALE After Abortion Or Miscarriage First-trimester After a first-trimester abortion or miscarriage, SEASONALE may be started immediately. An additional method of contraception is not needed if SEASONALE is started immediately. If SEASONALE is not started within 5 days after termination of the pregnancy, the patient should use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of her first 91-day course of SEASONALE. Second-trimester Do not start until 4 weeks after a second-trimester abortion or miscarriage, due to the increased risk of thromboembolic disease. Start SEASONALE following the instructions in Table 1 for Sunday start. Use additional non-hormonal contraception (such as condoms or spermicide) for the first seven days of the patient's first 91-day course of SEASONALE [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, and FDA-approved Patient Labeling]. Starting SEASONALE After Childbirth Do not start until 4 weeks after delivery, due to the increased risk of thromboembolic disease. Start contraceptive therapy with SEASONALE following the instructions in Table 1 for women not currently using hormonal contraception. SEASONALE is not recommended for use in lactating women [see Use in Specific Populations and FDA-Approved Patient Labeling]. If the woman has not yet had a period postpartum, consider the possibility of ovulation and conception occurring prior to use of SEASONALE [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS, Use in Specific Populations, and FDA-approved Patient Labeling]. Tablet Dispenser Instructions The Tablet Dispenser consists of 3 trays with cards that hold 91 individually sealed pills (a 13-week, or 91-day, cycle). The 91 pills consist of 84 pink pills (active pills with hormones) and 7 white pills (inactive pills without hormone). The cards in trays 1 and 2 each contain 28 pink pills (4 rows of 7 pills). See Figure A. Figure A The card in tray 3 contains 35 pills consisting of 28 pink pills (4 rows of 7 pills) and 7 white pills (1 row of 7 pills). See Figure B. Figure B Advise the patient to remove the first pill in the upper left corner by pushing down on the pill. The pill will come out through a hole in the back of the Tablet Dispenser. Advise the patient to wait 24 hours to take the next pill, and continue to take one pill each day until all the pills have been taken. Advise the patient, after taking the last white pill, to start taking the first pink pill from a new Tablet Dispenser the very next day, regardless of when their period started. Missed Tablets Table 2: Instructions for Missed SEASONALE Tablets If one active tablet (pink) is missed in Days 1 through 84 Take the tablet as soon as possible. Take the next tablet at the regular time and continue taking one tablet a day until the 91-day course is finished. If two consecutive active tablets (pink) are missed in Days 1 through 84 Take 2 tablets on the day remembered and 2 tablets the next day. Then continue taking one tablet a day until the 91-day course is finished. Additional non-hormonal contraception (such as condoms or spermicide) should be used as back-up if the patient has sex within 7 days after missing 2 tablets. If three or more consecutive active tablets (pink) are missed in Days 1 through 84 Do not take the missed tablets. Continue taking one tablet a day until the 91-day course is finished. Additional non-hormonal contraception (such as condoms or spermicide) must be used as back-up if the patient has sex within 7 days after missing 3 tablets. Advice In Case Of Gastrointestinal Disturbances In case of severe vomiting or diarrhea, absorption may not be complete and additional contraceptive measures should be taken. If vomiting or diarrhea occurs within 3-4 hours after taking a pink tablet, handle this as a missed tablet [see FDA-approved patient labeling]. HOW SUPPLIED Dosage Forms And Strengths SEASONALE (levonorgestrel and ethinyl estradiol tablets) are available as round, film-coated, biconvex, unscored tablets with a debossed S on one side, packaged in Extended-Cycle Tablet Dispensers, each containing a 13-week supply of tablets in the following order: 84 pink tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol; debossed with 62 on the other side 7 white inert tablets debossed with 197 on the other side. Storage And Handling SEASONALE (levonorgestrel and ethinyl estradiol tablets) are available as round, film-coated, biconvex, unscored tablets with a debossed S on one side, packaged in Extended-Cycle Tablet Dispensers, each containing a 13-week supply of tablets in the following order: 84 pink tablets, each containing 0.15 mg of levonorgestrel and 0.03 mg ethinyl estradiol: debossed with 62 on the other side 7 white inert tablets debossed with 197 on the other side Box of 2 Extended-Cycle Tablet Dispensers NDC 51285-058-66 Storage Conditions Store at 20° to 25° C (68° to 77° F), excursions permitted to 15° to 30°C (59° to 86° F) [See USP Controlled Room Temperature]. Protect from light. Manufactured by: TEVA WOMEN'S HEALTH, INC. Subsidiary of TEVA PHARMACEUTICALS USA, INC North Wales, PA 19454. Revised Mar 2017

PATIENT INFORMATION Guide for Using Seasonique (levonorgestrel, ethinyl estradiol) WARNING TO WOMEN WHO SMOKE Do not use Seasonique (levonorgestrel, ethinyl estradiol) if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke. Birth control pills help to lower the chances of becoming pregnant. They do not protect against HIV infection (AIDS) and other sexually transmitted diseases. What Is Seasonique (levonorgestrel, ethinyl estradiol) ? Seasonique (levonorgestrel, ethinyl estradiol) is a birth control pill. It contains two female hormones, an estrogen called ethinyl estradiol, and a progestin called levonorgestrel. How Well Does Seasonique (levonorgestrel, ethinyl estradiol) Work? Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The more carefully you follow the directions, the less chance you have of getting pregnant. Based on the results of a single clinical study lasting 12 months, 1 to 3 women, out of 100 women, may get pregnant during the first year they use Seasonique (levonorgestrel, ethinyl estradiol) . The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant. How Do I Take Seasonique (levonorgestrel, ethinyl estradiol) ? 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 few months of taking Seasonique (levonorgestrel, ethinyl estradiol) . 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 healthcare provider. Missing pills can also cause spotting or light bleeding, even when you take the missed pills later. 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 trouble remembering to take Seasonique (levonorgestrel, ethinyl estradiol) , talk to your healthcare provider about how to make pill-taking easier or about using another method of birth control. Before you start taking Seasonique (levonorgestrel, ethinyl estradiol) 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 Extended-Cycle Tablet Dispenser. Your Tablet Dispenser consists of 3 trays with cards that hold 91 individually sealed pills (a 13-week or 91-day cycle). The 91 pills consist of 84 light blue-green and 7 yellow pills. Trays 1 and 2 each contain 28 light blue-green pills (4 rows of 7 pills). Tray 3 contains 35 pills consisting of 28 light blue-green pills (4 rows of 7 pills) and 7 yellow pills (1 row of 7 pills). Also find: Where on the first tray in the pack to start taking pills (upper left corner at the start arrow) and In what order to take the pills (follow the weeks and arrow). Be sure you have ready at all times another kind of birth control (such as condoms or spermicides), to use as a backup in case you miss pills. When to Start Seasonique (levonorgestrel, ethinyl estradiol) Take the first light blue-green pill on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the first light blue-green pill that same day. Use another method of birth control (such as condoms or spermicides) as a back-up method if you have sex anytime from the Sunday you start your first light blue-green pill until the next Sunday (first 7 days). If you have been using a different hormonal method of birth control (such as a different pill, the "patch," or the "vaginal ring"), you need to use another method of birth control (such as condoms or spermicides) each time you have sex after stopping your old method of birth control until you have taken Seasonique (levonorgestrel, ethinyl estradiol) for 7 days. How to Take Seasonique (levonorgestrel, ethinyl estradiol) Take one pill at the same time every day until you have taken the last pill in the tablet dispenser. Do not skip pills even if you are experiencing spotting or bleeding or feel sick to your stomach (nausea). Do not skip pills even if you do not have sex very often. When you finish a tablet dispenser After taking the last yellow pill, start taking the first light blue-green pill from a new Extended-Cycle Tablet Dispenser the very next day (this should be on a Sunday) regardless of when your period started. If you miss your scheduled period when you are taking the yellow pills, contact your healthcare provider because you may be pregnant. If you are pregnant, you should stop taking Seasonique (levonorgestrel, ethinyl estradiol) . What To Do If You Miss Pills If you MISS 1 light blue-green 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 light blue-green pills in a row: 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 in the 7 days after you miss two pills. You MUST use another birth control method (such as condoms or spermicide) as a back up for the 7 days after you restart your pills. If you MISS 3 OR MORE light blue-green pills in a row: Do not take the missed pills. Keep taking 1 pill every day as indicated on the pack until you have completed all of the remaining pills in the pack. For example: If you resume taking the pill on Thursday, take the pill under "Thursday" and do not take the missed pills. You may experience bleeding during the week following the missed pills. You could become pregnant if you have sex during the days of 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 when you miss pills and for the first 7 days after you restart your pills. If you do not have your period when you are taking the yellow pills, call your healthcare provider because you may be pregnant. If you MISS ANY of the 7 yellow pills: Throw away the missed pills. Keep taking the scheduled pills until the pack is finished. 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 pill each day until you contact your healthcare provider. Who Should Not Take Seasonique (levonorgestrel, ethinyl estradiol) ? Your healthcare provider will not give you Seasonique (levonorgestrel, ethinyl estradiol) if you have: Ever had breast cancer or any cancer that is sensitive to female hormones Liver disease, including liver tumors Ever had blood clots in your arms, legs, or lungs Ever had a stroke Ever had a heart attack Certain heart valve problems or heart rhythm abnormalities that can cause blood clots to form in the heart An inherited problem with your blood that makes it clot more than normal High blood pressure that medicine can't control Diabetes with kidney, eye, or blood vessel damage Certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision Also, do not take birth control pills if you: Smoke and are over 35 years old Are pregnant Birth control pills may not be a good choice for you if you have ever had jaundice (yellowing of the skin or eyes) caused by pregnancy. What Else Should I Know About Taking Seasonique (levonorgestrel, ethinyl estradiol) ? Birth control pills do not protect you against any sexually transmitted disease, including HIV, the virus that causes AIDS. Do not skip any pills, even if you do not have sex often. Birth control pills should not be taken during pregnancy. However, birth control pills taken by accident during pregnancy are not known to cause birth defects. If you are breastfeeding, consider another birth control method until you are ready to stop breastfeeding. Birth control pills that contain estrogen, like Seasonique (levonorgestrel, ethinyl estradiol) , may decrease the amount of milk you make. A small amount of the pill's hormones pass into breast milk. Tell your healthcare provider about all medicines and herbal products that you take. Some medicines and herbal products may make birth control pills less effective, including: barbiturates bosentan carbamazepine felbamate griseofulvin oxcarbazepine phenytoin rifampin St. John's wort topiramate Consider using another birth control method when you take medicines that may make birth control pills less effective. Birth control pills may interact with lamotrigine, an anticonvulsant used for epilepsy. This may increase the risk of seizures, so your physician may need to adjust the dose of lamotrigine. If you have vomiting or diarrhea, your birth control pills may not work as well. Use another birth control method, like condoms or a spermicide, until you check with your healthcare provider. What Are The Most Serious Risks Of Taking Birth Control Pills? Like pregnancy, birth control pills increase the risk of serious blood clots, especially in women who have other risk factors, such as smoking, obesity, or age > 35. It is possible to die from a problem caused by a blood clot, such as a heart attack or a stroke. Some examples of serious blood clots are blood clots in the: Legs (thrombophlebitis) Lungs (pulmonary embolus) Eyes (loss of eyesight) Heart (heart attack) Brain (stroke) Women who take birth control pills may get: High blood pressure Gallbladder problems Rare cancerous or noncancerous liver tumors All of these events are uncommon in healthy women. Call your healthcare provider right away if you have: Persistent leg pain Sudden shortness of breath Sudden blindness, partial or complete Severe pain in your chest Sudden, severe headache unlike your usual headaches Weakness or numbness in an arm or leg, or trouble speaking Yellowing of the skin or eyeballs What Are Common Side Effects Of Birth Control Pills? The most common side effects of birth control pills are: Spotting or bleeding between menstrual periods Nausea Breast tenderness Headache These side effects are usually mild and usually disappear with time. Less common side effects are: Acne Less sexual desire Bloating or fluid retention Blotchy darkening of the skin, especially on the face High blood sugar, especially in women who already have diabetes High fat levels in the blood Depression, especially if you have had depression in the past. Call your healthcare provider immediately if you have any thoughts of harming yourself. Problems tolerating contact lenses Weight changes This is not a complete list of possible side effects. Talk to your healthcare provider if you develop any side effects that concern you. You may report side effects to the FDA at 1-800-FDA-1088. No serious problems have been reported from a birth control pill overdose, even when accidentally taken by children. Do Birth Control Pills Cause Cancer? Birth control pills do not appear to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones. Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners. What Should I Know About My Period When Taking Seasonique (levonorgestrel, ethinyl estradiol) ? When you take Seasonique (levonorgestrel, ethinyl estradiol) , which has a 91-day extended dosing cycle, you should expect to have 4 scheduled periods per year (bleeding when you are taking the 7 yellow pills). Each period is likely to last about 3 days. However, you will probably have more bleeding or spotting between your scheduled periods than if you were using a birth control pill with a 28-day dosing cycle. During the first Seasonique (levonorgestrel, ethinyl estradiol) 91-day treatment cycle, about 3 in 10 women may have 20 or more days of unplanned bleeding or spotting. This bleeding or spotting tends to decrease with time. Do not stop taking Seasonique (levonorgestrel, ethinyl estradiol) because of this bleeding or spotting. If the spotting continues for more than 7 consecutive days or if the bleeding is heavy, call your healthcare provider. What If I Miss My Scheduled Period When Taking Seasonique (levonorgestrel, ethinyl estradiol) ? You should consider the possibility that you are pregnant if you miss your scheduled period (no bleeding on the days that you are taking yellow tablets). Since scheduled periods are less frequent when you are taking Seasonique (levonorgestrel, ethinyl estradiol) , notify your healthcare provider that you have missed your period and that you are taking Seasonique (levonorgestrel, ethinyl estradiol) . Also notify your healthcare provider if you have symptoms of pregnancy such as morning sickness or unusual breast tenderness. It is important that your healthcare provider evaluates you to determine if you are pregnant. Stop taking Seasonique (levonorgestrel, ethinyl estradiol) if it is determined that you are pregnant. What If I Want To Become Pregnant? You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill. General Advice About Seasonique (levonorgestrel, ethinyl estradiol) Your healthcare provider prescribed Seasonique (levonorgestrel, ethinyl estradiol) for you. Do not share Seasonique (levonorgestrel, ethinyl estradiol) with anyone else. Keep Seasonique (levonorgestrel, ethinyl estradiol) out of the reach of children. If you have concerns or questions, ask your healthcare provider. You may also ask your healthcare providers for a more detailed label written for medical professionals.

PATIENT INFORMATION SEASONALE [see zuh nel] (levonorgestrel and ethinyl estradiol) Tablets What is the most important information I should know about SEASONALE? Do not use SEASONALE if you smoke cigarettes and are over 35 years old. Smoking increases your risk of serious cardiovascular side effects from hormonal birth control pills, including death from heart attack, blood clots or stroke. This risk increases with age and the number of cigarettes you smoke. What is SEASONALE? SEASONALE is a birth control pill (oral contraceptive) used by women to prevent pregnancy. How does SEASONALE work for contraception? Your chance of getting pregnant depends on how well you follow the directions for taking your birth control pills. The better you follow the directions, the less chance you have of getting pregnant. Based on the results of clinical studies, about 1 to 5 out of 100 women may get pregnant during the first year they use SEASONALE. The following chart shows the chance of getting pregnant for women who use different methods of birth control. Each box on the chart contains a list of birth control methods that are similar in effectiveness. The most effective methods are at the top of the chart. The box on the bottom of the chart shows the chance of getting pregnant for women who do not use birth control and are trying to get pregnant. Who should not take SEASONALE? Do not take SEASONALE if you: smoke and are over 35 years of age had blood clots in your arms, legs, lungs, or eyes had a problem with your blood that makes it clot more than normal have certain heart valve problems or irregular heart beat had a stroke had a heart attack have high blood pressure that cannot be controlled by medicine have diabetes with kidney, eye, nerve, or blood vessel damage have certain kinds of severe migraine headaches with aura, numbness, weakness or changes in vision, or any migraine headaches if you are over 35 years of age have liver problems, including liver tumors have any unexplained vaginal bleeding are pregnant had breast cancer or any cancer that is sensitive to female hormones If any of these conditions happen while you are taking SEASONALE, stop taking SEASONALE right away and talk to your healthcare provider. Use non-hormonal contraception when you stop taking SEASONALE. What should I tell my healthcare provider before taking SEASONALE? Tell your healthcare provider if you: are pregnant or think you may be pregnant are depressed now or have been depressed in the past had yellowing of your skin or eyes (jaundice) caused by pregnancy (cholestasis of pregnancy) are breastfeeding or plan to breastfeed. SEASONALE may decrease the amount of breast milk you make. A small amount of the hormones in SEASONALE may pass into your breast milk. Talk to your healthcare provider about the best birth control method for you while breastfeeding. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements. SEASONALE may affect the way other medicines work, and other medicines may affect how well SEASONALE works. Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take SEASONALE? Read the Instructions for Use at the end of this Patient Information. What are the possible serious side effects of SEASONALE? Like pregnancy, SEASONALE may cause serious side effects, including blood clots in your lungs, heart attack, or a stroke that may lead to death. Some other examples of serious blood clots include blood clots in the legs or eyes. Serious blood clots can happen especially if you smoke, are obese, or are older than 35 years of age. Serious blood clots are more likely to happen when you: first start taking birth control pills restart the same or different birth control pills after not using them for a month or more Call your healthcare provider or go to a hospital emergency room right away if you have: leg pain that will not go away a sudden, severe headache unlike your usual headaches sudden severe shortness of breath weakness or numbness in your arm or leg sudden change in vision or blindness trouble speaking chest pain Other serious side effects include: liver problems, including: rare liver tumors jaundice (cholestasis), especially if you previously had cholestasis of pregnancy. Call your healthcare provider if you have yellowing of your skin or eyes. high blood pressure. You should see your healthcare provider for a yearly check of your blood pressure. gallbladder problems changes in the sugar and fat (cholesterol and triglycerides) levels in your blood new or worsening headaches including migraine headaches irregular or unusual vaginal bleeding and spotting between your menstrual periods, especially during the first 3 months of taking SEASONALE. depression possible cancer in your breast and cervix swelling of your skin especially around your mouth, eyes, and in your throat (angioedema). Call your healthcare provider if you have a swollen face, lips, mouth tongue or throat, which may lead to difficulty swallowing or breathing. Your chance of having angioedema is higher is you have a history of angioedema. dark patches of skin around your forehead, nose, cheeks and around your mouth, especially during pregnancy (chloasma). Women who tend to get chloasma should avoid spending a long time in sunlight, tanning booths, and under sun lamps while taking SEASONALE. Use sunscreen if you have to be in the sunlight. What are the most common side effects of SEASONALE? headache (migraine) acne heavier or longer periods, pain with periods breast tenderness increase in weight nausea These are not all the possible side effects of SEASONALE. For more information, ask your healthcare provider or pharmacist. You may report side effects to the FDA at 1-800-FDA-1088. What else should I know about taking SEASONALE? If you are scheduled for any lab tests, tell your healthcare provider you are taking SEASONALE. Certain blood tests may be affected by SEASONALE. SEASONALE does not protect against HIV infection (AIDS) and other sexually transmitted infections. How should I store SEASONALE? Store SEASONALE at room temperature between 68°F to 77°F (20°C to 25°C). Protect from light. General information about the safe and effective use of SEASONALE. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use SEASONALE for a condition for which it was not prescribed. Do not give SEASONALE to other people, even if they have the same symptoms that you have. This Patient Information summarizes the most important information about SEASONALE. You can ask your pharmacist or healthcare provider for information about SEASONALE that is written for health professionals. For more information, call 1-888-483-8279 (1-888-4Teva-RX). Do birth control pills cause cancer? Birth control pills do not seem to cause breast cancer. However, if you have breast cancer now, or have had it in the past, do not use birth control pills because some breast cancers are sensitive to hormones. Women who use birth control pills may have a slightly higher chance of getting cervical cancer. However, this may be due to other reasons such as having more sexual partners. What if I want to become pregnant? You may stop taking the pill whenever you wish. Consider a visit with your healthcare provider for a pre-pregnancy checkup before you stop taking the pill. What should I know about my period when taking SEASONALE? When you take SEASONALE, which has a 91-day extended dosing cycle, you should have 4 scheduled periods a year (bleeding when you are taking the 7 white pills). However, you will probably have more bleeding or spotting between your scheduled periods than if you were using a birth control pill with a 28-day dosing cycle. During the first SEASONALE 91-day treatment cycle, about 1 in 3 women may have 20 or more days of unplanned bleeding or spotting. This bleeding or spotting tends to decrease with time. Do not stop taking SEASONALE because of this bleeding or spotting. If the spotting continues for more than 7 days in a row or if the bleeding is heavy, call your healthcare provider. What are the ingredients in SEASONALE? Active ingredients: Each pink pill contains levonorgestrel and ethinyl estradiol. Inactive ingredients: Pink pills: anhydrous lactose NF, FD&C blue no. 1, FD&C red no. 40, hydroxypropyl methylcellulose USP, microcrystalline cellulose NF, polyethylene glycol NF, magnesium stearate NF, polysorbate 80 NF, and titanium dioxide USP. White pills: anhydrous lactose NF, hydroxypropyl methylcellulose USP, microcrystalline cellulose NF, and magnesium stearate NF. Instructions For Use SEASONALE [see zuh nel] (levonorgestrel and ethinyl estradiol tablets) Important Information about taking SEASONALE Take 1 pill every day at the same time. Take the pills in the order directed on your pill dispenser. Do not skip your pills, even if you do not have sex often. If you miss pills (including starting the pack late) you could get pregnant. The more pills you miss, the more likely you are to get pregnant. If you have trouble remembering to take SEASONALE, talk to your healthcare provider. When you first start taking SEASONALE, spotting or light bleeding in between your periods may occur. Contact your healthcare provider if this does not go away after a few months. You may feel sick to your stomach (nauseous), especially during the first few months of taking SEASONALE. If you feel sick to your stomach, do not stop taking the pill. The problem will usually go away. If your nausea does not go away, call your healthcare provider. Missing pills can also cause spotting or light bleeding, even when you take the missed pills later. On the days you take 2 pills to make up for missed pills (see What should I do if I miss any SEASONALE pills? below), you could also feel a little sick to your stomach. It is not uncommon to miss a period. However, if you miss a period and have not taken SEASONALE according to directions, or feel like you may be pregnant, call your healthcare provider. If you have a positive pregnancy test, you should stop taking SEASONALE. If you have vomiting or diarrhea within 3-4 hours of taking a pink pill, take another pink pill as soon as possible. Continue taking one pill a day until the 91-day course is finished. If you have vomiting or diarrhea for more than 1 day, your birth control pills may not work as well. Use an additional birth control method, like condoms or spermicide, until you check with your healthcare provider. Stop taking SEASONALE at least 4 weeks before you have major surgery and do not restart after the surgery without asking your healthcare provider. Be sure to use other forms of contraception (like condoms or spermicide) during this time period. Before you start taking SEASONALE: 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 Extended-Cycle Tablet Dispenser. Your Tablet Dispenser consists of 3 trays with cards that hold 91 individually sealed pills (a 13-week or 91-day cycle). The 91 pills consists of 84 pink and 7 white pills. The cards in trays 1 and 2 each contain 28 pink pills (4 rows of 7 pills). See Figure A. The card in tray 3 contains 35 pills consisting of 28 pink pills (4 rows of 7 pills) and 7 white pills (1 row of 7 pills). See Figure B. Figure A Figure B Also find: Where on the first tray in the pack to start taking pills (upper left corner) and In what order to take the pills (follow the weeks) 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. When should I start taking SEASONALE? If you start taking SEASONALE and you have not used a hormonal birth control method before: Take the first pink pill on the Sunday after your period starts, even if you are still bleeding. If your period begins on Sunday, start the first pink pill that same day. Use another method of birth control (such as condoms or spermicides) as a back-up method if you have sex anytime from the Sunday you start your first pink pill until the next Sunday (first 7 days). If you start taking SEASONALE and you are switching from another birth control pill: Start your new SEASONALE pack on the same day that you would start the next pack of your previous birth control method. Do not continue taking the pills from your previous birth control pack. If you start taking SEASONALE and previously used a vaginal ring: Start using SEASONALE on the day you would have reapplied the next ring. If you start taking SEASONALE and previously used a transdermal patch: Start using SEASONALE on the day you would have started a new cycle (first patch application). If you start taking SEASONALE and you are switching from a progestin-only method such as an implant or injection: Start taking SEASONALE on the day of removal of your implant, or on the day when you would have had your next injection. If you start taking SEASONALE and you are switching from an intrauterine device or system (IUD or IUS): Start taking SEASONALE on the day of removal of your IUD or IUS. You do not need back-up contraception if your IUD or IUS is removed on the first day (Day 1) of your period. If your IUD or IUS is removed on any other day, use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days that you take SEASONALE. Keep a calendar to track your period: If this is the first time you are taking birth control pills, read, “When should I start taking SEASONALE?” above. Follow these instructions for a Sunday Start. Instructions for using your SEASONALE Extended-Cycle Tablet Dispenser:   Sunday Start: Take pill 1 on the Sunday after your period starts. To remove your pill from the dispenser, press the pill through the hole in the bottom of the dispenser. See Figure C. Figure C If your period starts on a Sunday, take pill “1” that same day. Take 1 pill at about the same time every day until you have taken the last pill in the tablet dispenser. After taking the last white pill on Day 91 from the pill dispenser, start taking the first pink pill from a new Extended-Cycle Tablet Dispenser on the very next day (this should be a Sunday). Take the first pill in the new pack whether or not you are having your period. Use non-hormonal back-up contraception such as condoms or spermicide for the first 7 days of the first cycle that you take SEASONALE. What should I do if I miss any SEASONALE pills? If you miss 1 pink pill, follow these steps: 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. Then continue taking 1 pill every day until you finish the pack. You do not need to use a back-up birth control method if you have sex. If you miss 2 pink pills in a row, follow these steps: Take 2 pills on the day you remember and 2 pills the next day. Then continue to take 1 pill every day until you finish the pack. You could become pregnant if you have sex in the 7 days after you miss two pills. You must use a non-hormonal birth control method (such as a condom or spermicide) as a back-up if you have sex during the first 7 days after you restart your pills. If you miss 3 or more pink pills in a row, follow these steps: Do not take the missed pills. Keep taking 1 pill every day until you have completed all of the remaining pills in the pack. For example, if you start taking the pill on Thursday, take the pill under “Thursday” and do not take the missed pills. You may have bleeding during the week following the missed pills. You could become pregnant if you have sex during the days of missed pills or during the first 7 days after restarting your pills. You must use a non-hormonal birth control method (such as a condom or spermicide) as a back-up when you miss pills and for the first 7 days after you restart your pills. If you do not have your period when you are taking the white pills, call your healthcare provider because you may be pregnant. If you have any questions or are unsure about the information in this leaflet, call your healthcare provider.

SIDE EFFECTS The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and smoking [see BOXED WARNING and WARNINGS AND PRECAUTIONS] Vascular events [see WARNINGS AND PRECAUTIONS] Liver disease [see WARNINGS AND PRECAUTIONS] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice. The clinical trial that evaluated the safety and efficacy of Seasonique (levonorgestrel, ethinyl estradiol) was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18-40, of whom 1,006 took at least one dose of Seasonique (levonorgestrel, ethinyl estradiol) . Adverse Reactions Leading to Study Discontinuation: 16.3% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions (≥ 1% of women) leading to discontinuation were irregular and/or heavy uterine bleeding (5.9%), weight gain (2.4%), mood changes (1.5%), and acne (1.0%). Common Treatment-Emergent Adverse Reactions (≥ 5% of women): irregular and/or heavy uterine bleeding (17%), weight gain (5%), acne (5%). Serious Adverse Reactions: migraine, cholecystitis, cholelithiasis, pancreatitis, abdominal pain, and major depressive disorder. Postmarketing Experience The following adverse reactions have been identified during post-approval use of Seasonique (levonorgestrel, ethinyl estradiol) . Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency of establish a causal relationship to drug exposure. Gastrointestinal disorders: abdominal distension, vomiting General disorders and administration site conditions: chest pain, fatigue, malaise, edema peripheral, pain Immune system disorders: hypersensitivity reaction Investigations: blood pressure increased Musculoskeletal and connective tissue disorders: muscle spasms, pain in extremity Nervous system disorders: dizziness, loss of consciousness Psychiatric disorders: insomnia Reproductive and breast disorders: dysmenorrhea Respiratory, thoracic and mediastinal disorders: pulmonary embolism, pulmonary thrombosis Skin and subcutaneous tissue disorders: alopecia Vascular disorders: thrombosis DRUG INTERACTIONS No drug-drug interaction studies were conducted with Seasonique (levonorgestrel, ethinyl estradiol) . Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Products If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception. Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include: barbiturates bosentan carbamazepine felbamate griseofulvin oxcarbazepine phenytoin rifampin St. John's wort topiramate HIV protease inhibitors and non-nucleoside reverse transcriptase inhibitors: Significant changes (increase or decrease) in the plasma levels of the estrogen and progestin have been noted in some cases of co-administration of HIV protease inhibitors or with non-nucleoside reverse transcriptase inhibitors. Antibiotics: There have been reports of pregnancy while taking hormonal contraceptives and antibiotics, but clinical pharmacokinetic studies have not shown consistent effects of antibiotics on plasma concentrations of synthetic steroids. Consult the labeling of all concurrently-used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Increase in Plasma Levels of Estradiol Associated with Co-Administered Drugs Co-administration of atorvastatin and certain COCs containing ethinyl estradiol increase AUC values for ethinyl estradiol by approximately 20%. Ascorbic acid and acetaminophen may increase plasma ethinyl estradiol levels, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole or ketoconazole may increase plasma hormone levels. Changes in Plasma Levels of Co-Administered Drugs COCs containing some synthetic estrogens (e.g., ethinyl estradiol) may inhibit the metabolism of other compounds. COCs have been shown to significantly decrease plasma concentrations of lamotrigine likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Consult the labeling of the concurrently-used drug to obtain further information about interactions with COCs or the potential for enzyme alterations.

SIDE EFFECTS The following serious adverse reactions with the use of COCs are discussed elsewhere in the labeling: Serious cardiovascular events and stroke [see BOXED WARNING and WARNINGS AND PRECAUTIONS] Vascular events [see WARNINGS AND PRECAUTIONS] Liver disease [see WARNINGS AND PRECAUTIONS] Adverse reactions commonly reported by COC users are: Irregular uterine bleeding Nausea Breast tenderness Headache Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The clinical trial that evaluated the safety and efficacy of SEASONALE was a 12-month, randomized, multicenter, open-label study, which enrolled women aged 18-40, of whom 456 took at least one dose of SEASONALE (345.14 woman-years of exposure) [see Clinical Studies]. Adverse Reactions Leading to Study Discontinuation: 14.9% of the women discontinued from the clinical trial due to an adverse reaction; the most common adverse reactions ( ≥ 1% of women) leading to discontinuation in the SEASONALE group were menorrhagia (5.7%), mood swings (1.9%), weight/appetite increase (1.5%), and acne (1.3%). Common Adverse Reactions ( ≥ 2% of women): headache (20.6%), menorrhagia (11.6%), nausea (7.5%), dysmenorrhea (5.7%), acne (4.6%), migraine (4.4%), breast tenderness (3.5%), weight increased (3.1%), and depression (2.1%). Serious Adverse Reactions: pulmonary embolus, cholecystitis. Postmarketing Experience The following adverse reactions have been identified during post-approval use of SEASONALE. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Gastrointestinal disorders: abdominal distension, vomiting General disorders and administration site conditions: chest pain, fatigue, malaise, edema peripheral, pain Immune system disorder: hypersensitivity reactions, including itching, rash, and angioedema Investigations: blood pressure increased Musculoskeletal and connective tissue disorders: muscle spasms, pain in extremity Nervous system disorders: dizziness, loss of consciousness Psychiatric disorders: insomnia Reproductive and breast disorders: dysmenorrhea Skin and subcutaneous tissue disorders: alopecia Vascular disorders: thrombosis, pulmonary embolism, pulmonary thrombosis DRUG INTERACTIONS Consult the labeling of concurrently used drugs to obtain further information about interactions with hormonal contraceptives or the potential for enzyme alterations. Effects Of Other Drugs On Combined Oral Contraceptives Substances Decreasing The Plasma Concentrations Of COCs And Potentially Diminishing The Efficacy Of COCs Drugs or herbal products that induce certain enzymes, including cytochrome P450 3A4 (CYP3A4), may decrease the plasma concentrations of COCs and potentially diminish the effectiveness of COCs or increase breakthrough bleeding. Some drugs or herbal products that may decrease the effectiveness of hormonal contraceptives include phenytoin, barbiturates, carbamazepine, bosentan, felbamate, griseofulvin, oxcarbazepine, rifampicin, topiramate, rifabutin, rufinamide, aprepitant, and products containing St. John's wort. Interactions between oral contraceptives and other drugs may lead to breakthrough bleeding and/or contraceptive failure. Counsel women to use an alternative method of contraception or a back-up method when enzyme inducers are used with COCs, and to continue back-up contraception for 28 days after discontinuing the enzyme inducer to ensure contraceptive reliability. Colesevelam Colesevelam, a bile acid sequestrant, given together with a COC, has been shown to significantly decrease the AUC of EE. The drug interaction between the contraceptive and colesevelam was decreased when the two drug products were given 4 hours apart. Substances Increasing The Plasma Concentrations Of COCs Co-administration of atorvastatin or rosuvastatin and certain COCs containing ethinyl estradiol (EE) increase AUC values for EE by approximately 20-25%. Ascorbic acid and acetaminophen may increase plasma EE concentrations, possibly by inhibition of conjugation. CYP3A4 inhibitors such as itraconazole, voriconazole, fluconazole, grapefruit juice, or ketoconazole may increase plasma hormone concentrations. Human Immunodeficiency Virus (HIV)/ Hepatitis C Virus (HCV) Protease Inhibitors And Non-Nucleoside Reverse Transcriptase Inhibitors Significant changes (increase or decrease) in the plasma concentrations of estrogen and/or progestin have been noted in some cases of co-administration with HIV protease inhibitors(decrease [e.g., nelfinavir, ritonavir, darunavir/ritonavir, (fos)amprenavir/ritonavir, lopinavir/ritonavir, and tipranavir/ritonavir] or increase [e.g., indinavir and atazanavir/ritonavir])/HCV protease inhibitors (decrease [e.g., nevirapine] or increase [e.g., etravirine]). Effects Of Combined Oral Contraceptives On Other Drugs COCs containing EE may inhibit the metabolism of other compounds (e.g., cyclosporine, prednisolone, theophylline, tizanidine, and voriconazole) and increase their plasma concentrations. COCs have been shown to decrease plasma concentrations of acetaminophen, clofibric acid, morphine, salicylic acid, temazepam and lamotrigine. Significant decrease in plasma concentration of lamotrigine has been shown, likely due to induction of lamotrigine glucuronidation. This may reduce seizure control; therefore, dosage adjustments of lamotrigine may be necessary. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because the serum concentration of thyroid-binding globulin increases with use of COCs [see WARNINGS AND PRECAUTIONS]. Interactions With Laboratory Tests The use of contraceptive steroids may influence the results of certain laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Thrombotic and Other Vascular Events Stop Seasonique (levonorgestrel, ethinyl estradiol) if an arterial or deep venous thrombotic event occurs. Although the use of COCs increases the risk of venous thromboembolism, pregnancy increases the risk of venous thromboembolism as much or more than the use of COCs. The risk of venous thromboembolism in women using COCs is 3 to 9 per 10,000 woman-years. The excess risk is highest during the first year of use of a COC. Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. The risk of thromboembolic disease due to COCs gradually disappears after COC use is discontinued. Use of Seasonique (levonorgestrel, ethinyl estradiol) provides women with more hormonal exposure on a yearly basis than conventional monthly oral contraceptives containing the same strength synthetic estrogens and progestins (an additional 9 and 13 weeks of exposure to progestin and estrogen, respectively, per year). If feasible, stop Seasonique (levonorgestrel, ethinyl estradiol) at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of thromboembolism. Start Seasonique (levonorgestrel, ethinyl estradiol) no earlier than 4-6 weeks after delivery, in women who are not breastfeeding. The risk of postpartum thromboembolism decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes), although, in general, the risk is greatest among older (>35 years of age), and hypertensive women who also smoke. COCs also increase the risk for stroke in women with other underlying risk factors. Oral contraceptives must be used with caution in women with cardiovascular disease risk factors. Stop Seasonique (levonorgestrel, ethinyl estradiol) if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately. Carcinoma of the Breast and Cervix Women who currently have or have had breast cancer should not use Seasonique (levonorgestrel, ethinyl estradiol) because breast cancer may be hormonally sensitive. There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings. Some studies suggest that COCs are associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there is controversy about the extent to which these findings are due to differences in sexual behavior and other factors. Liver Disease Discontinue Seasonique (levonorgestrel, ethinyl estradiol) ifjaundice develops. Steroid hormones may be poorly metabolized in patients with impaired liver function. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term (> 8 years) COC users. However, the attributable risk of liver cancers in COC users is less than one case per million users. Oral contraceptive-related cholestasis may occur in women with a history of pregnancy-related cholestasis. Women with a history of COC-related cholestasis may have the condition recur with subsequent COC use. High Blood Pressure For women with well-controlled hypertension, monitor blood pressure and stop Seasonique (levonorgestrel, ethinyl estradiol) if blood pressure rises significantly. Women with uncontrolled hypertension or hypertension with vascular disease should not use COCs. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use. The incidence of hypertension increases with increasing concentration of progestin. Gallbladder Disease Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Carbohydrate and Lipid Metabolic Effects Carefully monitor prediabetic and diabetic women who are taking Seasonique (levonorgestrel, ethinyl estradiol) . COCs may decrease glucose tolerance in a dose-related fashion. Consider alternative contraception for women with uncontrolled dyslipidemias. A small proportion of women will have adverse lipid changes while on COCs. Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs. Headache If a woman taking Seasonique (levonorgestrel, ethinyl estradiol) develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue Seasonique (levonorgestrel, ethinyl estradiol) if indicated. An increase in frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) may be a reason for immediate discontinuation of the COC. Bleeding Irregularities Unscheduled (breakthrough) bleeding and spotting sometimes occur in patients on COCs, especially during the first 3 months of use. If bleeding persists, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different COC. When prescribing Seasonique (levonorgestrel, ethinyl estradiol) , the convenience of fewer planned menses (4 per year instead of 13 per year) should be weighed against the inconvenience of increased unscheduled bleeding and/or spotting. The primary clinical trial (PSE-301) that evaluated the efficacy of Seasonique (levonorgestrel, ethinyl estradiol) also assessed unscheduled bleeding. The participants in the 12-month clinical trial (N=1,006) completed the equivalent of 8,681 28-day cycles of exposure and were composed primarily of women who had used oral contraceptives previously (89%) as opposed to new users (11%). A total of 82 (8.2%) of the women discontinued Seasonique (levonorgestrel, ethinyl estradiol) , at least in part, due to bleeding or spotting. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with an average of 3 days of bleeding and/or spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 1 below presents the number of days with unscheduled bleeding in treatment cycles 1 and 4. Table 2 presents the number of days with unscheduled spotting in treatment cycles 1 and 4. Table 1: Total Number of Days with Unscheduled Bleeding 91-Day Treatment Cycle Days per 84-Day Interval Days per 28-Day Interval Q1 Median Q3 Mean Mean 1st 1 4 10 6.9 1.7 4th 0 1 4 3.2 0.8 Q1=Quartile 1: 25% of women had this number of days of unscheduled bleeding Median: 50% of women had ≤ this number of days of unscheduled bleeding Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding Table 2: Total Number of Days with Unscheduled Spotting 91-Day Treatment Cycle Days per 84-Day Interval Days per 28-Day Interval Q1 Median Q3 Mean Mean 1st 1 4 11 7.4 1.9 4th 0 2 7 4.4 1.1 Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled spotting Median: 50% of women had ≤ this number of days of unscheduled spotting Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled spotting Figure 1 shows the percentage of Seasonique (levonorgestrel, ethinyl estradiol) subjects participating in trial PSE-301 with ≥ 7 days or ≥ 20 days of unscheduled bleeding and/or spotting, or only unscheduled bleeding, during each 91-day treatment cycle. Figure 1. Percent of Women Taking Seasonique (levonorgestrel, ethinyl estradiol) who Reported Unscheduled Bleeding and/or Spotting or only Unscheduled Bleeding Amenorrhea sometimes occurs in women who are using COCs. Pregnancy should be ruled out in the event of amenorrhea. Some women may encounter amenorrhea or oligomenorrhea after stopping COCs, especially when such a condition was pre-existent. COC 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. Oral contraceptive use should be discontinued if pregnancy is confirmed. The administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations]. Emotional Disorders Women with a history of depression should be carefully observed and Seasonique (levonorgestrel, ethinyl estradiol) discontinued if depression recurs to a serious degree. Interference with Laboratory Tests The use of COCs may change the results of some laboratory tests, such as coagulation factors, lipids, glucose tolerance, and binding proteins. Women on thyroid hormone replacement therapy may need increased doses of thyroid hormone because serum concentrations of thyroid binding globulin increase with use of COCs. Monitoring A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated health care. Other Conditions In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema. Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to chloasma should avoid exposure to the sun or ultraviolet radiation while taking COCs. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment of Fertility [See WARNINGS AND PRECAUTIONS]. Use In Specific Populations Pregnancy There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy. The administration of COCs to induce withdrawal bleeding should not be used as a test for pregnancy. COCs should not be used during pregnancy to treat threatened or habitual abortion. Women who do not breastfeed may start COCs no earlier than four to six weeks postpartum. Nursing Mothers When possible, advise the nursing mother to use other forms of contraception until she has weaned her child. Estrogen-containing COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk. Pediatric Use Safety and efficacy of Seasonique (levonorgestrel, ethinyl estradiol) have been established in women of reproductive age. Safety and efficacy are expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of Seasonique (levonorgestrel, ethinyl estradiol) before menarche is not indicated. Geriatric Use Seasonique (levonorgestrel, ethinyl estradiol) has not been studied in women who have reached menopause and is not indicated in this population. Hepatic Impairment No studies have been conducted to evaluate the effect of hepatic disease on the disposition of Seasonique (levonorgestrel, ethinyl estradiol) . However, steroid hormones may be poorly metabolized in patients with impaired liver function. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal. [See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Renal Impairment No studies have been conducted to evaluate the effect of renal disease on the disposition of Seasonique (levonorgestrel, ethinyl estradiol) .

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Thrombotic Disorders And Other Vascular Problems Stop SEASONALE if an arterial thrombotic event or venous thromboembolic (VTE) event occurs. Stop SEASONALE if there is unexplained loss of vision, proptosis, diplopia, papilledema, or retinal vascular lesions. Evaluate for retinal vein thrombosis immediately. If feasible, stop SEASONALE at least 4 weeks before and through 2 weeks after major surgery or other surgeries known to have an elevated risk of VTE as well as during and following prolonged immobilization. Start SEASONALE no earlier than 4 weeks after delivery, in women who are not breastfeeding. The risk of postpartum VTE decreases after the third postpartum week, whereas the risk of ovulation increases after the third postpartum week. The use of COCs increases the risk of VTE. However, pregnancy increases the risk of VTE as much or more than the use of COCs. The risk of VTE in women using COCs is 3 to 9 cases per 10,000 woman-years. The risk of VTE is highest during the first year of use of COCs and when restarting hormonal contraception after a break of 4 weeks or longer. The risk of thromboembolic disease due to COCs gradually disappears after use is discontinued. Use of SEASONALE provides women with more hormonal exposure on a yearly basis than conventional monthly COCs containing the same strength synthetic estrogens and progestins (an additional 9 weeks of exposure per year). In the clinical trial, one case of pulmonary embolism was reported. Postmarketing adverse reactions of VTE have been reported in women who used SEASONALE. Use of COCs also increases the risk of arterial thromboses such as strokes and myocardial infarctions, especially in women with other risk factors for these events. Stroke has been reported in women associated with the use of SEASONALE. COCs have been shown to increase both the relative and attributable risks of cerebrovascular events (thrombotic and hemorrhagic strokes). This risk increases with age, particularly in women over 35 years of age who smoke. Use COCs with caution in women with cardiovascular disease risk factors. Liver Disease Impaired Liver Function Do not use SEASONALE in women with liver disease, such as acute viral hepatitis or severe (decompensated) cirrhosis of the liver [see CONTRAINDICATIONS]. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded. Discontinue SEASONALE if jaundice develops. Liver Tumors SEASONALE is contraindicated in women with benign and malignant liver tumors [see CONTRAINDICATIONS]. Hepatic adenomas are associated with COC use. An estimate of the attributable risk is 3.3 cases/100,000 COC users. Rupture of hepatic adenomas may cause death through intra-abdominal hemorrhage. Studies have shown an increased risk of developing hepatocellular carcinoma in long-term ( > 8 years) COC users. However, the attributable risk of liver cancers in COC users is less than one case per million users. High Blood Pressure SEASONALE is contraindicated in women with uncontrolled hypertension or hypertension with vascular disease [see CONTRAINDICATIONS]. For women with well-controlled hypertension, monitor blood pressure and stop SEASONALE if blood pressure rises significantly. An increase in blood pressure has been reported in women taking COCs, and this increase is more likely in older women and with extended duration of use. The incidence of hypertension increases with increasing concentration of progestin. Gallbladder Disease Studies suggest a small increased relative risk of developing gallbladder disease among COC users. Use of COCs may worsen existing gallbladder disease. A past history of COC-related cholestasis predicts an increased risk with subsequent COC use. Women with a history of pregnancy-related cholestasis may be at an increased risk for COC-related cholestasis. Carbohydrate And Lipid Metabolic Effects Carefully monitor prediabetic and diabetic women who are taking SEASONALE. COCs may decrease glucose tolerance. Consider alternative contraception for women with uncontrolled dyslipidemia. A small proportion of women will have adverse lipid changes while on COCs. Women with hypertriglyceridemia, or a family history thereof, may be at an increased risk of pancreatitis when using COCs. Headache If a woman taking SEASONALE develops new headaches that are recurrent, persistent, or severe, evaluate the cause and discontinue SEASONALE if indicated. Consider discontinuation of SEASONALE in the case of increased frequency or severity of migraine during COC use (which may be prodromal of a cerebrovascular event) [see CONTRAINDICATIONS]. Bleeding Irregularities And Amenorrhea Bleeding and/or spotting that occurs at any time while taking the first 84 tablets of each extended-cycle regimen is considered “unscheduled” bleeding/spotting. Bleeding that occurs during the time a woman takes the seven white inert tablets is considered “scheduled” bleeding. Unscheduled And Scheduled Bleeding And Spotting Unscheduled (breakthrough) bleeding and spotting sometimes occur in patients on COCs, especially during the first 3 months of use. If unscheduled bleeding persists or occurs after previously regular cycles on SEASONALE, check for causes such as pregnancy or malignancy. If pathology and pregnancy are excluded, bleeding irregularities may resolve over time or with a change to a different COC. Before prescribing SEASONALE, advise the woman to weigh the convenience of fewer scheduled menses (4 per year instead of 13 per year) against the inconvenience of increased unscheduled bleeding and/or spotting. The clinical trial of the efficacy of SEASONALE (91-day cycles) in preventing pregnancy also assessed scheduled and unscheduled bleeding. The participants in the study were composed primarily of women who had used oral contraceptives previously as opposed to new users. Women with a history of breakthrough bleeding/spotting ≥ 10 consecutive days on oral contraceptives were excluded from the study. More SEASONALE subjects, compared to subjects on the comparator 28-day cycle regimen, discontinued prematurely for unacceptable bleeding (7.7% [SEASONALE] vs. 1.8% [28-day cycle regimen]). Unscheduled bleeding and unscheduled spotting decreased over successive 91-day cycles. Table 3 below presents the number of days with unscheduled bleeding and/or spotting for each respective 91-day cycle. Table 3: Number of Unscheduled Bleeding and/or Spotting Days per 91-day Cycle Cycle (N) Days of Unscheduled Bleeding and/or Spotting per 84-Day Interval Median Days Per Subject-Month Mean Q1 Median Q3 1 (446) 15.1 3.0 12 23.0 3.0 2 (368) 11.6 2.0 6 17.5 1.5 3 (309) 10.6 1.0 6 15.0 1.5 4(282) 8.8 1.0 4 14.0 1.0 Q1=Quartile 1: 25% of women had ≤ this number of days of unscheduled bleeding/spotting Median: 50% of women had ≤ this number of days of unscheduled bleeding/spotting Q3=Quartile 3: 75% of women had ≤ this number of days of unscheduled bleeding/spotting Table 4 shows the percentages of women with ≥ 7 days and ≥ 20 days of unscheduled spotting and/or bleeding in the SEASONALE and the 28-day cycle treatment groups. Table 4: Percentage of Subjects with Unscheduled Bleeding and/or Spotting Days of unscheduled bleeding and/or spotting Percentage of Subjects a SEASONALE Cycle 1 (N=385) Cycle 4 (N=261) ≥ 7 days 65% 42% ≥ 20 days 35% 15% 28-day regimen Cycles 1-4 (N=194) Cycles 10-13 (N=158) ≥ 7 days 38% 39% ≥ 20 days 6% 4% a Based on spotting and/or bleeding on days 1-84 of a 91 day cycle in the SEASONALE subjects and days 1-21 of a 28 day cycle over 4 cycles in the 28-day dosing regimen. Total days of bleeding and/or spotting (scheduled plus unscheduled) were similar over one year of treatment for SEASONALE subjects and subjects on the 28-day cycle regimen. Amenorrhea And Oligomenorrhea Women who are not pregnant and use SEASONALE may experience amenorrhea. Based on data from the clinical trial, amenorrhea occurred in approximately 0.8% of women during Cycle 1, 1.2% of women during Cycle 2, 3.7% of women during Cycle 3, and 3.4% of women during Cycle 4. Because women using SEASONALE will likely have scheduled bleeding only 4 times per year, rule out pregnancy at the time of any missed menstrual period. Some women may experience amenorrhea or oligomenorrhea after stopping COCs, especially when such a condition was pre-existent. COC 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 oral contraceptives are taken inadvertently during early pregnancy. Discontinue SEASONALE use if pregnancy is confirmed. Administration of oral contraceptives to induce withdrawal bleeding should not be used as a test for pregnancy [see Use in Specific Populations]. Depression Depression associated with the use of SEASONALE has been reported. Carefully observe women with a history of depression and discontinue SEASONALE if severe depression recurs. Carcinoma Of The Breast And Cervix SEASONALE is contraindicated in women who currently have or have had breast cancer because breast cancer may be hormonally sensitive [see CONTRAINDICATIONS]. There is substantial evidence that COCs do not increase the incidence of breast cancer. Although some past studies have suggested that COCs might increase the incidence of breast cancer, more recent studies have not confirmed such findings. Some studies suggest that COC use has been associated with an increase in the risk of cervical cancer or intraepithelial neoplasia. However, there continues to be controversy about the extent to which such findings may be due to differences in sexual behavior and other factors. Effect On Binding Globulins The estrogen component of COCs may raise the serum concentrations of thyroxine-binding globulin, sex hormone-binding globulin and cortisol-binding globulin. The dose of replacement thyroid hormone or cortisol therapy may need to be increased. Monitoring A woman who is taking COCs should have a yearly visit with her healthcare provider for a blood pressure check and for other indicated health care. Hereditary Angioedema In women with hereditary angioedema, exogenous estrogens may induce or exacerbate symptoms of angioedema. Chloasma Chloasma may occasionally occur, especially in women with a history of chloasma gravidarum. Women with a tendency to develop chloasma should avoid prolonged exposure to the sun or ultraviolet radiation while taking SEASONALE. Patient Counseling Information See FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use). Counsel patients on the following information: Cigarette smoking increases the risk of serious cardiovascular events from COC use, and that women who are over 35 years old and smoke should not use COCs [see BOXED WARNING]. Increased risk of VTE compared to non-users of COCs is greatest after initially starting a COC or restarting (following a 4-week or greater pill-free interval) the same or a different COC [see WARNINGS AND PRECAUTIONS]. SEASONALE does not protect against HIV-infection (AIDS) and other sexually transmitted infections. SEASONALE is not to be used during pregnancy; if pregnancy occurs during use of SEASONALE, instruct the patient to stop further use [see WARNINGS AND PRECAUTIONS]. Take one tablet daily by mouth at the same time every day. Instruct patients what to do in the event tablets are missed [see DOSAGE AND ADMINISTRATION]. Use a back-up or alternative method of contraception when enzyme inducers are used with SEASONALE [see DRUG INTERACTIONS]. COCs may reduce breast milk production; this is less likely to occur if breastfeeding is well established [see Use in Specific Populations]. Women who start on COCs postpartum, and who have not yet had a period, should use an additional method of contraception until they have taken a pink tablet for 7 consecutive days [see DOSAGE AND ADMINISTRATION]. Amenorrhea may occur. Because women using SEASONALE will likely have scheduled bleeding only 4 times per year, rule out pregnancy at the time of any missed menstrual period [see WARNINGS AND PRECAUTIONS]. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility [see WARNINGS AND PRECAUTIONS and Use in Specific Populations]. Use In Specific Populations Pregnancy There is little or no increased risk of birth defects in women who inadvertently use COCs during early pregnancy. Epidemiologic studies and meta-analyses have not found an increased risk of genital or non-genital birth defects (including cardiac anomalies and limb-reduction defects) following exposure to low dose COCs prior to conception or during early pregnancy. Do not administer COCs to induce withdrawal bleeding as a test for pregnancy. Do not use COCs during pregnancy to treat threatened or habitual abortion. Nursing Mothers Advise the nursing mother to use other forms of contraception, when possible, until she has weaned her child. COCs can reduce milk production in breastfeeding mothers. This is less likely to occur once breastfeeding is well established; however, it can occur at any time in some women. Small amounts of oral contraceptive steroids and/or metabolites are present in breast milk. Pediatric Use Safety and efficacy of SEASONALE have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal adolescents under the age of 18 as for users 18 years and older. Use of SEASONALE before menarche is not indicated. Geriatric Use SEASONALE has not been studied in postmenopausal women and is not indicated in this population. Hepatic Impairment The pharmacokinetics of SEASONALE have not been studied in subjects with hepatic impairment. However, steroid hormones may be poorly metabolized in patients with hepatic impairment. Acute or chronic disturbances of liver function may necessitate the discontinuation of COC use until markers of liver function return to normal and COC causation has been excluded [see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS]. Renal Impairment The pharmacokinetics of SEASONALE have not been studied in women with renal impairment.