Prescription Drugs

CLINICAL PHARMACOLOGY Mechanism Of Action Tazarotene is a retinoid prodrug that is converted to its active form, the cognate carboxylic acid of tazarotene, by rapid deesterification in animals and man. Tazarotenic acid binds to all 3 members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ but shows relative selectivity for RARβ and RARγ and may modify gene expression. The clinical significance of these findings is unknown. The mechanism of tazarotene action in acne vulgaris is not defined. However, the basis of tazarotene's therapeutic effect in acne may be due to its anti-hyperproliferative, normalizing-of-differentiation and anti-inflammatory effects. Tazarotene inhibited corneocyte accumulation in rhino mouse skin and crosslinked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown. Pharmacodynamics The pharmacodynamics of FABIOR Foam are unknown. Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Tazarotenic acid was highly bound to plasma proteins (greater than 99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones, and other polar metabolites which were eliminated through urinary and fecal pathways. Systemic exposure following topical application of FABIOR Foam 0.1% was evaluated in one trial. Patients aged 15 years and older with moderate-to-severe acne applied approximately 3.7 grams of FABIOR Foam 0.1% (N = 13) to approximately 15% body surface area (face, upper chest, upper back, and shoulders) once daily for 22 days. On Day 22, the mean (±SD) tazarotenic acid Cmax was 0.43 (±0.19) ng/mL, the AUC0-24h - was 6.98 (±3.56) ng·h/mL, and the half-life was 21.7 (±15.7) hours. The median Tmax was 6 hours (range: 4.4 to 12 hours). The AUC0-24h for tazarotenic acid was approximately 50-fold higher compared with the parent compound tazarotene. The mean (±SD) half-life of tazarotene was 8.1 (±3.7) hours. Accumulation was observed upon repeated once-daily dosing as the tazarotenic acid predose concentrations were measurable in the majority of subjects. Steady state was attained within 22 days of daily application. Once-daily dosing resulted in little to no accumulation of tazarotene as predose concentrations were mostly below the quantitation limit throughout the study. Clinical Studies In 2 multi-center, randomized, double-blind, vehicle-controlled trials, a total of 1,485 subjects with moderate-to-severe acne vulgaris were randomized 1:1 to FABIOR Foam or vehicle applied once daily for 12 weeks. Acne severity was evaluated using lesion counts and the 6-point Investigator's Global Assessment (IGA) scale (see Table 2). At baseline, 80% of subjects were graded as “moderate” or Grade 3 and 20% were graded as “severe” or Grade 4 on the IGA scale. At baseline, subjects had an average of 79.8 total lesions of which the mean number of inflammatory lesions was 31.9 and the mean number of non-inflammatory lesions was 47.8. Subjects ranged in age from 12 to 45 years, with 860 (58%) subjects aged 12 to 17 years; 428 (29%) subjects aged 18 to 25 years; 143 (10%) subjects aged 26 to 35 years and 54 (4%) subjects aged 36 to 45 years. Subjects enrolled in the trials by race were white (77%), black (15%), Asian (4%), and other (4%). Hispanics comprised 18% of the population. An equal number of males (49%) and females (51%) were enrolled. Treatment success was defined as a score of “clear” (Grade 0) or “almost clear” (Grade 1) and at least 2-grade improvement from the baseline score to Week 12. Table 2: Investigator's Global Assessment Scale Grade Description 0 Clear Clear skin with no inflammatory or non-inflammatory lesions. 1 AlmosL clear Rare non-inflammatory lesions with no more than rare papules. 2 Mild Greater than Grade 1, some non-inflammatory lesions with no more than a few inflammatory lesions (papules/pustules only, no nodular lesions). 3 Moderate Greater than Grade 2, up to many non-inflammatory lesions and may have some inflammatory lesions, but no more than one small nodular lesion. 4 Severe Greater than Grade 3, up to many non-inflammatory and inflammatory lesions, but no more than a few nodular lesions. 5 Very severe Many non-inflammatory and inflammatory lesions and more than a few nodular lesions. May have cystic lesions. Absolute and percent reductions in lesion counts and the IGA scale after 12 weeks of treatment in these 2 trials are shown in Table 3. Each trial needed to have a statistically significant reduction in 2 out of 3 lesion counts at Week 12. Table 3: Reductions in Lesion Counts and Improvements in Investigator's Global Assessment at Week 12 T rial 1 Trial 2 FABIOR Foam N = 371 Vehicle Foam N = 372 FABIOR Foam N = 373 Vehicle Foam N = 369 Inflammatory Lesions Mean absolute reduction from Baseline 18.0 14.0 18.0 15.0 Mean percent reduction from Baseline 58% 45% 55% 45% Non-inflammatory Lesions Mean absolute reduction from Baseline 28.0 17.0 26.0 18.0 Mean percent reduction from Baseline 55% 33% 57% 41% Total Lesions Mean absolute reduction from Baseline 46.0 31.0 43.0 33.0 Mean percent reduction from Baseline 56% 39% 56% 43% Investigator's Global Assessment (IGA), n (%) Minimum 2-grade improvement and IGA of 0 or 1 107 (29%) 60 (16%) 103 (28%) 49 (13%)

CLINICAL PHARMACOLOGY Tazarotene is a retinoid prodrug which is converted to its active form, the cognate carboxylic acid of tazarotene (AGN 190299), by rapid deesterification in animals and man. AGN 190299 (“tazarotenic acid”) binds to all three members of the retinoic acid receptor (RAR) family: RARα, RARβ, and RARγ, but shows relative selectivity for RARβ, and RARγand may modify gene expression. The clinical significance of these findings is unknown. The mechanism of tazarotene action in the amelioration of fine wrinkling, facial mottled hypo- and hyperpigmentation, and benign facial lentigines is unknown. A histological study of tazarotene cream 0.1% applied in subjects with fine wrinkling and mottled hyperpigmentation but otherwise normal skin for 24 weeks showed that tazarotene cream was associated with significantly greater proportions of patients who had an increase from baseline in the number of granular cell layers and in epidermal edema. The clinical significance of these changes is unknown. Pharmacokinetics Following topical application, tazarotene undergoes esterase hydrolysis to form its active metabolite, tazarotenic acid. Little parent compound could be detected in the plasma. Tazarotenic acid was highly bound to plasma proteins (>99%). Tazarotene and tazarotenic acid were metabolized to sulfoxides, sulfones, and other polar metabolites which were eliminated through urinary and fecal pathways. The half-life of tazarotenic acid was approximately 18 hours. Tazarotene cream 0.1% was topically applied once daily to either the face (6 females and 2 males) or to 15% of body surface area (8 females and 8 males) over four weeks in patients with fine wrinkling and mottled hyperpigmentation. In the “face-only” dosing group, the maximum average Cmax and AUC0-24 hr values of tazarotenic acid occurred on Day 15 with mean ± SD values of Cmax and AUC0-24 hr of tazarotenic acid being 0.236 ± 0.255 ng/mL (N = 8) and 2.44 ± 1.38 ng·hr/mL (N = 8), respectively. The mean Cmax and AUC0-24 hr values of tazarotenic acid from patients in the 15% body surface area dosing group were approximately 10 times higher than those from patients in the face-only dosing group. The single highest Cmax throughout the study period was 3.43 ng/mL on day 29 from patients in the 15% body surface area dosing group. Gender had no influence on the systemic bioavailability of tazarotenic acid. Blood samples were collected from one of the two phase 3 studies to evaluate the systemic exposure following application of tazarotene cream 0.1% once daily for 24 weeks (double-blind period) followed by 28 weeks (open-label) under clinical conditions. The mean plasma tazarotenic acid concentrations following topical treatment with tazarotene cream 0.1% over 52 weeks ranged between 0.092 ± 0.073 ng/mL and 0.127 ± 0.142 ng/mL. The single highest observed tazarotenic acid concentration throughout the 52-week study was 0.705 ng/mL (observed at week 36). Systemic availability of tazarotenic acid was minimal and remained steady following once daily application of tazarotene cream 0.1% to the faces of patients in the study for up to 52 weeks. Clinical Studies In two double-blind controlled studies in which tazarotene cream 0.1% was compared with its vehicle, applications were made once daily for 24 weeks to the facial skin of subjects with mild to severe fine wrinkling, facial mottled hypo- and hyperpigmentation, and benign facial lentigines due to overexposure to the sun. Treatment was as an adjunct to a comprehensive skin care and sun avoidance program which included use of sunscreens, protective clothing, and non-prescription emollient cream. At two to four week intervals the severity of fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines were graded on a scale of 0=none, 1=minimal, 2=mild, 3=moderate, and 4=severe. The results of both studies demonstrate that tazarotene cream 0.1% was significantly superior to its vehicle for fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines expressed as the proportion of subjects with an improvement of at least one grade from baseline. Approximately 97% of subjects in clinical trials were white (Caucasian) with 80% of subjects in the clinical studies having Fitzpatrick skin type classifications I-III. The distribution of subject skin types were: Type I –12%; Type II – 26%; Type III – 40%; and Type IV 22%. Patients with skin types V and VI were not studied. Insufficient non-white patients (Asian, Hispanic, or other) were studied to make an adequate determination of efficacy of AVAGE® (tazarotene) Cream in such patients. Percentage of Patients with Improvement in Fine Wrinkling after 24 Weeks of Treatment StudyA StudyB Taz. 0.1% N=283 Vehicle N=280 Taz. N=284 0.1% N=284 2 or more Grades Improvement 5% 1% 13% 5% 1 Grade Improvement 35% 15% 45% 18% No Change 59% 83% 42% 76% Worsened 1% 1% 0% 1% Fine Wrinkling was graded on a 5-point scale (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe) using a photonumeric guideline for investigators. Percentage of Patients with Improvement in Mottled Hyperpigmentation after 24 Weeks of Treatment StudyA StudyB Taz. 0.1% N=283 Vehicle N=280 Taz. N=284 0.1% N=284 2 or more Grades Improvement 17% 1% 28% 10% 1 Grade Improvement 42% 17% 54% 30% No Change 41% 80% 18% 59% Worsened <1% 3% <1% 1% Mottled Hyperpigmentation was graded on a 5-point scale (0=none, 1=minimal, 2=mild, 3=moderate, 4=severe) using a photonumeric guideline for investigators. In the 24 week studies, efficacy was also demonstrated in mottled hypopigmentation and benign facial lentigines, which were secondary endpoints in those studies. The duration of the mitigating effects on facial fine wrinkling, mottled hyper- and hypopigmentation, and benign facial lentigines following discontinuation of AVAGE® (TAZAROTENE) Cream 0.1% has not been studied.

Find Lowest Prices on FABIOR (tazarotene) Foam DESCRIPTION FABIOR (tazarotene) Foam, 0.1% contains the compound tazarotene, a member of the acetylenic class of retinoids. It is for topical use only. Chemically, tazarotene is ethyl 6-[(4,4-dimethylthiochroman-6-yl)ethynyl]nicotinate. The structural formula is represented below: Molecular Formula: C21H21NO2S Molecular Weight: 351.46 Tazarotene is a pale yellow to yellow substance. FABIOR Foam contains tazarotene, 1 mg/g, in aqueous-based white to off-white foam vehicle consisting of butylated hydroxytoluene, ceteareth-12, citric acid anhydrous, diisopropyl adipate, light mineral oil, potassium citrate monohydrate, potassium sorbate, purified water, and sorbic acid. FABIOR Foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/n-butane/isobutane) propellant.

Find Lowest Prices on AVAGE® (tazarotene) Cream, 0.1% FOR TOPICAL USE ONLY. NOT FOR OPHTHALMIC, ORAL, OR INTRAVAGINAL USE. DESCRIPTION AVAGE® (tazarotene) Cream is a white cream and contains the compound tazarotene; this formulation of tazarotene cream is also marketed for the treatment of plaque psoriasis and acne vulgaris as TAZORAC® (tazarotene) Cream, 0.1%. Tazarotene is a member of the acetylenic class of retinoids and is represented by the following structural formula: Formula: C21H21NO2S Molecular Weight: 351.46 Chemical Name: Ethyl 6-[2-(4,4-dimethylthiochroman-6-yl)ethynyl] nicotinate Contains Active: Tazarotene 0.1% (w/w) Preservative: Benzyl alcohol 1.0% (w/w) Inactives: Carbomer 934P, carbomer 1342, edetate disodium, medium chain triglycerides, mineral oil, purified water, sodium thiosulfate, sorbitan monooleate and sodium hydroxide to adjust the pH.

INDICATIONS FABIOR® (tazarotene) Foam, 0.1% is indicated for the topical treatment of acne vulgaris in patients 12 years of age or older. DOSAGE AND ADMINISTRATION FABIOR Foam is for topical use only. FABIOR Foam is not for oral, ophthalmic, or intravaginal use. FABIOR Foam should be applied once daily in the evening after washing with a mild cleanser and fully drying the affected area. Dispense a small amount of foam into the palm of the hand. Using fingertips, apply only enough foam to lightly cover the entire affected areas of the face and/or upper trunk with a thin layer; gently massage the foam into the skin until the foam disappears. Avoid the eyes, lips, and mucous membranes. Wash hands after application. Patients may use moisturizer as needed. If undue irritation (redness, peeling, or discomfort) occurs, patients should reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides. Treatment should be discontinued if irritation persists. HOW SUPPLIED Dosage Forms And Strengths 0.1%, white to off-white foam FABIOR Foam, 0.1% (1 mg/g) is a white to off-white foam, supplied as follows: 50-g aluminum can NDC 51862-295-50 100-g aluminum can NDC 51862-295-10 Storage And Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). See USP-controlled room temperature. Store upright. Protect from freezing. Flammable. Avoid fire, flame, or smoking during and immediately following application. Contents under pressure. Do not puncture or incinerate. Do not expose to heat or store at temperatures above 120°F (49°C). Shake can before use. Hold can at an upright angle and press firmly to dispense. Distributed by: Mayne Pharma, Greenville, NC 27834. Revised: Nov 2016

INDICATIONS (To understand fully the indication for this product, please read the entire INDICATIONS AND USAGE section of the labeling.) AVAGE® (TAZAROTENE) Cream 0.1% is indicated as an adjunctive agent for use in the mitigation (palliation) of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines in patients who use comprehensive skin care and sunlight avoidance programs. AVAGE® (TAZAROTENE) Cream 0.1% DOES NOT ELIMINATE or PREVENT WRINKLES, REPAIR SUNDAMAGED SKIN, REVERSE PHOTOAGING, or RESTORE MORE YOUTHFUL or YOUNGER SKIN. AVAGE® (TAZAROTENE) Cream 0.1% has NOT DEMONSTRATED A MITIGATING EFFECT on significant signs of chronic sunlight exposure such as coarse or deep wrinkling, tactile roughness, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, or dermal elastosis. AVAGE® (TAZAROTENE) Cream 0.1% should be used under medical supervision as an adjunct to a comprehensive skin care and sunlight avoidance program that includes the use of effective sunscreens (minimum SPF of 15) and protective clothing. Neither the safety nor the effectiveness of AVAGE® (TAZAROTENE) Cream 0.1% for the prevention or treatment of actinic keratoses, skin neoplasms, or lentigo maligna has been established. Neither the safety nor the efficacy of using AVAGE® (TAZAROTENE) Cream 0.1% daily for greater than 52 weeks has been established, and daily use beyond 52 weeks has not been systematically and histologically investigated in adequate and wellcontrolled trials. (See WARNINGS section.) DOSAGE AND ADMINISTRATION General Application may cause excessive irritation in the skin of certain sensitive individuals. In cases where it has been necessary to temporarily discontinue therapy, or the dosing has been reduced to an interval the patient can tolerate, therapy can be resumed, or the frequency of application can be increased as the patient becomes able to tolerate the treatment. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. Efficacy has not been established for less than once daily dosing frequencies. Apply a pea-sized amount once a day at bedtime to lightly cover the entire face including the eyelids if desired. Facial moisturizers may be used as frequently as desired. If any makeup is present it should be removed before applying AVAGE® (TAZAROTENE) Cream 0.1% to the face. If the face is washed or a bath or shower is taken prior to application, the skin should be dry before applying the cream. If emollients or moisturizers are used, they can be applied either before or after application of tazarotene cream ensuring that the first cream or lotion has absorbed into the skin and has dried completely. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. If the frequency of dosing is reduced, it should be noted that efficacy at a reduced frequency of application has not been established. The duration of the mitigating effects on facial fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines following discontinuation of AVAGE® (TAZAROTENE) Cream 0.1% has not been studied. HOW SUPPLIED AVAGE® (tazarotene) Cream is available in a concentration of 0.1%. It is available in a collapsible aluminum tube with a tamper-evident aluminum membrane over the opening and a white polypropylene screw cap, in a 30g size. AVAGE® (tazarotene) Cream 0.1% 30 gm NDC 0023-9236-30 Store at 25°C (77°F). Excursions permitted from -5° to 30°C (23° to 86°F). May 2004. ALLERGAN, Irvine, California 92612, USA. FDA rev date: 9/30/2002

PATIENT INFORMATION FABIOR® (fab'ee ore) (tazarotene) Foam IMPORTANT: For skin use only. Do not get FABIOR Foam in your eyes, mouth, or vagina. Read the Patient Information that comes with FABIOR Foam before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. What is FABIOR Foam? FABIOR Foam is a prescription medicine used on the skin (topical) to treat acne in people 12 years and older. It is not known if FABIOR Foam is safe and effective in children under 12 years of age. Who should not use FABIOR Foam? Do not use FABIOR Foam if you are pregnant or plan to become pregnant. FABIOR Foam may harm your unborn baby, if used during pregnancy. If you are a female who can become pregnant: Use an effective method of birth control during treatment with FABIOR Foam. Talk with your doctor about birth control methods that are right for you during treatment with FABIOR Foam. Your doctor should do a blood or urine pregnancy test within 2 weeks before you begin to use FABIOR Foam to be sure you are not pregnant. If you have menstrual periods, begin using FABIOR Foam during a normal menstrual period to help assure that you are not pregnant when you begin use. Stop using FABIOR Foam and call your doctor right away if you become pregnant during treatment with FABIOR Foam. What should I tell my doctor before using FABIOR Foam? Before you use FABIOR Foam, tell your doctor if you: or a family member have or had skin cancer. have eczema. have had a reaction to topical products in the past. have any condition that makes you sensitive to light. have any other medical conditions. are pregnant or plan to become pregnant. See “Who should not use FABIOR Foam?” are breastfeeding or plan to breastfeed. It is not known if tazarotene passes into your breast milk. You and your doctor should decide if you will use FABIOR Foam or breastfeed. You should not do both. Talk to your doctor about the best way to feed your baby if you use FABIOR Foam. Tell your doctor about all the medicines you take including prescription and nonprescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you: use other medicines or products that make your skin dry take other medicines that may increase your sensitivity to sunlight Ask your doctor or pharmacist if you are not sure if your medicine is one that is listed above. Know the medicines you take. Keep a list of your medicines and show it to your doctor and pharmacist when you get a new medicine. How should I use FABIOR Foam? Use FABIOR Foam exactly as your doctor tells you to. Do not use more FABIOR Foam than prescribed and do not use it more often than your doctor tells you to. If you are a female and have menstrual periods, begin using FABIOR Foam during a normal menstrual period to help assure that you are not pregnant when you begin use. See “Who should not use FABIOR Foam?” FABIOR Foam is flammable. Avoid fire, flame, and smoking during and right after you apply FABIOR Foam. Gently clean the affected area (face and/or upper trunk) with a mild cleanser and dry completely before using FABIOR Foam. Apply FABIOR Foam one time each day, before going to bed, to the affected areas (face and/or upper trunk) where you have acne lesions. Use enough foam to cover the entire affected area with a thin film of FABIOR Foam. Keep FABIOR Foam away from your eyes, mouth, and vagina. If FABIOR Foam comes into contact with your eyes, rinse them well with water. Wash your hands after applying FABIOR Foam. If you use too much FABIOR Foam, you may get redness, peeling, or skin irritation in the treated area. Call your doctor if this happens, or if you accidentally swallow FABIOR Foam. Follow your doctor's directions for other routine skin care and the use of make-up. You may also use a moisturizer as needed. Instructions for applying FABIOR Foam 1. Shake the FABIOR Foam can before use. 2. Remove cap from can. Nozzle should be lined up with black mark on rim of can. If black mark is not lined up with the nozzle, twist nozzle to line up with black mark. See Figure A. Figure A 3. Hold the FABIOR Foam can upright at a slight angle and press the nozzle. See Figure B. Figure B 4. Dispense a small amount of FABIOR Foam into the palm of your hand. See Figure C. Figure C 5. Use the fingertips of your other hand to apply enough FABIOR Foam to cover the affected area with a thin layer. Gently rub the foam into the affected area until it disappears into the skin. See Figure D. Figure D 6. Wash hands after applying FABIOR Foam. See Figure E. Figure E Avoid getting FABIOR Foam in your eyes, mouth, or vagina. What should I avoid while using FABIOR Foam? Avoid using abrasive soaps or cleansers that might dry or irritate your skin, unless your doctor tells you it is ok. Avoid sunlight. FABIOR Foam can make your skin sensitive to sunlight and the light from sunlamps or tanning beds. You could get a sunburn. Use sunscreen and protective clothing during the day if you must be in sunlight. Avoid using FABIOR Foam if you have a sunburn. If you have a sunburn, wait until it is fully healed before using FABIOR Foam. Talk to your doctor before using FABIOR Foam if you are sensitive to sunlight, take medications that increase your sensitivity to sunlight, or you must spend a lot of time in the sun for your job. Avoid weather extremes, such as wind and cold, because they may irritate your skin more while you are using FABIOR Foam. What are the possible side effects of FABIOR Foam? FABIOR Foam may harm your unborn baby, if used during pregnancy. Do not use FABIOR Foam during pregnancy. See “Who should not use FABIOR Foam?” The most common side effects of FABIOR Foam are: burning or stinging dry skin red skin peeling or flaking skin Sometimes these symptoms can become severe and may be uncomfortable. Tell your doctor if these side effects become uncomfortable for you. Your doctor may tell you to stop using FABIOR Foam until your skin heals and your symptoms improve, or to use FABIOR Foam less often to help you tolerate it better. These are not all the possible side effects of FABIOR Foam. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088. You may also report side effects to Mayne Pharma at 1-844-825-8500. How should I store FABIOR Foam? Store FABIOR Foam at room temperature, between 68°F to 77°F (20°C to 25°C). Store FABIOR Foam upright. Do not freeze FABIOR Foam. FABIOR Foam is flammable. Keep the can away from fire and heat. Do not spray FABIOR Foam near fire or direct heat. Do not puncture the can or throw it into a fire, even if the can is empty. Keep FABIOR Foam and all medicines out of the reach of children. General Information about FABIOR Foam Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use FABIOR Foam for a condition for which it was not prescribed. Do not give FABIOR Foam to other people even if they have the same symptoms that you have. It may harm them. This Patient Information leaflet summarizes the most important information about FABIOR Foam. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about FABIOR Foam that is written for health professionals. What are the ingredients in FABIOR Foam? Active ingredient: tazarotene Inactive ingredients: butylated hydroxytoluene, ceteareth-12, citric acid anhydrous, diisopropyl adipate, light mineral oil, potassium citrate monohydrate, potassium sorbate, purified water, and sorbic acid. The foam is dispensed from an aluminum can pressurized with a hydrocarbon (propane/n-butane/isobutane) propellant.

PATIENT INFORMATION AVAGE® (TAZAROTENE) Cream, 0.1% Use only on the face. Read this leaflet carefully before you start to use your medicine. Read the information you get every time you get more medicine. There may be new information about the drug. This leaflet does not take the place of talks with your doctor. If you have any questions, or are not sure about something, ask your doctor or pharmacist. What is the most important information I should know about AVAGE® (tazarotene) Cream? AVAGE® (tazarotene) Cream can cause birth defects in unborn children of women who are pregnant when they use the product. If you are a woman who can become pregnant, you must not be pregnant when you start using AVAGE® (tazarotene) Cream, and you must avoid pregnancy while you use it. See the sections “Who should not use AVAGE® (tazarotene) Cream?” “How should I use AVAGE® (tazarotene) Cream?” and “What should I avoid while using AVAGE® (tazarotene) Cream?” for more information. Avoid sunlight and other medicines that may increase your sensitivity to sunlight (See “Who should not use AVAGE® (tazarotene) Cream?” and “What should I avoid while using AVAGE® (tazarotene) Cream?”) AVAGE® (tazarotene) Cream does not remove wrinkles or repair sun-damaged skin. (See “What is AVAGE® (tazarotene) Cream?” for more details.) What is AVAGE® (tazarotene) Cream? AVAGE® (tazarotene) Cream is a prescription medicine that may reduce fine facial wrinkles and certain types of dark and light spots on your face. AVAGE® (tazarotene) is for patients who are using a total skin care program and avoiding sunlight. AVAGE® (tazarotene) Cream does not remove wrinkles, repair sun-damaged skin, reverse skin aging from the sun (photoaging), or bring back more youthful or younger skin. AVAGE® (tazarotene) does not work for everyone who uses it. It may work better for some patients than for others. The active ingredient in AVAGE® Cream is tazarotene. Who should not use AVAGE® (tazarotene) Cream? Do not use AVAGE® (tazarotene) Cream if: you are pregnant, plan to become pregnant, or may become pregnant. AVAGE® (tazarotene) Cream may harm your unborn child. Women who can become pregnant must have proof they are not pregnant from a reliable pregnancy test, done within 2 weeks before starting AVAGE® (tazarotene) Cream. Talk with your doctor about effective birth control if you are a woman who is able to become pregnant. you have sunburn or eczema. If you have sunburn, wait until full recovery before using AVAGE® (tazarotene) Cream. AVAGE® (tazarotene) Cream may cause severe irritation if used on eczema. Wait until your doctor tells you your eczema has cleared up before starting AVAGE® (tazarotene) treatment. you are allergic to the ingredients in AVAGE® Cream. The active ingredient is tazarotene. See the end of this information for a list of inactive ingredients. Tell your doctor before using AVAGE® (tazarotene) if: you are breast feeding. We do not know if AVAGE® (tazarotene) Cream can pass through your milk and harm the baby. you are sensitive to sunlight. AVAGE® (tazarotene) may not be right for you or you may need extra protection from sunlight. you take certain other medicines, vitamins, and supplements that increase your sensitivity to sunlight. These include Vitamin A and medicines that are called thiazides, tertracyclines, fluoroquinolones, phenothiazines, and sulfonamides. Therefore, tell your doctor if you take any prescription or non-prescription medicines, vitamins, or supplements. This will help your doctor decide if you can take AVAGE® (tazarotene) Cream. you take any other prescription or non-prescription medicines, supplements or vitamins. Some of them may make you more sensitive to sunlight. How should I use AVAGE® (tazarotene) Cream? If you are able to become pregnant, take a reliable pregnancy test within 2 weeks before beginning to use AVAGE® (tazarotene) Cream to be sure you are not pregnant. If you have menstrual periods, start taking AVAGE® (tazarotene) Cream during a normal menstrual period. These actions help assure you are not pregnant when you begin use. If you get pregnant while using AVAGE® (tazarotene) Cream, stop use and contact your doctor right away. Use AVAGE® (tazarotene) Cream only under the guidance of your doctor as part of a total skin care program in which you avoid sunlight. This program should include avoiding sunlight as much as possible, using clothing to protect you from sunlight, using sunscreens with an SPF of 15 or higher, and using face creams that add moisture to your skin. Follow these directions: Use AVAGE® (tazarotene) Cream once a day in the evening. In the evening, gently wash your face with mild soap. Pat your skin dry and wait 20-30 minutes before applying AVAGE® (tazarotene) Cream. Be sure your skin is dry before you use AVAGE® (tazarotene) Cream. Apply only a pea-sized amount (about ¼ inch or 5mm wide) to your face at one time. This should be enough to cover the wrinkled or discolored areas lightly. You can include your eyelids, if desired. Wash your hands after applying the medicine. If the cream gets on areas you do not need to treat, wash it off. In the morning, apply a moisturizing sunscreen of SPF 15 or greater. You can use a cream or lotion to soften or moisten your skin before or after you apply AVAGE® (tazarotene) Cream. Just be sure there is no more of the first cream or lotion on your skin and your skin is dry before you apply the second product. Keep AVAGE® (tazarotene) Cream out of your eyes and mouth. If it gets in your eyes, wash them off with large amounts of cool water. Contact your doctor if irritation continues. If you miss a dose, do not try to make it up. Continue with your normal schedule. In general, you can use facial moisturizers, such as lotions, oils, and creams, as often as you want. However, follow your doctor's advice for routine skin care and for using makeup, moisturizers, and sunscreens. Do not use more AVAGE® (tazarotene) Cream than instructed or more often than instructed. Using larger amounts of medicine than recommended will not lead to faster or better results and may cause more side effects. Wear clothing that protects your skin from the sun, and use non-prescription creams to help keep your skin soft. Watch your reaction to AVAGE® (tazarotene) Cream carefully if you are also using other skin products or processes with strong drying or irritating effects. These include products with high amounts of alcohol, astringents, spices, lime peel, medicated or abrasive soaps, medicated shampoos, and permanent wave solution. Avoid electrolysis, hair depilatories, waxes, and other products or processes that may dry or irritate your skin. If AVAGE® (tazarotene) Cream is swallowed, contact your doctor or call your poison control center right away. What should I avoid while using AVAGE® (tazarotene) Cream? Do not become pregnant while using AVAGE® (tazarotene) Cream. See the section “How should I use AVAGE® (tazarotene) Cream?” for more information. Use effective birth control while using AVAGE® (tazarotene) Cream, and be sure you are not pregnant before you start using AVAGE® (tazarotene) Cream. If you become pregnant while using AVAGE® (tazarotene) Cream, stop use and contact your doctor right away. AVAGE® (tazarotene) Cream makes you more sensitive to sunlight. It works only in patients who follow a sun avoidance program. Therefore, avoid sunlight as much as possible. Use cover-up clothing and sunscreens of at least SPF 15 during the day when using AVAGE® (tazarotene) Cream. Also, do not use sunlamps, unless your doctor tells you to. If you are sensitive to sunlight or in the sun a lot on your job, be especially careful to protect your skin. Use sunscreens and protective clothing. Stay out of the sun as much as possible. Avoid cosmetics, medicines and supplements that may make you more sensitive to sunlight, including Vitamin A. What are the possible side effects of AVAGE® (tazarotene) Cream? AVAGE® (tazarotene) can cause increased skin irritation and increased chance of sunburn. While you use AVAGE® (tazarotene) Cream, strong wind or cold may irritate your skin more than usual. The most common side effects of AVAGE® (TAZAROTENE) Cream 0.1% are peeling, redness, burning, dryness, and irritated and itching skin. These are not all the side effects possible with AVAGE® (tazarotene) Cream. For more information, ask your doctor or pharmacist. Tell your doctor if side effects become problems. Your doctor may adjust your dose of AVAGE® (tazarotene) Cream. However, the effectiveness of AVAGE® (tazarotene) Cream when used less often than once a day has not been proven. What are the ingredients of AVAGE® Cream? The active ingredient is tazarotene. The inactive ingredients are benzyl alcohol, carbomer 934P, carbomer l342, edetate disodium, medium chain triglycerides, mineral oil, purified water, sodium hydroxide, sodium thiosulfate, and sorbitan monooleate. General advice about prescription medicines This medicine is for your use only. Never give it to other people. It may harm them even if their skin problem appears to be the same as yours. Medicines are sometimes prescribed for conditions not mentioned in patient information leaflets. Do not use AVAGE® (tazarotene) Cream for a condition for which it was not prescribed. Do not use AVAGE® (tazarotene) Cream after the expiration date on the bottom seal of the tube. Where can I get more information about AVAGE® (tazarotene) Cream? You can contact Allergan by calling 800-433-8871. You can ask your doctor or pharmacist for the information about AVAGE® (tazarotene) Cream that is written for health professionals.

OVERDOSE Excessive topical application of FABIOR Foam may lead to marked redness, peeling, or discomfort. [see WARNINGS AND PRECAUTIONS]. Management of accidental ingestion or excessive application to the skin should be as clinically indicated. CONTRAINDICATIONS FABIOR Foam is contraindicated in pregnancy. FABIOR Foam may cause fetal harm when administered to a pregnant woman. Tazarotene elicits teratogenic and developmental effects associated with retinoids after topical or systemic administration in rats and rabbits [see Use in Specific Populations]. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient apprised of the potential hazard to the fetus [see WARNINGS AND PRECAUTIONS, Use in Specific Populations].

OVERDOSE Excessive topical use of AVAGE® (tazarotene) Cream 0.1% may lead to marked redness, peeling, or discomfort (see PRECAUTIONS: General). AVAGE® (tazarotene) Cream 0.1% is not for oral use. Oral ingestion of the drug may lead to the same adverse effects as those associated with excessive oral intake of Vitamin A (hypervitaminosis A) or other retinoids. If oral ingestion occurs, the patient should be monitored and appropriate supportive measures should be administered as necessary. CONTRAINDICATIONS Retinoids may cause fetal harm when administered to a pregnant woman. In rats, tazarotene 0.05% gel administered topically during gestation days 6 through 17 at 0.25 mg/kg/day resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. Systemic exposure (AUC0-24h) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits represented 2.4 and 26 times, respectively, the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. As with other retinoids, when tazarotene was given orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at doses producing 2.1 and 52 times, respectively, the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. In a study of the effect of oral tazarotene on fertility and early embryonic development in rats, decreased number of implantation sites, decreased litter size, decreased number of live fetuses, and decreased fetal body weights, all classic developmental effects of retinoids, were observed when female rats were administered 2 mg/kg/day from 15 days before mating through gestation day 7. A low incidence of retinoid-related malformations at that dose were reported to be related to treatment. That dose produced an AUC0-24h that was 6.7 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for signs of fine wrinkling and mottled hyperpigmentation. Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. IN PATIENTS TREATED TOPICALLY OVER SUFFICIENT BODY SURFACE AREA, EXPOSURE COULD BE IN THE SAME ORDER OF MAGNITUDE AS IN THESE ORALLY TREATED ANIMALS. As a retinoid, tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans. However, there may be less systemic exposure in the treatment of the face alone, due to less surface area for application (see CLINICAL PHARMACOLOGY: Pharmacokinetics). There were thirteen reported pregnancies in patients who participated in clinical trials for topical tazarotene. Nine of the patients were found to have been treated with topical tazarotene, and the other four had been treated with vehicle. One of the patients who was treated with tazarotene cream elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown. AVAGE® (tazarotene) Cream is contraindicated in women who are or may become pregnant. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, treatment should be discontinued and the patient apprised of the potential hazard to the fetus. Women of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when AVAGE® (tazarotene) Cream is used. The possibility that a woman of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to AVAGE® (tazarotene) Cream therapy, which should begin during a normal menstrual period (See also PRECAUTIONS: Pregnancy: Teratogenic Effects). AVAGE® (tazarotene) Cream is contraindicated in individuals who have shown hypersensitivity to any of its components.

SIDE EFFECTS Clinical Trials 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety data reflect exposure to FABIOR Foam in 744 subjects with acne vulgaris. Subjects were aged 12 to 45 years and were treated once daily in the evening for 12 weeks. Adverse reactions reported in ≥ 1% of subjects treated with FABIOR Foam are presented in Table 1. Most adverse reactions were mild to moderate in severity. Severe adverse reactions represented 3.0% of the subjects treated. Overall, 2.7% (20/744) of subjects discontinued FABIOR Foam because of local skin reactions. Table 1: Incidence of Adverse Reactions in ≥ 1 % of Subjects Treated with FABIOR Foam FABIOR Foam N = 744 Vehicle Foam N = 741 Patients with any adverse reaction, n (%) 163 (22) 19 (3) Application site irritation 107 (14) 9 (1) Application site dryness 50 (7) 8 (1) Application site erythema 48 (6) 3 ( < 1) Application site exfoliation 44 (6) 3 ( < 1) Application site pain 9 (1) 0 Application site photosensitivity (including sunburn) 8 (1) 3 ( < 1) Application site pruritus 7 (1) 3 ( < 1) Application site dermatitis 6 (1) 1 ( < 1) Additional adverse reactions that were reported in < 1% of subjects treated with FABIOR Foam included application site reactions (including discoloration, discomfort, edema, rash, and swelling), dermatitis, impetigo, and pruritus. Local skin reactions, dryness, erythema, and peeling actively assessed by the investigator and burning/stinging and itching reported by the subject were evaluated at baseline, during treatment, and end of treatment. During the 12 weeks of treatment, each local skin reaction peaked at Week 2 and gradually reduced thereafter with the continued use of FABIOR Foam. DRUG INTERACTIONS No formal drug-drug interaction studies were conducted with FABIOR Foam. Concomitant dermatologic medications and cosmetics that have a strong drying effect should be avoided. It is recommended to postpone treatment until the effects of these products subside before use of FABIOR Foam is started. Concomitant use with oxidizing agents, such as benzoyl peroxide, may cause degradation of tazarotene and may reduce the clinical efficacy of tazarotene. If combination therapy is required, they should be applied at different times of the day (e.g., one in the morning and the other in the evening). The impact of tazarotene on the pharmacokinetics of progestin-only oral contraceptives (i.e., minipills) has not been evaluated. In a trial of 27 healthy female subjects between the ages of 20 to 55 years receiving a combination oral contraceptive tablet containing 1 mg norethindrone and 35 mcg ethinyl estradiol, concomitant use of tazarotene did not affect the pharmacokinetics of norethindrone and ethinyl estradiol over a complete cycle.

SIDE EFFECTS In human dermal safety studies, tazarotene 0.05% and 0.1% creams did not induce allergic contact sensitization, phototoxicity or photoallergy. The most frequent treatment-related adverse reactions ( ≥ 5%) reported during the clinical trials with AVAGE® (TAZAROTENE) Cream 0.1% in the treatment of facial fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines were limited to the skin. Those occurring in >10%, in descending order, included: desquamation, erythema, burning sensation, and dry skin. Events occurring in ≥ 1% to ≤ 10% of patients, in descending order included: skin irritation, pruritus, irritant contact dermatitis, stinging, acne, rash or cheilitis. Common adverse events observed in the clinical trials are presented in the following table: TABLE OF ADVERSE EVENTS SEEN IN CLINICAL TRIALS WITH AVAGE® (TAZAROTENE) Cream 0.1% Adverse Event AVAGE ® N=567 Vehicle N=564 Desquamation 40% 3% Erythema 34% 3% BurningSensation 26% <1% DrySkin 16% 3% Irritation Skin 10% 1% Pruritus 10% 1% Irritant Contact Dermatitis 8% 1% Stinging 3% <1% Acne 3% 3% Rash 3% 1% Cheilitis 1% 0% A few patients reported adverse events at Week 0; however, for patients who were treated with AVAGE® (tazarotene) the highest number of new reports for each adverse event was at Week 2. When combining data from the two pivotal studies, 5.3% of patients in the tazarotene cream group and 0.9% of patients in the vehicle group discontinued due to adverse events. Overall, 20/567 (3.5%) patients in the AVAGE® (TAZAROTENE) Cream 0.1% group and 16/564 (2.8%) patients in the vehicle group reported adverse events (including edema, irritation, and inflammation) directly related to the eye or eyelid. The majority of these conditions were mild. DRUG INTERACTIONS Concomitant dermatologic medications and cosmetics that have a strong drying effect should be avoided. It is also advisable to “rest” a patient's skin until the effects of such preparations subside before use of AVAGE® (tazarotene) Cream is begun.

WARNINGS Included as part of the PRECAUTIONS section. PRECAUTIONS Fetal Risk Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In patients treated topically over sufficient body surface area, exposure could be in the same order of magnitude as in orally treated animals. Tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans [see CLINICAL PHARMACOLOGY]. There were 5 reported pregnancies in subjects who participated in clinical trials for topical tazarotene foam. One of the subjects was found to have been treated with topical tazarotene for 25 days, 2 were treated with vehicle foam, and the other 2 did not receive either tazarotene foam or vehicle foam. The subjects were discontinued from the trials when their pregnancy was reported. The one pregnant woman who was inadvertently exposed to topical tazarotene during the clinical trial delivered a full-term healthy infant. Females Of Childbearing Potential Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when tazarotene foam is used. The possibility of pregnancy should be considered in females of child-bearing potential at the time of institution of therapy. A negative serum or urine result for pregnancy test having a sensitivity down to at least 25 mIU/mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to therapy with FABIOR Foam, which should begin during a normal menstrual period for females of childbearing potential. Advise patients of the need to use an effective method of contraception to avoid pregnancy [see Use in Specific Populations]. Local Irritation FABIOR Foam should be used with caution in patients with a history of local tolerability reactions or local hypersensitivity. Retinoids should not be used on abraded or eczematous skin, as they may cause severe irritation. Contact with the mouth, eyes, and mucous membranes should be avoided. In case of accidental contact, rinse well with water. Some individuals may experience skin redness, peeling, burning or excessive pruritus. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the dosing should be reduced to an interval the patient can tolerate. However, efficacy at reduced frequency of application has not been established. Weather extremes, such as wind or cold, may be more irritating to patients using FABIOR Foam. Potential Irritant Effect With Concomitant Topical Medications Concomitant topical acne therapy should be used with caution because a cumulative irritant effect may occur. If irritancy or dermatitis occurs, reduce frequency of application or temporarily interrupt treatment and resume once the irritation subsides. Treatment should be discontinued if the irritation persists. Photosensitivity And Risk For Sunburn Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided. Patients must be warned to use sunscreens and protective clothing when using FABIOR Foam. Patients with sunburn should be advised not to use FABIOR Foam until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using FABIOR Foam and ensure that the precautions are observed [see FDA-approved patient labeling]. Due to the potential for photosensitivity resulting in greater risk for sunburn, FABIOR Foam should be used with caution in patients with a personal or family history of skin cancer. FABIOR Foam should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. Flammability The propellant in FABIOR Foam is flammable. Instruct the patient to avoid fire, flame, and/or smoking during and immediately following application. Patient Counseling Information See FDA-approved patient labeling (PATIENT INFORMATION). Inform the patient of the following: Fetal risk associated with FABIOR Foam for females of childbearing potential. Advise patients to use an effective method of contraception during treatment to avoid pregnancy. Advise the patient to stop medication if she becomes pregnant and call her doctor. If undue irritation (redness, peeling, or discomfort) occurs, reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides. Do not place FABIOR Foam in the freezer. Avoid exposure of the treated areas to either natural or artificial sunlight, including tanning beds and sun lamps. Avoid contact with the eyes. If FABIOR Foam gets in or near their eyes, to rinse thoroughly with water. Wash their hands after applying FABIOR Foam. Avoid fire, flame, or smoking during and immediately following application since FABIOR Foam is flammable. Keep out of the reach of children. Not for ophthalmic, oral, or intravaginal use. Nonclinical Toxicology Carcinogenesis, Mutagenesis, Impairment Of Fertility Carcinogenesis A long-term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risk. Based on pharmacokinetic data from a shorter-term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in rats approximately 2 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. A long-term topical application study of up to 0.1% tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared with vehicle control animals. AUC at the highest dose in mice was 49 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. In evaluation of photocarcinogenicity, median time to onset of tumors was decreased and the number of tumors increased in hairless mice following chronic topical dosing with exposure to ultraviolet radiation at tazarotene concentrations of 0.001%, 0.005%, and 0.01% in a gel formulation for up to 40 weeks. Mutagenesis Tazarotene was non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test. Impairment Of Fertility No impairment of fertility was observed in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure at the 0.125 mg/kg/day dose in rats would be equivalent to 7.6 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1 mg/kg/day tazarotene. AUC at the highest dose in rats was 23 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. No effect on parameters of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through gestation day 7 with oral doses of tazarotene up to 2 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose [see Pregnancy]. AUC at the highest dose in rats was 42 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. Reproductive capabilities of F1 animals, including F2 survival and development, were not affected by topical administration of tazarotene gel to female F0 parental rats from gestation day 16 through lactation day 20 at the maximum tolerated dose of 0.125 mg/kg/day. Based on data from another study, the AUC in rats would be equivalent to 7.6 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. Use In Specific Populations Pregnancy Pregnancy Category X. FABIOR Foam is contraindicated in pregnancy [see CONTRAINDICATIONS]. There are no adequate and well-controlled studies with FABIOR Foam in pregnant women. FABIOR Foam is contraindicated in females who are or may become pregnant [see CONTRAINDICATIONS]. Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when FABIOR Foam is used. The possibility that a female of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative serum or urine result for pregnancy test having a sensitivity down to at least 25 mIU/mL for hCG should be obtained within 2 weeks prior to therapy with FABIOR Foam, which should begin during a normal menstrual period for females of childbearing potential. In rats, tazarotene 0.05% gel administered topically during gestation days 6 through 17 at 0.25 mg/kg/day resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel during gestation days 6 through 18 were noted with single incidences of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies. Systemic exposure (AUC) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits were 15 and 166 times, respectively, the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. As with other retinoids, when tazarotene was administered orally to experimental animals, developmental delays were seen in rats, and teratogenic effects and post-implantation loss were observed in rats and rabbits at doses 13 and 325 times, respectively, the AUC to tazarotenic acid in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. In female rats orally administered 2 mg/kg/day tazarotene from 15 days before mating through gestation day 7, a number of classic developmental effects of retinoids were observed including decreased number of implantation sites, decreased litter size, decreased numbers of live fetuses, and decreased fetal body weights. A low incidence of retinoid-related malformations was also observed. AUC in rats was 42 times the AUC in acne patients treated with 2 mg/cm² of FABIOR Foam 0.1% over a 15% body surface area. Nursing Mothers After single topical doses of 14C-tazarotene to the skin of lactating rats, radioactivity was detected in milk, suggesting that there would be transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. The safe use of FABIOR Foam during lactation has not been established. A decision should be made whether to discontinue breastfeeding or to discontinue therapy with FABIOR Foam taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman. Pediatric Use The safety and effectiveness of FABIOR Foam in pediatric patients younger than 12 years have not been established. Clinical studies of FABIOR Foam included 860 patients aged 12 to 17 years with acne vulgaris. Geriatric Use FABIOR Foam for the treatment of acne has not been clinically evaluated in persons over the age of 65.

WARNINGS Pregnancy Category X. See CONTRAINDICATIONS section. Women of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when AVAGE® (tazarotene) Cream is used. The possibility that a woman of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for hCG should be obtained within 2 weeks prior to AVAGE® (tazarotene) Cream therapy, which should begin during a normal menstrual period. PRECAUTIONS General: AVAGE® (tazarotene) Cream should be applied only to the affected areas. For external use only. Avoid contact with eyes and mouth. If contact with eyes occurs, rinse thoroughly with water. Retinoids should not be used on eczematous skin, as they may cause severe irritation. Because of heightened burning susceptibility, exposure to sunlight (including sunlamps) should be avoided unless deemed medically necessary, and in such cases, exposure should be minimized during the use of AVAGE® (tazarotene) Cream. Patients must be warned to use sunscreens (minimum SPF of 15) and protective clothing when using AVAGE® (tazarotene) Cream. Patients with sunburn should be advised not to use AVAGE® (tazarotene) Cream until fully recovered. Patients who may have considerable sun exposure due to their occupation and those patients with inherent sensitivity to sunlight should exercise particular caution when using AVAGE® (tazarotene) Cream and ensure that the precautions outlined in the Information for Patients subsection are observed. AVAGE® (tazarotene) Cream should be administered with caution if the patient is also taking drugs known to be photosensitizers (e.g., thiazides, tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the increased possibility of augmented photosensitivity. Some individuals may experience excessive pruritus, burning, skin redness, or peeling. If these effects occur, the medication should either be discontinued until the integrity of the skin is restored, or the dosing should be reduced to an interval the patient can tolerate. However, efficacy at reduced frequency of application has not been established. Weather extremes, such as wind or cold, may be more irritating to patients using AVAGE® (tazarotene) Cream. Some facial pigmented lesions are not lentigines, but rather lentigo maligna, a type of melanoma. Facial pigmented lesions of concern should be carefully assessed by a qualified physician (e.g. dermatologist) before application of AVAGE® (TAZAROTENE) Cream. Lentigo maligna should not be treated with AVAGE® (TAZAROTENE) Cream. Information for Patients: AVAGE® (TAZAROTENE) Cream 0.1% is to be used as described below when used for treatment of facial fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines, unless otherwise directed by your physician: It is for use on the face. Avoid contact with the eyes and mouth. AVAGE® (TAZAROTENE) Cream 0.1% may cause severe redness, itching, burning, stinging, and peeling. Before applying AVAGE® (TAZAROTENE) Cream 0.1% once per day, gently wash your face with a mild soap. Make sure skin is dry before applying AVAGE® (TAZAROTENE) Cream 0.1%. Apply only a small pea sized amount (about ¼ inch or 5 millimeter diameter) of AVAGE® (TAZAROTENE) Cream 0.1% to your face at one time. This should be enough to lightly cover the entire face. For best results, you are advised that if emollients or moisturizers are used, they can be applied either before or after tazarotene cream, ensuring that the first cream or lotion has absorbed into the skin and dried completely. In the morning, apply a moisturizing sunscreen, SPF 15 or greater. AVAGE® (TAZAROTENE) Cream 0.1% is a serious medication. Do not use AVAGE® (TAZAROTENE) Cream 0.1% if you are pregnant or attempting to become pregnant. If you become pregnant while using AVAGE® (TAZAROTENE) Cream 0.1%, please contact your physician immediately. Avoid sunlight and other medicines that may increase your sensitivity to sunlight. For the mitigation of fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines, avoidance of excessive sun exposure and the use of sunscreens with protective measures (hat, visor) are recommended. AVAGE® (TAZAROTENE) Cream 0.1% does not remove or prevent wrinkles or repair sun-damaged skin. Please refer to the Patient Package Insert for additional patient information. Carcinogenesis, Mutagenesis, Impairment of Fertility A long term study of tazarotene following oral administration of 0.025, 0.050, and 0.125 mg/kg/day to rats showed no indications of increased carcinogenic risks. Based on pharmacokinetic data from a shorter term study in rats, the highest dose of 0.125 mg/kg/day was anticipated to give systemic exposure in the rat equivalent to 1.4 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. In evaluation of photo co-carcinogenicity, median time to onset of tumors was decreased, and the number of tumors increased in hairless mice following chronic topical dosing with intercurrent exposure to ultraviolet radiation at tazarotene concentrations of 0.001%, 0.005%, and 0.01% in a gel formulation for up to 40 weeks. A long-term topical application study of up to 0.1% tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1.0 mg/kg/day (reduced to 0.5 mg/kg/day for males after 41 weeks due to severe dermal irritation) revealed no apparent carcinogenic effects when compared to vehicle control animals; untreated control animals were not completely evaluated. Systemic exposure (AUC0-12h) at the highest dose was 7.8 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. Tazarotene was found to be non-mutagenic in the Ames assays using Salmonella and E. coli and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was also non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test. No impairment of fertility occurred in rats when male animals were treated for 70 days prior to mating and female animals were treated for 14 days prior to mating and continuing through gestation and lactation with topical doses of tazarotene gel of up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat would be equivalent to 1.2 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. No impairment of mating performance or fertility was observed in male rats treated for 70 days prior to mating with oral doses of up to 1.0 mg/kg/day tazarotene. That dose produced an AUC0-24h that was 3.7 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. No effect on parameters of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through day 7 of gestation with oral doses of tazarotene up to 2.0 mg/kg/day. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose (see CONTRAINDICATIONS). That dose produced an AUC0-24h that was 6.7 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for signs of fine wrinkling and mottled hyperpigmentation. Reproductive capabilities of F1 animals, including F2 survival and development, were not affected by topical administration of tazarotene gel to female F0 parental rats from gestation day 16 through lactation day 20 at the maximum tolerated dose of 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat would be equivalent to 1.2 times the maximum AUC0-24h in patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. Pregnancy: Teratogenic Effects: Pregnancy Category X See CONTRAINDICATIONS section. Women of child-bearing potential should use adequate birth-control measures when AVAGE® (tazarotene) Cream is used. The possibility that a woman of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test having a sensitivity down to at least 50 mIU/mL for hCG should be obtained within 2 weeks prior to AVAGE® (tazarotene) Cream therapy, which should begin during a normal menstrual period. There are no adequate and well-controlled studies in pregnant women. As a retinoid, tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans. However, there may be less systemic exposure in the treatment of the face alone, due to less surface area for application (see CLINICAL PHARMACOLOGY: Pharmacokinetics). Nursing mothers After single topical doses of 14C-tazarotene gel to the skin of lactating rats, radioactivity was detected in milk, suggesting that there would be transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. Caution should be exercised when tazarotene is administered to a nursing woman. Pediatric Use The safety and efficacy of tazarotene cream have not been established in patients under the age of 17 years with facial fine wrinkling, facial mottled hypo- and hyperpigmentation, and benign facial lentigines. Geriatric Use In the studies of facial fine wrinkling, facial mottled hypo- and hyperpigmentation, and benign facial lentigines, 44 male patients and 180 female patients out of the total population of 1131 patients were older than 65 years of age. No overall differences in safety or effectiveness were observed between these patients and younger patients, and other clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.