FABIOR

6 ADVERSE REACTIONS Most common adverse reactions reported at an incidence ≥6% are application site irritation, application site dryness, application site erythema, and application site exfoliation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 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.

4 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 (8.1) ]. 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 (5.1) , Use in Specific Populations (8.1) ]. Pregnancy. ( 4 , 8.1 )

11 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: C 21 H 21 NO 2 S 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. Chemical Structure

2 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. Apply a thin layer to the entire affected areas of the face and/or upper trunk once daily in the evening. Avoid the eyes, lips, and mucous membranes. Wash hands after application. ( 2 )

1 INDICATIONS AND USAGE FABIOR ® (tazarotene) Foam, 0.1% is indicated for the topical treatment of acne vulgaris in patients 12 years of age or older. FABIOR Foam is a retinoid indicated for the topical treatment of acne vulgaris in patients 12 years of age or older. ( 1 )

10 OVERDOSAGE Excessive topical application of FABIOR Foam may lead to marked redness, peeling, or discomfort. [see Warnings and Precautions (5.2) ]. Management of accidental ingestion or excessive application to the skin should be as clinically indicated.

7 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. Avoid concomitant dermatologic medications and cosmetics that have a strong drying effect. ( 7 )

12 CLINICAL PHARMACOLOGY 12.1 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 cross- linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown. 12.2 Pharmacodynamics The pharmacodynamics of FABIOR Foam are unknown. 12.3 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 C max was 0.43 (±0.19) ng/mL, the AUC 0 - 24h was 6.98 (±3.56) ng∙h/mL, and the half-life was 21.7 (±15.7) hours. The median T max was 6 hours (range: 4.4 to 12 hours). The AUC 0-24h 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.

12.1 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 cross- linked envelope formation in cultured human keratinocytes. The clinical significance of these findings is unknown.

12.2 Pharmacodynamics The pharmacodynamics of FABIOR Foam are unknown.

12.3 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 C max was 0.43 (±0.19) ng/mL, the AUC 0 - 24h was 6.98 (±3.56) ng∙h/mL, and the half-life was 21.7 (±15.7) hours. The median T max was 6 hours (range: 4.4 to 12 hours). The AUC 0-24h 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.

20230228

4

3 DOSAGE FORMS AND STRENGTHS 0.1%, white to off-white foam 0.1%, foam. ( 3 )

FABIOR tazarotene tazarotene tazarotene BUTYLATED HYDROXYTOLUENE CETEARETH-12 ANHYDROUS CITRIC ACID DIISOPROPYL ADIPATE LIGHT MINERAL OIL POTASSIUM CITRATE POTASSIUM SORBATE WATER SORBIC ACID

13.1 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/cm 2 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/cm 2 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/cm 2 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/cm 2 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 (8.1) ]. AUC at the highest dose in rats was 42 times the AUC in acne patients treated with 2 mg/cm 2 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/cm 2 of FABIOR Foam 0.1% over a 15% body surface area.

13 NONCLINICAL TOXICOLOGY 13.1 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/cm 2 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/cm 2 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/cm 2 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/cm 2 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 (8.1) ]. AUC at the highest dose in rats was 42 times the AUC in acne patients treated with 2 mg/cm 2 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/cm 2 of FABIOR Foam 0.1% over a 15% body surface area.

NDA202428

FABIOR

tazarotene

51862-295

HUMAN PRESCRIPTION DRUG

TOPICAL

PRINCIPAL DISPLAY PANEL - 100 gram Can Carton NDC 51862-295-10 Fabior ® (tazarotene) Foam, 0.1% 100 grams Rx only For topical use only STORE UPRIGHT mayne pharma Recyclable Aluminum Container PRINCIPAL DISPLAY PANEL - 100 gram Can Carton

FABIOR is a registered trademark of Mayne Pharma LLC. ©2016 Mayne Pharma All rights reserved. Distributed by: Mayne Pharma Raleigh, NC 27609 141298

17 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.

14 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 Almost 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 Trial 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%)

8.5 Geriatric Use FABIOR Foam for the treatment of acne has not been clinically evaluated in persons over the age of 65.

8.3 Nursing Mothers After single topical doses of 14 C-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.

8.4 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.

8.1 Pregnancy FABIOR Foam is contraindicated in pregnancy [see Contraindications (4) ]. 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 (4) ]. 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/cm 2 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/cm 2 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/cm 2 of FABIOR Foam 0.1% over a 15% body surface area.

8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy FABIOR Foam is contraindicated in pregnancy [see Contraindications (4) ]. 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 (4) ]. 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/cm 2 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/cm 2 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/cm 2 of FABIOR Foam 0.1% over a 15% body surface area. 8.3 Nursing Mothers After single topical doses of 14 C-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. 8.4 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. 8.5 Geriatric Use FABIOR Foam for the treatment of acne has not been clinically evaluated in persons over the age of 65.

16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied: FABIOR Foam, 0.1% (1 mg/g) is a white to off-white foam, supplied as follows: 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.

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.