Fabior

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

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 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.

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.

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.

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.

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.

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. 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. 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.

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. 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.

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

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.

Pregnancy Category X.

FABIOR Foam is contraindicated in pregnancy.

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. 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.

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

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.

Excessive topical application of FABIOR Foam may lead to marked redness, peeling, or discomfort.. Management of accidental ingestion or excessive application to the skin should be as clinically indicated.

The pharmacodynamics of FABIOR Foam are unknown.

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.