Tazorac Cream

Important Administration Instructions

Tazorac Cream is for topical use only. Tazorac Cream is not for ophthalmic, oral, or intravaginal use. If contact with mucous membranes occurs, rinse thoroughly with water [see Warnings and Precaution (5.2)].

Wash hands thoroughly after application.

Psoriasis

It is recommended that treatment starts with Tazorac Cream, 0.05%, with strength increased to 0.1% if tolerated and medically indicated. Apply a thin film (2 mg/cm2) of Tazorac Cream once per day, in the evening, to cover only the psoriatic lesions. If a bath or shower is taken prior to application, the skin should be dry before applying the cream. If emollients are used, they should be applied at least an hour before application of Tazorac Cream. Because unaffected skin may be more susceptible to irritation, application of Tazorac Cream to these areas should be carefully avoided.

Acne

Cleanse the face gently. After the skin is dry, apply a thin layer (2 mg/cm2) of Tazorac Cream 0.1% once per day, in the evening, to the skin areas where acne lesions appear. Use enough to cover the entire affected area.

Use effective sunscreens and wear protective clothing while using Tazorac Cream [see Warnings and Precaution (5.3)].

The following serious adverse reactions are discussed in more detail in other sections of the labeling:

• Embryofetal toxicity [see Warnings and Precautions (5.1)]
• Photosensitivity and Risk of Sunburn [see Warnings and Precautions (5.3)]

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 to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

In human dermal safety trials, Tazorac Cream, 0.05% and 0.1% did not induce allergic contact sensitization, phototoxicity, or photoallergy.

Psoriasis

The most frequent adverse reactions reported with Tazorac Cream, 0.05% and 0.1% occurring in 10 to 23% of subjects, in descending order, included pruritus, erythema, and burning. Reactions occurring in greater than 1 to less than 10% of subjects, in descending order, included irritation, desquamation, stinging, contact dermatitis, dermatitis, eczema, worsening of psoriasis, skin pain, rash, hypertriglyceridemia, dry skin, skin inflammation, and peripheral edema.

Tazorac Cream, 0.1% was associated with a greater degree of local irritation than the 0.05% cream. The rates of irritation adverse reactions reported during psoriasis trials with Tazorac Cream, 0.1% were 0.1-0.4% higher than those reported for Tazorac Cream, 0.05%.

Acne

The most frequent adverse reactions reported during clinical trials with Tazorac Cream 0.1% in the treatment of acne, occurring in 10-30% of subjects, in descending order included desquamation, dry skin, erythema, and burning sensation. Reactions occurring in 1 to 5% of subjects included pruritus, irritation, face pain, and stinging.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of tazarotene. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skin and subcutaneous tissue disorders: blister, dermatitis, urticaria, skin exfoliation, skin discoloration (including skin hyperpigmentation or skin hypopigmentation), swelling at or near application sites, and pain.

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Pregnancy

Risk Summary

Based on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, Tazorac Cream may cause fetal harm when administered to a pregnant female and is contraindicated during pregnancy. Safety in pregnant females has not been established. The potential risk to the fetus outweighs the potential benefit to the mother from Tazorac Cream during pregnancy; therefore, Tazorac Cream should be discontinued as soon as pregnancy is recognized [see Contraindications (4), Warnings and Precautions (5.1), Clinical Pharmacology (12.3)]. Limited case reports of pregnancy in females enrolled in clinical trials for Tazorac Cream have not established a clear association with tazarotene and major birth defects or miscarriage risk. Because the exact timing and extent of exposure in relation to the gestational age are not certain, the significance of these findings is unknown.

In animal reproduction studies with pregnant rats, tazarotene dosed topically during organogenesis at 2 times the maximum systemic exposure in subjects treated with the maximum recommended human dose (MRHD) of tazarotene cream, 0.1% resulted in reduced fetal body weights and reduced skeletal ossification. In animal reproduction studies with pregnant rabbits dosed topically with tazarotene gel at 26 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%, there was a single incident of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies.

In animal reproduction studies with pregnant rats and rabbits, tazarotene dosed orally during organogenesis at 2 and 52 times, respectively, the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% resulted in malformations, fetal toxicity, developmental delays, and/or behavioral delays. In pregnant rats, tazarotene dosed orally prior to mating through early gestation resulted in decreased litter size, decreased numbers of live fetuses, decreased fetal body weights, and increased malformations at doses approximately 7 times higher than the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% [see Data].

The background risk of major birth defects and miscarriage for the indicated population is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Data

Animal Data

In rats, a tazarotene gel, 0.05% formulation dosed topically during gestation days 6 through 17 at 0.25 mg/kg/day, which represented 2 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1% (i.e., 2 mg/cm2 over a 15% body surface area), resulted in reduced fetal body weights and reduced skeletal ossification. Rabbits dosed topically with 0.25 mg/kg/day tazarotene gel, which represented 26 times the maximum systemic exposure in subjects treated with MRHD of tazarotene cream, 0.1%, during gestation days 6 through 18, had a single incident of known retinoid malformations, including spina bifida, hydrocephaly, and heart anomalies.

When tazarotene was given orally to animals, developmental delays were seen in rats, and malformations and post-implantation loss were observed in rats and rabbits at doses representing 2 and 52 times, respectively, the maximum systemic exposure seen in subjects treated with the MRHD of tazarotene cream, 0.1%.

In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, which represented 7 times the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%, 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 observed at that dose.

In a pre- and postnatal development toxicity study, topical administration of tazarotene gel (0.125 mg/kg/day) to pregnant female rats from gestation day 16 through lactation day 20 reduced pup survival, but did not affect the reproductive capacity of the offspring. Based on data from another study, the maximum systemic exposure in the rat would be equivalent to the maximum systemic exposure in subjects treated with the MRHD of tazarotene cream, 0.1%.

Lactation

Risk Summary

There is no information regarding the presence of tazarotene in human milk, the effects on the breastfed infant, or the effects on milk production. After single topical doses of 14C-tazarotene gel to the skin of lactating rats, radioactivity was detected in rat milk. The lack of clinical data during lactation precludes a clear determination of the risk of Tazorac Cream to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Tazorac Cream and any potential adverse effects on the breastfed child from Tazorac Cream or from the underlying maternal condition.

Females and Males of Reproductive Potential

Pregnancy Testing

Pregnancy testing is recommended for females of reproductive potential within 2 weeks prior to initiating Tazorac Cream therapy which should begin during a menstrual period.

Contraception

Females

Based on animal studies, Tazorac Cream may cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Tazorac Cream.

Pediatric Use

The safety and efficacy of Tazorac Cream have not been established in patients with psoriasis under the age of 18 years, or in patients with acne under the age of 12 years.

Geriatric Use

Tazorac Cream for the treatment of acne has not been clinically tested in persons 65 years of age or older.

Of the total number of subjects in clinical trials of Tazorac Cream for plaque psoriasis, 120 were over the age of 65. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Currently there is no other clinical experience on the differences in responses between the elderly and younger subjects, but greater sensitivity of some older individuals cannot be ruled out.