Pregnancy Category X

See CONTRAINDICATIONS section. Women of childbearing potential should be warned of the potential risk and use adequate birth-control measures when TAZORAC® Gel is used. The possibility that a woman of childbearing 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 TAZORAC® Gel therapy, which should begin during a normal menstrual period.

General

TAZORAC® Gel should only be applied to the affected areas. For external use only. Avoid contact with eyes, eyelids, and mouth. If contact with eyes occurs, rinse thoroughly with water. The safety of use of TAZORAC® Gel over more than 20% of body surface area has not been established in psoriasis or acne.

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 TAZORAC® Gel. Patients must be warned to use sunscreens (minimum SPF of 15) and protective clothing when using TAZORAC® Gel. Patients with sunburn should be advised not to use TAZORAC® Gel 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 TAZORAC® Gel and ensure that the precautions outlined in the Information for Patients subsection are observed.

TAZORAC® Gel 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. Alternatively, patients with psoriasis who are being treated with the 0.1% concentration can be switched to the lower concentration.

Weather extremes, such as wind or cold, may be more irritating to patients using TAZORAC® Gel.

Information for Patients

See attached Patient Package Insert.

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 (AUC_de) in the rat equivalent to 0.32 times the AUC_0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 0.38 times the maximum AUC_0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) body surface area.

In evaluation of photo cocarcinogenicity, 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 2.0 times the AUC_0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 2.5 times the maximum AUC_0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) body surface area.

Tazarotene was found to be nonmutagenic in the Ames assay using Salmonella and E. coli and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was also nonmutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was nonclastogenic 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 up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure (AUCde) in the rat would be equivalent to 0.31 times the AUC_0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 0.38 times the maximum AUC_0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) 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 1.0 mg/kg/day tazarotene, which produced an AUC_de that was 0.95 times the AUC_0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 1.2 times the maximum AUC_0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) 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 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 2.0 mg/kg/day (see CONTRAINDICATIONS). This dose produced an AUC_0-24h which was 1.7 times that observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 2.1 times the maximum AUC_0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) 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 systemic drug exposure (AUC_de) in the rat would be equivalent to 0.31 times the AUC_0-24h observed in psoriatic patients treated with 2 mg/cm² of tazarotene gel 0.1% (extrapolated for topical application over 20% body surface area), and 0.38 times the maximum AUC_0-24h in acne patients treated with 2 mg/cm² of tazarotene gel 0.1% over 15% (targeted) body surface area.

Pregnancy

Teratogenic Effects: Pregnancy Category X: See CONTRAINDICATIONS section. Women of childbearing potential should use adequate birth-control measures when TAZORAC® Gel is used. The possibility that a woman of childbearing 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 TAZORAC® Gel therapy, which should begin during a normal menstrual period. There are no adequate, well-controlled studies in pregnant women. Although there may be less systemic exposure in the treatment of acne of the face alone due to less surface area for application, tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans (see CLINICAL PHARMACOLOGY: Pharmacokinetics).

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. Caution should be exercised when tazarotene is administered to a nursing woman.

Pediatric Use

The safety and efficacy of tazarotene have not been established in pediatric patients under the age of 12 years.

Geriatric Use

Of the total number of subjects in clinical studies of tazarotene gels, 0.05% and 0.1% for plaque psoriasis, 163 were over the age of 65. Subjects over 65 years of age experienced more adverse events and lower treatment success rates after 12 weeks of use of TAZORAC® Gel compared with those 65 years of age and younger. Currently there is no other reliable clinical experience on the differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals can not be ruled out. Tazarotene gel for the treatment of acne has not been clinically evaluated in persons over the age of 65.

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