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 TAZORAC® (tazarotene cream) 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 TAZORAC® (tazarotene cream) Cream therapy, which should begin during a normal menstrual period.

General

TAZORAC® (tazarotene cream) Cream should be applied only to the affected areas. For external use only. Avoid contact with eyes, eyelids, 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 TAZORAC® (tazarotene cream) Cream. Patients must be warned to use sunscreens (minimum SPF of 15) and protective clothing when using TAZORAC® (tazarotene cream) Cream. Patients with sunburn should be advised not to use TAZORAC® (tazarotene cream) 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 TAZORAC® (tazarotene cream) Cream and ensure that the precautions outlined in the Information for Patients subsection are observed.

TAZORAC® (tazarotene cream) 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. 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® (tazarotene cream) Cream.

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 in the rat equivalent to 0.6 times that seen in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/kg/cm² over 35% body surface area in a controlled pharmacokinetic study. This estimated systemic exposure in rats was 2.0 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area.

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 3.9 times that (AUC0-24h) seen in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over 35% body surface area in a controlled pharmacokinetic study, and 13 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15 % body surface area.

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 up to 0.125 mg/kg/day. Based on data from another study, the systemic drug exposure in the rat would be equivalent to 0.6 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over 35% body surface area in a controlled pharmacokinetic study, and 2.0 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene cream 0.1% over 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 1.0 mg/kg/day tazarotene. That dose produced an AUC0-24h that was 1.9 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over 35% body surface area, and 6.3 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene cream 0.1% over 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 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 3.4 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over 35% body surface area and 11 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene cream 0.1% over 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 systemic drug exposure in the rat would be equivalent to 0.6 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over 35% body surface area, and 2.0 times the maximum AUC0-24h in acne patients treated with 2 mg/cm² of tazarotene cream 0.1% over 15% body surface area.

Pregnancy: Teratogenic Effects: Pregnancy Category X

See CONTRAINDICATIONS section.Women of child-bearing potential should use adequate birth-control measures when TAZORAC® (tazarotene cream) Cream 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® (tazarotene cream) Cream therapy, which should begin during a normal menstrual period. There are no adequate and 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 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 with psoriasis under the age of 18 years or in patients with acne under the age of 12 years.

Geriatric Use: Of the total number of patients in clinical studies of tazarotene cream for plaque psoriasis, 120 were over the age of 65. No overall differences in safety or effectiveness were observed between these patients and younger patients. Currently there is no other clinical experience on the differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Tazarotene cream for the treatment of acne has not been clinically tested in persons 65 years of age or older.

Last reviewed on RxList: 6/24/2008
This monograph has been modified to include the generic and brand name in many instances.