INDICATIONS AND USAGE (To understand fully the indication for this product, please read the entire INDICATIONS AND USAGE section of the labeling.) AVAGE® (tazarotene) Cream 0.1% is indicated as an adjunctive agent for use in the mitigation (palliation) of facial fine wrinkling, facial mottled hyper- and hypopigmentation, and benign facial lentigines in patients who use comprehensive skin care and sunlight avoidance programs. AVAGE® (TAZAROTENE) Cream 0.1% DOES NOT ELIMINATE or PREVENT WRINKLES, REPAIR SUN-DAMAGED SKIN, REVERSE PHOTOAGING, or RESTORE MORE YOUTHFUL or YOUNGER SKIN. AVAGE® (tazarotene) Cream 0.1% has NOT DEMONSTRATED A MITIGATING EFFECT on significant signs of chronic sunlight exposure such as coarse or deep wrinkling, tactile roughness, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, or dermal elastosis. AVAGE® (tazarotene) Cream 0.1% should be used under medical supervision as an adjunct to a comprehensive skin care and sunlight avoidance program that includes the use of effective sunscreens (minimum SPF of 15) and protective clothing. Neither the safety nor the effectiveness of AVAGE® (tazarotene) Cream 0.1% for the prevention or treatment of actinic keratoses, skin neoplasms, or lentigo maligna has been established. Neither the safety nor the efficacy of using AVAGE® (tazarotene) Cream 0.1% daily for greater than 52 weeks has been established, and daily use beyond 52 weeks has not been systematically and histologically investigated in adequate and well-controlled trials (see WARNINGS section).
CONTRAINDICATIONS Retinoids may cause fetal harm when administered to a pregnant woman. 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 (AUC0-24hr) to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits represented 2.4 and 26 times, respectively, the maximum AUC0-24hr in patients treated with 2 mg/cm2 of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. As with other retinoids, when tazarotene was given 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 producing 2.1 and 52 times, respectively, the maximum AUC0-24hr in patients treated with 2 mg/cm2 of tazarotene cream 0.1% over 15% body surface area for fine wrinkling and mottled hyperpigmentation. In a study of the effect of oral tazarotene on fertility and early embryonic development in rats, decreased number of implantation sites, decreased litter size, decreased number of live fetuses, and decreased fetal body weights, all classic developmental effects of retinoids, were observed when female rats were administered 2 mg/kg/day from 15 days before mating through gestation day 7. A low incidence of retinoid-related malformations at that dose were reported to be related to treatment. That dose produced an AUC0-24hr that was 6.7 times the maximum AUC0-24hr in patients treated with 2 mg/cm2 of tazarotene cream 0.1% over 15% body surface area for signs of fine wrinkling and mottled hyperpigmentation. 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 THESE ORALLY TREATED ANIMALS. As a retinoid, tazarotene is a teratogenic substance, and it is not known what level of exposure is required for teratogenicity in humans. However, there may be less systemic exposure in the treatment of the face alone, due to less surface area for application (see CLINICAL PHARMACOLOGY: Pharmacokinetics). There were thirteen reported pregnancies in patients who participated in the clinical trials for topical tazarotene. Nine of the patients were found to have been treated with topical tazarotene, and the other four had been treated with vehicle. One of the patients who was treated with tazarotene cream elected to terminate the pregnancy for non-medical reasons unrelated to treatment. The other eight pregnant women who were inadvertently exposed to topical tazarotene during the clinical trials subsequently delivered apparently healthy babies. As the exact timing and extent of exposure in relation to the gestation times are not certain, the significance of these findings is unknown. AVAGE® Cream is contraindicated in women who are or may become pregnant. 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. Women of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when AVAGE® 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 milli International Units per mL for human chorionic gonadotropin (hCG) should be obtained within 2 weeks prior to AVAGE® Cream therapy, which should begin during a normal menstrual period (See also PRECAUTIONS: Pregnancy: Teratogenic Effects). AVAGE® Cream is contraindicated in individuals who have shown hypersensitivity to any of its components.
ADVERSE REACTIONS In human dermal safety studies, tazarotene 0.05% and 0.1% creams did not induce allergic contact sensitization, phototoxicity, or photoallergy. The most frequent treatment-related adverse reactions (greater than or equal to 5%) reported during the clinical trials with AVAGE® (tazarotene) Cream 0.1% in the treatment of facial fine wrinkling, mottled hypo- and hyperpigmentation, and benign facial lentigines were limited to the skin. Those occurring in greater than 10%, in descending order, included: desquamation, erythema, burning sensation, and dry skin. Events occurring in greater than or equal to 1% to less than or equal to 10% of patients, in descending order included: skin irritation, pruritus, irritant contact dermatitis, stinging, acne, rash, or cheilitis. Common adverse events observed in the clinical trials are presented in the following table: TABLE OF ADVERSE EVENTS SEEN IN CLINICAL TRIALS WITH AVAGE® (TAZAROTENE) CREAM 0.1% Adverse Event AVAGE® N=567 Vehicle N=564 Desquamation 40% 3% Erythema 34% 3% Burning Sensation 26% <1% Dry Skin 16% 3% Irritation Skin 10% 1% Pruritus 10% 1% Irritant Contact Dermatitis 8% 1% Stinging 3% <1% Acne 3% 3% Rash 3% 1% Cheilitis 1% 0% A few patients reported adverse events at Week 0; however, for patients who were treated with AVAGE® the highest number of new reports for each adverse event was at Week 2. When combining data from the two pivotal studies, 5.3% of patients in the tazarotene cream group and 0.9% of patients in the vehicle group discontinued due to adverse events. Overall, 20/567 (3.5%) patients in the AVAGE® (tazarotene) Cream 0.1% group and 16/564 (2.8%) patients in the vehicle group reported adverse events (including edema, irritation, and inflammation) directly related to the eye or eyelid. The majority of these conditions were mild.
Drug Interactions Concomitant dermatologic medications and cosmetics that have a strong drying effect should be avoided. It is also advisable to "rest" a patient's skin until the effects of such preparations subside before use of AVAGE® Cream is begun.