Retinoid

Tazarotene

Approved 3 Apr 2017TopicalCream

The FDA lists this product in 13 strengths and forms.

Indications

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. Tazarotene cream, 0.1% is a retinoid 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.

( 1 ) Limitations of Use: Does not eliminate or prevent wrinkles or restore more youthful skin. ( 1 ) Does not repair sun damaged skin or reverse photoaging. ( 1 ) Safety and effectiveness for the prevention or treatment of actinic keratoses, skin neoplasms, or lentigo maligna have not been established. ( 1 , 5.4 ) Limitations of Use: Tazarotene cream does not eliminate or prevent wrinkles or restore more youthful skin.

Tazarotene cream does not reverse photoaging or repair sun damaged skin; tazarotene cream does not mitigate coarse or deep wrinkling, tactile roughness, telangiectasia, skin laxity, keratinocytic atypia, melanocytic atypia, or dermal elastosis. The safety and the effectiveness of tazarotene cream for the prevention or treatment of actinic keratoses, skin neoplasms, or lentigo maligna have not been established.

Contraindications

Tazarotene cream is contraindicated in: Pregnancy. Retinoids may cause fetal harm when administered to a pregnant female [see Warnings and Precautions (5.1) , Use in Specific Populations (8.1 , 8.3) ] . Individuals who have known hypersensitivity to any of its components. [see Warnings and Precautions (5.2) ]. Pregnancy. ( 4 , 8.1 ) Known Hypersensitivity. ( 4 )

Warnings and precautions

Embryo-Fetal Toxicity: May cause fetal harm when administered to a pregnant woman. Obtain a pregnancy test in females of reproductive potential within 2 weeks prior to initiating treatment. Advise females of reproductive potential to use effective contraception. ( 5.1 ) Local Irritation: Some individuals may experience excessive pruritus, burning, skin redness, or peeling. If these adverse reactions occur, discontinue tazarotene cream until the integrity of the skin has been restored or reduce dosing interval.

Avoid using tazarotene cream on eczematous skin, as such use may cause severe irritation. ( 5.2 ) Photosensitivity and Risk of Sunburn: Avoid exposure to sunlight, sunlamps, and weather extremes. Wear sunscreen daily. Avoid using tazarotene cream if the patient is also taking drugs known to be photosensitizers. ( 5.3 ) Lentigo Maligna: Carefully assess facial pigmented lesions of concern before application of tazarotene cream.

At a glance

Brand name: Tazarotene
Pharmacologic class: Retinoid
Route: Topical
Dosage form: Cream
Applicant: Sun Pharma Canada
Status: Prescription
FDA approval: 3 Apr 2017
Application: ANDA208258-001

Indications

Contraindications

Warnings and precautions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

on data from animal reproduction studies, retinoid pharmacology, and the potential for systemic absorption, tazarotene 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 tazarotene cream during pregnancy; therefore, tazarotene 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 tazarotene 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 to 4% and 15 to 20%, respectively. Data Animal Data In rats, a tazarotene 0.05% gel 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/cm 2 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 the 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%.

Adverse reactions

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) ] Most common adverse events (occurring in ≥10% of patients) are desquamation, erythema, burning sensation, dry skin, skin irritation, and pruritus. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Taro Pharmaceuticals U.S.A., Inc. at 1-866-923-4914 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1Clinical 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. The most frequent adverse reactions reported with tazarotene cream, 0.1% that occurred in greater than 10% of subjects, included desquamation, erythema, burning sensation, and dry skin (in descending order).

Reactions that occurred in 1 to 10% of subjects, included skin irritation, pruritus, irritant contact dermatitis, stinging, rash, and cheilitis (in descending order). Common adverse events that occurred at a rate of at least 1% and at a higher rate in the tazarotene cream group than in the vehicle group in the clinical trials are presented in the following table. TABLE OF ADVERSE EVENTS SEEN IN 24-WEEK CLINICAL TRIALS WITH TAZAROTENE CREAM 0.1% Adverse Event Tazarotene Cream, 0.1% 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% Rash 3% 1% Cheilitis 1% 0% A few subjects reported adverse events at Week 0; however, for patients who were treated with tazarotene cream, the highest number of new reports for each adverse event was at Week 2.

When combining data from the two trials, 5.3% of subjects in the tazarotene cream group and 0.9% of subjects in the vehicle group discontinued because of adverse events. Overall, 20/567 (3.5%) subjects in the tazarotene cream group and 16/564 (2.8%) subjects 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.

6.2Postmarketing 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.

Tazarotene

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

Tazarotene

Indications

Contraindications

Warnings and precautions

At a glance

Two medicines in one question?

5.1Embryofetal Toxicity Based

5.2Local Irritation and Hypersensitivity Reactions

5.3Photosensitivity and Risk of Sunburn Because

5.4Lentigo Maligna

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information