Retinoid

Avage

Approved 29 Sept 2000TopicalCream

Indications

TAZORAC ® Cream 0.05% and 0.1% is a retinoid indicated for the topical treatment of plaque psoriasis. ( 1.1 ) TAZORAC Cream 0.1% is indicated for the topical treatment of acne vulgaris. ( 1.2 )

1.1Plaque Psoriasis

TAZORAC ® (tazarotene) Cream, 0.05% and 0.1% are indicated for the topical treatment of patients with plaque psoriasis.

1.2Acne Vulgaris TAZORAC (tazarotene) Cream,

0.1% is also indicated for the topical treatment of patients with acne vulgaris.

Contraindications

TAZORAC 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 ) Hypersensitivity ( 4 )

Warnings and precautions

Embryofetal Toxicity: TAZORAC Cream contains tazarotene, which is a teratogenic substance. TAZORAC Cream is contraindicated in pregnancy. Females of child-bearing potential should have a negative pregnancy test within 2 weeks prior to initiating treatment and use an effective method of contraception during treatment. ( 5.1 ) Local Irritation: Some individuals may experience excessive pruritus, burning, skin redness or peeling.

If these effects occur, discontinue until the integrity of the skin has been restored, or reduce dosing interval, or in the case of psoriasis, may switch to the lower concentration. TAZORAC Cream should not be used on eczematous skin, as it may cause severe irritation. ( 5.2 ) Photosensitivity and Risk for Sunburn: Avoid exposure to sunlight, sunlamps, and weather extremes. Wear sunscreen daily. TAZORAC Cream should be administered with caution if the patient is also taking drugs known to be photosensitizers.

( 5.3 )

5.1Embryofetal Toxicity

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 orally treated animals. 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 ( 12.3 )] .

At a glance

Brand name: Avage
Active substance: tazarotene
Pharmacologic class: Retinoid
Route: Topical
Dosage form: Cream
Applicant: Almirall
Status: Prescription
FDA approval: 29 Sept 2000
Application: NDA021184-003

Indications

TAZORAC ® Cream 0.05% and 0.1% is a retinoid indicated for the topical treatment of plaque psoriasis. ( 1.1 ) TAZORAC Cream 0.1% is indicated for the topical treatment of acne vulgaris. ( 1.2 )

1.1Plaque Psoriasis

TAZORAC ® (tazarotene) Cream, 0.05% and 0.1% are indicated for the topical treatment of patients with plaque psoriasis.

1.2Acne Vulgaris TAZORAC (tazarotene) Cream,

0.1% is also indicated for the topical treatment of patients with acne vulgaris.

Contraindications

Warnings and precautions

( 5.3 )

5.1Embryofetal Toxicity

Pregnancy and breastfeeding

8.1Pregnancy 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/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 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 )] Plaque psoriasis: Most common adverse reactions occurring in 10 to 23% of patients are pruritus, erythema, and burning. ( 6.1 ) Acne Vulgaris: Most common adverse reactions occurring in 10 to 30% of patients are desquamation, dry skin, erythema, and burning sensation.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Allergan at 1-800-678-1605 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. 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.

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.

Avage

Indications

1.1Plaque Psoriasis

1.2Acne Vulgaris TAZORAC (tazarotene) Cream,

Contraindications

Warnings and precautions

5.1Embryofetal Toxicity

At a glance

Two medicines in one question?

Avage

Indications

1.1Plaque Psoriasis

1.2Acne Vulgaris TAZORAC (tazarotene) Cream,

Contraindications

Warnings and precautions

5.1Embryofetal Toxicity

At a glance

Two medicines in one question?

5.2Local Irritation and Hypersensitivity Reactions

5.3Photosensitivity and Risk for Sunburn Because

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary Based

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information