Tazorac Cream

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Embryofetal 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].

There were thirteen reported pregnancies in subjects who participated in the clinical trials for topical tazarotene. Nine of the subjects were found to have been treated with topical tazarotene, and the other four had been treated with vehicle. One of the subjects 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 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.

Females of Child-bearing Potential

Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when TAZORAC® Cream is used. The possibility that a female of child-bearing potential is pregnant at the time of institution of therapy should be considered.

A negative result for pregnancy test should be obtained within 2 weeks prior to TAZORAC® Cream therapy. TAZORAC® Cream therapy should begin during a menstrual period [see Use in Specific Populations].

Local Irritation

Application of TAZORAC® Cream may cause excessive irritation in the skin of certain sensitive individuals. 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. Frequency of application should be closely monitored by careful observation of the clinical therapeutic response and skin tolerance. Therapy can be resumed, or the drug concentration or frequency of application can be increased as the patient becomes able to tolerate treatment.

Concomitant topical 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 TAZORAC® Cream is begun.

TAZORAC® Cream, should not be used on eczematous skin, as it may cause severe irritation.

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

Photosensitivity And Risk For Sunburn

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® Cream. Patients must be warned to use sunscreens (minimum SPF of 15) and protective clothing when using TAZORAC® Cream. Patients with sunburn should be advised not to use TAZORAC® 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® Cream.

TAZORAC® 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.

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION).

Advise the patient of the following:

  • Fetal risk associated with TAZORAC® Cream for females of childbearing potential. Advise patients to use an effective method of contraception during treatment to avoid pregnancy. Advise the patient to stop medication if she becomes pregnant and call her doctor [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and Use In Specific Populations].
  • For the patient with psoriasis, apply TAZORAC® Cream only to psoriasis skin lesions, avoiding uninvolved skin.
  • If undue irritation (redness, peeling, or discomfort) occurs, reduce frequency of application or temporarily interrupt treatment. Treatment may be resumed once irritation subsides [see DOSAGE AND ADMINSTRATION].
  • Moisturizers may be used as frequently as desired.
  • Patients with psoriasis may use a cream or lotion to soften or moisten skin at least 1 hour before applying TAZORAC® Cream.
  • Avoid exposure of the treated areas to either natural or artificial sunlight, including tanning beds and sun lamps. Use sunscreen and protective clothing if exposure to sunlight is unavoidable when using TAZORAC® Cream.
  • Avoid contact with the eyes. If TAZORAC® Cream gets in or near their eyes, rinse thoroughly with water.
  • Not for ophthalmic, oral, or intravaginal use.
  • Wash their hands after applying TAZORAC® Cream.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

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/cm²over a 35% body surface area in a controlled pharmacokinetic study. This estimated systemic exposure in rats was 2 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% cream at 2 mg/cm² over a 15% body surface area.

A long-term topical application study of up to 0.1% of tazarotene in a gel formulation in mice terminated at 88 weeks showed that dose levels of 0.05, 0.125, 0.25, and 1 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. Systemic exposures at the highest dose was 3.9 times that seen in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over a 35% body surface area in a controlled pharmacokinetic study, and 13 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 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.

Mutagenesis

Tazarotene was found to be non-mutagenic in the Ames assay and did not produce structural chromosomal aberrations in a human lymphocyte assay. Tazarotene was non-mutagenic in the CHO/HGPRT mammalian cell forward gene mutation assay and was non-clastogenic in the in vivo mouse micronucleus test.

Impairment of Fertility

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 a 35% body surface area in a controlled pharmacokinetic study, and 2 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 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 mg/kg/day tazarotene. That dose produced a systemic exposure that was 1.9 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over a 35% body surface area, and 6.3 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 15% body surface area.

No impairment of mating performance or fertility was observed in female rats treated for 15 days prior to mating and continuing through gestation day 7 with oral doses up to 2 mg/kg/day of tazarotene. However, there was a significant decrease in the number of estrous stages and an increase in developmental effects at that dose [see Use in Specific Populations]. That dose produced a systemic exposure that was 3.4 times that observed in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over a 35% body surface area and 11 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 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 a 35% body surface area, and 2 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 15% body surface area.

Use In Specific Populations

Pregnancy

Pregnancy Category X

[see CONTRAINDICATIONS].

There are no adequate and well-controlled studies with TAZORAC® Cream in pregnant women. TAZORAC® Cream is contraindicated in women who are or may become pregnant. Females of child-bearing potential should be warned of the potential risk and use adequate birth-control measures when TAZORAC® Cream is used. The possibility that a female of child-bearing potential is pregnant at the time of institution of therapy should be considered. A negative result for pregnancy test should be obtained within 2 weeks prior to TAZORAC® Cream therapy, which should begin during a menstrual period. Systemic exposure to tazarotenic acid is dependent upon the extent of the body surface area treated. In subjects 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].

In rats, a tazarotene gel, 0.05% formulation, 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 to tazarotenic acid at topical doses of 0.25 mg/kg/day tazarotene in a gel formulation in rats and rabbits represented 1.2 and 13 times, respectively, that in a psoriatic patient treated with 0.1% tazarotene cream at 2 mg/cm² over a 35% body surface area in a controlled pharmacokinetic study, and 4 and 44 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 15% body surface area.

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 1.1 and 26 times, respectively, the systemic exposure seen in a psoriatic patient treated topically with tazarotene cream, 0.1% at 2 mg/cm² over a 35% body surface area in a controlled pharmacokinetic study and 3.5 and 85 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 15% body surface area.

In female rats orally administered 2 mg/kg/day of tazarotene from 15 days before mating through gestation day 7, a number of 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 at that dose was observed. The dose produced a systemic exposure 3.4 times that observed in a psoriatic patient treated with tazarotene cream, 0.1% at 2 mg/cm² over a 35% body surface area and 11 times the maximum systemic exposure in acne patients treated with tazarotene cream, 0.1% at 2 mg/cm² over a 15% body surface area.

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. The safe use of TAZORAC® Cream during lactation has not been established. A decision should be made whether to discontinue breast-feeding or to discontinue TAZORAC® Cream therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Pediatric Use

The safety and efficacy of tazarotene 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

TAZORAC® Cream for the treatment of acne has not been clinically tested in persons 65 years of age or older.

Of the total number of subjects in clinical trials of TAZORAC® Cream for plaque psoriasis, 120 were over the age of 65. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. 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.

Last reviewed on RxList: 1/22/2014
This monograph has been modified to include the generic and brand name in many instances.

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