Tazorac cream

Following application, the drug undergoes esterase hydrolysis to its primary active metabolite, “tazarotenic acid” (the only metabolite of tazarotene known to have retinoid activity), and oxidative metabolism to inactive sulfoxide and sulfone derivatives. Little parent compound can be detected in the plasma. “Tazarotenic acid” is highly bound to plasma proteins (>99%). The half-life of “tazarotenic acid” following topical application of tazarotene is similar in normal and psoriatic subjects, approximately 18 hours.

During clinical trials for the treatment of psoriasis with 0.05 and 0.1% tazarotene creams, plasma concentrations of tazarotene and “tazarotenic acid” were monitored. In 139 patients tested, quantifiable tazarotene was detected in only 3 patients, with the highest concentration at 0.09 ng/mL. The majority of plasma samples were quantitated at less than the limit of the assay for “tazarotenic acid” (<0.1 ng/mL). Only 6 patients had plasma “tazarotenic acid” concentrations greater than 1 ng/mL, the highest of which was 2.4 ng/mL.

In a Phase 3 clinical trial, tazarotene 0.1% cream was applied once daily to each patient with facial acne vulgaris for 12 weeks. The mean ±SD values of plasma tazarotenic acid at weeks 4 and 8 were 0.078±0.073 ng/mL (N=47) and 0.052±0.037 ng/mL (N=42), respectively. The highest observed individual plasma tazarotenic acid concentration was 0.41 ng/mL at week 4 from a female patient. The magnitude of plasma tazarotenic acid concentrations appears to be independent of gender, age, and body weight.

In a phase 3 study tazarotene cream 0.1% was applied once daily for 24 weeks under clinical conditions (double-blind period) to patients with photodamaged skin. The mean plasma tazarotenic acid concentrations following topical treatment with tazarotene cream 0.1% were 0.092±0.073 ng/mL (week 2; N=55), 0.108±0.081 ng/mL (week 12; N=54), and 0.108±0.098 ng/mL (week 24; N=50). The single highest observed tazarotenic acid concentration throughout the 24-week study was 0.423 ng/mL (observed at week 24). Systemic availability of tazarotenic acid was minimal and remained steady following once daily application of tazarotene cream 0.1% to the faces of patients with photodamaged facial skin for up to 24 weeks. The plasma tazarotenic concentrations observed are much lower than the endogenous concentrations of retinoids which are naturally present in plasma: all-trans retinoic acid has been reported to be present at concentrations of 1.32±0.46 ng/mL, 13-cis retinoic acid at 1.63±0.85 ng/mL, and 13-cis-4-oxo retinoic acid at 3.68±0.99 ng/mL.

Results from the well-controlled clinical pharmacokinetic and therapeutic drug monitoring studies using tazarotene cream in the treatment of plaque psoriasis, acne vulgaris, and photodamaged skin demonstrated limited systemic exposure after daily topical applications of tazarotene cream.

Concomitant dermatologic medications and cosmetics that have a strong drying effect or high amounts of alcohol, astringents, spices, lime peel, medicated soaps or shampoos, permanent wave solution, or other products that may irritate the skin should be avoided. It is also advisable to “rest” a patient's skin until the effects of such preparations subside before use of tazarotene cream 0.05 or 0.1% begins.

Tazarotene 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.

After single topical doses of ¹⁴C-tazarotene gel to the skin of lactating rats, secretion of radioactivity at very low levels was detected in milk, suggesting that there would be limited transfer of drug-related material to the offspring via milk. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when tazarotene is administered to a nursing woman.

The safety and efficacy of tazarotene have not been established in pediatric patients under the age of 12 years.

For external use only.

Because of heightened susceptibility to sunlight, excessive exposure to ultraviolet light, either natural source (sunlight) or artificial (ultraviolet lamps) should be minimized or avoided unless deemed medically necessary. Patients who have considerable sun exposure due to occupation and those inherently sensitive to the sun should exercise particular caution when using tazarotene. Sunscreen (minimum SPF of 15) and protective clothing should be used when using tazarotene and exposure to sunlight cannot be avoided.

Patients with sunburn should be advised not to use tazarotene until fully recovered.

Weather extremes such as wind or cold may be more irritating to patients using tazarotene.

The treatment area should not be covered with dressings or bandages.

Application to normal skin should be avoided in the treatment of psoriasis. In acne the whole of the skin prone to acne should be treated. In the treatment of photodamaged skin, the entire face should be treated.

Each g of white to slightly off-white emollient cream contains: tazarotene 0.05% (w/w). Nonmedicinal ingredients: benzyl alcohol (as preservative), Carbomer 934P, Carbomer 1342, edetate disodium, medium chain triglycerides, mineral oil, purified water, sodium thiosulfate, sodium hydroxide (to adjust the pH) and sorbitan monooleate. Collapsible aluminum tubes of 30 g. Physician's sample sizes of 3.5 g.

Each g of white to slightly off-white emollient cream contains: tazarotene 0.1% (w/w). Nonmedicinal ingredients: benzyl alcohol (as preservative), Carbomer 934P, Carbomer 1342, edetate disodium, medium chain triglycerides, mineral oil, purified water, sodium thiosulfate, sodium hydroxide (to adjust the pH) and sorbitan monooleate. Collapsible aluminum tubes of 30 g. Physician's sample sizes of 3.5 g.

Store at room temperature (15 to 25°C).

Tazarotene cream 0.1% in the treatment of photodamaged (sun-damaged) skin should be used under medical supervision as part of a comprehensive skin protection programme, including use of sunscreen products and protective clothing.

Retinoids can cause severe irritation of eczematous skin and should therefore be used with the utmost caution in patients with this condition.

Excessive use of tazarotene cream 0.05 and 0.1% should be avoided. Keep away from the eyes, nose, mouth, and other mucous membranes. When using tazarotene for the treatment of photodamaged skin, care should be used when treating wrinkles around the eyes (Crows's feet) and mouth. In the event of contact with the eye, flush with cold water. Tazarotene should not be applied to severely inflamed skin or open lesions.

In some patients, temporary skin irritation may occur, especially during the early weeks of treatment. If excessive pruritus, burning, skin redness or peeling occur, the medication should either be discontinued until the integrity of the skin is restored, or the dosing should be adjusted to a level or interval the patient can tolerate. Efficacy at reduced frequency of application has not been established.

Topical tazarotene should be used by a female of childbearing age only after contraceptive counselling. It is recommended that topical tazarotene should not be used by pregnant women.

There have been no adequate and well-controlled prospective studies on the use of tazarotene or other topical retinoids in pregnant women. There have been rare reports of birth defects among babies born to women exposed to topical retinoids during pregnancy, although a causal relationship has not been determined. A retrospective study of mothers exposed to topical tretinoin during the first trimester of pregnancy found no increase in the incidence of birth defects.

As with all retinoids oral tazarotene is teratogenic.

Tazarotene 0.05% gel, administered topically during gestation days 6 through 17 in rats and days 6 through 18 in rabbits, has been shown to be nonteratogenic and nonfetotoxic at maximum tolerated doses of 0.25 mg/kg/day. However, at these doses, slightly reduced fetal body weights and reduced skeletal ossification occurred in rats. These changes may be considered variants of normal development and were usually corrected after weaning. Multiple topical dosing to pregnant rats at 0.2 mg/kg daily resulted in undetectable radioactivity in the fetus. These findings indicate very little drug exposure to the rat fetus via placental transfer after topical treatment with tazarotene.

Excessive topical use of tazarotene creams 0.05 and 0.1% may lead to marked redness, peeling, or discomfort (see Warnings). Inadvertent oral ingestion of tazarotene may lead to the same adverse effects as those associated with excessive oral intake of vitamin A including teratogenesis in women of child-bearing age.

If accidental oral ingestion occurs, the patient should be monitored, and appropriate supportive measures should be administered as necessary, including pregnancy testing in women of childbearing age.