A multicenter, randomized, double-blind trial of tazarotene 0.1% cream in the treatment of photodamage.

BACKGROUND: Previous studies indicate that tazarotene is efficacious in reducing signs of photodamage. Objective We sought to confirm the efficacy and tolerability of tazarotene 0.1% cream in the treatment of facial photodamage. METHODS: A total of 568 patients with at least moderate fine wrinkling or mottled hyperpigmentation applied tazarotene 0.1% cream or vehicle cream to their face once daily for 24 weeks. RESULTS: Tazarotene cream was significantly more effective than vehicle in reducing fine wrinkles, mottled hyperpigmentation, lentigines, irregular depigmentation, apparent pore size, elastosis, tactile roughness, and an overall integrated assessment of photodamage. Significance was achieved as early as week 2 for some parameters and had not plateaued by week 24. The majority of patients reported improvements in their photodamage as early as week 4. Adverse events were predominantly mild or moderate signs or symptoms of skin irritation. CONCLUSION: Once-daily tazarotene 0.1% cream is effective in ameliorating multiple signs of facial photodamage.

Effects of tazarotene 0.1 % cream in the treatment of facial acne vulgaris: pooled results from two multicenter, double-blind, randomized, vehicle-controlled, parallel-group trials.

BACKGROUND: Topical retinoids are one of the most effective classes of topical drugs used to treat acne vulgaris. The effects of the gel formulation of the topical retinoid tazarotene have been widely reported, but few data on the cream formulation are available. OBJECTIVE: The primary aim of the 2 studies reported in this article was to determine the effects of tazarotene 0.1 % cream in patients with facial acne vulgaris. METHODS: Two randomized, double-blind, parallel-group studies were performed. The first was conducted at 14 investigational sites across the United States, and the second took place at 15 sites, with 5 of these providing blood samples for analysis of tazarotenic acid. In both studies, patients aged > or =12 years with facial acne vulgaris were randomized to receive tazarotene or vehicle cream QD for 12 weeks. Lesion counts (noninflammatory, inflammatory, and total) and overall clinical and global assessments were made at weeks 0 (baseline), 4, 8, and 12. Adverse events (AEs) were monitored throughout the study In one of the studies, therapeutic drug monitoring was performed at weeks 4 and 8 in members of the study population who gave consent for blood withdrawal. RESULTS: Eight hundred forty-seven patients were enrolled in the 2 studies (430 males, 417 females; mean age,19 years; age range, 11-52 years [1 patient was entered into the study at age 11 years, in violation of the protocol]). At 12 weeks, the median percentage changes from baseline in all 3 lesion counts were significantly lower with tazarotene than with vehicle (all, P < 0.001), as were the overall clinical and global responses (both, P < 0.001). Treatment-related AEs whose incidence was higher with tazarotene than with vehicle included desquamation, dry skin, erythema, a burning sensation on the skin, and skin irritation (all, P < 0.001) and pruritus (P < 0.01); most (83%-98%) were mild or moderate. Systemic exposure to tazarotenic acid was limited (mean, <0.1 ng/mL) and did not increase with time. CONCLUSIONS: In these 2 studies in adolescent and adult patients with facial acne vulgaris, tazarotene 0.1%cream QD for 12 weeks was effective and well tolerated. Systemic exposure to tazarotenic acid was limited.

Pharmacokinetics of tazarotene cream 0.1% after a single dose and after repeat topical applications at clinical or exaggerated application rates in patients with acne vulgaris or photodamaged skin.

OBJECTIVE: To evaluate the safety and pharmacokinetics of tazarotene cream 0.1% under standard (face only) or exaggerated (15% body surface area, including the face) application conditions after a single dose and after repeat topical applications once daily to patients with acne vulgaris or photodamaged skin. METHODS: Two separate, randomised, single-centre, nonblinded, parallel-group pharmacokinetic studies were conducted. In one study, tazarotene cream 0.1% was applied either to the face of eight female patients with moderate acne or to 15% body surface area of ten female patients with severe acne. In the other study, tazarotene cream 0.1% was applied either to the face (six females, two males) or to 15% body surface area (8 females, 8 males) of patients with photodamaged skin. In both studies, tazarotene cream 0.1% was applied once daily (except on days 1 and 2) for 30 days. Blood was drawn for measurement of plasma concentrations of tazarotenic acid at defined time intervals after application of the cream. Plasma tazarotenic acid concentrations were determined by a validated gas chromatography-tandem mass spectrometry method with a lower limit of quantification of 0.005 microg/L. RESULTS: At exaggerated application rates in patients with acne vulgaris, the maximum average peak concentration (C(max)) and 24-hour area under the concentration-time curve (AUC) values of tazarotenic acid were (mean +/- SD) 1.20 +/- 0.41 microg/L (n = 10) and 17.0 +/- 6.1 microg. h/L (n = 10), respectively, and occurred on day 15. The single highest C(max) was 1.91 microg/L. At standard application rates in patients with acne vulgaris, the maximum average C(max) and AUC values of tazarotenic acid were 0.10 +/- 0.06 microg/L (n = 8) and 1.54 +/- 1.01 microg. h/L (n = 8), respectively, and occurred on day 15. At exaggerated application rates in patients with photodamaged skin, the maximum average C(max) and AUC values of tazarotenic acid were (mean +/- SD) 1.75 +/- 0.53 microg/L (n = 16) and 23.8 +/- 7.0 microg. h/L (n = 16), respectively, and occurred on day 22. The single highest C(max) was 3.43 microg/L on day 29. At standard application rates in patients with photodamaged skin, the maximum average C(max) and AUC values of tazarotenic acid were 0.236 +/- 0.255 microg/L (n = 8) and 2.44 +/- 1.38 microg. h/L (n = 8), respectively, and occurred on day 15. Gender had no influence on the systemic exposure of tazarotenic acid. The most common treatment-related adverse events were signs and symptoms of local irritation, of mild or moderate severity. CONCLUSIONS: The pharmacokinetics of tazarotene cream 0.1% in patients with acne vulgaris or photodamaged skin are similar. The maximum average plasma concentrations of tazarotenic acid after topical application of tazarotene cream 0.1% to the face were less than 0.25 microg/L. The maximum average plasma concentrations of tazarotenic acid following application to an exaggerated body surface area (15%) were less than 1.8 microg/L.

Tazarotene cream in the treatment of psoriasis: Two multicenter, double-blind, randomized, vehicle-controlled studies of the safety and efficacy of tazarotene creams 0.05% and 0.1% applied once daily for 12 weeks.

BACKGROUND: Tazarotene in a gel formulation is widely used in the treatment of psoriasis. OBJECTIVE: To determine the efficacy and safety of tazarotene 0.1% and 0.05% creams in the treatment of psoriasis. METHODS: A total of 1303 patients participated in 2 clinical trials. Patients applied tazarotene creams 0.1% and 0.05% or vehicle once daily to all psoriatic lesions for 12 weeks followed by a 12-week posttreatment period. RESULTS: Both creams were significantly more effective than vehicle on the basis of an overall assessment of psoriasis, a global response to treatment, and reduction in plaque elevation and scaling. Therapeutic effect was maintained during the posttreatment period. Common adverse events included signs and symptoms of skin irritation. CONCLUSION: Tazarotene creams were associated with significant reductions in the severity of the clinical signs of psoriasis and were found to be safe with acceptable tolerability. Tazarotene cream 0.1% was generally more effective, although slightly less well tolerated, than the 0.05% cream.

Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial.

OBJECTIVE: To determine the efficacy and safety of 0.1% tazarotene cream for the treatment of photodamage. DESIGN: A 24-week multicenter, double-blind, randomized, vehicle-controlled intervention study followed by a 28-week open-label extension. SETTING: Ambulatory patients in private and institutional practice. PATIENTS: Of 563 patients with facial photodamage, 91% and 86% completed the double-blind and open-label phases, respectively. In the double-blind phase, 20 of 283 tazarotene-treated patients and 1 of 280 vehicle-treated patients discontinued treatment owing to adverse events. INTERVENTION: Once-daily application of 0.1% tazarotene cream or nonmedicated vehicle cream to the face for 24 weeks. Then, all continuing patients received treatment with 0.1% tazarotene cream for another 28 weeks. MAIN OUTCOME MEASURES: Primarily, fine wrinkling and mottled hyperpigmentation. Also, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, telangiectasia, actinic keratoses, overall integrated assessment of photodamage, global response to treatment, patients' overall assessment of photodamage, and plasma levels of tazarotenic acid. RESULTS: Compared with the vehicle, at week 24 tazarotene resulted in a significantly greater incidence of patients achieving treatment success (>or=50% global improvement) and at least a 1-grade improvement in fine wrinkling, mottled hyperpigmentation, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, and the overall integrated assessment of photodamage (P<.01). Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52. Plasma tazarotenic acid concentrations did not exceed 0.71 ng/mL. CONCLUSIONS: Once-daily applications of 0.1% tazarotene cream significantly reduced multiple signs of photodamage. Plasma levels of tazarotenic acid remained below those of endogenous retinoids.