Tazarotene (Tazorac(R)) is a topical retinoid indicated for the treatment of plaque psoriasis. When used as monotherapy, topical tazarotene was effective at controlling signs and symptoms of plaque psoriasis, and had significantly lower post-treatment relapse rates than fluocinonide cream. The most common adverse events associated with tazarotene therapy are skin-associated events, such as pruritus, burning, and erythema. Combination therapy with tazarotene and mid-to-high potency topical corticosteroids generally resulted in a greater therapeutic effect than that with tazarotene alone, reduced the irritancy of tazarotene, and decreased the risk of post-treatment disease flare seen with corticosteroids; it also has the potential to reduce the degree of skin atrophy associated with topical corticosteroids. The combination of tazarotene and phototherapy also appears promising. Thus, tazarotene, as monotherapy or in combination with topical corticosteroids or UV light therapy, represents a useful treatment option in patients with plaque psoriasis. The active form of tazarotene, tazarotenic acid, has selective affinity for the retinoic acid receptors -gamma and -beta. The exact molecular mechanism of action of topical tazarotene in the treatment of psoriasis has not been elucidated. However, the drug appears to modulate abnormal differentiation of keratinocytes, increased keratinocyte proliferation, and inflammation. Topical tazarotene is metabolized, in part, to tazarotenic acid by esterases in the skin. In animal studies, oral tazarotene was teratogenic. However, the penetration across the skin and systemic absorption of topical tazarotene are limited. In patients with psoriasis, the bioavailability (relative to an intravenous dose) of tazarotene from topical tazarotene 0.05% or 0.1% gel varied over 12 weeks but ranged from <1% to 5.3%. In 12-week clinical trials of topical tazarotene, 1-3% of patients with plaque psoriasis had detectable plasma levels of tazarotene and 47-69% of patients had low but detectable levels of tazarotenic acid. Both tazarotene and tazarotenic acid are metabolized to sulfoxides, sulfones, and other polar metabolites. In healthy volunteers and patients with psoriasis who applied topical tazarotene, the half-life of tazarotenic acid was approximate to 18 hours. Tazarotene and its metabolites are eliminated by urinary and fecal routes. Monotherapy Once-daily topical tazarotene 0.05% or 0.1% cream or gel effectively controlled signs and symptoms of plaque psoriasis in adult patients in randomized, single- or double-blind studies of 12 weeks' duration. Clinical success (mild, minimal, or no psoriasis) rates were significantly higher for patients with plaque psoriasis receiving tazarotene 0.05% or 0.1% cream than for those receiving vehicle cream in two trials. In these trials, and two trials of tazarotene 0.05% or 0.1% gel, topical tazarotene was significantly more effective than vehicle in terms of global treatment success (>= 50% improvement in overall psoriasis from baseline) rates, reduction in plaque elevation and, generally, reduction in scaling scores. Using the same endpoints, tazarotene gel had similar efficacy to twice-daily fluocinonide 0.05% cream in one trial. In two unpublished trials, once-daily tazarotene gel 0.05% or 0.4% was generally significantly less effective than twice-daily fluocinonide 0.05% cream or calcipotriol 0.005% ointment. Erythema was generally not as responsive to tazarotene treatment, and fluocinonide cream reduced erythema scores from baseline significantly more than tazarotene gel. For many patients, the efficacy of tazarotene cream or gel was maintained over a 12-week post-treatment period. Moreover, significantly more fluocinonide than tazarotene 0.1% gel recipients experienced relapse of psoriasis by the end of the 12-week, post-treatment phase of one trial. Combination Therapy The addition of some, but not all, mid-to-high-potency topical corticosteroids to tazarotene 0.1% gel monotherapy significantly improved global success rates, and afforded greater reductions in plaque elevation, scaling, and erythema scores in several 12-week trials in patients with stable plaque psoriasis. Treatment with tazarotene 0.1% gel plus clobetasol propionate 0.05% ointment (applied on alternate days, with a total of five treatments per week) was significantly more effective than that with vehicle get (at all timepoints) or tazarotene plus vehicle gel (at some timepoints) in the 20-week, double-blind, maintenance phase of a trial in patients with plaque psoriasis. At the end of 12 weeks, treatment with once-daily tazarotene 0.1% gel plus once-daily mometasone furoate 0.1% cream was significantly more effective than twice-daily mometasone furoate cream in terms of reduction in scaling scores, but similar in terms of reduction in plaque elevation, erythema, and pruritus scores. However, at the end of the 4-week, post-treatment phase, patients who had received tazarotene plus mometasone furoate had significantly better results for global treatment success rates, plaque elevation, and scaling than those who had received mometasone furoate monotherapy. Additionally, in this phase significantly more mometasone furoate monotherapy recipients discontinued the trial because of disease flare. After treatment for 8 weeks, there were no significant differences between tazarotene 0.1% gel plus mometasone furoate 0.1% cream (both once-daily) and twice-daily calcipotriol 0.005% ointment in the proportion of patients achieving a >= 75% global improvement in psoriasis, or in the mean reductions from baseline in plaque elevation, scaling, or erythema scores, or the percentage of body surface area affected by psoriasis. The most common adverse events associated with tazarotene gel or cream monotherapy in patients with plaque psoriasis were mild-to-moderate, skin-associated events, such as pruritus, burning, and erythema. In trials of tazarotene gel monotherapy, 9-20% of patients discontinued treatment because of adverse events. When tazarotene gel was applied in combination with a topical corticosteroid or phototherapy, the most common adverse events were generally mild-to-moderate local irritation, pruritus, erythema, and burning sensation. Although statistical analyses were generally not reported, it was noted that the addition of a corticosteroid to tazarotene therapy generally reduced the incidence of adverse events, compared with tazarotene monotherapy.
