DRUGS FOR PSORIASIS
Acitretin (Soriatane), a metabolite of the aromatic retinoid etreti-nate, is quite effective in the treatment of psoriasis, especially pustular forms. It is given orally at a dosage of 25–50 mg/d. Adverse effects attributable to acitretin therapy are similar to those seen with isotretinoin and resemble hypervitaminosis A. Elevations in cholesterol and triglycerides may be noted with acitretin, and hepatotoxicity with liver enzyme elevations has been reported. Acitretin is more teratogenic than isotretinoin in the animal spe-cies studied to date, which is of special concern in view of the drug’s prolonged elimination time (more than 3 months) after chronic administration. In cases where etretinate is formed by concomitant administration of acitretin and ethanol, etretinate may be found in plasma and subcutaneous fat for many years.
Acitretin must not be used by women who are pregnant or may become pregnant while undergoing treatment or at any time for at least 3 years after treatment is discontinued. Ethanol must be strictly avoided during treatment with acitretin and for 2 months after discontinuing therapy. Patients must not donate blood dur-ing treatment and for 3 years after acitretin is stopped.
Tazarotene (Tazorac) is a topical acetylenic retinoid prodrug that is hydrolyzed to its active form by an esterase. The active metabo-lite, tazarotenic acid, binds to retinoic acid receptors, resulting in modified gene expression. The precise mechanism of action in psoriasis is unknown but may relate to both anti-inflammatory and antiproliferative actions. Tazarotene is absorbed percutane-ously, and teratogenic systemic concentrations may be achieved if applied to more than 20% of total body surface area. Women of childbearing potential must therefore be advised of the risk prior to initiating therapy, and adequate birth control measures must be utilized while on therapy.
Treatment of psoriasis should be limited to once-daily application of either 0.05% or 0.1% gel not to exceed 20% of total body surface area. Adverse local effects include a burning or stinging sensation (sensory irritation) and peeling, erythema, and localized edema of the skin (irritant dermatitis). Potentiation of photosensitizing medi-cation may occur, and patients should be cautioned to minimize sunlight exposure and to use sunscreens and protective clothing.
Calcipotriene (Dovonex) is a synthetic vitamin D3 derivative (available as a 0.005% cream or scalp lotion) that is effective in the treatment of plaque-type psoriasis vulgaris of moderate severity.Improvement of psoriasis was generally noted following 2 weeks of therapy, with continued improvement for up to 8 weeks of treatment. However, fewer than 10% of patients demonstrate total clearing while on calcipotriene as single-agent therapy. Adverse effects include burning, itching, and mild irritation, with dryness and erythema of the treatment area. Care should be taken to avoid facial contact, which may cause ocular irritation. A once-daily two-compound ointment containing calcipotriene and betame-thasone dipropionate (Taclonex) is available. This combination is more effective than its individual ingredients and is well tolerated, with a safety profile similar to betamethasone dipropionate.
Calcitriol (Vectical) contains 1,25-dihydroxycholecalciferol, the hormonally active form of vitamin D3. Calcitriol 3 mcg/g ointment is similar in efficacy to calcipotriene 0.005% ointment for the treatment of plaque-type psoriasis on the body and is better tolerated in intertriginous and sensitive areas of the skin. Clinical studies show comparable safety data regarding adverse cutaneous and systemic reactions between topical calcitriol and calcipotriene ointment.