Acitretin. A review of its pharmacology and therapeutic use

Abstract

Acitretin (etretin), a second generation monoaromatic retinoid for use in the treatment of severe psoriasis and other dermatoses, is the major active metabolite of etretinate and possesses a similar therapeutic index; i.e. a similar ratio of clinical efficacy to adverse effects. When used alone at a maintenance dosage of 30 to 50mg daily, acitretin is effective in the treatment of psoriasis, causing a reduction in the severity of scaling, erythema and induration. Efficacy appears to be further enhanced by combination with psoralen-ultraviolet A photochemotherapy (PUVA) or ultraviolet B irradiation (UVB). These combinations reduce the time to lesion clearance and reduce the total radiation dose, improving overall safety. Comparative studies have confirmed the equivalence of acitretin and etrtinate with regard to efficacy and toxicity. Adverse reactions are dose-related and generally typical of hypervitaminosis A. Alopecia and mucocutaneous symptoms such as cheilitis and drying of the mucous membranes are particularly prevalent. Hypertriglyceridaemia and elevation of cholesterol levels also occur. Examination of the pharmacokinetic profile of acitretin reveals its main advantage over etretinate. Acitretin is less lipophilic than etretinate, and its lack of sequestration into 'deep' fatty storage sites is reflected in a comparatively short terminal elimination half-life of 50 to 60 hours, compared with 120 days for etretinate. Due to its teratogenic potential, acitretin is strictly contraindicated in women of childbearing potential unless effective contraceptive measures are employed. Etretinate has been identified in plasma samples of some patients treated with acitretin. Thus, acetretin has an established place in the treatment of keratinising disorders, although its use in women of child-bearing potential must be accompanied by effective contraceptive measures, with a further 2-year contraceptive period after therapy completion.