Isotretinoin: new therapy for severe acne

Abstract

The chemistry, pharmacology, pharmacokinetics, clinical use, adverse effects, dosage and administration, and FDA-approved indications of isotretinoin, a new agent used for treating acne, are reviewed. Isotretinoin is a synthetic retinoid compound with pharmacologic actions similar to those of other retinoids. Isotretinoin's effects on nodulocystic acne lesions apparently result from its reduction of the size of sebaceous glands, inhibition of sebum production, and inhibition of follicular keratinization. Isotretinoin is administered orally; peak serum drug concentrations occur approximately three hours after ingestion. The drug is widely distributed throughout body tissues and metabolized by the liver by oxidation and glucuronidation; both parent drug and metabolites are excreted in the urine and feces. Clinical trials of isotretinoin have shown the drug to be effective in treating cystic or conglobate acne that is unresponsive to therapy with oral or topical antibiotics, topical tretinoin, or topical benzoyl peroxide. Isotretinoin is unique in that acne remission continues after discontinuance of therapy. The most frequent adverse effects involve mucocutaneous tissues and include cheilitis, xerosis, xerostomia, dry nose, epistaxis, and pruritus. Other adverse effects--including some serious ones--have been found rarely in humans or animals receiving isotretinoin. The usual oral dosage of isotretinoin for patients with cystic acne is 1-2 mg/kg/day in two divided doses; administration should continue for 15-20 weeks. Isotretinoin is currently more expensive than other acne treatments. Isotretinoin is an effective agent for treating cystic acne; pending accumulation of further data, its use should be limited to patients with severe conditions that do not respond to older therapies because of isotretinoin's cost and sometimes serious adverse effects.