Isotretinoin

Abstract

Isotretinoin is a new orally active retinoic acid derivative for the treatment of severe refractory nodulocystic acne. The pharmacological profile of isotretinoin suggests that it acts primarily by reducing sebaceous gland size and sebum production, and as a result alters skin surface lipid composition. Bacterial skin microflora is reduced, probably as a result of altered sebaceous factors. Isotretinoin 1 to 2 mg/kg/day for 3 to 4 months produces 60 to 95% clearance of inflammatory lesions in patients with severe, recalcitrant nodulocystic acne, with evidence of continued healing and prolonged remissions in many patients after treatment withdrawal. Doses as low as 0.1 mg/kg/day have also proven successful in the clearance of lesions; however, with such low doses the duration of remission after discontinuation of therapy is usually shorter. Encouraging results have also been seen in small numbers of patients with rosacea, Gram-negative folliculitis, Darier's disease, ichthyosis and pityriasis rubra pilaris, the response in keratinising disorders resembling that with the related drug etretinate. While long term follow-up studies in these patients have not been reported, prolonged remission after withdrawal of isotretinoin in disorders of keratinisation is unlikely, as with other drugs used in these conditions. Isotretinoin is only partially effective in psoriasis, in contrast to etretinate which is very effective in psoriasis but ineffective in severe acne. Some encouraging results have also been reported with isotretinoin in patients with squamous and basal cell carcinomas, but isotretinoin has proven unsuccessful in non-squamous cell epithelial and non-epithelial cancer. Side effects affecting the mucocutaneous system occur in nearly all patients receiving isotretinoin, but rarely lead to drug withdrawal. Raised serum triglyceride levels are also commonly reported. The possibility of long term spinal or skeletal bone toxicity may restrict the use of isotretinoin in severe disorders of keratinisation requiring prolonged administration. Isotretinoin is strictly contraindicated in women of childbearing potential due to its severe teratogenic properties, unless an effective form of contraception is used. Thus, isotretinoin offers an effective advance on the treatment options available in a difficult therapeutic area - those patients with severe, nodulocystic acne not responding to 'traditional' therapy.

Comparative study of oral isotretinoin versus oral isotretinoin + 20% salicylic acid peel in the treatment of Active Acne

“…Oral isotretinoin at a dose of 0.5-2.0 mg/kg/day[3] reduces sebaceous gland activity within 6 weeks[4] of starting therapy. Isotretinoin induces a dose-dependent decrease in size and cross-sectional area of sebaceous glands; dose-dependent reduction in sebum production; sebocyte apoptosis[56] and histological changes, such as lobular collapse, follicular atrophy and greater preponderance of undifferentiated acinar cells. Augmented production of neutrophil gelatinase associated lipocalin[7] in the skin by isotretinoin has been correlated with human sebocyte apoptosis within sebaceous glands, which leads to decreased production of sebum within the sebaceous glands and lobular collapse.…”

Acne Pathogenesis: History of Concepts

“…The action of isotretinoin was supported by numerous publications that led to hypothesize that some pharmacokinetic properties result in the specific targeting of sebaceous glands in reducing its size and sebum production [348,349]. Isotretinoin is actually considered as the most potent inhibitor of sebum production.…”

Pretreatment Effect of Folic Acid on 13-Cis-RA-Induced Cellular Damage of Developing Midfacial Processes in Cultured Rat Embryos

“…The severity of malformation depends on the dose and embryonic stage at the time of drug administration [11, 15-17]. The 13-cis-RA or Acccutane ® is a retinoic acid derivative that poses several benefits such as treating severe cystic acne [18]. However, the clinical observations strongly have suggested that the 13-cis-RA is a human teratogen.…”