Acitretin teratogenicity

A 35-year-old mother of two has moderate psoriasis. She tells you that her mother had a similar condition 3 years ago and was successfully treated with the agent acitretin. She has come to you because her regular physician refused to write her a prescription for acitretin, and she is very uncomfortable with her skin condition. You tell her that there is a serious risk of teratogenicity if she should become pregnant. She informs you that she is taking oral contraceptives and that the possibility of pregnancy is very low. Do you prescribe the drug she has requested anyway ... 

Acitretin (Soriatane), a metabolite of the aromatic retinoid etretinate, 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 species 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 [P] Increased conversion of acitretin to etretinate (teratogenic). 

Vitamin A (retinols) plays a role in epithelial function and the retinoic acid derivative, acitretin (Neotigason, orally), inhibits psoriatic hyperkeratosis over 4-6 weeks. Acitretin should be used in courses (6-9 months) with intervals (3-4 months). It is teratogenic, like the other vitamin A derivatives. Rigorous precautions for use in women of childbearing potential are laid down by the manufacturer and must be followed, including contraception for 2 years after cessation, because the drug is stored in the liver and in fat and released over many months. The plasma t) is 3 months. It can cause other serious toxicity (see Vitamin A, p. 739). Tazarotene, a topical retinoid, is of some benefit in mild psoriasis, but is irritant. 

Retinoids are strongly teratogenic (21). Pregnancy should be ruled out and an effective form of contraception must be used for at least 1 month before starting therapy, during therapy, and for at least 1 month (isotretinoin) or 2 years (acitretin) after therapy is stopped. Retinoid-induced teratogenicity has been reviewed (22,23). 

Eckhoff, C. Chari, S. Kromka, M. Staudner, H. Juhasz, L. Rudiger, H. Agnish, N. Teratogenicity and transplacental pharmacokinetics of 13-cis-retinoic acid in rabbits. Toxicol.Appl.Pharmacol., 1994, 125, 34-41 [plasma acitretin (IS) SPE column temp 35 tissue extracted metabolites, isotretinoin, tretinoin]... 

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