Can isotretinoin (Roaccutan) cause hypercholesterolemia?/nThe question concerns a 26-year-old man t

Fråga: Can isotretinoin (Roaccutan) cause hypercholesterolemia?

The question concerns a 26-year-old man treated with isotretinoin (dose unknown) who after two weeks of treatment showed a serum cholesterol value of 9.2 mmol/L (normal value < 5 mmol/L). The patient had previously elevated plasma lipids which decreased (s-cholesterol 6 mmol/L) after dieting.

Sammanfattning: Hypercholesterolemia and other types of hyperlipidemia are known adverse effects of isotretinoin and other retinoids. The incidence of hypercholesterolemia has been reported to vary from 7% to 19% of isotretinoin treated patients. It is advisable to monitor plasma lipids at baseline and after two and four weeks of treatment. Family history of elevated plasma lipids, diabetes mellitus, increased alcohol intake or obesity are risk factors for developing hypercholesterolemia in patients treated with isotretinoin.

Svar: Dose related dyslipidemia including elevation in total cholesterol, triglycerides and LDL-C, and decrease in HDL-C is a well known adverse drug reaction of isotretinoin (1-3) as well as other retinoids (2,4). Hypercholesterolemia usually appears some weeks after initiation of treatment and resolves within a few weeks after discontinuation of therapy (2,3,5,6). The mechanism of this side effect is not known but it is suggested that the likeliest explanation is increased VLDL levels possibly due to decreased uptake of VLDL by the liver (7,8). The incidence of hypercholesterolemia as a side effect of isotretinoin therapy has been documented to vary from 7% (5) up to 19% among treated patients (6). These effects seem to be unrelated to age or gender (3,6). The elevation in plasma lipids is often mild but severe hypertriglyceridemia with pancreatitis has also been reported (3,5). Patients with diabetes mellitus, increased alcohol intake, obesity (2,3) or familial history of elevated plasma lipids (3), seem to be at higher risk of developing hyperlipidemia (2,5).

One case of hypercholesterolemia judged as a probable adverse effect of isotretinoin has been reported to the Swedish adverse drug reactions advisory committee (SADRAC) (9). The patient´s cholesterol value increased to 9 mmol/L after six months of treatment with isotretinoin. When the drug was withdrawn the cholesterol values was normalised within a few of months. There are 9 other cases of different elevated plasma lipids in relation to isotretinoin reported to SADRAC. Additionally, 462 cases of hypercholesterolemia in relation to isotretinoin treatment have been reported in the WHO adverse drug registry (Intdis) (9,10).

It has been recommended that triglyceride levels should be monitored at baseline and after two and four weeks of treatment (6).

We recommend this case be reported to the regional centre of SADRAC. 1 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. 2 Davies DM, Ferner RE, de Glanville H, editors. Davie´s textbook of adverse drug reactions. 5th ed. Philadelphia: Lippincott-Raven Publishers; 1998. 3 Isotretinoin. Martindale, The complete drug reference. Micromedex Inc., Englewood, Colorado (Edition expires (9/2001)). 4 Drugline no 13706 (year 1996). 5 Isotretinoin. Drugdex (R) System. Micromedex Inc., Englewood, Colorado (Edition expires (9/2001)). 6 Ragos GA, Houlden RL, Danby FW. Effect of isotretinoin therapy on serum total cholesterol and triglycerides. Can J Clin Pharmacol 1998;5:43-7. 7 Marsden JR. Lipid metabolism and retinoid therapy. Pharmacol Ther 1989;40:55-65. 8 Vahlquist C. Effects of retinoids on lipoprotein metabolism. In: Vermeer BJ, Wuepper KD, van Vloten WA, de la Faille BH, van der Schroeff JG, editors. Metabolic disorders and nutrition correlated with skin. Curr Probl Dermatol. Vol 20. Basel: Karger; 1991. p. 73-8. 9 Swedis (The Swedish Drug Information System) 10 Intdis (International Drug Information System): WHO:s adverse drug reactions database