Is Roaccutan (isotretinoin) safe in patients with mild renal failure?/nA 23-year-old woman with sli

Fråga: Is Roaccutan (isotretinoin) safe in patients with mild renal failure?

A 23-year-old woman with slightly reduced GFR (creatinine clearance: 80 ml/min). Because of severe acne isotretinoin (1 mg per kg per day) is being considered.

Sammanfattning: Documentation on isotretinoin in patients with renal failure is lacking. Isotretinoin is extensively metabolised and its metabolites are excreted equally via the bile and urine in the form of glucuronides. The metabolites are much less potent than the parent drug and they do not contribute much to the pharmacological activity. The present patient has a mild reduction of GFR (creatinine clearance 80 ml/min) and the risk of accumulation of isotretinoin or its metabolites can be regarded negligible. Some accumulation of the major metabolite cannot however be ruled out in patients with severe renal failure.

Svar: In an extensive literature search including Medline, Drugline, SWEDIS and major pharmacological textbooks, we could not retrieve any reports concerning the use of isotretinoin in patients with renal failure.

The available pharmacokinetic data on isotretinoin is derived from healthy volunteers (1,2) and from patients with cystic acne or advanced cancer (2). No major pharmacokinetic differences of isotretinoin were observed among these different population study groups. Isotretinoin is extensively metabolised to several metabolites and only a negligible amount is excreted in the urine as the parent drug (2,3). Isotretinoin and its metabolites undergo glucuronidation before they are excreted to a similar extent in urine and faeces. In the gut, the glucuronides are hydrolysed and metabolites reabsorbed (enterohepatic recirculation) (1,2). In vitro, the metabolites are 10 to 100-fold less potent than isotretinoin and they are assumed to contribute little to the pharmacological activity of the drug (3).