Can hydroxyzine interact and inhibit the metabolism of risperidone?

Fråga: Can hydroxyzine interact and inhibit the metabolism of risperidone?

Sammanfattning: No reports of drug interactions between risperidone and hydroxyzine have been found in the literature available. In vitro, hydroxyzine appears to inhibit CYP2D6.

Svar: Hydroxyzine is primarily metabolised in the liver, mainly to the pharmacologically active metabolite cetirizine, which further is eliminated by the kidneys (1,2). The cytochrome P-450 (CYP) enzymes are presumed to catalyse the metabolism of hydroxyzine, but the specific isoenzymes responsible are not known. Risperidone is mainly metabolised by CYP2D6 in the liver (3).

There are no reports of drug interactions between risperidone and hydroxyzine in the literature available.

It has been suggested, based on in vitro data, that antihistamines can inhibit cytochrome metabolising enzymes (1,4). Cetirizine, the metabolite of hydroxyzine, given in therapeutic concentrations, had no inhibitory effect on CYP2D6 (1). However, hydroxyzine appears to inhibit CYP2D6 at clinically relevant concentration in vitro, suggesting that under specific circumstances, clinically relevant interactions between risperidone and hydroxyzine might occur (4). 1 Drugline no 17938 (year 2001) 2 Renwick AG. The metabolism of antihistamines and drug interactions: the role of cytochrome P450 enzymes. Clin Exp Allergy 1999;29(suppl 3):116-24. 3 Drugline no 17811 (year 2001) 4 Hamelin BA, Bouayad A, Drolet B, Gravel A, Turgeon J. In vitro characterization of cytochrome P450 2D6 inhibition by classic histamine H1 receptor antagonists. Drug Metab Dispos 1998;26:536-9.