Is there any information concerning interactions between ranitidine and mirtazapine or venlafaxine?

Fråga: Is there any information concerning interactions between ranitidine and mirtazapine or venlafaxine?

A 24-year-old female with anxiety disorder has been treated for several months with Efexor (venlafaxine) 37.5+0+37.5 mg and Remeron (mirtazapine) 30 mg. Co-medication with Zantac (ranitidine) 150 mg/d is being considered.

Sammanfattning: Ranitidine has been shown in one study to be a weak inhibitor of cytochrome P450 which might lead to some increase in the plasma levels of venlafaxine and mirtazapine. The clinical impact of such an interaction is probably low.

Svar: Venlafaxine and mirtazapine are both metabolised by cytochrome P 450 (1-3). It is well known that cimetidine, an H2-antagonist binds to cytochrome P450 and inhibits the metabolism of drugs eliminated by this enzyme (4,5). An in vitro study using human liver microsomes has shown that ranitidine is a weak inhibitor of cytochrome P4501A2, 2D6, 3A4 (5). Since 2D6 and 3A4 are involved in the metabolism of venlafaxine and mirtazapine, co-medication with ranitidine might lead to some increase in plasma levels of both antidepressants. Monitoring of plasma concentration of these drugs should be considered if any unexpected symptoms arise. 1 Dollery C Sir, editor. Therapeutic drugs. 2nd ed. Edinburgh: Churchill Livingstone; 1999. p. V17 2 Drugline no 16537 (year 2000) 3 Parfitt K, editor. Martindale, The complete drug reference. 32nd ed. London: Pharmaceutical Press; 1999, 298:2 4 Smith S R, Kendall M J: Ranitidine versus cimetidine: a comparison of their potential to cause important drug interactions. Clin Pharmacokinet 1988; 15: 44-56 5 Martinez C, Albert C, Agundez JAG, Herrero E, Carillo JA, Marquez M, Benitez J, Alfonso Ortiz J: Comparitive in virto and in vivo inhibition of cytochrome P450 CYP1A2, CYP2D6, and CYP3A4 by H2-receptor antagonists. Clin Pharmacol Ther 1999; 65: 369-376