Are there any known interactions between venlafaxine and sotalol or clopidogrel?/nA man with chroni

Fråga: Are there any known interactions between venlafaxine and sotalol or clopidogrel?

A man with chronic atrial fibrillation is medicating with Sotacor (sotalol) and Plavix (clopidogrel) in unknown doses. Treatment with Efexor (venlafaxine) for depression is considered.

Sammanfattning: No pharmacokinetic interactions would be expected between venlafaxin and sotalol or clopidogrel. Theoretically, sotalol could attenuate the noradrenergic effects of venlafaxin, by beta-receptor inhibition. However, one drug interactions book states that no important interactions normally appear with the two substances. Venlafaxine could hypothetically enhance the anticoagulant effect of clopidogrel, through a poorly understood serotonin effect on platelet function. Tachycardia is a common adverse effect of venlafaxine that could possibly aggravate the atrial fibrillation in this patient.

Svar: In one drug interactions book, it is stated that no important interactions normally appear to occur with venlafaxine and beta-blockers (1). No other information on interactions between the substances was found in Medline, Drugline or standard pharmacological literature.

Unlike several other beta-blockers, sotalol does not undergo significant hepatic metabolism and it is not known to affect the hepatic metabolism of other substances (2). Clopidogrel is metabolised by cytochrome P450 isoenzyme CYP1A2 (3). The metabolism of venlafaxine is mainly mediated by CYP2D6 (4) and venlafaxine does not inhibit or induce CYP1A2 (4). Hence, no important pharmacokinetic interactions between the substances would be anticipated.

Sotalol is a non-selective beta-receptor-antagonist (5). Since the effect of venlafaxine is partially due to inhibited noradrenaline uptake (6), there is a theoretical risk of attenuated anti-depressive effect in co-medication. As mentioned above, there are no clinical data supporting this theory.

There are indications of increased bleeding risk in medication with antidepressants with high serotonin selectivity (eg venlafaxine), possibly due to a disturbed platelet function (7). Since clopidogrel inhibits platelet aggregation (3), concomitant use of venlafaxine could possibly increase the anticoagulant effect.

Tachycardia is a common adverse effect of venlafaxine (8), and this could theoretically aggravate a pre-existing atrial fibrillation. However, fibrillation is not a contraindication of venlafaxine (8), and the simultaneous use of sotalol in this patient should decrease the risk. 1 Stockley IH. Drug interactions. 5th ed. London: The Pharmaceutical Press; 1999. p. 765 2 Micromedex: Drugdex Drug Evaluations, sotalol 3 Micromedex: Drugdex Drug Evaluations, clopidogrel 4 Ball SE, Ahern D, Scatina J, Kao J: Venlafaxine: in vitro inhibition of CYP2D6 dependent imipramine and desipramine metabolism; comparative studies with selected SSRIs, and effects on human hepatic CYP3A4, CYP2C9 and CYP1A2. Br J Clin Pharmacol 1997; 43: 619-626 5 Produktresume: sotacor injektionsvätska, MPA 6 Drugline no 16058 (year 1999) 7 Drugline no 16320 (year 1999) 8 FASS 2000 (The Swedish catalogue of approved medical products), p 465-466