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Drug Interaction between Benadryl and Effexor.....

Posted by ed_uk on March 25, 2005, at 15:38:45

I'm posting a study which may be of interest, I have a few things to say first.....

Effexor = venlafaxine
Benadryl = diphenhydramine

To summarise the study, Benadryl can inhibit the metabolism of Effexor, reducing its clearance.

Since Effexor is metabolised to O-desmethylvenlafaxine, an active metabolite, the clinical significance of this finding is not clear.

Since Effexor has been implicated in causing arrhythmias, it is possible that combining a high dose of Effexor with Benadryl might cause cardiovascular side effects.

It is possible that Benadryl attenuates Effexor withdrawal symptoms by reducing its clearance. It might be advisable to avoid combining high doses of Effexor with Benadryl.

Nefopam, a derivative of diphenhydramine (Benadryl) is thought to be a weak serotonin reuptake inhibitor. I've been wondering whether Benadryl is also a serotonin reuptake inhibitor- this may partly explain its apparant efficacy in relieving Effexor withdrawal symptoms.

Benadryl is sedative and anti-emetic, these properties may be helpful in treating insomnia and nausea respectively, symptoms which may occur during Effexor withdrawal.

The study.....

J Clin Psychopharmacol. 2001 Apr;21(2):175-84.

Diphenhydramine alters the disposition of venlafaxine through inhibition of CYP2D6 activity in humans.

Lessard E, Yessine MA, Hamelin BA, Gauvin C, Labbe L, O'Hara G, LeBlanc J, Turgeon J.

Quebec Heart Institute, Laval Hospital, Canada.

CYP2D6 is the major enzyme involved in the metabolism of venlafaxine. Subjects with a low CYP2D6 activity have increased plasma concentrations of venlafaxine that may predispose them to cardiovascular side effects. In vitro and in vivo studies showed that diphenhydramine, a nonprescription antihistamine, can inhibit CYP2D6 activity. Therefore, the authors investigated in this study a potential drug interaction between diphenhydramine and venlafaxine. Fifteen male volunteers, nine with the extensive metabolizer (EM) and six with the poor metabolizer (PM) phenotype of CYP2D6, received venlafaxine hydrochloride 18.75 mg orally every 12 hours for 48 hours on two occasions (1 week apart): once alone and once during the concomitant administration of diphenhydramine hydrochloride (50 mg every 12 hours). Blood and urine samples were collected for 12 hours under steady-state conditions. In EMs, diphenhydramine decreased venlafaxine oral clearance from 104+/-60 L/hr to 43+/-23 L/hr (mean +/- SD; p < 0.05) without any effect on renal clearance (4+/-1 L/hr during venlafaxine alone and 4+/-2 L/hr during venlafaxine plus diphenhydramine). In PMs, coadministration of diphenhydramine did not cause significant changes in oral clearance and partial metabolic clearances of venlafaxine to its various metabolites. Diphenhydramine disposition was only slightly affected by genetically determined low CYP2D6 activity or concomitant administration of venlafaxine. In conclusion, diphenhydramine, at therapeutic doses, inhibits CYP2D6-mediated metabolism of venlafaxine in humans. Clinically significant interactions could be encountered during the concomitant administration of diphenhydramine and other antidepressant or antipsychotic drugs that are substrates of CYP2D6.





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