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Re: Benzo interactions

Posted by Ame Sans Vie on March 31, 2004, at 18:52:13

In reply to Benzo interactions, posted by Civ on March 30, 2004, at 21:15:13

I have to concur with the others -- I've tried all six SSRIs combined with various benzodiazepines (i.e. Ativan, Valium, Xanax, Tranxene, Serax, Klonopin, Paxipam, Centrax, Librium, Halcion, ProSom, Doral, Dalmane, Rohypnol, and Restoril). My most recent SSRI + benzo combination was 40mg Prozac along with a very high (8mg) dose of Klonopin, as well as a few other drugs. I've never had a single problem. And there really is no basis to fear any significant interaction between Prozac and Ativan because the latter is not, unlike most benzodiazepines, oxidatively-metabolized (a process called Phase I or first-pass metabolism) through the cytochrome P450 pathway.

Prozac is an inhibitor of the cytochrome P450 3A4,5,7 enzyme (aka CYP3A), but is not as potent an inhibitor as many other drugs (e.g. citalopram, escitalopram, fluvoxamine, lovastatin, sertraline, erythromycin, clarithromycin, troleandomycin, -azole antifungals, rifampin, mibefradil, cimetidine, protease inhibitors, grapefruit juice).

Still, Prozac *may* slightly increase blood levels and half-lives (and therefore therapeutic effects/adverse effects) of benzos like Valium, Tranxene, Librium, Klonopin, Paxipam, ProSom, Doral, Dalmane, Centrax, and especially the triazolobenzodiazepines Xanax, Halcion, Rohypnol, and Versed, which are metabolized via CYP3A4,5,7. But it will not affect the metabolism of Restoril, Serax, or Ativan as they are conjugated through glucouronidation (Phase II metabolism) and do not succumb to the effects of the P450 enzyme system.

The only interaction I can foresee between fluoxetine and glucouronidated benzodiazepines is a potential increase in sedation due to taking two psychotropic drugs at the same time.


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