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Drugs metabolized by CYP-2D6 Cecilia

Posted by cache-monkey on October 11, 2004, at 4:45:22

In reply to Re: Cymbalta @ 2 Weeks-question for hawkeye, posted by Cecilia on October 11, 2004, at 2:46:47

I figured I might as well butt in, since this is something I've been thinking about lately...

Do you think you're CYP2D6 deficient, or is one of the drugs you're on an inhibitor of that enzyme? I had the same reaction to Cymbalta and ended up having to discontinue. As it happens, I got a CYP2D6 genotype test based on a couple of drug reactions in the past and it turns out that I'm naturally an intermediate CYP2D6 metabolizer. Add that on to Cymbalta's natural inhibition of the enzyme and, well, it sucked.

If you think you're CYP2D6 deficient you should look into whether your insurance covers a genotyping test. I had to do all the legwork with mine, including informing my GP as to what the test even was. But I think it's worth it so that I know now to be careful with 2D6-metabolized drugs. Anyway, since I've been aware of this, I've started looking more carefully at the various drugs I've been on or have contemplated going on in relation to 2D6.

If you have CYP2D6 issues, you might want to stay away from Serzone. I had a horrible reaction to it, which I think could be based on my 2D6 status. One of its metabolites (mCPP) is known to cause anxiety and is metabolized by 2D6. For most people (extensive metabolizers) this doesn't cause a problem, but for people slow in 2D6 mCPP can accumulate to the point of washing out any of the "normally" calming effects of Serzone.

I currently take BuSpar, whose primary metabolite (1-PP) is metabolized on the second pass by 2D6. But 1-PP is anxiolytic and pro-sexual, which could explain my pretty good relationship with BuSpar so far. (It's not leaving me anxiety-free, but it's helping a lot.)

I've been looking at going on selegiline, which is an MAO-B inhibitor at low concentrations and only at higher concentrations is an MAO-A inhibitor (necessitating the special diet). It's metabolized by 2D6, so I'm going to start out at half of the normal starting dose so that it doesn't over accumulate and go MAO-A on me.

Other drugs that I know to be metabolized at least in part by 2D6: Lexapro, Prozac, as well as primary metabolites of Celexa and Wellbutrin. So, if you have reason to suspect that you have 2D6 issues, you would want to start low and go slow with these.

The following links have useful, but not complete, information on the enzymes that metabolize, and are inhibited by, various drugs:
Neither of those links seems to be a complete listing, so I usually round out the information with a web search.

Sorry if this is information overload, but I hope it helps.


<< What other drugs are affected by the CYP2D6 enzyme? I`m also having very bad side effects at only 10 mg/day of Cymbalta (sweating, hot flashes, nausea, fatigue, dilated pupils, heart palpitations). I also take clonazepam, atenolol, levothyroxine regularly, ambien, benadryl, xanax prn. Is there a link somewhere saying what drugs are metabolized by what enzyme? I`m definitely getting discouraged, I was so hoping the Cymbalta would work as there`s really nothing else left for me to try. Cecilia




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