Trileptal & Grapefruit
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Q:  Trileptal & Grapefruit


How does grapefruit effect the drug Trileptal?  My husband has continued to cycle back and forth from being stable to mania.  his doctor perscrined Trileptal and all was well for 2 months.  them all of a sudden he became angry and aggressive like before.  The only thing different was that he had started a grapefruit diet without asking any doctor.  He will eat two or three at a time.  He loves them.  Now I see this aggressive, verbally abusive person with all the manic symptoms.  I heard grapefruit does have an effect on many drugs and I think I read somewhere that it did affect anti-seizure drugs.  What is your opinion. 

Thank you. 
marty


Dear Marty -- 
Generally the effect of grapefruit is to inhibit a particular liver enzyme that breaks down some medications.  So if somebody is taking one of those medications, and they consume a large amount of grapefruit (what you describe could do it all right), they can end up with more of the medication in their bloodstream because their liver is not breaking it down as fast as before.  Xanax is well known to act like this, amongst the psychiatric medications.  (The specific enzyme is called cytochrome P-450, number 3A4).  

However, Trileptal is metabolized by the liver through a different route.  In general it is not supposed to be affected by changing liver enzyme activities, so should not be affected by grapefruit, at all.  However, it does itself increase the activity of the 3A4 enzyme, the one that grapefruit decreases.  So I suppose in some odd way it could somehow end up being affected by grapefruit consumption, although theoretically because it is not really "oxidized" by the liver, it still theoretically should not be affected.  Here's a reference for these statements, in case somebody cared. 

All that said, real life results are supposed to trump theories.  So, we should not rule out the idea that you're wondering about here.  But I've never heard of any other references to this phenomenon.  A PUB MED search of "oxcarbazepine grapefruit" yielded no results, which means this has not been reported in the journals indexed by the National Library of Medicine.  

I did learn something interesting, hunting around, which just might have something to do with this.  If you're really interested in all this, look at this Australian Adverse Drug Reactions site, which says the grapefruit do not actually affect the liver 3A4, but rather the gut wall version of that enzyme.   Note that this contradicts the standard teaching about grapefruit, which you'll see represented on this other Australian doctors' site (scroll down to "non-drug").  I don't know how to interpret this contradiction. 

Dr. Phelps


Published May, 2003
 

 

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