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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 12 of 12. This is the beginning of the thread.
Posted by crittercuddler on December 18, 2008, at 2:06:14
I read that grapefruit and grapefruit juice should be avoided when taking Luvox because it can cause an increase in plasma levels of Luvox.Has anyone had experience combining the two with no ill effects?
I just bought some fancy new packaged grapefruit from the produce section and don't want to throw it out.
Thanks.
Posted by SLS on December 18, 2008, at 7:20:36
In reply to Luvox(fluvoxamine) and grapefruit?, posted by crittercuddler on December 18, 2008, at 2:06:14
> I just bought some fancy new packaged grapefruit from the produce section and don't want to throw it out.
Throw it out.
Keeping a stable level of Luvox flowing through the brain is more important than a few grapefruit. There are several substances in grapefruit that prevent the body from breaking down Luvox, thereby allowing its levels to rise significantly.
The dynamics of this effect can be found here:
http://www.powernetdesign.com/grapefruit/general/mechanism.html
Sorry about the new packaged grapefruits...
Good luck with Luvox.
- Scott
Posted by Phillipa on December 18, 2008, at 11:13:39
In reply to Re: Luvox(fluvoxamine) and grapefruit?, posted by SLS on December 18, 2008, at 7:20:36
Seems luvox is making a comeback it also intensifies benzos and caffeine I belive. But now there is the 120 extended release guess that's why. Grapefruit juice is contraindicated with a good number of meds from what I've read. Phillipa
Posted by yxibow on December 18, 2008, at 13:37:53
In reply to Luvox(fluvoxamine) and grapefruit?, posted by crittercuddler on December 18, 2008, at 2:06:14
>
> I read that grapefruit and grapefruit juice should be avoided when taking Luvox because it can cause an increase in plasma levels of Luvox.
>
> Has anyone had experience combining the two with no ill effects?
>
> I just bought some fancy new packaged grapefruit from the produce section and don't want to throw it out.
>
> Thanks.
I've never eaten a grapefruit with Luvox, but that interaction, while listed still as "important" on some people's lists, varies a lot for some people. Over the long haul, if you ate a quarter of that grapefruit for breakfast every so often, nothing would probably ever happen.
If you ate several grapefruits, especially at the same time as taking your Luvox, you could conceivably see differences, and I wouldn't do it.
I'm not particularly a fan of grapefruit juice though, especially since it makes other things taste wierd, so I havent eaten one for a while.
I wonder if the same thing is true for a Pomello -- probably.
It's probably a good idea to check with your doctor -- that interaction can also depend on your genetics I believe, as to the P450.-- Jay
Posted by crittercuddler on December 20, 2008, at 17:14:26
In reply to Re: Luvox(fluvoxamine) and grapefruit?, posted by SLS on December 18, 2008, at 7:20:36
Thank you everyone for the replies.
Posted by Larry Hoover on December 20, 2008, at 21:38:28
In reply to Luvox(fluvoxamine) and grapefruit?, posted by crittercuddler on December 18, 2008, at 2:06:14
Fluvoxamine (Luvox) is a primary substrate of enzyme 1A2, with lesser dependency on 2C9, and 2C19. Even lower still are its dependencies upon 2D6 and finally 3A4, the latter being the enzyme on this list which is inhibited by grapefruit. In the end, I can only conclude that the warning with respect to grapefruit and Luvox is based on an abundance of caution, rather than a truly important interaction.
An interaction that might concern you, however, is Luvox with caffeine. Metabolism of caffeine is severely inhibited by Luvox, with a half-life about five times what would normally occur.
Regards,
Lar
Posted by SLS on December 20, 2008, at 21:50:46
In reply to Re: Luvox(fluvoxamine) and grapefruit? » crittercuddler, posted by Larry Hoover on December 20, 2008, at 21:38:28
I read that in a study of healthy volunteers, ingestion of 250 ml (approximately 8 ounces) of grapefruit juice along with fluvoxamine increased the blood level of fluvoxamine by 60%
http://www.cop.ufl.edu/fdic/pdfs/Gj%20-%20fluvoxamine%20interaction.pdf
- Scott
Posted by Larry Hoover on December 20, 2008, at 22:55:25
In reply to Re: Luvox(fluvoxamine) and grapefruit? » Larry Hoover, posted by SLS on December 20, 2008, at 21:50:46
> I read that in a study of healthy volunteers, ingestion of 250 ml (approximately 8 ounces) of grapefruit juice along with fluvoxamine increased the blood level of fluvoxamine by 60%
>
> http://www.cop.ufl.edu/fdic/pdfs/Gj%20-%20fluvoxamine%20interaction.pdf
>
>
> - ScottGood find, Scott. That paper had no abstract in Pubmed.
Interesting how variable the results were in this sample. In at least 3 of the 10 subjects, peak blood concentration actually decreased with grapefruit juice. If you kick that one obvious outlier subject out, I bet the mean change was non-signficant (based on eye-balling the rest of the curves). I wish there were more subjects.
The AUC (integrated area under the curve, i.e. blood concentration times time of exposure, in nanogram hours/ml) was up 60%, rather than Cmax (maximum concentration in ng/ml), the peak blood concentration, which was up 30% (including that one outlier subject). With T1/2 (half-life) unaffected, it's hard to understand how AUC could have increased so much.
My sources were e.g. Merck Manual, pharmacokinetic analyses of CYP450 products, and binding affinities at the enzyme active sites. All sources I found indicated that 3A4 was a minor pathway. I guess that would depend, however, on the relative potency of your 1A2 and 3C enzymes. There was no observed effect of poor or extensive metabolizers at 2D6, so I ignored that issue altogether. There are so many assumptions that underly what is thought of as "normal" or "typical". Nothing like a real experiment to test the assumptions.
Regards,
Lar
Posted by Larry Hoover on December 21, 2008, at 8:07:56
In reply to Re: Luvox(fluvoxamine) and grapefruit?, posted by Larry Hoover on December 20, 2008, at 22:55:25
Sometimes I solve problems in my sleep. This is one of those times. I'm going to answer my own question.
> Interesting how variable the results were in this sample. In at least 3 of the 10 subjects, peak blood concentration actually decreased with grapefruit juice. If you kick that one obvious outlier subject out, I bet the mean change was non-signficant (based on eye-balling the rest of the curves). I wish there were more subjects.
I noted large variability in this small sample.
> The AUC (integrated area under the curve, i.e. blood concentration times time of exposure, in nanogram hours/ml) was up 60%, rather than Cmax (maximum concentration in ng/ml), the peak blood concentration, which was up 30% (including that one outlier subject). With T1/2 (half-life) unaffected, it's hard to understand how AUC could have increased so much.
I noted increased Cmax and AUC, *without* increased half-life. That's inconsistent, if the only influence on drug concentration, and thus exposure, is metabolic breakdown. There is another influence, that I forgot about. Grapefruit influences intestinal uptake of some drugs.
The mechanism of uptake can be very complicated. There are influx pumps working at the same time as efflux pumps. Drug molecules are simultaneously pumped into the body, and out of it. It's the balance, net uptake, that determines the drug's bioavailability. Grapefruit can slow the efflux pumps, tipping the balance to higher net uptake of the drug. And just as we saw here (this is actually a good example of the phenonomenon), the effect is quite variable across a sample of different individuals. Most are not much affected, if at all, but a few are significantly influenced.
Here are a couple of links that give further details of the process.
http://www.medscape.com/viewarticle/459176_4
http://www.ncbi.nlm.nih.gov/pubmed/18855612In contrast, when a drug depends on enzyme 3A4 for metabolic destruction (or activation), grapefruit affects everyone, sometimes profoundly.
And, just for the record, drug bioavailability is affected by a number of other fruit juices, e.g. orange and apple. When a person habitually drinks these juices, and they titrate to a specific drug dose, the effect of the juice is of no consequence whatsoever. The only way its going to ever matter is if you change your fruit juice ingestion pattern significantly, *and* you happen to be one of those rarer folk who are susceptible to changes in intestinal transporter activity, *and* you're taking a drug that depends on those transporters for absorption.
The same goes for Luvox and grapefruit, btw. If your pattern has been to use both, it's of no consequence. If you're using Luvox, and you suddenly begin consuming fruit juice, you may potentially have a modest effect similar to an increase in oral dose of the drug.
Regards,
Lar
Posted by crittercuddler on December 21, 2008, at 12:27:33
In reply to Re: Luvox(fluvoxamine) and grapefruit?, posted by Larry Hoover on December 21, 2008, at 8:07:56
Lar, you are one smart cookie. Thank you for the thorough analysis of the subject. :D
So, from what I gather, it is likely not as big of an issue as it is made out to be?
Posted by Larry Hoover on December 21, 2008, at 13:14:27
In reply to Re: Luvox(fluvoxamine) and grapefruit?, posted by crittercuddler on December 21, 2008, at 12:27:33
> Lar, you are one smart cookie. Thank you for the thorough analysis of the subject. :D
You're very welcome.
> So, from what I gather, it is likely not as big of an issue as it is made out to be?
A majority of people will be unaffected. A few will have a mild to moderate interaction. It's not a big issue for anyone, but it may be noticed by a few.
Take care,
Lar
Posted by Phillipa on December 21, 2008, at 18:47:35
In reply to Re: Luvox(fluvoxamine) and grapefruit? » crittercuddler, posted by Larry Hoover on December 21, 2008, at 13:14:27
Same with caffeine it does not seem stronger with luvox albeit dose is low same with benzos. No problems cutting down. Wierd huh? Phillipa
This is the end of the thread.
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