Pharmacology - Grapefruit Juice and Benzodiazepines

[azrael2600]

swim receved a new script for xanax and picked it up at the prescription at a local pharmacy. what suprised swim was the patient education paper that usually comes along with prescriptions. Swim was particularly interested in the part on how to use the medicine. Swim will quote the paper:
Eating grapefruit or drinking grapefruit juice while you are taking this medicine may increase the amount of this medicine in your blood, which may increase your risk for serious side effects.
swim was wondering what this was all about? how does grapefruit juice increase the amount of xanax in your blood?
could anybody clarify what this is about?

[allyourbase]

grapefruit juice is a cytochrome inhibitor; theyre afraid SWIY might get high. and that could lead to dancing.

Reputation Comments on this post:

	thanks for the info
	deep insight into the minds of medical professionals

[Forthesevenlakes]

to SWIMs understanding, grapefruit juice would slow the metabolism of xanax, thus increasing the amount of xanax in the bloodstream, and the amount available to the brain.

This grapefruit juice phenomena works with many other drugs, too, SWIM's found it effective with potentiating DXM and opiates.

like ayb says...this combination could lead to dancing, so use caution and put on swiy's dancin' shoes.

[azrael2600]

swim tried an experiment this morning before taking swim's morning dose of xanax. swim drank an 8oz. glass of grapefruit juice on an empty stomach 30 min prior to taken swims morning dose. swim did notice a slight difference, in that swim felt slightly more buzzed, than if swim took swim's normal dose without without the grape fruit juice.

[Wyborowa]

Not i know that grapfruit potentiates xanax's effect, would it also work well with klonopin?

Siwm takes .5mg 4x's a day. If swim started drinkin grapefruit juice, would it increase the effects? Doesn't it have to be ocean spray only? thanks!

[Riconoen {UGC}]

I think it would since they are closely related. but I don't know.

[Jatelka]

Clonazepam (like alprazolam) is metabolised by the cytochrome P450 system of liver enzymes. Grapefruit juice is an inhibitor of these enzymes. Fewer enzymes = more clonazepam around.

Bear in mind that inhibiting P450 may well increase SWIY's risk of od: Proceed with caution.

SWIJ doesn't think the brand of juice will have much effect

[Blur]

This trick only works with triazolobenzodiazepines (Xanax, Halcion) and Cimetidine inhibits the P450 enzyme subtypes that metabolize these drugs much more strongly than grapefruit juice. You get an increase in the AUC (area under the curve), Cmax, and drug clearance is also decreased. Try about 600 mg of generic tagamet about an hour before a xanax dose. Serzone is an even more potent inhibitor. Basically you can half your dose by predosing with cimetidine (w/ xanax or halcion).

Reputation Comments on this post:

Very informative post. Thank you.

[calmascanbe]

SWIM might be a little confused by the difference of oppinions about grapefruit juice doubling the potentcy of clonazepam. Would another SWIM be willing to clarify if it works or not with clonazepam? Thanks
Any experience is very welcome.

[Jatelka]

From rxlixt:

"Although clinical studies have not been performed, based on the involvement of the cytochrome P-450 3A family in clonazepam metabolism, inhibitors of this enzyme system, should be used cautiously in patients receiving clonazepam."

SWIJ has no direct experience to report however.

[calmascanbe]

Thanks for the reply Jatelka. SWIM personally has never tried the combination , but SWIM might in the near future.If SWIM does SWIM will update the results.

[DrMuffy]

SWIdr has tried potentiating many benzos using different brands of grapefruit juice. This trick works on all the benzos SWIdr has tried it on (alprazolam, clonazepam, lorazepam, and diazepam). SWIY might want to be careful though, because different people metabolized their stomach contents different and one could OD or get basically the same results by using this trick.

How much grapefruit juice does one have to drink in order to get noticeable effects? And should it be done 30 mins or so before taking the pill?

[DrMuffy]

Well like SWIdr said, it depends on one's metabolisim to deduce the amount of grapefruit juice one would have to drink. SWIdr is roughly 200lbs and has a moderate (more on the slower side) metabolism and can drink up to 32 fl oz of pure grapefruit juice (most of the time less) to acheive the potentiate his benzos enough. Of course SWIY would (ballpark guess) probably have to drink around 8-16 fl oz, but decide for yourself. And yes, it works much better if SWIY drinks the juice from an hour to thirty minutes before he plans on ingesting the benzos.

[Jatelka]

There’s been quite a lot of conflicting information about whether or not various benzos are potentiated by grapefruit juice or not: So here for SWIY’s viewing pleasure is what SWIJ has been able to dig up.

Grapefruit juice inhibits Cytochrome P450 (CY3PA specifically), which is found both in the liver and the wall of the small intestine. These enzymes metabolise benzodiazepines. The theory is, is that if the enzymes are inhibited then there will be greater bioavailability of the drug (for example, requiring lower doses to get the same effect). However it’s not quite so simple. This effect only comes into play if the parent drug is subject to extensive first pass metabolism. Drugs with high oral bioavailability (because of low first pass metabolism) are not affected by enzyme inhibition significantly.

Obviously grapefruit juice does not have an effect if benzodiazepines are taken parenterally (IV or IM), because first pass metabolism is eliminated.

SWIJ has seen it stated in various places on the net that it is only ruby grapefruit that has effect: Not so. Most of the studies were done with normal white grapefruit.

So, here we go.

Benzos definitely potentiated by grapefruit juice:

Triazolam (Halcion), Diazepam (Valium) and Midazolam (Versed)

Benzos definitely NOT potentiated by grapefruit juice:

Alprazolam (Xanax)

Benzos theoretically potentiated by grapefruit juice, but effects probably not clinically significant (because of high oral bioavailability):

Clonazepam (Klonopin), Lorazepam (Ativan), Chlordiazepoxide, Flurazepam (Dalmane), Temazepam (Restoril)

NB: No studies have been done on these benzos specifically

Another factor that comes into play is the duration of intake of grapefruit juice. Triazolam particularly has been studied. Studies have shown that although a single glass of juice increases plasma concentrations and half-life, repeated glasses of juice over three days has an even greater effect. This effect lasts for about 3 days after discontinuation of grapefruit juice.

Some other tit bits gleaned: Grapefruit juice is not the only juice to inhibit CY3PA. Others having an effect are: black mulberry > wild grape > pomegranate > black raspberry. All however have less of an effect than grapefruit. Star Fruit also appears to be a potent enzyme inhibitor. Pomegranate juice also inhibits CY3PA

On a side note: Other downers affected by grapefruit juice are: Buspirone (strongly clinically significant), Zaleplon (moderate significance), and Zolpidem (unlikely to be clinically significant).

See here for some papers from our wonderful archive:

Triazolam and Grapefruit Juice
Repeated Consumption af Grapefruit Juice and Triazolam and Alprazolam
Repeated consumption of Grapefruit Juice and Alprazolam
Inhibition of CY3PA by Grapefruit Juice
Interaction between Grapefruit Juice and Diazepam
Interaction between Grapefruit Juice and Midazolam

Reputation Comments on this post:

	Great post
	excellent info, well presented
	Very thorough research
	good info

[Alicia]

Swia herself noticed a potentiation in effects with clonazepam when she was using them. she had read it increased the effect and got curious so tried it with a smaller amount then normal she had drunk the gf juice a hour before hand on an empty stomach before swia had 2 mg. She does not condone this but had noticed an increase in effects comparing to what would of been a small dose. DO not combine this mix with alcohol specially spirits, if u do the end result is not pretty..

[DrMuffy]

SWIdr has tried the grapefruit potentiation on several benzos. In his experiences, grapefruit juice (ingested approx. 30 minutes before benzo) has a good potentiation effect on: Valium (Diazepam), Klonopin (Clonazepam), and Tranxene (Chlorazepate). Grapefruit juice seems to have a mild potentiation effect on: Xanax (Alprazolam), Ativan (Lorazepam), and Librium (Chlordiazepoxide).

Reputation Comments on this post:

Good information.

[csharpprogrammer]

Does drinking grapefruit juice only work when taking benzos by mouth, or does it potentiate an IV dose too?

[DrMuffy]

Originally Posted by csharpprogrammer

Does drinking grapefruit juice only work when taking benzos by mouth, or does it potentiate an IV dose too?

The answer is no. Grapefruit juice works by inhibiting liver enzymes, which can help potentiate a number of drugs. But when one IV's a drug, the first-pass metabolism in the liver is skipped, so grapefuit juice wouldn't help.

[Sickpup]

Just take and do all the things the warnings say not to,and SWIY will be styling,J/k.SWIM tested this with xanax and grapefruit juice,and would say got a 30% boost in effectiveness.Tagement tip sounds good.SWIM wouldn't mess around potentiating k-pin,they have a rediculus long half life as it is,SWIM is a benzoid ,and I cant take that build up after 2-3 months.If someone added to that build up,SWIY would probably lose basic motor control within a week.

[rod]

after reading this swim drank 2 glasses of g/f juice and swim tried 10m of valium and could tell a diff. to me it added to it

[Nargyle]

SWIM drank 500ml of grapefruit juice and then popped 20mg valium, the effects were clearly potentiated. SWIM felt as if he had popped 40mg valium, nice way to make his benzos last longer!

[rod]

Any 1 kno if orange would juice up valium. Swim would tyr but im outta juice, and 25 miles from a store w/fresh juice

[Nargyle]

Not all citrus juices contain narningenin or DHB. For this reason, citrus juices such as orange juice have not been shown to affect this enzyme.2

Different parts of the grapefruit also contain different amounts of these two substances. The peel of the grapefruit is thought to contain more than any other part of the fruit. It is uncertain if eating a grapefruit will cause the same effects as drinking grapefruit juice.


I just found this on the internet, so I think SWIrod is out of luck, only grapefruit seems to work.

[hoodabudda]

does vitamin c play a role in this because all of these jucies sound like hi vitamin c juices.