medications and grapefruit?

[A R Picket]

I've noticed more and more warnings on various medications
along the lines of "do not take with grapefruit or
grapefruit juice."

What does this mean, exactly?

If you like grapefruit in the winter months, foreswear your
medication?

If you must have your medicine, foreswear grapefruit?

Can timing help? If a specific medication should not be taken
at the same meal with grapefruit, will waiting an hour or two
remove the threat? (whatever the threat is, I guess I've never
understood that either)

For example, I take Felodipine 5 mg daily, almost always with
my evening meal, on occasion at bedtime. If I wish to have
half a grapefruit with dinner, should I wait till bedtime for
the medicine? Or must I scrap the grapefruit altogether? Or
eat it earlier in the day? Oh, bother!

Thanks in advance for any help.

--
A R Pickett aka Woodstock

"Sometimes the facts threaten the truth" Amos Oz, prize
winning Israeli author

Read my book reviews at:
http://www.booksnbytes.com/reviews/_idx_ws_all_byauth.html

Now blogging! http://www.journalscape.com/woodstock/

Remove lower case "e" to respond

[Mark Thors]

A R Pickett wrote:
>
> I've noticed more and more warnings on various medications
> along the lines of "do not take with grapefruit or
> grapefruit juice."
>
> What does this mean, exactly?

Grapefruit juice is known to have various interactions with
drugs, in ways that are difficult to predict. It's best to
avoid it completely when using prescription medications.

Geriatrics. 2006 Nov;61(11):12-8.

Grapefruit juice and drug interactions. Exploring mechanisms
of this interaction and potential toxicity for certain
drugs. Bressler R. Department of Medicine, College of
Medicine, University of Arizona, Arizona Health Sciences
Center, AZ, USA.

Concomitant administration of grapefruit juice can increase
the plasma concentration of numerous drugs in humans and
decrease the concentration of a few others. Such elevations of
drug plasma concentrations have, on occasion, resulted in
adverse clinical effects. Increased concentrations are
primarily mediated by chemicals in grapefruit juice, which
inhibit the CYP 3A4 drug-metabolizing enzyme in the small
intestines. This inhibition decreases the first-pass
metabolism of drugs using the CYP 3A4 intestinal system and
increases the bioavailability and maximal plasma drug
concentrations (Cmax) of the CYP 3A4 substrates. The effect of
grapefruit juice on drug metabolism is most pronounced in
drugs with a high first-pass metabolism (eg, felodipine,
amiodarone), in which it inhibits the first-pass metabolism of
the CYP 3A4 substrates leading to an increase in Cmax and area
under the concentration time curve (AUC). The use of
grapefruit juice with a few specific drugs (eg, fexofenadine,
digoxin) may lower plasma drug concentrations by inhibiting
drug absorption catalyzed by the organic anion transporting
polypeptide (OATP).

J Clin Pharmacol. 2006 Dec;46(12):1390-416. Grapefruit-drug
interactions: can interactions with drugs be avoided?
Mertens-Talcott SU, Zadezensky I, De Castro WV, Derendorf H,
Butterweck V. Department of Pharmaceutics, Center for Food
Drug Interaction Research and Education, JHMHC, POB 110494,
Gainesville, FL 32610-0494.

Grapefruit is rich in flavonoids, which have been demonstrated
to have a preventive influence on many chronic diseases, such
as cancer and cardiovascular disease. However, since the early
1990s, the potential health benefits of grapefruit have been
overshadowed by the possible risk of interactions between
drugs and grapefruit and grapefruit juice. Several drugs
interacting with grapefruit are known in different drug
classes, such as HMG-CoA reductase inhibitors, calcium
antagonists, and immunosupressives. Currently known mechanisms
of interaction include the inhibition of cytochrome P450 as a
major mechanism, but potential interactions with
P-glycoprotein and organic anion transporters have also been
reported. This review is designed to provide a comprehensive
summary of underlying mechanisms of interaction and human
clinical trials performed in the area of grapefruit drug
interactions and to point out possible replacements for drugs
with a high potential for interactions.

Am Fam Physician. 2006 Aug 15;74(4):605-8. Management of
grapefruit-drug interactions. Stump AL, Mayo T, Blum A.
University of Alabama School of Medicine, Tuscaloosa,
Alabama, USA.

Grapefruit is a healthy addition to a well-balanced diet.
However, the fruit has been shown to affect the metabolism of
many medications, increasing the risk of toxicity and adverse
effects. Characteristics of oral medications that may interact
with grapefruit include extensive metabolism through the
intestinal cytochrome P450 3A4 system, low bioavailability,
and a narrow therapeutic index. Prominent medications known to
interact with grapefruit include statins, antiarrhythmic
agents, immunosuppressive agents, and calcium channel
blockers. There are equally effective alternatives to these
drug classes that do not have the potential to interact with
grapefruit. These alternative drugs may be substituted if a
patient experiences or is at risk of a grapefruit-drug
interaction. Patients also may choose to exclude grapefruit
from their diets and consume other fruits, including other
types of citrus, to avoid an interaction.