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This document Copyright © 2003 D.McAuley, GlobalRPh Inc. All Rights Reserved.

grapefruit  +   drugvials

Background information:

         Grapefruit juice is a potent inhibitor of the intestinal cytochrome P-450 3A4 system (specifically: CYP3A4 - mediated drug metabolism) which is responsible for the first-pass metabolism of many medications.  This interaction can lead to increases in bioavailability and corresponding increases in serum drug levels.  In many cases, the increased  serum drug levels can  produce some readily observable symptoms.

Here are a few examples of adverse effects  that are possible when  the following medications are taken concurrently with  grapefruit.
(1)  Excessive sedation: benzodiazepines.
(2) Increased risk of rhabdomyolyis: HMG-CoA reductase inhibitors (statins)-- there are some exceptions.
(3)  Symptomatic hypotension: dihydropyridine calcium antagonists (some exceptions exist).
(4) QT interval prolongation: astemizole, cisapride, pimozide,  terfenadine.

"Drug interactions may be most apparent when patients are stabilized on the affected drug and the CYP3A4 inhibitor is then added to the regimen." 5

There may be some pharmacological advantages to this interaction.   If the interaction is taken into account during the initialization of drug therapy it is possible to decrease drug dosages.  This concept can be applied to cyclosporine therapy.  If a patient regularly consumes grapefruit, lower dosages of cyclosporine will be required, which will lead to lower drug costs.

Grapefruit juice is not the only inhibitor of this enzyme system. Other drugs which have a similar effect include: clarithromycin (Biaxin ®),  erythromycin (E-Mycin ®, others),  itraconazole (Sporonox ®),   ketoconazole (Nizoril ®),  nefazodone (Serzone ®),  and ritonavir (Norvir ®).

Drugs which may exhibit increased serum concentrations based on this interaction

amiodarone astemizole alprazolam atorvastatin
benzodiazepines buspirone carbamazepine carvedilol
cerivastatin cilostazol clarithromycin Clomipramine
codeine cyclosporine dapsone dextromethorphan
diazepam diltiazem estrogens erythromycin
felodipine fentanyl finasteride haloperidol
indinavir lercanidipine lidocaine lovastatin
midazolam methadone nelfinavir nifedipine
nicardipine nimodipine nisoldipine nitrendipine
ondansetron paclitaxel progestins progesterone
quinidine ritonavir salmeterol saquinavir
simvastatin tacrolimus trazodone triazolam
vincristine zaleplon zolpidem

Note: there may be omissions on this list. Absence of a drug
does not necessarily indicate that the drug lacks this potential


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Drug – Grapefruit Interactions  (Review)