June 3, 2015

Update: Grapefruit Juice Dangers if you take Lipitor or many other medicines.

Twenty years ago, around the time I was a graduate student in London Ontario at Western University (formerly called the University of Western Ontario), a clinical pharmacologist (David Bailey) at the Lawson Research Institute in London discovered that chemicals in grapefruit can cause normal doses of several drugs to become overdoses. This results from grapefruit causing the drug to become adsorbed much more efficiently than it would normally.


Since that first discovery, more than 85 drugs are now in the list of those that should not be taken with grapefruit. Overdose effects can include sudden death!

Many of the drugs are in common use and often taken daily by patients, and include: cholesterol lowering statins, calcium channel blockers and other blood pressure medications, antibiotics, anti-rejection and cancer chemotherapeutics.

Related fruit to be avoided (fruit or juice) are seville oranges, limes and pomelos.
From the story in the CBC news website (below), here is a list of some drugs that interact with grapefruit:


Anti-cancer
Crizotinib.
Dasatinib.
Erlotinib.
Everolimus.
Lapatinib.
Nilotinib.
Pazopanib.
Sunitinib.
Vandetanib.
Venurafenib.
Anti-infective
Erythromycin.
Halofantrine.
Maraviroc.
Primaquine.
Quinine.
Rilpivirine.
Anti-cholesterol
Atorvastatin.
Lovastatin.
Simvastatin.
Cardiovascular
Amiodarone.
Apixaban.
Clopidogrel.
Dronedarone.
Eplerenone.
Felodipine.
Nifedipine.
Quinidine.
Rivaroxaban.
Ticagrelor.
Central nervous system
Alfentanil (oral).
Buspirone.
Dextromethorphan.
Fentanyl (oral).
Ketamine (oral).
Lurasidone.
Oxycodone.
Pimozide.
Quetiapine.
Triazolam.
Ziprasidone.
Gastrointestinal
Domperidone.
Immunosuppressants
Cyclosporine.
Everolimus.
Sirolimus.
Tacrolimus.
Urinary tract
Darifenacin.
Fesoterodine.
Solifenacin.
Silodosin.
Tamsulosin.


How can this be? Some chemicals in grapefruit, called flavanoids, can cause the expression of important intestinal enzymes to decrease. At least one enzyme of the cytochrome-P450 family is reduced, a protein that would normally start to pre-metabolize some ingested drugs and reduce the amount of active drug that gets adsorbed into our blood stream. The dose of a drug is developed in humans to give a specific range of concentration in the blood. When grapefruit juice decreases intestinal cytochrome P450, this allows more active drug than usual to enter the blood stream. Thus, the concentrations of the drugs, listed above, get higher than desired and cause side effects or toxicity.

You can read or watch more about this topic here, here at CBC NEWS

One of the original papers on this discovery is found here, in the British Journal of Clinical Pharmacology (1998):

"Grapefruit juice–drug interactions"

by David G Bailey, J Malcolm, O Arnold, and J David Spence
Br J Clin Pharmacol. 1998 Aug; 46(2): 101–110.

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