Food, Juice, and Drugs: Hold the Grapefruit
Do your patients know about the interactions between common foods and drugs?
More than 85 drugs are known to have interactions with grapefruit juice, according to the American Pharmacists Association website.1 Grapefruit plays hob with the metabolism of these drugs because it contains furanocoumarins. Furanocoumarins are metabolized by the intestinal cytochrome P450 (CYP)3A4 enzyme into reactive intermediates that then bond covalently to the active site of the enzyme, which irreversibly inactivates it. This inactivation leads to the increased bioavailability of the affected drugs and a potential for toxic effects. Intravenous drugs are usually not affected because grapefruit primarily targets intestinal CYP3A4 and not liver CYP3A4. This interaction is also seen with citrus fruits similar to grapefruit, such as pomelos and tangelos, which are eaten fresh, and Seville oranges, which are primarily used to make marmalade.
Grapefruit products also interact with efflux transporter P-glycoprotein and uptake transporters such as organic anion-transporting polypeptides (OATPs). This reduces absorption, which leads to decreases in blood levels of certain drugs. Apple and orange juice also appear to inhibit OATPs. There have been reports of interactions between warfarin and cranberry juice, as well, possibly due to salicylic acid in cranberries.
The identification of isoenzymes and isoenzyme pathways has led to a larger number of juice/drug interactions being identified, Plogsted said. “Blood levels go up or go down or the drug doesn’t get absorbed.”
The interactions between grapefruit and medications that cause decreased blood levels may be less well known, said Kaefer. Much of the information on these interactions has come out in the last several years or so, she noted.
Plogsted noted that grapefruit juice can be used to enhance absorption for some drugs, such as cyclosporine or tacrolimus. “When we were having bad absorption, we were asking people to take cyclosporine with grapefruit juice rather than escalate their dose and increase the drug costs,” he explained.
“In theory that makes sense, but in practice I don’t know that I would recommend that,” said Kaefer. If a patient suddenly takes a dislike to grapefruit juice or they run out, it can throw everything off, she noted.
But Plogsted admitted that it is probably simpler for a pharmacist to tell a patient not to drink grapefruit juice while taking a medication rather than go into any exceptions to that advice that could confuse the patient.