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Grapefruit Juice: Forbidden Fruit?

Grapefruit juice may interfere with some anticancer agents.

BY Jeanne Erdmann
PUBLISHED June 19, 2013

Fruit juice can be refreshing and nutritious. Sometimes, though, certain ingredients in juice, particularly in grapefruit juice, can work against cancer therapies.

Natural doesn't always equal safe, says Mary Paine, a registered pharmacist and assistant professor at the University of North Carolina at Chapel Hill, N.C. More than 20 years ago, researchers discovered that grapefruit juice had compounds, called furanocoumarins, that could interact with certain medications.

Our bodies consider drugs as foreign substances and clear them away via enzymes called cytochromes, such as CYP3A4, which break down some oral medications, limiting the amount that reaches the bloodstream. Furanocoumarins block CYP3A4 in the intestine, preventing the enzyme from breaking down some anticancer agents. If CYP3A4 can’t work, too much medication might reach the bloodstream with potentially harmful consequences. High levels of a class of anticancer drugs (tyrosine kinase inhibitors) have the possibility to cause a heart rhythm so erratic that blood can no longer be pumped effectively to the body, causing cardiac arrest in some cases.

In addition to grapefruit juice, furanocoumarins can be found in pomelos (a cousin of grapefruits), limes and Seville oranges, which are used to make marmalade. David Bailey, a clinical pharmacologist at the Lawson Health Research Institute and professor emeritus at Western University in Ontario, Canada, discovered this interaction and emphasizes the need for education by a healthcare provider, such as a pharmacist or physician, before patients take a medication that interacts with grapefruit juice or foods that contain furanocoumarins.

Anticancer agents that could react negatively with grapefruit juice include: Xalkori (crizotinib), Sprycel (dasatinib), Tarceva (erlotinib), Afinitor (everolimus), Gleevec (imatinib), Tykerb (lapatinib), Tasigna (nilotinib), Votrient (pazopanib) and Sutent (sunitinib). Additional drugs that are being studied include cyclophosphamide, Nexavar (sorafenib), Capresla (vandetanib) and Zelboraf (vemurafenib).

There could be an upside to such interactions, however. One group of researchers is examining how to turn the negative action of grapefruit juice into a positive one by mixing grapefruit juice with susceptible anticancer agents, deliberately raising the blood levels of the drug. With more of the drug absorbed from one pill, the dose could be lowered and still be effective.

Taking less medication could ease gastrointestinal side effects and could potentially be less expensive, says Ezra Cohen, a cancer specialist at the University of Chicago. Cohen’s team recently published preliminary results of such an effort in Clinical Cancer Research. In the study, one group of people with incurable cancer drank a glass of grapefruit juice with Rapamune (sirolimus), an oral medication approved by the Food and Drug Administration to prevent rejection of organ transplantations. (The drug is not approved for cancer treatment.) The grapefruit juice boosted blood levels of Rapamune by 350 percent. Cohen’s group is working to extend their findings to larger trials.

It is not that grapefruit and related fruits or interacting drugs are bad. It's all about the circumstances of use.

But Bailey and Paine express concern that mixing grapefruit juice in such a manner would likely make blood levels of anticancer agents unpredictable, and there’s currently no simple test to forecast the intended response beforehand.

"It is not that grapefruit and related fruits or interacting drugs are bad," Bailey says. "It's all about the circumstances of use. Although these adverse interactions may occur in low frequency in the patient population, which we don’t currently know, the consequences [can be] dire and easily preventable. Caution is by far the wisest approach."

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