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More cancer patients are turning to complementary and alternative medicines, either as primary cancer treatment, an augmentation to cancer treatment or to help in the relief of side effects caused by treatment or cancer itself. Since complementary/alternative agents or methods are not closely regulated in the U.S., it is important for patients to be aware of possible adverse events that may occur with the use of these products. As research on these drug-CAM interactions continues, potentially adverse effects of drugs and common food items have also been reported.

Grapefruit and grapefruit juice are commonly consumed fruit/fruit juices. An unusual discovery in 1989 found that grapefruit juice has the potential to interact with an important biologic pathway, known as cytochrome P450, that is involved in the metabolism of many commonly used drugs. A specific form of this pathway, known as CYP3A4, is present in the liver and the intestines. Grapefruit juice appears to bind to this pathway in the intestine, preventing the drugs from being absorbed through the intestine and elevating the circulating level of the drug in the body.

As little as 250 ml of grapefruit juice can affect metabolism of some drugs, lasting for up to 24 hours. Research has indicated that grapefruit produces the same effect as grapefruit juice, but that oranges do not. Because of the prolonged response, separating the intake of grapefruit/grapefruit juice and the drug does not appear to lessen interference. Additionally, because individuals have different levels of CYP3A4 expression, some people are more susceptible to the interaction than others.

It is possible that scientists could use this interaction to their benefit, intentionally increasing the bioavailability (the degree to which a drug becomes available to the target tissue/organs) of specific drugs. In the meantime, however, the potential side effects from elevated levels of drugs pose a serious threat. The table below is an incomplete list of potential drug interactions between grapefruit/grapefruit juice and drugs metabolized by CYP3A4.

Table 1: Possible interactions between grapefruit juice (GJ)* and drugs metabolized by CYP3A4.

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* Grapefruit juice and the whole fruit.

†Clinical significance unknown.

Reference: Maskalyk, J. Grapefruit juice: potential drug interactions.

Canadian Medical Association Journal. 2002; 167: 279–280.