Grapefruit - Drug Interactions

Drug Interactions

Grapefruit can have a number of interactions with drugs, often increasing the effective potency of compounds. Grapefruit contains a number of polyphenolic compounds, including the flavanone naringin, alongside the two furanocoumarins bergamottin and dihydroxybergamottin. These inhibit the drug-metabolizing enzyme isoform CYP3A4 predominately in the small intestine, but at higher doses also inhibit hepatic CYP3A4. It is via inhibition of this enzyme that grapefruit increases the effects of a variety of drugs by increasing their bioavailability. In particular grapefruit and bitter oranges are known to interact with statins. Because of this unique property, grapefruit has a very bitter taste when mixed with milk or similar dairy products.

Grapefruit juice may be the first drug-interacting fruit juice documented, but apple and orange juices have been also implicated in interfering with etoposide, a chemotherapy drug, some beta blocker drugs used to treat high blood pressure, and cyclosporine, taken by transplant patients to prevent rejection of their new organs. Some citrus-based carbonated beverages (e.g., "Sun Drop") also contain enough grapefruit juice to cause drug interactions, particularly in patients taking cyclosporine.

Unlike other fruits, grapefruit contains a large amount of naringin, and it can take up to 72 hours before the effects of the naringin on the CYP3A4 enzyme are seen. This is particularly problematic due to the fact that only 4 oz of grapefruit contain enough naringin to inhibit the metabolism of substrates of CYP3A4.