Grapefruit juice
Grapefruit juice contains a psoralen which inhibits the metabolism of certain drugs by enzymes of the CYP3A4 subfamily of cytochrome P450. As CYP3A4 is involved in the metabolism of many drugs that are currently in use therapeutically, there are many clinically significant drugs interactions that have been reported with grapefruit juice. These drugs include cyclosporin, terfenadine, ergot derivatives, calcium channel blockers and statins.
Evidence for these interactions comes largely from studies of simultaneous administration of grapefruit juice and the relevant drugs. As little as one glass of grapefruit juice (250 mL) has been reported to result in a drug interaction. The importance of the interaction appears to be influenced by various factors including individual patient susceptibility, type and amount of grapefruit juice.
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Recommendations
Some sources recommend not to ingest grapefruit juice within 2 hours before and 5 hours after intake of a drug while others suggest that the inhibitory effects of grapefruit juice may last for 3 days or longer. A safer alternative is to avoid consuming grapefruit and its juice when taking drugs known to be metabolised by CYP3A4.
Whilst sweet oranges and their juice do not appear to cause similar type of drug interactions, sour orange juice such as that from Seville oranges, may have similar effect to grapefruit juice. Tangelos are a hybrid of grapefruit and may also interfere with drugs. Most other citrus fruits, such as lemons, limes, naturally sweet oranges and tangerines are considered safe.
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Cranberry juice
One fatal case involved a man whose INR dramatically increased (INR > 50) 6 weeks after starting to drink cranberry juice. The patient died from gastrointestinal and pericardial haemorrhage. In another 2 cases, less dramatic INR increases were noted whilst the patients were taking cranberry juice. One of these 2 patients was stabilized on a lower dose of warfarin and the other, after stopping cranberry juice. In the 4th case, the INR was reported to be generally unstable after cranberry ingestion and in the 5th case, an INR decrease was reported. The CSM conjectured that the interaction was biologically plausible based on 2 grounds:
i) Cranberry juice contains various antioxidants including flavonoids, which are known to inhibit cytochrome P450 activity; and warfarin is predominantly metabolised by CYP2C9.
ii) The constituents of different brands of cranberry juice may vary, and that such variations might affect the potential for drug interactions.
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Recommendations
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