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 Adverse Cases

Back Reported Adverse Drug Reaction Cases
Interactions with grapefruit juice
The serendipitous discovery in 1991 of the interaction of grape fruit juice with drugs occurred when grapefruit juice was used to mask the taste of ethanol in a study testing an interaction between the dihydropyridine calcium channel blocker felodipine and ethanol.1 It is now known that grapefruit juice can interact with a number ofdrugs, the basis of the interaction being the local inhibition of one of the cytochrome P450 enzymes (CYP3A4) and P-glycoprotein (Pgp) in enterocytes in the intestinal wall.2 It has been shown that grapefruit juice does not affect hepatic CYP3A4.

Interactions with grapefruit juice have been most frequently studied with the dihydropyridine calcium channel blockers (CCBs) including felodipine and nifedipine. Significant interactions have also been found for some of the HMG-CoA reductase inhibitors (statins), particularly simvastatin but possibly also atorvastatin; the benzodiazepines midazolam and triazolam; as well as cyclosporin, saquinavir, and cisapride. This is not an exhaustive list and there are a number of other drugs with a potential for interaction which have not been studied. A recent article in the Australian Prescriber contains a more comprehensive list.3 The two most important characteristics of the "target" drugs are metabolism by gut wall CYP3A4 and/or Pgp and associated low oral bioavailability.

ADRAC has received 14 reports describing possible interactions with grapefruit juice. Most have involved either the dihydropyridine
CCBs (5) or statins (5). Three of the reports with CCBs have involved amlodipine, an interaction which is usually considered
clinically insignificant. Grapefruit juice can inhibit the metabolism of target drugs and increase the amount of parent drug available for absorption, which may result in an increase in its pharmacological or toxic effects. For the CCBs, the reports usually describe
hypotension and related symptoms, and for the statins, most reports describe myalgia and associated effects.

Prescribers should be aware that there are several groups of drugs that may interact with grapefruit juice and patients taking these drugs should be made aware of the possibility. It should also be noted that problems can arise from whole grapefruit (as in four of the ADRAC reports), and that the extent of the interaction can vary  with different brands and strengths of juice. It is believed that with the exception of bitter Seville oranges, the interaction does not occur with other citrus fruits.

Options for discussion with patients include:

             -Avoid grapefruit juice all together 
             -Take medication with grapefruit juice every day (with
              dose adjustment if necessary) 
             -Separate grapefruit juice and medication by a minimum
              of 2 hours


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