Grapefruit Juice and Medications: A Potential for Adverse Events

July 5, 2001

Many patients may take their medications with a glass of juice. However, since the accidental discovery of an interaction between the calcium channel blocker, felodipine, with grapefruit juice¹, it has now become evident that grapefruit juice has the potential to alter the plasma concentrations of many medications

when they are taken by mouth. In some cases, this may result in undesirable clinical effects of medications.

Administration of grapefruit juice in humans results in a decrease in the level of CYP3A in the intestine², an important site for metabolism for many medications. This mechanism would account for the increase in levels of medications that are metabolized by CYP3A when concomitantly administered with grapefruit juice.

A list of medications that have been shown, in clinical studies, to have an interaction with grapefruit juice can be found in the table below. All of the medications, except for theophylline and itraconazole, are known to be substrates of CYP3A. When given with grapefruit juice in pharmacokinetic studies their availability increases. In most cases, the clinical consequence of the pharmacokinetic interaction has not been evaluated. However, for midazolam and triazolam, as well as for buspirone, impairment of CNS function was observed, and for the calcium channel blocker felodipine greater blood pressure lowering has been observed. In contrast to the increased levels of the other medications, the grapefruit juice interaction observed with theophylline and itraconazole was reduced plasma concentrations. The mechanism for this effect has not been determined.

Although the clinical consequence of the grapefruit juice interaction with most of the listed drugs has not been evaluated, increased plasma concentrations of many of these drugs could result in adverse outcomes. Examples include excessive lowering of blood pressure with the calcium channel blockers, rhabdomyolysis and the potential for renal impairment with the HMG CoA reductase inhibitors, and adverse pulmonary effects of amiodarone. Inconsistent use of grapefruit juice or variability in its effect on drug metabolism could result in variable and difficult to control plasma concentrations of other medications, where maintaining a certain plasma concentration may be especially important, such as for cyclosporine or for HIV protease inhibitors like saquinavir.

In light of the potential for serious adverse outcomes, patients taking medications with a potential for interaction with grapefruit juice should be advised to avoid drinking grapefruit juice. Possible interactions with whole grapefruit have not been evaluated but it would be assumed to have similar effects.

Note: Medication names are hyperlinked to references in PubMed

Reference

1. Bailey DG, Spence JD, Munoz C, Arnold JMO. Interaction of citrus juices with felodipine and nifedipine. Lancet 1991; 337:268-9.
2. Lown KS, Bailey DG, Fontana RJ, et al. Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression.

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