Intraoperative Rhabdomyolysis in a Patient Receiving Pravastatin, a 3-Hydroxy-3-methylglutaryl Coenzyme A (HMG CoA) Reductase Inhibitor

Rosenberg, Andrew D.; Neuwirth, Michael G.; Kagen, Lawrence J.; Singh, Kumkum; Fischer, Harry D.; Bernstein, Ralph L.

doi:10.1213/00000539-199511000-00034

Cited by 1 publication

(1 citation statement)

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“…Lovastatin and active metabolite AUCs were increased more than twenty‐fold when administered with itraconazole suggesting the adverse effect has a pharmacokinetic basis [86]. Rhabdomyolysis has also been reported with simvastatin [88, 89] and pravastatin [90, 91]. Thus, a clinically important interaction may occur between grapefruit juice and lovastatin and possibly other HMG‐CoA reductase inhibitors.…”

Section: Drugs Interacting With Grapefruit Juicementioning

confidence: 99%

Grapefruit juice–drug interactions

Bailey

Malcolm

Arnold

et al. 1998

Brit J Clinical Pharma

628

165

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The novel finding that grapefruit juice can markedly augment oral drug bioavailability was based on an unexpected observation from an interaction study between the dihydropyridine calcium channel antagonist, felodipine, and ethanol in which grapefruit juice was used to mask the taste of the ethanol. Subsequent investigations showed that grapefruit juice acted by reducing presystemic felodipine metabolism through selective post-translational down regulation of cytochrome P450 3A4 (CYP3A4) expression in the intestinal wall. Since the duration of effect of grapefruit juice can last 24 h, repeated juice consumption can result in a cumulative increase in felodipine AUC and C max . The high variability of the magnitude of effect among individuals appeared dependent upon inherent differences in enteric CYP3A4 protein expression such that individuals with highest baseline CYP3A4 had the highest proportional increase. At least 20 other drugs have been assessed for an interaction with grapefruit juice. Medications with innately low oral bioavailability because of substantial presystemic metabolism mediated by CYP3A4 appear affected by grapefruit juice. Clinically relevant interactions seem likely for most dihydropyridines, terfenadine, saquinavir, cyclosporin, midazolam, triazolam and verapamil and may also occur with lovastatin, cisapride and astemizole. The importance of the interaction appears to be influenced by individual patient susceptibility, type and amount of grapefruit juice and administration-related factors. Although in vitro findings support the flavonoid, naringin, or the furanocoumarin, 6∞,7∞-dihydroxybergamottin, as being active ingredients, a recent investigation indicated that neither of these substances made a major contribution to grapefruit juice-drug interactions in humans.

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