Does pomegranate juice interact pharmacologically with simvastatin, enalapril or amlodipine?

Fråga: Does pomegranate juice interact pharmacologically with simvastatin, enalapril or amlodipine?

Sammanfattning: There is no clear evidence that pomegranate juice could interact pharmacologically with simvastatin, enalapril or amlodipine, but theoretically it could inhibit the elimination of simvastatin and amlodipine. If continuous use of concentrated pomegranate juice is initiated, intensified blood pressure monitoring could be recommended and the patient should be informed about symptoms compatible with simvastatin toxicity (e.g. myalgia).

Svar: We have found no reports of interactions between pomegranate and the three drugs in Drugline, Medline or standard pharmacologic literature.

In vitro studies indicate that pomegranate juice may inhibit the drug metabolizing enzymes cytochrome P450 2C9 (CYP2C9) and CYP3A4 (1). In addition, there are case reports describing increased effect of warfarin and increased concentrations of tacrolimus (metabolised by CYP2C9 and CYP3A4) in patients ingesting pomegranate juice (2). Both simvastatin and amlodipine are metabolised by CYP3A4 and hence there is a theoretical risk that pomegranate juice could inhibit the metabolism of these drugs (3, 4). This notion is contradicted by an unpublished study in 12 healthy volunteers failing to demonstrate an effect of pomegranate on the pharmacokinetics of simvastatin (3). In addition, two crossover studies in healthy volunteers (n=13 and n=16) have failed to show an effect of pomegranate juice on the pharmacokinetics of orally administered midazolam, a probe drug for determination of CYP3A4 activity (6, 7). In a newly published in vitro study in cultured macrophages, pomegranate increased the cholesterol lowering effect of simvastatin. However, this effect could not be attributed to increased simvastatin levels but rather to an inhibitory effect on cholesterol synthesis by pomegranate juice per se (5). Drugline nr 24236 (år 2011)

SFINX (Swedish, Finnish INteraction X-referencing) (citerat 2013-04-09)
Drugline nr 23552 (år 2008)
SPC Norvasc

Rosenblat M, Volkova N, Aviram M. Pomegranate phytosterol (beta-sitosterol) and polyphenolic antioxidant (punicalagin) addition to statin, significantly protected against macrophage foam cells formation. Atherosclerosis. 2013;226:110-7. Farkas D, Oleson LE, Zhao Y, Harmatz JS, Zinny MA, Court MH et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 2007;47(3):286-294 Misaka S, Nakamura R, Uchida S, Takeuchi K, Takahashi N, Inui N et al. Effect of 2 weeks´ consumption of pomegranate juice on the pharmacokinetics of a single dose of midazolam: an open-label, randomized, single-center, 2-period crossover study in healthy Japanese volunteers. Clin Ther 2011;33(2):246-252