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Editorials

Drug-grapefruit juice interactions

BMJ 2013; 346 doi: https://doi.org/10.1136/bmj.f1 (Published 07 January 2013) Cite this as: BMJ 2013;346:f1

Re: Drug-grapefruit juice interactions

Backman and Bakhai question the clinical importance of drug-grapefruit juice interactions, focusing on statins. The risk of statin-related myopathy is concentration-dependent, but not everybody who has the same (high) plasma statin concentration will develop muscle injury (because susceptibility varies)1.

However, one cannot conclude that this risk is absent based on anecdotal evidence or the sparseness of case reports. Frankly, drug histories are poorly documented in case-notes, and direct questioning of dietary habits is virtually non-existent. Thus, we have no data on either the numerator (patients with statin myopathy while taking grapefruit juice) or denominator (all patients who consume grapefruit juice while on statins). There is also significant under-reporting of serious adverse reactions, reflected by the fact that there are only 4 reports of an interaction between simvastatin and grapefruit juice on the Yellow Card database (M Foy, MHRA, personal communication, Feb 2013).

Moreover, 200ml of grapefruit juice can increase the kinetic parameters of 40mg simvastatin between 3.3-4.3 fold2. Given the dose proportionality of simvastatin pharmacokinetics, an increase in its dose from 40mg to 80mg/day leads to doubling of the kinetic parameters. We now rarely use 80mg/day simvastatin because of the risk of muscle injury, and so why should we have different rules for the interaction between grapefruit juice and simvastatin?

To conclude, we can neither predict who will develop statin myopathy, nor quantify the risk in patients who drink grapefruit juice. Thus, I would stand by my recommendation to avoid grapefruit juice in patients who take simvastatin or atorvastatin. Of course, there are statins (e.g. rosuvastatin and pravastatin) which do not interact with grapefruit juice providing an option for patients who do not want to change their dietary habits.

Finally, other fruit juices, which do not interact with CYP3A4-metabolised drugs are likely to have health benefits similar to those of grapefruit juice.

1. Link E, Parish S, Armitage J, Bowman L, Heath S, et al. SLCO1B1 variants and statin-induced myopathy--a genomewide study. N Engl J Med 2008;359(8):789-99.
2. Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004;58(1):56-60.

Competing interests: No competing interests

15 February 2013
Munir Pirmohamed
Professor of Clinical Pharmacology
The University of Liverpool
Wolfson Centre for Personalised Medicine, 1-5 Brownlow Street, Liverpool, L3 5TY