Author’s reply to Backman and BakhaiBMJ 2013; 346 doi: http://dx.doi.org/10.1136/bmj.f1078 (Published 26 February 2013) Cite this as: BMJ 2013;346:f1078
- Munir Pirmohamed, professor of clinical pharmacology1
- 1Wolfson Centre for Personalised Medicine, Institute of Translational Medicine, University of Liverpool, Liverpool L69 3GL, UK
Backman and Bakhai question the clinical importance of drug-grapefruit juice interactions, focusing on statins.1 2 The risk of statin related myopathy is concentration dependent, but not everybody with the same (high) plasma statin concentration develops muscle injury (because susceptibility varies).3 However, anecdotal evidence or the sparseness of case reports cannot prove there is no risk. Drug histories are poorly documented in case notes, and direct questioning of dietary habits is virtually non-existent.
Thus, we have no data on the numerator (patients with statin myopathy while consuming grapefruit juice) or denominator (all patients who consume grapefruit juice while on statins). Serious adverse reactions are also under-reported—the Yellow Card database has only four reports of an interaction between simvastatin and grapefruit juice (M Foy, Medicines and Healthcare Products Regulatory Agency, personal communication, 2013).
Moreover, 200 mL grapefruit juice can increase the kinetic parameters of 40 mg simvastatin 3.3-4.3 fold.4 Given the dose proportionality of simvastatin pharmacokinetics, increasing its dose from 40 mg/day to 80 mg/day doubles the kinetic parameters. We now rarely use 80 mg/day simvastatin because of the risk of muscle injury, so why should we have different rules for the interaction between grapefruit juice and simvastatin?
We cannot predict who will develop statin myopathy or quantify the risk in patients who drink grapefruit juice, so I stand by my recommendation to avoid grapefruit juice in patients taking simvastatin or atorvastatin. Statins that do not interact with grapefruit juice, such as rosuvastatin and pravastatin, provide an option for patients who do not want to change their dietary habits. Fruit juices that do not interact with CYP3A4 metabolised drugs probably have health benefits similar to those of grapefruit juice.
Cite this as: BMJ 2013;346:f1078
Competing interests: None declared.