Effects of Grapefruit
Juice on the Toxicity of
Statins in Clinical Practice
HMG CoA reductase inhibitors such as simvastatin, lovastatin and atorvastatin have been extensively prescribed in patients with coronary heart disease, with a substantial decrease in cardiovascular mortality. They have low and highly variable oral bioavailability (5 to 40%) mainly due to an extensive, cytochrome P450 3A4 mediated intestinal metabolism. Because intestinal CYP3A4 activity can be modulated by numerous drugs and food products, these medications are subject to clinically relevant drug/drug or drug/food interaction, especially with grapefruit juice which contains high amount of furanocoumarins known as potent inhibitors of intestinal CYP3A4. Coadministration of one of these three statins with grapefruit juice increases their serum concentrations by 3 to 16 fold, leading to an increased risk of severe rhabdomyolysis. Moreover, a single glass of 200 mL grapefruit juice can inhibit intestinal CYP3A4 activity for three days. Consequently, the use of simvastatin, lovastatin or atorvastatin should be avoided in association with grapefruit juice. Pravastatin, fluvastatin and rosuvastatin should be preferred, as they are not CYP3A4 substrates and to date, no interaction have been described with grapefruit juice.