Grapefruit and grapefruit juice can alter the metabolism of atorvastatin, lovastatin, and simvastatin by interfering with the cytochrome P-450 (CYP4) enzyme system.1 This system is responsible for the first pass metabolism of certain drugs, including these specific statins. Grapefruit consumption has been shown to increase the serum levels of these drugs to varying degrees.2,3 The increased bioavailability of these statins after co-administration with other CYP4 enzyme substrates has led to the occurrence of the drug’s known serious adverse effects.4–6 For this reason, doctors have generally discouraged the use of grapefruit and grapefruit juice in people taking these statins to avoid potential toxicity.7 However, there are no case reports of adverse effects due to the co-administration of statins with grapefruit juice.
Reddy et al. conducted a drug trial to determine if regular exposure to grapefruit juice had a measurable impact on serum concentration of atorvastatin, lipid profiles, and adverse effects.8 The daily addition of 300 ml of grapefruit juice for 90 days among patients taking atorvastatin (10, 20, or 40 mg/day) resulted in small increases in drug bioavailability, but had no meaningful effect on lipid profile or adverse effects (liver function, creatine phosphokinase levels, myalgias).
More recently, studies have been done to better estimate the effects of a single glass of grapefruit juice when taken with these statins.9,10 Lee et al. conducted pharmacokinetic studies on the effect of grapefruit juice co-administered with simvastatin, lovastatin, and atorvastatin. A single glass of grapefruit juice co-administered with a statin increased blood levels of simvastatin and lovastatin by 260%. Taking simvastatin and lovastatin 12 hours apart from the grapefruit juice increased the blood levels by 90%. The effect on atorvastatin blood levels was an 80% increase regardless of timing. The authors pointed out that the effect of the grapefruit juice was to increase the effective dose of the statin. Rather than discourage the consumption of grapefruit or grapefruit juice among people taking these statins, they emphasized its beneficial effect on lowering cholesterol. The authors estimated the risk of rhabdomyolysis among statin users to be about 4 per 100,000 person-years. In their view, the added therapeutic benefit of the increased bioavailability that may occur when these statins are taken with grapefruit far outweighs the extremely small risk of a serious adverse effect. Other authors have proposed that co-administration of grapefruit with statins could be considered for its potential to reduce the dosage requirements of the statin.10
References
- Kane GC, Lipsky JJ. Drug-grapefruit juice interactions. Mayo Clin Proc. 2000;75(9):933-942. doi:10.4065/75.9.933
- Lilja JJ, Kivistö KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther. 1999;66(2):118-127. doi:10.1053/cp.1999.v66.100453001
- Rogers JD, Zhao J, Liu L, et al. Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Clin Pharmacol Ther. 1999;66(4):358-366. doi:10.1053/cp.1999.v66.a101208
- Schmassmann-Suhijar D, Bullingham R, Gasser R, Schmutz J, Haefeli WE. Rhabdomyolysis due to interaction of simvastatin with mibefradil. Lancet. 1998;351(9120):1929-1930. doi:10.1016/S0140-6736(05)78613-X
- Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med. 1995;333(10):664-665. doi:10.1056/NEJM199509073331015
- Spach DH, Bauwens JE, Clark CD, Burke WG. Rhabdomyolysis associated with lovastatin and erythromycin use. West J Med. 1991;154(2):213-215.
- Lim GE, Li T, Buttar HS. Interactions of grapefruit juice and cardiovascular medications: A potential risk of toxicity. Exp Clin Cardiol. 2003;8(2):99-107.
- Reddy P, Ellington D, Zhu Y, et al. Serum concentrations and clinical effects of atorvastatin in patients taking grapefruit juice daily. Br J Clin Pharmacol. 2011;72(3):434-441. doi:10.1111/j.1365-2125.2011.03996.x
- Lee JW, Morris JK, Wald NJ. Grapefruit juice and statins. Am J Med. 2016;129(1):26-29. doi:10.1016/j.amjmed.2015.07.036
- Kiani J, Imam SZ. Medicinal importance of grapefruit juice and its interaction with various drugs. Nutr J. 2007;6:33. doi:10.1186/1475-2891-6-33
