Should statins be taken with or without food?

The package inserts for statins available for use in the US generally do not discourage their administration with food.^1–7 Inserts for pitavastatin, rosuvastatin, and fluvastatin specifically state they can be taken with or without food. Lovastatin product information specifically recommends it be taken with food.⁴ However, administration of a drug with food is known to potentially alter the pharmacokinetics.⁸ The product information for pravastatin and fluvastatin reports that the systemic bioavailability of this statin is reduced when taken with food, but the lipid-lowering effect is the same when taken with or without food. Clinical trials for atorvastatin produced data showing that plasma concentration of the drug was lower when administered with food compared to fasting administration.⁹

McClean et al. investigated the association of fed and fasted rosuvastatin administration in patients with dyslipidemia whose statin dosage was titrated to achieve therapeutic benefit. The average dose of rosuvastatin was not significantly different between the two groups, suggesting the food did not alter the low-density lipoprotein cholesterol-lowering effects.¹⁰ Patients were stratified into fed (n=75) and unfed (n=82) dosing based on patient report. In a separate arm of the study, taking rosuvastatin with food reduced the serum levels (area under the curve) of the drug in 12 healthy Asian and 11 healthy Caucasian individuals by almost 40%. (Rosuvastatin clearance is known to differ among Caucasians compared to Asians due to variable prevalence of certain genetic polymorphisms.)^11,12  The authors conclude that these results taken together suggest that while food does not affect lipid-lowering benefits, it may reduce systemic exposure to the medication, which might lower the risk of adverse side effects. However, there are no long-term mortality studies that looked at vascular events in these comparison groups.

^References

1. Rosuvastatin [package insert]. Wilmington DE: AstraZeneca Pharmaceticals, 2010.
2. Atorvastatin [package insert]. Dublin Ireland: Pfizer Parke-Davis, 2009.
3. Simvastatin [package insert]. Cramlington UK: Merck, Sharpe & Dohne, LTD, 2010.
4. Lovastatin [package insert]. Morgantown WV: Mylan Pharmaceuticals.
5. Fluvastatin [package insert]. East Hanover NJ: Novartis Pharmaceuticals, 2012.
6. Pitavastatin [package insert]. Tokyo, Japan: Kowa Pharmaceuticals, 2012.
7. Pravastatin [package insert]. Princeton, NJ: Bristol-Myers Squibb Company
8. Singh BN. Effects of food on clinical pharmacokinetics. Clin Pharmacokinet. 1999;37(3):213-255.
9. Radulovic LL, Cilla DD, Posvar EL, Sedman AJ, Whitfield LR. Effect of food on the bioavailability of atorvastatin, an HMG-CoA reductase inhibitor. J Clin Pharmacol. 1995;35(10):990-994.
10. McLean CC, Teft WA, Morse BL, Gryn SE, Hegele RA, Kim RB. Food effect on rosuvastatin disposition and low-density lipoprotein cholesterol. Clin Pharmacol Ther. 2018;104(3):525-533.
11. Birmingham BK, Bujac SR, Elsby R, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States. Eur J Clin Pharmacol. 2015;71(3):329-340.
12. Lee E, Ryan S, Birmingham B, et al. Rosuvastatin pharmacokinetics and pharmacogenetics in white and Asian subjects residing in the same environment. Clin Pharmaco