Pharmacological interactions of statins

Atheroscler Suppl. 2002 May;3(1):35-40. doi: 10.1016/s1567-5688(02)00002-8.


The 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are effective in reducing the risk of coronary events, and are generally very well tolerated. However, simvastatin, lovastatin, cerivastatin and atorvastatin are biotransformed in the liver primarily by cytochrome P450 (CYP) 3A4, and clinical experience has shown that the risk of adverse effect, such as myopathy, increases with concomitant use of statins with drugs that substantially inhibit CYP 3A4 at therapeutic doses. Indeed, pharmacokinetic interactions (e.g. increased bioavailability), myositis, and rhabdomyolysis have been reported following concurrent use of atorvastatin, cerivastatin, simvastatin or lovastatin and cyclosporine A, mibefradil or nefazodone. In contrast, fluvastatin (mainly metabolized by CYP 2C9) and pravastatin (eliminated by other metabolic routes) are less subject to this interaction. Nevertheless, an increase in pravastatin bioavailability has been reported in the presence of cyclosporine A, possibly because of an interaction at the level of biliary excretion. In summary, some statins may have lower adverse drug interaction potential than others, which is an important determinant of safety during long-term therapy.

Publication types

  • Review

MeSH terms

  • Atorvastatin
  • Cytochrome P-450 Enzyme System / drug effects*
  • Drug Interactions
  • Drug Tolerance
  • Heptanoic Acids / adverse effects
  • Heptanoic Acids / pharmacology
  • Heptanoic Acids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / adverse effects*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Hypercholesterolemia / drug therapy*
  • Lovastatin / adverse effects*
  • Lovastatin / pharmacology
  • Lovastatin / therapeutic use
  • Muscular Diseases / etiology*
  • Pyrroles / adverse effects
  • Pyrroles / pharmacology
  • Pyrroles / therapeutic use
  • Rhabdomyolysis / etiology


  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Pyrroles
  • Cytochrome P-450 Enzyme System
  • Lovastatin
  • Atorvastatin