Disease-drug-drug interaction involving tocilizumab and simvastatin in patients with rheumatoid arthritis

Clin Pharmacol Ther. 2011 May;89(5):735-40. doi: 10.1038/clpt.2011.35. Epub 2011 Mar 23.


In rheumatoid arthritis (RA), interleukin-6 (IL-6) concentration is elevated, which may cause reduced cytochrome P450 (CYP) activity and increased exposure (peak plasma concentration and area under the plasma concentration-vs.-time curve (AUC)) to certain drugs. Tocilizumab may reverse IL-6-induced suppression of CYP3A4 activity. In this study, exposure to simvastatin was significantly reduced at 1 and 5 weeks after tocilizumab infusion in 12 patients with RA. The mean effect ratio for simvastatin AUC(last) was 43% (90% confidence interval (CI), 34-55%) at 1 week after tocilizumab infusion (day 15) and 61% (90% CI, 47-78%) at 5 weeks after tocilizumab infusion, as compared with baseline (day 1); both ratios were significantly lower than the bioequivalence boundary (80-125%). Mean plasma C-reactive protein (CRP) levels normalized within 1 week after tocilizumab was initiated; the time course of tocilizumab's CRP-reducing effect paralleled that of simvastatin pharmacokinetics. The study findings suggest that caution should be exercised when starting tocilizumab in RA patients who are taking simvastatin.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / blood*
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents / blood*
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy*
  • Drug Interactions / physiology
  • Female
  • Humans
  • Interleukin-6 / blood
  • Male
  • Middle Aged
  • Simvastatin / blood*
  • Simvastatin / therapeutic use


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antirheumatic Agents
  • Interleukin-6
  • Simvastatin
  • tocilizumab