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

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

Author information

1
Department of Clinical Pharmacology, F. Hoffmann-La Roche AG, Basel, Switzerland. christophe.schmitt@roche.com

Erratum in

  • Clin Pharmacol Ther. 2011 Sep;90(3):479. Dosage error in article text.

Abstract

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.

PMID:
21430660
DOI:
10.1038/clpt.2011.35
[Indexed for MEDLINE]

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