Drug Interactions

Limited studies have evaluated drug-drug interactions for etanercept. Concomitant treatment with methotrexate, warfarin, or digoxin does not significantly affect the pharmacokinetic profile of etanercept (Zhou 2005). This is particularly important in the case of methotrexate, which is often given concomitantly with etanercept in patients with rheumatoid arthritis. A pharmacokinetic modeling study reported that etanercept absorption, bioavailability, volume of distribution, and clearance were similar in patients receiving etaner-cept monotherapy and in those receiving combination therapy with etanercept and methotrexate (Zhou et al. 2004a). Digoxin reduced the mean peak concentration of etanercept by 4.2 % and the area under the curve by 12.5 %. This attenuation was not considered to be clinically relevant (Zhou 2005). Likewise, etanercept does not significantly affect the pharmacokinetics of any of these agents (methotrexate, warfarin, or digoxin); therefore, no dosage adjustment must be made for the coadministration of these agents with etanercept.

Etanercept should not be coadministered with ana-kinra. Concomitant administration has been associated with an increased risk of serious infections and neutropenia (European Medicines Agency 2005; Enbrel: US Full Prescribing Information 2006). In a clinical study of patients who were receiving established doses of sulfasalazine, those patients who were receiving a combination of etanercept and sulfasalazine experienced statistically significant reductions in mean white blood cell counts relative to patients receiving sulfasalazine alone. No interactions have been observed in clinical trials with the concurrent administration of etanercept with glucocorticoids, salicylates (except sulfasalazine), nonsteroidal anti-inflammatory drugs, analgesics, or methotrexate.

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