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| |  Monitoring of Methotrexate Toxicity Needed When Etoricoxib Is Added to Methotrexate in Rheumatoid Arthritis: Presented at AACP By Maggie Schwarz PHILADELPHIA -- September 21, 2008 -- No dosage adjustment is needed when etoricoxib is added to methotrexate in patients with rheumatoid arthritis, but methotrexate toxicity needs to be monitored in these patients, according to research presented here at the American College of Clinical Pharmacology (ACCP) 37th Annual Meeting. Patients with rheumatoid arthritis often require multimodal management of disease progression and symptoms that includes nonsteroidal anti-inflammatory drugs, biological response modifiers, and disease-modifying antirheumatic drugs (DMARDs). Jules I. Schwartz, PharmD, MPH, Merck Research Laboratories, Rahway, New Jersey, presented the results of his group's dose-escalation study on September 15. Methotrexate is among the most widely used DMARD in rheumatoid arthritis, though it is often associated with dose-dependent toxicities that require consideration of potential drug interactions that might increase methotrexate exposure. Dr. Schwartz and colleagues conducted 2 double-blind, randomised, controlled trials to determine the influence of etoricoxib on the pharmacokinetics of methotrexate in patients with rheumatoid arthritis who were receiving stable doses of oral methotrexate (7.5 and 20 mg) at baseline, day 7, and day 14. In the first study, 14 patients were randomised to etoricoxib 60 mg QD from days 1 to 7 and 120 mg QD from days 8 to 14. Four patients were randomised to placebo from days 1 to 14. In the second study, 25 patients were randomised to etoricoxib at 90 mg QD from days 1 to 7 and 120 mg QD from days 8 to 14. Four patients were randomised to placebo from days 1 to 14. Etoricoxib 60 and 90 mg had no effect on plasma concentrations or renal clearance of methotrexate. In study 1, with etoricoxib 120 mg, a 28% increase in plasma concentration of methotrexate (by area under the curve) and a 13% decrease in methotrexate renal clearance were observed. In study 2, etoricoxib 120 mg exerted no effect on methotrexate pharmacokinetics. No reliable explanation could be found for the difference in results for the effect of 120-mg etoricoxib on methotrexate plasma concentrations in studies 1 and 2. Dr. Schwartz concluded that no adjustment to the dose of methotrexate is needed when etoricoxib is added to a regimen including methotrexate. Standard monitoring of methotrexate-related toxicity, however, should be continued when etoricoxib and methotrexate are administered concurrently, especially with doses greater than 90 mg etoricoxib, according to the researchers.
[Presentation title: Effect of Increasing Doses of Etoricoxib on Oral Methotrexate Pharmacokinetics in Patients With Rheumatoid Arthritis. Abstract 124]
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