Effect of Rofecoxib on Renal Function is Similar to Nonselective NSAIDs

Swan et al published results (Annals of Int Med 133:1-9, 2000) of a two- part study comparing effects on renal function in patients receiving rofecoxib or indomethacin. Glomerular filtration rate, creatinine clearance and urinary and serum sodium and potassium levels were assessed. Patients (n=15) received a single dose of either 250 mg rofecoxib (5-20-fold higher than the recommended dose), 75 mg indomethacin, or placebo in the first study. In the second study, patients (n=60) received multiple doses of 12.5 mg/day rofecoxib, 25 mg/day rofecoxib, 50 mg tid indomethacin, or placebo for 5 days. All patients in both groups were on low-sodium diets. Blood and urine specimens were taken every 30 minutes 2 hours pre- and 6 hours post-drug administration in the single dose study. In the multiple dose study, glomerular filtration was assessed pre (day 1) and post (day 6) of drug administration.

Single doses of rofecoxib and indomethacin reduced the glomerular filtration rate by 0.23 mL/s (P<0.001) and 0.18 mL/s (P<0.003), respectively. In the multiple dose study, the rate was reduced by 0.14, 0.13, and 0.10 mL/s in patients receiving 12.5 mg/day rofecoxib (P=0.019), 25 mg/day rofecoxib (P=0.029), and indomethacin (P=0.086), respectively. Changes in sodium and potassium serum levels were seen, although less pronounced. No significant differences were noted in creatinine clearance between treatment groups and placebo. These data suggest that the COX-2 selective drug, rofecoxib, has effects on renal function that are similar to nonselective NSAIDs. Therefore, rofecoxib should be used cautiously in patients at risk for renal insufficiency.

Editorial comment: Similar results were published for the other COX-2 selective agent, celecoxib (Rosat, et al. Clin Pharmacol Ther 66:76-84, 1999).