BACKGROUND: Postmenopausal osteoporosis and renal insufficiency become more prevalent with increasing age. Following oral administration, risedronate is primarily eliminated via the kidneys. Reduced drug clearance and consequent elevated serum levels could potentially increase the likelihood of adverse events. OBJECTIVES: This analysis investigates the influence of renal function on the safety profile of risedronate 15 mg/day. This dose is 3 times the daily dosage approved for the prevention and treatment of postmenopausal osteoporosis in the U.S. and Europe. METHODS: The analysis included patients enrolled in the placebo-controlled phase III osteoarthritis clinical trials. Patients were randomized to receive placebo (N=622, female 70%: male 30%) or risedronate 15mg daily (N=609, female 71%: male 29%). For each patient, creatinine clearance was estimated using the Cockcroft-Gault methodology based on baseline serum creatinine, body weight and age. The incidence of adverse events was summarized for patients possessing a wide variety of renal function. RESULTS: The mean age (SE) of the risedronate-treated population was 61.6 (8.6) years and 61.9 years (8.8) for the placebo. The baseline range of creatinine clearance was 37.2 to 270.0 ml/min for the risedronate arm and 31.8 to 213.1 ml/min for placebo arm. The average duration of drug exposure was 104 weeks. There was no observed relationship between AE incidence rate and baseline renal function in the two treatment groups (placebo: R2=0.001; 15mg risedronate: R2=0.001). The AE incidence observed was also not statistically different between the treatment groups. CONCLUSION: This analysis shows, based on phase III clinical trial experience, that risedronate 15mg/day, which is 3 times higher than the usual dose for treatment of postmenopausal osteoporosis, demonstrates an excellent safety profile, similar to placebo, over a wide spectrum of renal function.
Disclosure Information:
Faculty Member's Name: Paul D. Miller, MD
Grants/Research Support: P&G Pharmaceuticals, Aventis, Roche, Eli Lilly, Pharmacia, Merck, Novartis, Pfizer, Amgen
Consultant: Procter & Gamble Pharmaceuticals, Aventis, Merck, Eli Lilly, Amgen, NPS, Novartis, Roche
Stock Shareholder (directly purchased): none
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