Risedronate sodium has been studied in phase III clinical trials involving >15,000 patients. The majority of the adverse effects observed in clinical trials were mild to moderate in severity and usually did not require cessation of therapy.
Adverse experiences reported in phase III clinical trials in postmenopausal women with osteoporosis treated for up to 36 months with risedronate sodium 5 mg/day (n=5020) or placebo (n=5048) and considered possibly or probably related to risedronate sodium are listed as follows using the following convention (incidences versus placebo are shown in parentheses): Very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (<1/10,000).
Nervous System Disorders: Common: Headache (1.8% vs 1.4%).
Eye Disorders: Uncommon: Iritis*.
Gastrointestinal Disorders: Common: Constipation (5% vs 4.8%), dyspepsia (4.5% vs 4.1%), nausea (4.3% vs 4%), abdominal pain (3.5% vs 3.3%), diarrhoea (3% vs 2.7%). Uncommon: Gastritis (0.9% vs 0.7%), oesophagitis (0.9% vs 0.9%), dysphagia (0.4% vs 0.2%), duodenitis (0.2% vs 0.1%), oesophageal ulcer (0.2% vs 0.2%). Rare: Glossitis (<0.1% vs 0.1%), oesophageal stricture (<0.1% vs 0%).
Musculoskeletal and Connective Tissue Disorders: Common: Musculoskeletal pain (2.1% vs 1.9%).
Investigations (Hepatobiliary): Rare: Abnormal liver function tests*.
*No relevant incidences from phase III osteoporosis studies; frequency based on adverse event/laboratory/rechallenge findings in earlier clinical trials.
In a 1-year, double-blind, multicenter study comparing risedronate sodium 5 mg daily (n=480) and risedronate sodium 35 mg weekly (n=485) in postmenopausal women with osteoporosis, the overall safety and tolerability profiles were similar. The following additional adverse experiences considered possibly or probably drug-related by investigators have been reported (incidence greater in risedronate sodium 35-mg than in risedronate sodium 5-mg group): Gastrointestinal disorder (1.6% vs 1%) and pain (1.2% vs 0.8%).
In a 2-year study in men with osteoporosis, the overall safety and tolerability were similar between the treatment and the placebo groups. Adverse experiences were consistent with those previously observed in women.
Laboratory Findings: Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some patients.
The following additional adverse reactions have been reported during post-marketing use (unknown frequency):
Eye Disorders: Iritis, uveitis.
Musculoskeletal and Connective Tissue Disorders: Osteonecrosis of the jaw.
Skin and Subcutaneous Tissue Disorders: Hypersensitivity and skin reactions, including angioedema, generalised rash, and bullous skin reactions, some severe.