Risedronate sodium has been studied in phase III clinical trials involving more than 15,000 patients.
The majority of undesirable 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 below using the following convention (incidences versus placebo are shown in brackets): Very common (≥1/10); common (≥1/100; <1/10); uncommon (≥1/1,000; <1/100); rare (≥1/10,000; <1/1,000); very rare (<1/10,000).
Nervous system disorders:
Common: Headache (1.8% vs. 1.4%).
Common: constipation (5.0% vs. 4.8%), dyspepsia (4.5% vs. 4.1%), nausea (4.3% vs. 4.0%), abdominal pain (3.5% vs. 3.3%), diarrhoea (3.0% 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. 0.0%).
Musculoskeletal and connective tissues disorders:
Common: Musculoskeletal pain (2.1% vs. 1.9%).
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 one-year, double-blind, multicentre 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 35 mg than in risedronate sodium 5 mg group): gastrointestinal disorder (1.6% vs. 1.0%) 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.
Early, transient, asymptomatic and mild decreases in serum calcium and phosphate levels have been observed in some patients.
During post-marketing experience the following reactions have been reported (frequency rare): Atypical subtrochanteric and diaphyseal femoral fractures (bisphosphonate class adverse reaction).
The following additional adverse reactions have been reported during post-marketing use (frequency unknown): Eye disorders:
Muskuloskeletal and connective tissues disorders:
Osteonecrosis of the jaw.
Skin and subcutaneous tissue disorders:
Hypersensitivity and skin reactions, including angioedema, generalised rash, urticaria, bullous skin reactions and leukocytoclastic vasculitis, some severe including isolated reports of Stevens Johnson syndrome and toxic epidermal necrolysis; hair loss.
Immune system disorders:
Serious hepatic disorders.
In most of the reported cases the patients were also treated with other products known to cause hepatic disorders.