Clinical Trials: Treatment of postmenopausal osteoporosis: Once-monthly dosing: In a two-year study in postmenopausal women with osteoporosis (BM16549) the overall safety of Bonviva 150 mg once monthly and Bonviva 2.5 mg daily was similar. The overall proportion of patients who experienced an adverse drug reaction, i.e. adverse event with a possible or probable relationship to trial medication, was 22.7 % and 25.0 % for Bonviva 150 mg once monthly and 21.5 % and 22.5 % for Bonviva 2.5 mg daily after one and two years, respectively. The majority of adverse drug reactions were mild to moderate in intensity. Most cases did not lead to cessation of therapy.
Tables 2 and 3 list adverse drug reactions occurring in more than 1 % of patients treated with Bonviva 150 mg monthly or 2.5 mg daily in study BM16549 and in patients treated with Bonviva 2.5 mg daily in study MF4411. The tables show the adverse drug reactions in the two studies that occurred with a higher incidence than in patients treated with placebo in study MF4411. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Data at one year from study BM16549 are represented in Table 2 and cumulative data for the two years from study BM16549 are represented in Table 3. (See Tables 2 and 3.)
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Click on icon to see table/diagram/image
Adverse drug reactions occurring at a frequency of less than or equal to 1%: The following list provides information on adverse drug reactions (considered possibly or probably related to treatment by the investigator) reported in study MF4411 occurring more frequently with Bonviva 2.5 mg daily than with placebo and study BM16549 occurring more frequently with Bonviva 150 mg once monthly than with Bonviva 2.5 mg daily. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness: Uncommon (1/100 - 1/1,000): Gastrointestinal Disorders: gastritis, esophagitis, including esophageal ulcerations or strictures, vomiting, dysphagia.
Nervous System Disorders: dizziness.
Musculoskeletal and Connective Tissue Disorders: back pain.
Rare (1/1,000 - 1/10,000): Gastrointestinal Disorders: duodenitis.
Immune System Disorders: hypersensitivity reactions.
Skin and Subcutaneous Tissue Disorders: angioedema, face edema, urticaria.
Patients with a previous history of gastrointestinal disease including patients with peptic ulcer without recent bleeding or hospitalization, and patients with dyspepsia or reflux controlled by medication were included in the once-monthly treatment study. For these patients, there was no difference in the incidence of upper gastrointestinal adverse events with the 150 mg once-monthly regimen compared to the 2.5 mg daily regimen.
Laboratory Abnormalities: In the pivotal three-year study with Bonviva 2.5 mg daily (MF4411) there was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, impaired hematologic system, hypocalcemia or hypophosphatemia. Similarly, no differences were noted between the groups in study BM16549 after one and two years.
Post Marketing: Musculoskeletal and connective tissue disorders: Osteonecrosis of the jaw and other oro-facial sites, including the external auditory canal has been reported very rarely in patients treated with ibandronic acid (see Precautions).
Eye disorders: Ocular inflammation events such as uveitis, episcleritis and scleritis have been reported with bisphosphonates, including ibandronic acid. In some cases, these events did not resolve until the bisphosphonate was discontinued.
Immune system disorders: Cases of anaphylactic reaction/shock, including fatal events, have been reported in patients treated with ibandronic acid.
Allergic reactions including asthma exacerbation have been reported.
Severe Cutaneous Adverse Reactions including Stevens-Johnson Syndrome, Erythema Multiforme, and Bullous Dermatitis, have been reported.
Injury, poisoning and procedural complications: Atypical subtrochanteric and diaphyseal femoral fractures have been reported with bisphosphonate therapy, including ibandronate, however causality has not been established.