Daily Dosing

Daily treatment with oral BONIVA was studied in over 3900 patients in postmenopausal osteoporosis trials of up to 3 years duration.The overall adverse event profile of BONIVA 2.5 mg once daily in these studies was similar to that of placebo.

Treatment and Prevention of Postmenopausal Osteoporosis

Most adverse events were mild or moderate and did not lead to discontinuation. The incidence of serious adverse events was 20% in the placebo group and 23% in the BONIVA 2.5 mg daily group. The percentage of patients who withdrew from treatment due to adverse events was approximately 17% in both the BONIVA 2.5 mg daily group and the placebo group. Overall, and according to body system, there was no difference between BONIVA and placebo, with adverse events of the digestive system being the most common reason for withdrawal.

Table 3 lists adverse events from the Treatment and Prevention Studies reported in ≥ 2% of patients and in more patients treated daily with BONIVA than patients treated with placebo. Adverse events are shown without attribution of causality.

Table 3 : Adverse Events Occurring at a Frequency ≥ 2% and in More Patients Treated with BONIVA than in Patients Treated with Placebo Daily in the Osteoporosis Treatment and Prevention Studies

Once-Monthly Dosing

In a 1-year, double-blind, multicenter study comparing BONIVA 2.5 mg once daily and BONIVA 150 mg once monthly in women with postmenopausal osteoporosis, the overall safety and tolerability profiles of the two oral dosing regimens were similar. The incidence of serious adverse events was 4.8% in the BONIVA 2.5 mg daily group and 7.1% in the BONIVA 150 mg once-monthly group. The percentage of patients who withdrew from treatment due to adverse events was approximately 8.9% in the BONIVA 2.5 mg daily group and 7.8% in the BONIVA 150 mg once-monthly group. Table 4 lists the adverse events reported in ≥ 2% of patients without attribution of causality.

Table 4 : Adverse Events With an Incidence of at Least 2% in Patients Treated with BONIVA 150 mg Once Monthly or 2.5 mg Daily

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 upper gastrointestinal adverse events with the 150 mg once-monthly regimen compared to the 2.5 mg once-daily regimen.

Ocular Adverse Events

Reports in the medical literature indicate that bisphosphonates may be associated with ocular inflammation such as uveitis and scleritis. In some cases, these events did not resolve until the bisphosphonate was discontinued. There were no reports of ocular inflammation in studies with BONIVA 2.5 mg daily. Two patients who received BONIVA once monthly experienced ocular inflammation, one was a case of uveitis and the other scleritis.

Laboratory Test Findings

In the 3-year treatment study with BONIVA 2.5 mg daily, there were no clinically significant changes from baseline values or shifts in any laboratory variable for each of the treatment groups. As expected with bisphosphonate treatment, a decrease in total alkaline phosphatase levels was seen in the active treatment groups compared to placebo. There was no difference compared with placebo for laboratory abnormalities indicative of hepatic or renal dysfunction, hypocalcemia, or hypophosphatemia. Similarly, no changes were noted for the 150 mg once-monthly administration in the 1-year study.

See CLINICAL PHARMACOLOGY: Pharmacokinetics: Drug Interactions.

Calcium Supplements/Antacids

Products containing calcium and other multivalent cations (such as aluminum, magnesium, iron) are likely to interfere with absorption of BONIVA. BONIVA should be taken at least 60 minutes before any oral medications containing multivalent cations (including antacids, supplements or vitamins) (see PRECAUTIONS: INFORMATION FOR PATIENTS).

H2 Blockers and Proton Pump Inhibitors (PPIs)

Of over 3500 patients enrolled in the BONIVA osteoporosis Treatment and Prevention Studies, 15% used anti-peptic agents (primarily H2 blockers and PPIs). Among these patients, the incidence of upper gastrointestinal adverse experiences in the patients treated with BONIVA was similar to that in placebo-treated patients. Similarly, of over 1600 patients enrolled in a study comparing once-monthly with daily dosing regimens of ibandronate, 14% of patients used anti-peptic agents. Among these patients, the incidence of upper gastrointestinal adverse experiences in the patients treated with BONIVA 150 mg once monthly was similar to that in patients treated with BONIVA 2.5 mg once daily.

Aspirin/Nonsteroidal Antiinflammatory Drugs (NSAIDs)

In the large, placebo-controlled osteoporosis Treatment Study, aspirin and nonsteroidal antiinflammatory drugs were taken by 62% of the 2946 patients. Among aspirin or NSAID users, the incidence of upper gastrointestinal adverse events in patients treated with ibandronate 2.5 mg daily (28.9%) was similar to that in placebo-treated patients (30.7%). Similarly, in the 1-year monthly comparison study, aspirin and nonsteroidal antiinflammatory drugs were taken by 39% of the 1602 patients. The incidence of upper gastrointestinal events in patients concomitantly taking aspirin or NSAIDs was similar in patients taking ibandronate 2.5 mg daily (21.7%) and 150 mg once monthly (22.0%). However, since aspirin, NSAIDs, and bisphosphonates are all associated with gastrointestinal irritation, caution should be exercised in the concomitant use of aspirin or NSAIDs with BONIVA.

Drug/Laboratory Test Interactions

Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with ibandronate have not been performed.

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