Once-monthly ibandronate for postmenopausal osteoporosis: Review of a new dosing regimen

Background: Ibandronate, a nitrogen-containing bisphosphonate, was approved by the US Food and Drug Administration (FDA) in May 2003 as a daily oral regimen for the treatment and prevention of postmenopausal osteoporosis. In March 2005, the FDA approved once-monthly dosing with ibandronate for the same indications. Objective: The purpose of this article was to review the efficacy and tolerability of ibandronate 150 mg once monthly in the treatment and prevention of postmenopausal osteoporosis. Methods: A search of MEDLINE (1966-September 2005) and International Pharmaceutical Abstracts (1971-September 2005) for articles relating to the efficacy and tolerability of once-monthly ibandronate in the treatment of postmenopausal osteoporosis was conducted using the terms ibandronate and ibandronic acid. Additional searches were conducted to identify publications relevant to compliance and pharmacoeconomic considerations using the terms bisphosphonate, compliance, cost, and pharmacoeconomics. The reference lists of identified articles and presentations from recent scientific meetings also were reviewed. Selected safety information from the manufacturer was incorporated. Results: Ibandronate 2.5 mg/d and intermittent ibandronate (20 mg QOD for 12 doses every 3 months) have been shown to effectively reduce the incidence of vertebral fractures; after 3 years of therapy in a placebo-controlled clinical trial, the relative risk reductions for new vertebral fractures with daily and intermittent ibandronate were 62% and 50%, respectively (both, P < 0.001 vs placebo). Once-monthly ibandronate has been evaluated in 2 clinical trials: a Phase I dose-ranging trial in 144 healthy post-menopausal women and a Phase III noninferiority trial in 1609 women with postmenopausal osteoporosis who were randomized to receive ibandronate 2.5 mg/d or 1 of 3 monthly ibandronate regimens: 50150 mg (50 mg given on 2 consecutive days) once monthly; 100 mg once monthly; and 150 mg once monthly. The primary end point of the Phase III trial was the change from baseline in lumbar spine bone mineral density (BMD). After I year of therapy, patients who received ibandronate 150 mg once monthly had a significantly greater increase from baseline in lumbar spine BMD compared with those who received ibandronate 2.5 mg/d (4.9% vs 3.9%, respectively; P = 0.002). The overall adverse-event profile was similar between the daily and monthly regimens. Drug-related, adverse events were reported in 32.4% of patients receiving ibandronate 2.5 mg/d and 36.9% of patients receiving ibandronate 150 mg monthly. Upper gastrointestinal adverse events occurred in a respective 22.8% and 22.5% of the 2 groups. After I year of therapy, patients receiving ibandronate 150 mg monthly reported more flulike symptoms (8.3%) compared with those receiving ibandronate 2.5 mg/d (2.8%). In a crossover study comparing preference for and convenience of monthly ibandronate and weekly alendronate in 342 ambulatory women with postmenopausal osteoporosis, significantly more patients preferred the monthly ibandronate regimen to the weekly alendronate regimen (71.4% vs 28.5%, respectively; P < 0.001). Conclusion: Once-monthly ibandronate is an effective and well-tolerated treatment option for postmenopausal osteoporosis.