- James E. FramptonAffiliated withWolters Kluwer Health ¦ AdisWolters Kluwer Health Email author
- , Caroline M. PerryAffiliated withWolters Kluwer Health ¦ AdisWolters Kluwer Health
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Ibandronate (ibandronic acid; Bonviva®, Boniva®), a nitrogen-containing bisphosphonate available in once-monthly oral and quarterly intravenous formulations for intermittent administration, has been approved for the treatment of osteoporosis in postmenopausal women in the EU, the US and many other countries worldwide. The once-monthly oral formulation has also been approved for the prevention of postmenopausal osteoporosis in the US.
Ibandronate is an effective and generally well tolerated bisphosphonate that offers an alternative to other bisphosphonates as a first-line treatment for postmenopausal osteoporosis. It occupies a similar position with respect to the prevention of osteoporosis in postmenopausal women at risk for the disease. The once-monthly oral and quarterly intravenous dosage regimens have the potential to improve treatment adherence and persistence, and hence clinical outcomes, compared with more frequently administered oral bisphosphonates. Intravenous ibandronate may be particularly useful for postmenopausal osteoporotic women who are noncompliant with, or are unable to tolerate or receive, oral bisphosphonates. Thus, intermittent ibandronate extends the range of pharmacological therapies for the treatment and prevention of postmenopausal osteoporosis.
Ibandronate is a potent, nitrogen-containing bisphosphonate and, like other bisphosphonates, it inhibits osteoclast-mediated bone résorption. In clinical trials in postmenopausal women with osteoporosis, approved oral and intravenous ibandronate dosage regimens reduced bone turnover, and increased lumbar spine and proximal femur bone mineral density (BMD) [areal and volumetric] and mechanical strength. Bone newly formed in the presence of ibandronate is normal in terms of quality and mineralization.
As with all bisphosphonates, absorption of oral ibandronate, although rapid, is low (bioavailability 0.63%) and markedly impaired by food and beverages (other than plain water). After initial systemic exposure, ibandronate is either sequestered in bone (≈40–50% of the circulating dose in postmenopausal women) or excreted in the urine (renal clearance of the drug is linearly related to creatinine clearance). The apparent terminal elimination half-life of ibandronate ranged from ≈10 to 72 hours following administration of single oral (150 mg) or intravenous (2 or 4 mg) doses to postmenopausal women. Ibandronate is only moderately bound to plasma proteins and does not undergo hepatic metabolism; hence, it has a low potential for displacement from plasma proteins and metabolic drug-drug interactions with other medications.
Compared with placebo, 3 years’ treatment with once-daily oral ibandronate 2.5 mg significantly reduced the adjusted relative risk of new morphometric vertebral fractures by 62% (52% unadjusted relative risk reduction), that of new or worsening vertebral fractures by 62% (52%), and that of clinical vertebral fractures by 49% (49%) in the randomized, double-blind, multicentre BONE study, which enrolled postmenopausal women with osteoporosis. Although ibandronate had no effect on nonvertebral fracture incidence in the overall population, the relative risk of clinical nonvertebral fractures was significantly reduced in high-risk subgroups of patients in post hoc analyses. Both the vertebral and nonvertebral antifracture efficacy of ibandronate are supported by the results of meta-analyses and a large observational study (VIBE).
In four randomized, double-blind, multicentre, clinical trials in postmenopausal women with osteoporosis (BONE, DIVA, MOBILE and MOTION), treatment for up to 3 years with approved oral (2.5 mg once daily and 150 mg once monthly) and intravenous (3 mg every 3 months) regimens of ibandronate led to progressive increases in lumbar spine and proximal femur BMD. Once-daily oral ibandronate therapy (in BONE) was superior to placebo in terms of increasing lumbar spine BMD, while once-monthly oral ibandronate (in MOBILE) and quarterly intravenous ibandronate (in DIVA) were noninferior and, moreover, superior to once-daily oral ibandronate in this regard. Once-monthly oral ibandronate therapy (in MOTION) was noninferior to once-weekly oral alendronate 70 mg in terms of increasing lumbar spine BMD and total hip BMD. Approved oral and intravenous ibandronate regimens produced similarly pronounced reductions in biochemical markers of bone resorption and formation that were seen after 3 months (first post-baseline assessment) and sustained through 2–3 years’ continuous treatment.
In two randomized, double-blind, placebo-controlled, multicentre studies, 1 or 2 years’ treatment with approved oral regimens of ibandronate effectively prevented bone loss from the lumbar spine and proximal femur of postmenopausal women with normal or osteopenic BMD levels. Bone resorption markers were suppressed at the first post-baseline assessment and remained decreased throughout the rest of the study period.
Postmenopausal women participating in 6-month, randomized, multicentre, clinical trials (BALTO I/II and PERSIST) have reported a preference for, the greater convenience of and increased persistence on, once-monthly oral ibandronate 150 mg versus once-weekly oral alendronate 70 mg. Additionally, adherence to once-monthly oral ibandronate was no less than that to quarterly intravenous ibandronate in a 12-month, nonrandomized, multicentre trial in postmenopausal women with osteoporosis or osteopenia who had previously discontinued oral bisphosphonate therapy because of gastrointestinal (GI) intolerance (PRIOR).
Treatment for up to 3 years with approved oral and intravenous ibandronate regimens was generally well tolerated in well designed clinical trials in postmenopausal women with, or without, osteoporosis. The tolerability profile of once-daily oral ibandronate 2.5 mg was similar to that of placebo, once-monthly oral ibandronate 150 mg and quarterly intravenous ibandronate 3 mg. In addition, the tolerability profile of once-monthly oral ibandronate was similar to that of once-weekly oral alendronate 70 mg. The majority of drug-related adverse events with approved ibandronate regimens (e.g. GI, musculoskeletal, general and nervous system disorders) were of mild to moderate intensity and seldom led to study withdrawal.
The upper GI tolerability profile of once-monthly oral ibandronate and the renal tolerability profile of quarterly intravenous ibandronate were similar to the respective profiles of once-daily oral ibandronate. While the incidence of drug-related influenza-like symptoms was moderately higher with the once-monthly oral and quarterly intravenous regimens compared with the once-daily oral regimen, symptoms were typically transient, generally mild to moderate in intensity, and mostly associated with the first administration only. To date, there have been no reports of osteonecrosis of the jaw in controlled clinical trials of ibandronate in women with postmenopausal osteoporosis.
Volume 68, Issue 18 , pp 2683-2707
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