Profiling the safety and tolerability of bisphosphonates

Because patients with metastatic bone disease suffer a significant burden from their illness and from anticancer treatments, it is therefore important to minimize the side effects of bisphosphonates. The intravenous bisphosphonates, zoledronic acid and pamidronate, have tolerability issues that include a flu-like syndrome, injection-site reactions, and occasional renal toxicity. Because of the potentially severe nature of the renal toxicity, renal monitoring is required before each dose, with drug withdrawal if the patients' renal function deteriorates. Oral clodronate often causes gastrointestinal disturbances, particularly diarrhea; compliance is often poor because of the large tablet size and multiple daily dosing. Long-term data have shown that the bisphosphonate ibandronate is well tolerated either intravenously or orally, with a renal safety profile similar to placebo and no evidence of cumulative renal damage. Studies investigating the effects of 15-minute infusions and intensive dosing indicate that intravenous ibandronate given rapidly or at high doses is also well tolerated with no renal safety concerns. Taken together, these results suggest that the favorable safety profile of ibandronate provides an important alternative to existing bisphosphonate options for metastatic bone disease. Using ibandronate could improve patient acceptability and simplify management, with reductions in the need for safety monitoring and management of adverse events.