Demonstrated Tolerability Profile

Common adverse events during the postinfusion period

		The most common adverse events following Reclast infusion included fever (18%), myalgia (9%), flu-like symptoms (8%), headache (7%), and arthralgia (7%)
		The majority occurred within 3 days of infusion; most resolved within 3 days of onset but could take up to 7-14 days
		The incidence of these symptoms decreased with subsequent doses of Reclast
		In other clinical trials, patients previously treated with bisphosphonate therapy experienced approximately half the symptoms of treatment-naïve patients
		Treatment with acetaminophen or ibuprofen can reduce the incidence of these symptoms

5.4% (209/3862) of Reclast-treated patients and 4.9% (187/3852) of placebo-treated patients discontinued due to adverse events over the course of 3 years.

Overall adverse event rate similar to placebo after postinfusion period

		No spontaneous reports of osteonecrosis of the jaw (ONJ). Expert adjudication identified 2 potential cases, 1 in the Reclast group and 1 in the placebo group. Both cases resolved with appropriate treatment
		The overall incidence of all atrial fibrillation adverse events in the Reclast group was 2.5% vs 1.9% in the placebo group. Serious adverse events incidence was 1.3% for the Reclast group vs 0.4% in the placebo group Over 90% of these events in both treatment groups occurred more than 30 days after infusion, when the drug is undetectable in the circulation. ECGs performed on a subset of 559 patients before and 9 to 11 days after treatment found no differences between treatment groups, suggesting these events were not related to the acute infusions Increased incidence has not been observed in other clinical trials with zoledronic acid
		No difference in mean serum creatinine clearance over 3 years between study groups Transient increases in serum creatinine observed within 10 days of dosing in 1.8% of Reclast-treated patients and 0.8% of placebo-treated patients All increases resolved without specific therapy