ZOLEDRONIC

Pharmacokinetic data in patients with hypercalcemia are not available.

DistributionSingle or multiple (every 28 days) 5-minute or 15-minute infusions of 2, 4, 8, or 16 mg zoledronic acid injection were given to 64 patients with cancer and bone metastases. The post-infusion decline of zoledronic acid concentrations in plasma was consistent with a triphasic process showing a rapid decrease from peak concentrations at end of infusion to less than 1% of C max 24 hours postinfusion with population h...

14.1 Hypercalcemia of Malignancy Two identical multicenter, randomized, double-blind, double-dummy studies of zoledronic acid injection 4 mg given as a 5-minute intravenous infusion or pamidronate 90 mg given as a 2-hour intravenous infusion were conducted in 185 patients with hypercalcemia of malignancy (HCM). NOTE: Administration of zoledronic acid injection 4 mg given as a 5-minute intravenous infusion has been shown to result in an increased risk of renal toxicity, as measured by increases in serum creatinine, which can progress to renal failure. The incidence of renal toxicity and renal f...

The most common adverse events (greater than 25%) were nausea, fatigue, anemia, bone pain, constipation, fever, vomiting, and dyspnea ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Avet Pharmaceuticals Inc. at 1-866-901-DRUG (3784) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in th...

Hypersensitivity to any component of zoledronic acid injection (4) Hypersensitivity to Zoledronic Acid or Any Components of Zoledronic Acid Injection Hypersensitivity reactions including rare cases of urticaria and angioedema, and very rare cases of anaphylactic reaction/shock have been reported [see Adverse Reactions (6.2) ].

Patients being treated with zoledronic acid injection should not be treated with Reclast ® . ( 5.1 ) Adequately rehydrate patients with hypercalcemia of malignancy prior to administration of zoledronic acid injection and monitor electrolytes during treatment. ( 5.2 ) Renal toxicity may be greater in patients with renal impairment. Do not use doses greater than 4 mg. Treatment in patients with severe renal impairment is not recommended. Monitor serum creatinine before each dose. ( 5.3 ) Osteonecr...

7 DRUG INTERACTIONS Aminoglycosides: May have an additive effect to lower serum calcium for prolonged periods. ( 7.1 ) Loop Diuretics: Concomitant use with zoledronic acid injection may increase risk of hypocalcemia. ( 7.2 ) Nephrotoxic Drugs: Use with caution. ( 7.3 ) In vitro studies indicate that the plasma protein binding of zoledronic acid is low, with the unbound fraction ranging from 60% to...