8.5 Geriatric Use
Clinical studies of Zometa in hypercalcemia of malignancy included 34patients who were 65years of age or older. No significant differences in response rate or adverse reactions were seen in geriatric patients receiving Zometa as compared to younger patients. Controlled clinical studies of Zometa in the treatment of multiple myeloma and bone metastases of solid tumors in patients over age65 revealed similar efficacy and safety in older and younger patients. Because decreased renal function occurs more commonly in the elderly, special care should be taken to monitor renal function.

10OVERDOSAGE
Clinical experience with acute overdosage of Zometa is limited. Two patients received Zometa 32mg over 5minutes in clinical trials. Neither patient experienced any clinical or laboratory toxicity. Overdosage may cause clinically significant hypocalcemia, hypophosphatemia, and hypomagnesemia. Clinically relevant reductions in serum levels of calcium, phosphorus, and magnesium should be corrected by intravenous administration of calcium gluconate, potassium or sodium phosphate, and magnesium sulfate, respectively.

In an open-label study of zoledronicacid 4mg in breast cancer patients, a female patient received a single 48-mg dose of zoledronicacid in error. Two days after the overdose, the patient experienced a single episode of hyperthermia (38°C), which resolved after treatment. All other eva luations were normal, and the patient was discharged seven days after the overdose.

A patient with non-Hodgkin’s lymphoma received zoledronicacid 4mg daily on four successive days for a total dose of 16mg. The patient developed paresthesia and abnormal liver function tests with increased GGT (nearly 100U/L, each value unknown). The outcome of this case is not known.

In controlled clinical trials, administration of Zometa 4mg as an intravenous infusion over 5minutes has been shown to increase the risk of renal toxicity compared to the same dose administered as a 15-minute intravenous infusion. In controlled clinical trials, Zometa 8mg has been shown to be associated with an increased risk of renal toxicity compared to Zometa 4mg, even when given as a 15-minute intravenous infusion, and was not associated with added benefit in patients with hypercalcemia of malignancy [see Dosage And Administration(2.4)].

11DESCRIPTION
Zometa contains zoledronicacid, a bisphosphonic acid which is an inhibitor of osteoclastic bone resorption. Zoledronicacid is designated chemically as (1-Hydroxy-2-imidazol-1-yl-phosphonoethyl) phosphonic acid monohydrate and its structural formula is

Zoledronicacid is a white crystalline powder. Its molecular formula is C5H10N2O7P2 • H2O and its molar mass is 290.1g/Mol. Zoledronicacid is highly soluble in 0.1Nsodium hydroxide solution, sparingly soluble in water and 0.1Nhydrochloric acid, and practically insoluble in organic solvents. The pH of a 0.7% solution of zoledronicacid in water is approximately2.0.

Zometa is available in 100-mL bottles as a sterile liquid ready-to-use solution for intravenous infusion and in 5-mL vials as a sterile liquid concentrate solution for intravenous infusion.

Each 100 mL ready-to-use bottle contains 4.264 mg zoledronic acid monohydrate, corresponding to 4 mg zoledronic acid on an anhydrous basis, 5100 mg of mannitol, USP, water for inject