Zolchoice Dosage/Direction for Use

Hypercalcemia of Malignancy: 4 mg (albumin corrected serum calcium ≥12 mg/dL [3.0 mmol/L]) is the maximum recommended dose of Zoledronic Acid in hypercalcemia of malignancy. The 4 mg dose must be given as a single dose intravenous infusion over no less than 15 minutes. Prior to each treatment with Zoledronic Acid, patients must have serum creatinine assessed. Dose adjustments of Zoledronic Acid are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine <400 μmol/L or <4.5 mg/dL). Prior to administration of Zoledronic Acid the patients should be adequately rehydrated.
Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of Zoledronic Acid. Vigorous saline hydration, an integral part of hypercalcemia therapy, should be initiated promptly and an attempt should be made to restore the urine output to about 2 L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics).
Throughout the treatment with Zoledronic Acid, patients should be hydrated adequately. Overhydration must be avoided especially in those patients who have cardiac failure. Diuretic therapy should not be employed prior to correction of hypovolemia. If serum calcium does not return to normal or remain normal after initial treatment, the retreatment with Zoledronic Acid 4 mg may be considered.
It is recommended that a minimum of 7 days elapse before retreatment, to allow for full response to the initial dose. Renal function must be carefully monitored in all patients receiving Zoledronic Acid.
Multiple Myeloma and Metastatic Bone Lesions of Solid Tumors: For patients with creatinine clearance >60 mL/min, 4 mg is the recommended dose of Zoledronic Acid in patients with multiple myeloma and metastatic bone lesions from solid tumors to be infused over no less than 15 minutes every 3-4 weeks. The optimal duration of therapy is not known. Upon treatment initiation, the recommended Zoledronic Acid doses for patients with reduced renal function (mild and moderate renal impairment) are listed in Table 1. These doses are calculated to achieve the same AUC as that achieved in patients with creatinine clearance of 75 mL/min. Creatinine clearance (CrCl) may be calculated using the Cockcroft-Gault. (See Table 1.)

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DIRECTION FOR RECONSTITUTION: 4 mg dose: Vials of Zoledronic Acid concentrate for infusion contain overfill allowing for the withdrawal of 5 mL of concentrate (equivalent to 4 mg zoledronic acid). This concentrate should immediately be diluted in 100 mL of sterile 0.9% Sodium Chloride USP or 5% Dextrose Injection USP. Do not store undiluted concentrate in a syringe to avoid inadvertent injection.
Preparing Reduced Doses for Patients with Baseline CrCl ≤60 mL/min: Withdraw the appropriate volume of the Zoledronic Acid concentrate from the vial for the dose required (see Table 2).

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For all prepared doses: The solution should be refrigerated at 2-8°C (36-46°F) if not used immediately after dilution with infusion media, for microbiological integrity. The refrigerated solution should then be equilibrated to room temperature prior to administration. The total time between dilution, storage in the refrigerator, and end of administration must not exceed 24 hours.
Zoledronic Acid must not be mixed with calcium or other divalent cation containing infusion solutions such as Lactated Ringer's solution and should be administered as a single intravenous solution in a line separate from all other drugs.
Method of administration: Due to the risk of clinically significant deterioration in renal function, which may progress to renal failure, single doses of Zoledronic Acid should not exceed 4 mg and the duration of infusion should be no less than 15 minutes. Studies showed that renal deterioration, progression to renal failure and dialysis, have occurred in patients, including those treated with the approved dose of 4 mg infused over 15 minutes. There have been instances of this occurring after the initial Zoledronic Acid dose.
Note: Not for direct injection, the dose must be diluted.