2.1 Hypercalcemia of Malignancy
The maximum recommended dose of Zometa in hypercalcemia of malignancy (albumin-corrected serum calcium greater than or equal to 12mg/dL [3.0mmol/L]) is 4mg. The 4-mg dose must be given as a single-dose intravenous infusion over no less than 15minutes. Patients who receive Zometa should have serum creatinine assessed prior to each treatment.

Dose adjustments of Zometa are not necessary in treating patients for hypercalcemia of malignancy presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine less than 400µmol/L or less than 4.5mg/dL).

Patients should be adequately rehydrated prior to administration of Zometa [see Warnings And Precautions(5.2)].

Consideration should be given to the severity of, as well as the symptoms of, tumor-induced hypercalcemia when considering use of Zometa. 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 2L/day throughout treatment. Mild or asymptomatic hypercalcemia may be treated with conservative measures (i.e., saline hydration, with or without loop diuretics). Patients should be hydrated adequately throughout the treatment, but overhydration, especially in those patients who have cardiac failure, must be avoided. Diuretic therapy should not be employed prior to correction of hypovolemia.

Retreatment with Zometa 4mg may be considered if serum calcium does not return to normal or remain normal after initial treatment. It is recommended that a minimum of 7days elapse before retreatment, to allow for full response to the initial dose. Renal function must be carefully monitored in all patients receiving Zometa and serum creatinine must be assessed prior to retreatment with Zometa [see Warnings And Precautions(5.2)].

2.2 Multiple Myeloma and Metastatic Bone Lesions of Solid Tumors
The recommended dose of Zometa in patients with multiple myeloma and metastatic bone lesions from solid tumors for patients with creatinine clearance greater than 60mL/min is 4mg infused over no less than15minutes every 3-4weeks. The optimal duration of therapy is not known.

Upon treatment initiation, the recommended Zometa doses for patients with reduced renal function (mild and moderate renal impairment) are listed in Table1. These doses are calculated to achieve the same AUC as that achieved in patients with creatinine clearance of 75mL/min. Creatinine clearance (CrCl) is calculated using the Cockcroft-Gault formula [see Warnings And Precautions(5.2)].

Table 1: Reduced Doses for Patients with Baseline CrCl less than or equal to 60mL/min Baseline Creatinine Clearance (mL/min) Zometa Recommended Dose*
greater than 60 4mg
50–60 3.5mg
40–49 3.3mg
30–39 3mg
*Doses calculated assuming target AUC of 0.66(mg•hr/L) (CrCl=75mL/min)

During treatment, serum creatinine should be measured before each Zometa dose and treatment should be withheld for renal deterioration. In the clinical studies, renal deterioration was defined as follows:
For patients with normal baseline creatinine, increase of 0.5mg/dL
For patients with abnormal baseline creatinine, increase of 1.0mg/dL

In the clinical studies, Zometa treatment was resumed only when the creatinine returned to within 10% of the baseline value. Zometa should be re