Dilution Zoledronic Acid - Zometa®

Zoledronic acid (Zometa®)

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Usual Diluents

D5W, NS

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate]

[4 mg] [100 ml] [15-30 minutes]

Stability / Miscellaneous

EXP: 24 hrs REF.
Label: Refrigerate.
Absolute minimum infusion time: 15 minutes.

Reconstitute 4 mg vial with 5ml sterile water. Do not withdraw the drug until it is completely dissolved.
Maximum dose: 4 mg

Indications: treatment of hypercalcemia of malignancy.

Vigorous saline hydration should be initiated promptly – urine output goal: 2 L/day throughout treatment. Do not overhydrate (use caution in cardiac patients, etc).

The safety and efficacy of Zometa in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.

The maximum recommended dose of Zometa is 4 mg (Patients with a corrected calcium > 12 mg/dl). Retreatment: Must wait at least 7 days to determine the full effect of the initial dose. Do not administer subsequent doses before this time.

Renal function must be carefully monitored in all patients receiving Zometa and possible deterioration in renal function must be assessed prior to retreatment with Zometa.

Corrected calcium = Ca + 0.8 (mid-range albumin-measured albumin in mg/dL).

RENAL DOSING
Dose adjustments of Zometa are not necessary in treating patients for hypercalcemia presenting with mild-to-moderate renal impairment prior to initiation of therapy (serum creatinine <4.5 mg/dL). For bone metastases, the use of Zometa in patients with severe renal impairment is not recommended. In studies of patients with bone metastases, patients with a serum creatinine >3.0 mg/dL were excluded.

DOSAGE AND ADMINISTRATION
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Hypercalcemia of Malignancy
The maximum recommended dose of Zometa in hypercalcemia of malignancy (albumin-corrected serum calcium ≥12 mg/dL [3.0 mmol/L]) is 4 mg. The 4-mg dose must be given as a single-dose intravenous infusion over no less than 15 minutes. 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 <400 µmol/L or <4.5 mg/dL).

Patients should be adequately rehydrated prior to administration of Zometa.

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 2 L/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 4 mg may be considered if serum calcium does not return to normal or remain normal after initial treatment. 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 Zometa and serum creatinine must be assessed prior to retreatment with Zometa.

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 >60 mL/min is 4 mg infused over no less than 15 minutes every 3-4 weeks. 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 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) is calculated using the Cockcroft-Gault formula.

Reduced Doses for Patients with Baseline CrCl <60 mL/min

Baseline Creatinine Clearance (mL/min)	Zometa Recommended Dose*
>60	4 mg
50 - 60	3.5 mg
40 - 49	3.3 mg
30 - 39	3 mg
*Doses calculated assuming target AUC of 0.66(mg•hr/L) (CrCl = 75 mL/min)

Source: [package insert]