In a clinical study, renal deterioration was defined as follows:

•
For patients with normal baseline creatinine, increase of 0.5 mg/dL.
•
For patients with abnormal baseline creatinine, increase of 1.0 mg/dL.
In this clinical study, pamidronate disodium treatment was resumed only when the creatinine returned to within 10% of the baseline value.

The optimal duration of therapy is not yet known, however, in a study of patients with myeloma, final analysis after 21 months demonstrated overall benefits (seeClinical Trials).

Osteolytic Bone Metastases of Breast Cancer
The recommended dose of pamidronate disodium in patients with osteolytic bone metastases is 90 mg administered over a 2 hour infusion given every 3 to 4 weeks.

Pamidronate disodium has been frequently used with doxorubicin, fluorouracil, cyclophosphamide, methotrexate, mitoxantrone, vinblastine, dexamethasone, prednisone, melphalan, vincristine, megesterol, and tamoxifen. It has been given less frequently with etoposide, cisplatin, cytarabine, paclitaxel, and aminoglutethimide.

Patients who receive pamidronate disodium should have serum creatinine assessed prior to each treatment. Treatment should be withheld for renal deterioration.

In a clinical study, renal deterioration was defined as follows:

•
For patients with normal baseline creatinine, increase of 0.5 mg/dL.
•
For patients with abnormal baseline creatinine, increase of 1.0 mg/dL.
In this clinical study, pamidronate disodium treatment was resumed only when the creatinine returned to within 10% of the baseline value.

The optimal duration of therapy is not known, however, in two breast cancer studies, final analyses performed after 24 months of therapy demonstrated overall benefits (see Clinical Trials).

Calcium and Vitamin D Supplementation
In the absence of hypercalcemia, patients with predominantly lytic bone metastases or multiple myeloma, who are at risk of calcium or vitamin D deficiency, and

patients with Paget’s disease of the bone, should be given oral calcium and vitamin D supplementation in order to minimize the risk of hypocalcemia.

Preparation of Solution

Reconstitution
Pamidronate disodium for injection is reconstituted by adding 10 mL of sterile water for injection, to each vial, resulting in a solution of 30 mg/10 mL or 90 mg/10 mL. The pH of the reconstituted solution is 6.0 to 7.4. The drug should be completely dissolved before the solution is withdrawn.

Method of Administration
DUE TO THE RISK OF CLINICALLY SIGNIFICANT DETERIORATION IN RENAL FUNCTION, WHICH MAY PROGRESS TO RENAL FAILURE, SINGLE DOSES OFPAMIDRONATE DISODIUM SHOULD NOT EXCEED 90 MG. (SEE WARNINGS.)

There must be strict adherence to the intravenous administration recommendations for pamidronate disodium in order to decrease the risk of deterioration in renal function.

Hypercalcemia of Malignancy
The daily dose must be administered as an intravenous infusion over at least 2 to 24 hours for the 60 mg and 90 mg doses. The recommended dose should be diluted in 1000 mL of sterile 0.45% or 0.9% sodium chloride injection, or 5% dextrose injection. This infusion solution is stable for up to 24 hours at room temperature.

Paget’s Disease
The recommended daily dose of 30 mg should be diluted in 500 mL of sterile 0.45% or 0.9% sodium chloride injection, or 5% d