Pamidronate Disodium

INDICATIONS AND USAGE Hypercalcemia of Malignancy Pamidronate disodium, in conjunction with adequate hydration, is indicated for the treatment of moderate or severe hypercalcemia associated with malignancy, with or without bone metastases. Patients who have either epidermoid or non-epidermoid tumors respond to treatment with pamidronate disodium. 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. The safety and efficacy of pamidronate disodium in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established. Paget’s Disease Pamidronate disodium is indicated for the treatment of patients with moderate to severe Paget’s disease of bone. The effectiveness of pamidronate disodium was demonstrated primarily in patients with serum alkaline phosphatase ≥ 3 times the upper limit of normal. Pamidronate disodium therapy in patients with Paget’s disease has been effective in reducing serum alkaline phosphatase and urinary hydroxyproline levels by ≥ 50% in at least 50% of patients, and by ≥ 30% in at least 80% of patients. Pamidronate disodium therapy has also been effective in reducing these biochemical markers in patients with Paget’s disease who failed to respond, or no longer responded to other treatments. Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma Pamidronate disodium is indicated, in conjunction with standard antineoplastic therapy, for the treatment of osteolytic bone metastases of breast cancer and osteolytic lesions of multiple myeloma. The pamidronate disodium treatment effect appeared to be smaller in the study of breast cancer patients receiving hormonal therapy than in the study of those receiving chemotherapy, however, overall evidence of clinical benefit has been demonstrated (see CLINICAL PHARMACOLOGY , Osteolytic Bone Metastases of Breast Cancer and Osteolytic Lesions of Multiple Myeloma, Clinical Trials section).

WARNINGS Deterioration in Renal Function Bisphosphonates, including pamidronate disodium, have been associated with renal toxicity manifested as deterioration of renal function and potential renal failure. DUE TO THE RISK OF CLINICALLY SIGNIFICANT DETERIORATION IN RENAL FUNCTION, WHICH MAY PROGRESS TO RENAL FAILURE, SINGLE DOSES OF PAMIDRONATE DISODIUM SHOULD NOT EXCEED 90 MG (see DOSAGE AND ADMINISTRATION for appropriate infusion durations). Renal deterioration, progression to renal failure, and dialysis have been reported in patients after the initial or a single dose of pamidronate disodium. Focal segmental glomerulosclerosis (including the collapsing variant) with or without nephrotic syndrome, which may lead to renal failure, has been reported in pamidronate disodium-treated patients, particularly in the setting of multiple myeloma and breast cancer. Some of these patients had gradual improvement in renal status after pamidronate disodium was discontinued. Patients who receive pamidronate disodium should have serum creatinine assessed prior to each treatment. Patients treated with pamidronate disodium for bone metastases should have the dose withheld if renal function has deteriorated (see DOSAGE AND ADMINISTRATION ). PREGNANCY: Bisphosphonates, such as pamidronate disodium, are incorporated into the bone matrix, from where they are gradually released over periods of weeks to years. Pamidronate disodium may cause fetal harm when administered to a pregnant woman. In reproductive studies in rats and rabbits, pamidronate doses equivalent to 0.6 to 8.3 times the highest human recommended dose resulted in maternal toxicity and embryo/fetal effects. There are no adequate and well-controlled studies of pamidronate disodium in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus (See PRECAUTIONS ).