Aredia, 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 Aredia.

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 Aredia in the treatment of hypercalcemia associated with hyperparathyroidism or with other non-tumor-related conditions has not been established.

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Hypercalcemia -- Abnormally high level of calcium in the blood.

Malignant Neoplasms -- A term for diseases in which abnormal cells divide without control. Cancer cells can invade nearby tissues and can spread through the bloodstream and lymphatic system to other parts of the body.

Primary malignant neoplasm --

Secondary malignant neoplasm of bone and bone marrow -- Cancer that has spread from the original (primary) tumor to the bone.

Neoplasms -- New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms.

Heart failure -- inability of the heart to pump blood at an adequate rate to fill tissue metabolic requirements or the ability to do so only at an elevated filling pressure.

Hyperparathyroidism -- WHAT: Hyperparathyroidism. Hyperparathyroidism: a condition due to an increase in the secretion of the parathyroids, causing generalized osteitis fibrosa cystica, elevated serum calcium, decreased serum phosphorus, and increased excretion of both calcium and phosphorus. WHY: Several rheumatological disorders are associated with hyperpara- thyroidism. First, hyperuricemia and gouty arthritis (which may mimic hyperparathyroidism with renal stone formation and colic) have an increased incidence in patients with hyperparathyroidism. Second, patients with primary hyperparathyroidism show an increased incidence of chondrocalcinosis with episodes of calcium pyrophosphate crystal induced synovitis. Approximately 25% of patients with hyperparathyroidism will show radiographic evidence of calcification of articular cartilage and joint capsules. Finally, there can be a synovial and cartilaginous lesion ("osteogenic synovitis") in patients with hyperparathyroidism which may mimic other primary rheumatic diseases such as rheumatoid arthritis. In osteogenic synovitis there is softening and collapse of subchondral bone. Eventually the cartilage overlying this area erodes and is replaced by an irregular fibrocartilage. Eventually the articular surface of the joint is destroyed and secondary degenerative arthritis may develop. REFS: 1) Zvaifler, NJ; Reefe, WE and Black, RL: Articular manifestations in primary hyperparathyroidism. Arthritis Rheum 5:237, 1962. 2) Scott, JT; Dixon, ASJ and Bywaters, EGL: Association of hyperuricemia and gout with hyperparathyroidism. Br Med J 1:1070, 1964. 3) Bywaters, EGL and Scott, JT : Joint lesions of hyperparathyroidism. Ann Rheum Dis 22:171-87, 1963.

Aredia is contraindicated in patients with clinically significant hypersensitivity to Aredia or other bisphosphonates.

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Hypersensitivity -- Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen.

Deterioration in Renal FunctionBisphosphonates, including Aredia, 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 AREDIA 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 Aredia.

      Focal segmental glomerulosclerosis (including the collapsing variant) with or without nephrotic syndrome, which may lead to renal failure, has been reported in Aredia-treated patients, particularly in the setting of multiple myeloma and breast cancer.

Some of these patients had gradual improvement in renal status after Aredia was discontinued.      Patients who receive Aredia should have serum creatinine assessed prior to each treatment.

Patients treated with Aredia for bone metastases should have the dose withheld if renal function has deteriorated.

(See DOSAGE AND ADMINISTRATION.)