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Hypercalcemia (PDQ®): Supportive care - Health Professional Information [NCI] - Management

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Calcitonin is usually well tolerated; adverse effects include mild nausea, transient cramping abdominal pain, and cutaneous flushing. Calcitonin is most useful within the first 24 to 36 hours of treatment of severe hypercalcemia and should be used in conjunction with more potent but slower-acting agents.

Plicamycin

Plicamycin (also referred to as mithramycin) is an inhibitor of osteoclast RNA synthesis. It has been shown to inhibit bone resorption in vitro and is clinically effective in the presence or absence of bone metastases. Onset of response occurs within 12 hours of a single IV dose of 25 to 30 μg/kg of body weight given as a short infusion for 30 minutes or longer. Maximum response, however, does not occur until approximately 48 hours after administration and may persist for 3 to 7 days or more after administration. Repeated doses may be given to maintain plicamycin's hypocalcemic effect but should not be given more frequently than every 48 hours to determine the maximum calcium-lowering effect produced by previous doses.[30] Multiple doses may control hypercalcemia for several weeks, but rebound hypercalcemia usually occurs without definitive treatment against the underlying malignancy.[31] Although single-dose treatment of hypercalcemia is generally well tolerated with few adverse effects,[32][Level of evidence: II] dysfibrinogenemia [33][Level of evidence: III] and nephrotoxicity [34] have been reported after single doses (20–25 μg/kg). Rapid IV administration is associated with nausea and vomiting.[31] High and repeated doses predispose the patient to thrombocytopenia, a qualitative platelet dysfunction that may be associated with a bleeding diathesis, transient increases in hepatic transaminases, nephrotoxicity (decreased creatinine clearance, increased serum creatinine and blood urea nitrogen, potassium wasting, and proteinuria), hypophosphatemia, a flulike syndrome, dermatologic reactions, and stomatitis.[31,34];[35][Level of evidence: II];[36,37,38,39][Level of evidence: III]

Gallium nitrate

Gallium nitrate was developed as an antineoplastic agent that was coincidentally found to produce a hypocalcemic effect. Gallium nitrate interferes with an adenosine triphosphatase–dependent proton pump in the membrane of osteoclasts. This impairs osteoclast acidification and the dissolution of the underlying bone matrix.[1] Gallium nitrate has been shown to be superior to etidronate in the percentage of patients who achieve normocalcemia and in the duration of normocalcemia.[40][Level of evidence: I] Drawbacks to its use include a continuous 5-day IV infusion schedule (200 mg/m2 of body surface area per day) [6] and the potential for nephrotoxicity, particularly when it is used concurrently with other potentially nephrotoxic drugs (e.g., aminoglycosides and amphotericin B).[1]

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