Table 1. . Treatments for hypercalcemia of malignancy.

Agent	Mechanism of action	Dose	Onset of action	Duration of action	Notable adverse reactions
Saline infusion	Volume repletion; increases renal excretion of Ca	200–500 ml/h (goal urine output >75 ml/h)	Within 6 h	Hours	Volume overload
Calcitonin	Inhibits OC activity; increases renal excretion of Ca; inhibits GI absorption of Ca	4–8 units/kg im./sc. every 12 h for 2–3 days	≈ 2 h	6–8 h	Nausea Local site reaction Flushing Hypersensitivity Hypocalcemia
Pamidronate	Inhibits OC activity	60–90 mg iv. over 2–6 h† (one dose)‡	≤24 h	7–14 days	Fever Hypocalcemia Hypophosphatemia Nephrotoxicity ONJ
Zoledronic acid	Inhibits OC activity	4 mg§ iv. over 15–30 min†(one dose)‡	24–48 h	32 days	Same as pamidronate
Denosumab	Inhibits RANKL binding to RANK	120 mg sc. every 4 weeks + loading doses on days 8/15	9 days (median time to response¶)	104 days (duration of response¶)	Fatigue Hypophosphatemia Hypocalcemia Nausea Dermatitis/rash ONJ

^†Use a longer infusion time in patients with lower glomerular filtration rate.

^‡Wait at least 7 days to pass before re-treatment.

^§Adjust dose for zoledronic acid based on creatinine clearance using the Crockcroft-Gault formula.

^¶Response defined as a corrected serum calcium less than or equal to 11.5 mg/dl.

Ca: Calcium; GI: Gastrointestinal; im.: Intramuscularly; iv.: Intravenously; OC: Osteoclast; ONJ: Osteonecrosis of the jaw; sc.: Subcutaneously.

Data taken from [13].