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Hypercalcemia in Emergency Medicine Medication

  • Author: Thomas E Green, DO, MPH, FACOEP, FACEP; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
Updated: Aug 09, 2016

Medication Summary

Several classifications of medications are used to treat elevations of serum calcium. Some can be used in acute life-threatening elevations, while others are used to help control calcium elevations after the acute event has been treated. Agents that help treat hypercalcemia include calcitonin, gallium nitrate, intravenous phosphate, bisphosphates, glucocorticoids, and calcimimetic agents.



Class Summary

These compounds are analogs of pyrophosphate that act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. These agents prevent osteoclast attachment to bone matrix and interfere with osteoclast recruitment and viability.

Pamidronate (Aredia)


Mechanism of action is inhibition of normal and abnormal bone resorption; appears to inhibit bone resorption without inhibiting bone formation and mineralization. Potent agent that has several regimens for administration. Adverse effects of IV administration include mild transient increases in temperature, leukopenia, and mild reduction in serum phosphate levels. PO maintenance therapy is available after acute event has resolved, but this therapy is experimental. With acute hypercalcemia, all of these agents are effective; pamidronate may be preferable because of its potency and efficacy..

Zoledronic acid (Zometa)


Inhibits bone resorption, possibly by acting on osteoclasts or osteoclast precursors. Median duration of complete response (maintaining normalized calcium levels) and time to relapse reported as 32 and 30 d, respectively. Indicated for hypercalcemia of malignancy.

Etidronate (Didronel)


Reduces bone formation; does not appear to alter renal tubular reabsorption of calcium. Does not affect hypercalcemia in patients with hyperparathyroidism where increased calcium reabsorption may increase blood calcium levels. Response generally observed within first 48 h; more effective if patient is well hydrated before initial dose. If patient responds well before 7 d, therapy can be discontinued. Generally well tolerated; most common adverse effect is a transient elevation of serum creatinine and phosphorous. PO therapy is experimental and not always effective.


Antidote, Hypercalcemia

Class Summary

Inhibit RNA synthesis in osteoclasts and effective in treatment of hypercalcemia.

Calcitonin (Miacalcin, Cibacalcin, Calcimar)


A naturally occurring hormone that inhibits bone reabsorption and increases excretion of calcium. Most rapid onset of action of anticalcemic agents. Effects may be observed within a few hours with peak response at 12-24 h; because of short duration of action, other more potent but slower-acting agents should be started in patients with severe hypercalcemia. Salmon calcitonin is used most often and is more potent than human calcitonin. Action of this agent is short-lived. If elevation of calcium is severe, coadminister 1-2 doses with fluids and Lasix to provide a rapid, although limited, reduction of the calcium level.

Gallium nitrate (Ganite)


Works by inhibiting bone reabsorption and altering structure of bone crystals.

Exerts hypocalcemic effect, possibly by reducing bone resorption; performs well against other anticalcium agents but has slow onset of action.



No longer manufactured and distributed in the United States. Inhibits cellular ribonucleic acid (RNA) and enzymatic RNA synthesis. Possibly blocks hypercalcemic action of pharmacologic doses of vitamin D and may act on osteoclasts or block action of parathyroid hormone. Effect in lowering calcium is not related to tumoricidal activity.


Phosphate salts

Class Summary

Use of IV phosphate is very effective in lowering serum calcium levels most likely because of a precipitation phenomenon. Significant risk exists with use of this agent. This agent is reserved for hypercalcemia unresponsive to other agents.

Potassium phosphate


IV preparations are available as sodium or potassium phosphate (K2PO4). Response to IV serum phosphorus supplementation is highly variable and is associated with hyperphosphatemia.



Class Summary

While these agents do not treat hypercalcemia directly, they are useful for treating hypercalcemia caused by vitamin D toxicity, certain malignancies (eg, multiple myeloma, lymphoma), sarcoidosis, and other granulomatous diseases. These agents generally are not effective in patients with solid tumors or primary hyperparathyroidism. Several different glucocorticoids may be used.

Hydrocortisone (Cortef)


Mineralocorticoid activity and glucocorticoid effects; onset of activity is rapid. Significant number of adverse reactions for those on long-term steroids. In acute phase, few severe reactions present.


Calcimimetic Agent

Class Summary

Binds to and modulates the parathyroid calcium-sensing receptor, increases sensitivity to extracellular calcium, and reduces parathyroid hormone secretion.

Cinacalcet (Sensipar)


Directly lowers parathyroid hormone (PTH) levels by increasing sensitivity of calcium sensing receptor on chief cell of parathyroid gland to extracellular calcium. Also results in concomitant serum calcium decrease. Indicated for hypercalcemia with parathyroid carcinoma.

Contributor Information and Disclosures

Thomas E Green, DO, MPH, FACOEP, FACEP Associate Dean for Clinical Affairs, Des Moines University College of Osteopathic Medicine; Attending Physician, Emergency Department, Emergency Practice Associates; Associate Professor of Emergency Medicine, Midwestern University, Chicago College of Osteopathic Medicine

Thomas E Green, DO, MPH, FACOEP, FACEP is a member of the following medical societies: American College of Emergency Physicians, American College of Osteopathic Emergency Physicians, American Association for Physician Leadership, American Osteopathic Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Jeffrey L Arnold, MD, FACEP Chairman, Department of Emergency Medicine, Santa Clara Valley Medical Center

Jeffrey L Arnold, MD, FACEP is a member of the following medical societies: American Academy of Emergency Medicine, American College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Romesh Khardori, MD, PhD, FACP Professor of Endocrinology, Director of Training Program, Division of Endocrinology, Diabetes and Metabolism, Strelitz Diabetes and Endocrine Disorders Institute, Department of Internal Medicine, Eastern Virginia Medical School

Romesh Khardori, MD, PhD, FACP is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Physicians, American Diabetes Association, Endocrine Society

Disclosure: Nothing to disclose.

Additional Contributors

Erik D Schraga, MD Staff Physician, Department of Emergency Medicine, Mills-Peninsula Emergency Medical Associates

Disclosure: Nothing to disclose.


Robin R Hemphill, MD, MPH Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University School of Medicine

Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

  1. Ariyan CE, Sosa JA. Assessment and management of patients with abnormal calcium. Crit Care Med. 2004 Apr. 32(4 Suppl):S146-54. [Medline].

  2. Dent DM, Miller JL, Klaff L, Barron J. The incidence and causes of hypercalcaemia. Postgrad Med J. 1987 Sep. 63(743):745-50. [Medline].

  3. Edelson GW, Kleerekoper M. Hypercalcemic crisis. Med Clin North Am. 1995 Jan. 79(1):79-92. [Medline].

  4. Cho KC. Electrolyte & Acid-Base Disorders. Papadakis MA, McPhee SJ, Rabow MW, eds. CURRENT Medical Diagnosis & Treatment 2013. New York, NY: McGraw-Hill; 2013. Chapter 21.

  5. Disorder of Calcium Metabolism. Alpern RJ, Moe OW, Caplan M, eds. Seldin and Giebisch's The Kidney. 5th ed. Elsevier; 2013. 2273-309.

  6. Blomqvist CP. Malignant hypercalcemia--a hospital survey. Acta Med Scand. 1986. 220(5):455-63. [Medline].

  7. Hypercalcemia. Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper, JE, eds. Abeloff's Clinical Oncology. 5th ed. Churchill Livingstone; 2014. 581-90.

  8. Mundy GR, Guise TA. Hypercalcemia of malignancy. Am J Med. 1997 Aug. 103(2):134-45. [Medline].

  9. Gastanaga VM, Schwartzberg LS, Jain RK, et al. Prevalence of hypercalcemia among cancer patients in the United States. Cancer Med. 2016 Aug. 5 (8):2091-100. [Medline]. [Full Text].

  10. McNeilly JD, Boal R, Shaikh MG, Ahmed SF. Frequency and aetiology of hypercalcaemia. Arch Dis Child. 2016 Apr. 101 (4):344-7. [Medline].

  11. Khosla S. Hypercalcemia and Hypocalcemia. Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson JL, Loscalzo J, eds. Harrison's Principles of Internal Medicine. 18th ed. New York, NY: McGraw-Hill; 2012. Chapter 46.

  12. Lindner G, Felber R, Schwarz C, Marti G, Leichtle AB, Fiedler GM, et al. Hypercalcemia in the ED: prevalence, etiology, and outcome. Am J Emerg Med. 2013 Apr. 31(4):657-60. [Medline].

  13. Tsao YT, Lee SW, Hsu JC, Ho FM, Wang WJ. Severe hypercalcemia in nonobstructive pyelonephritis with acute renal failure: hit or miss?. Am J Emerg Med. 2012 Oct. 30(8):1665.e5-7. [Medline].

  14. AlZahrani A, Sinnert R, Gernsheimer J. Acute kidney injury, sodium disorders, and hypercalcemia in the aging kidney: diagnostic and therapeutic management strategies in emergency medicine. Clin Geriatr Med. 2013 Feb. 29(1):275-319. [Medline].

  15. Grill V, Ho P, Body JJ, et al. Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. J Clin Endocrinol Metab. 1991 Dec. 73(6):1309-15. [Medline].

  16. Diaz Guardiola P, Vega Pinero B, Alameda Hernando C, Pavon de Paz I, Iglesias Bolanos P, Guijarro de Armas G. [Primary hyperparathyroidism. An alternative to the surgery.]. Endocrinol Nutr. 2009 Mar. 56(3):132-5. [Medline].

  17. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27. 352(4):373-9. [Medline].

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