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Hypercalcemia Medication

  • Author: Mahendra Agraharkar, MD, MBBS, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: Jun 23, 2015

Medication Summary

The first therapy for symptomatic hypercalcemia is volume repletion. More severe cases require saline infusion with concomitant loop diuretics (eg, furosemide) to increase calcium excretion and lower levels rapidly. Other therapies, outlined below, are for longer-term management. Note, however, that no current therapies generally are effective for long-term outpatient therapy. Definitive treatment often requires surgical management of the underlying cause.[9]

Bisphosphonates are effective in the treatment of malignancy-related hypercalcemia and hypercalcemia due to conditions causing increased bone resorption. Zoledronic acid is 100-850 times more potent than pamidronate and may be given as a bolus rather than an infusion. Clodronate (not available in the United States) can be given either intravenously or orally and may represent a better alternative in the future. The monoclonal antibody denosumab is approved for the treatment of hypercalcemia of malignancy that is refractory to bisphosphonate therapy.



Class Summary

Inhibit bone reabsorption.

Pamidronate (Aredia)


Used after initial hydration to inhibit bone reabsorption and maintain low serum calcium levels, especially in hypercalcemia of malignancy and Paget disease.

Etidronate (Didronel)


Reduces bone formation and does not alter renal tubular reabsorption of calcium. Does not affect hypercalcemia in patients with hyperparathyroidism.

Alendronate (Fosamax)


Available in the United States, but not yet indicated for treatment of hypercalcemia; alendronate probably is useful for long-term prevention of recurrence of hypercalcemia following use of more conventional therapy (ie, hydration and pamidronate). Useful in preventing and treating osteoporosis, which is a complication of prolonged mild hypercalcemia.


Monoclonal Antibodies, Endocrine

Class Summary

Binds RANKL and thereby prevents osteoclast formation resulting in decreased bone resorption and decreased calcium release from bone.

Denosumab (Xgeva)


Denosumab is a monoclonal antibody that specifically targets RANKL. It binds to RANKL, a transmembrane or soluble protein essential for the formation, function, and survival of osteoclasts, the cells responsible for bone resorption, thereby modulating calcium release from bone. It is indicated for hypercalcemia of malignancy refractory to bisphosphonate therapy.


Antidote, hypercalcemia agents

Class Summary

Inhibit bone resorption and increase renal calcium excretion.

Calcitonin (Miacalcin, Osteocalcin)


Lowers elevated serum calcium in patients with multiple myeloma, carcinoma, or primary hyperparathyroidism. Expect higher response when serum calcium levels are high.

Onset of action is approximately 2 h following injection, and activity lasts for 6-8 h. May lower calcium levels for 5-8 d by approximately 9% if given q12h. IM route is preferred at multiple injection sites with dose > 2 mL.



Class Summary

Inhibit cytokine release and have a direct cytolytic effect on some tumor cells.

Prednisone (Deltasone, Orasone, Sterapred)


Immunosuppressant for treatment of autoimmune disorders; may decrease inflammation by reversing increased capillary permeability and suppressing PMN activity. Stabilizes lysosomal membranes and suppresses lymphocytes and antibody production.



Class Summary

Phosphate inhibits calcium absorption and promotes calcium deposition. Theorized to help bind dietary calcium, thus rendering it an unabsorbable calcium-phosphorous product, but used rarely.

Potassium phosphate/sodium acid phosphate (Neutra-Phos-K)


Increases urinary pyrophosphate and complexes with calcium, thus decreasing urinary calcium level, while pyridoxine results in a reduction of urinary oxalate excretion. All dosage forms must be mixed in 6-8 oz of water. Never give IV. Never give if renal function is abnormal or if serum phosphorous levels are > 3 mg/dL.


Calcimimetic Agent

Class Summary

Binds to and modulates the parathyroid calcium-sensing receptor, increases sensitivity to extracellular calcium, and reduces parathyroid hormone secretion.[1, 14]

Marcocci et al performed an open-label, single-arm study to determine how effectively cinacalcet, a calcimimetic, reduces hypercalcemia in patients with intractable persistent primary hyperparathyroidism.[15] The investigation, performed on 17 patients, included a 2- to 16-week titration phase and a maintenance phase of up to 136 weeks. By the end of the titration phase, serum calcium had been reduced in 15 patients by at least 1 mg/dL. Although 15 patients suffered adverse events related to treatment (most commonly, nausea, vomiting, and paresthesias), none of these were considered to be serious.

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 secondary hyperparathyroidism in patients with chronic kidney disease on dialysis and in hypercalcemia with parathyroid carcinoma.

Contributor Information and Disclosures

Mahendra Agraharkar, MD, MBBS, FACP FASN, Clinical Associate Professor of Medicine, Baylor College of Medicine; President and CEO, Space City Associates of Nephrology

Mahendra Agraharkar, MD, MBBS, FACP is a member of the following medical societies: American College of Physicians, American Society of Nephrology, National Kidney Foundation

Disclosure: Received ownership interest/medical directorship from South Shore DaVita Dialysis Center for other; Received ownership/medical directorship from Space City Dialysis /American Renal Associates for same; Received ownership interest from US Renal Care for other.


O David Dellinger, III, MD Assistant Professor, Departments of Family Medicine and Internal Medicine, University of Alabama School of Medicine at Birmingham

O David Dellinger, III, MD is a member of the following medical societies: American Academy of Hospice and Palliative Medicine, American College of Physicians-American Society of Internal Medicine, American Geriatrics Society, AMDA - The Society for Post-Acute and Long-Term Care Medicine, American Society of Addiction Medicine

Disclosure: Nothing to disclose.

Arun Kumar Gangakhedkar, MD, FRACP Consultant in General Pediatrics, Starship Children's Hospital/Waitakere Hospital, New Zealand

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.

Christie P Thomas, MBBS, FRCP, FASN, FAHA Professor, Department of Internal Medicine, Division of Nephrology, Departments of Pediatrics and Obstetrics and Gynecology, Medical Director, Kidney and Kidney/Pancreas Transplant Program, University of Iowa Hospitals and Clinics

Christie P Thomas, MBBS, FRCP, FASN, FAHA is a member of the following medical societies: American College of Physicians, American Heart Association, American Society of Nephrology, Royal College of Physicians

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.

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Investigations flowchart.
Vitamin D metabolism.
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