eMedicine Specialties > Emergency Medicine > Endocrine & Metabolic
Hypercalcemia: Treatment & Medication
Updated: Aug 5, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Prehospital Care
Prehospital care is primarily supportive with management of the ABCs. If a patient has a history of hypercalcemia and displays evidence of acute hypercalcemia, immediately begin IV hydration.
Emergency Department Care
The treatment of hypercalcemia depends on the level, the chronicity, and the underlying cause of the problem. In mild-to-moderate elevations of calcium, few treatment options may be available in the ED. A physical evaluation to help delineate the source of the elevation is always appropriate, as is a subsequent timely follow-up visit.
- Initial goals of treatment
- Stabilization and reduction of the calcium level
- Adequate hydration
- Increased urinary calcium excretion
- Inhibition of osteoclast activity in the bone
- Discontinuation of pharmacologic agents associated with hypercalcemia
- Treatment of the underlying cause (when possible)
- The initial step in the care of severely hypercalcemic patients is hydration with saline. Hydration helps decrease the calcium level through dilution. The expansion of extracellular volume also increases the renal calcium clearance. The rate of fluid therapy is based upon the following:
- Degree of hypercalcemia
- Severity of dehydration
- Ability of the patient to tolerate rehydration - Vigilance to prevent volume overload is critical.
- Hydration is ineffective in patients with kidney failure because diuresis is impossible. Dialysis is necessary to correct hypercalcemia in patients with renal failure.
- Loop diuretics
- A loop diuretic (eg, furosemide) may be used with hydration to increase calcium excretion. This may also prevent volume overload during therapy.
- In contrast to loop diuretics, avoid thiazide diuretics because they increase the reabsorption of calcium.
- Bisphosphates - These agents will inhibit osteoclast activity for up to a month.
Consultations
- Patients with renal failure or heart failure may not be able to tolerate fluid hydration or some of the other medications. Patients in this group who present with severe elevations of calcium may require urgent dialysis. Consult a nephrologist immediately in such cases.
- Patients with primary hyperparathyroidism may require surgery to eliminate the condition,7 but surgery usually does not need to be performed on an urgent basis.
- Patients with malignancy may require surgery, chemotherapy, or radiation treatment. Appropriate consultation should be undertaken.
Medication
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 plicamycin (also known as Mithracin), calcitonin, gallium nitrate, intravenous phosphate, bisphosphates, and glucocorticoids.
Bisphosphonates
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.
Adult
Moderate hypercalcemia: 60 mg IV infusion over 4 h initial; alternatively, 90 mg IV infusion over 24 h initial
Severe hypercalcemia: 90 mg IV infusion over 24 h initial
Pediatric
Not established
None reported
Documented hypersensitivity; hypocalcemia
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Monitor hypercalcemia-related parameters, such as serum levels of calcium, phosphate, magnesium, and potassium once treatment begins; adequate intake of calcium and vitamin D is necessary to prevent severe hypocalcemia; caution when administering bisphosphonates in active upper GI problems; do not coadminister with alendronate for osteoporosis in postmenopausal women
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.
Adult
4 mg IV over at least 15 min once qmo; hydrate patient before infusion; may retreat following 7 d if desired response not observed
Pediatric
Not established
Concurrent administration with loop diuretics may increase risk of hypocalcemia, nephrotoxic agents; valacyclovir levels may be increased
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Caution in renal insufficiency; risk of renal deterioration increased with <15 min IV infusion; flulike syndrome (fever, arthralgias, myalgias, skeletal pain), gastrointestinal reactions, anemia, neutropenia, pancytopenia, insomnia, dyspnea, electrolyte and mineral disturbances, such as low serum phosphate, calcium, magnesium, and potassium may occur
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.
Adult
7.5 mg/kg IV over 4 h for 3-7 d; dilute in at least 250 mL of sterile saline; use beyond 3 d may increase risk of hypocalcemia; full initial doses may be used in repeat dosing situations if etidronate has not been used in previous 7 d
Pediatric
Not established
Coadministration with calcium-containing products and other multivalent cations decrease absorption
Documented hypersensitivity; hypocalcemia; renal impairment
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium and potassium); maintain adequate intake of calcium and vitamin D to prevent severe hypocalcemia; caution in active upper GI problems; do not administer with alendronate for osteoporosis in postmenopausal women
Antidote, Hypercalcemia
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.
Adult
2-8 U/kg IM/SC q6-12h
Pediatric
Not established
None reported
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Hypocalcemia may occur; examine urine sediment during prolonged therapy
Effective in only 60-70% of patients and tachyphylaxis will usually develop in 48-72 h
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.
Adult
Severe hypercalcemia: 200 mg/m2/d IV for 5 d in 1 L of NS or D5W
Mild hypercalcemia: 100 mg/m2/d IV for 5 d in 1 L of NS or D5W
Pediatric
Not established
Nephrotoxic effects increase when administered with amphotericin B or aminoglycosides
Documented hypersensitivity; renal failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in renal failure
Plicamycin
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.
Adult
25 mcg/kg/d IV for 3-4 d
Alternatively, 25 mcg/kg IV once and repeat in 48 h if no response
Alternatively, 25-50 mcg/kg/dose IV qod for 3-8 doses
Pediatric
Not established
Coadministration with glucagon, calcitonin, and etidronate, may increase toxicity
Documented hypersensitivity; thrombocytopenia, coagulation disorders, impairment of bone marrow function
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Monitor platelets, prothrombin and bleeding times periodically during therapy and for several days after last dose; discontinue therapy if significant prolongation of bleeding times occurs and thrombocytopenia is observed; correct any electrolyte imbalance (especially hypokalemia, hypocalcemia, and hypophosphatemia) prior to treatment
Phosphate salts
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 (K2 PO4). Response to IV serum phosphorus supplementation is highly variable and is associated with hyperphosphatemia.
Adult
Initial: 8 mmol IV q6h (32 mmol/24 h)
Aggressive: 15 mmol IV over 6 h
Pediatric
0.25-0.5 mmol/kg IV over 4-6 h; repeat prn
Magnesium and aluminum-containing antacids or sucralfate can act as phosphate binders and decrease serum phosphate levels; potassium-sparing diuretics, ACE inhibitors, and salt substitutes may increase serum phosphate levels
Documented hypersensitivity; hyperphosphatemia; hypocalcemia; hypomagnesemia; hyperkalemia; renal failure
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in patients with renal insufficiency, and metabolic alkalosis; admixture of phosphate and calcium in IV fluids can result in calcium phosphate precipitation
Corticosteroids
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.
Adult
200-300 mg IV for 3 d
Pediatric
10 mg/kg/d IV divided qid
Corticosteroid clearance may decrease with estrogens; may increase digitalis toxicity secondary to hypokalemia
Documented hypersensitivity; viral, fungal, or tubercular skin infections
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in hyperthyroidism, osteoporosis, peptic ulcer, cirrhosis, nonspecific ulcerative colitis, diabetes, and myasthenia gravis
Calcimimetic Agent
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.
Adult
30 mg PO qd initially; titrate q2-4wk as needed to normalize calcium levels by sequential doses of 30 mg bid, 60 mg bid, 90 mg bid, and 90 mg tid/qid
Take with meals or immediately following; do not crush, chew, or cut tabs
Pediatric
Not established
Strong CYP2D6 inhibitor; may increase serum levels of CYP2D6 substrates (eg, flecainide, vinblastine, thioridazine, tricyclic antidepressants); coadministration with CYP3A4 inhibitors (eg, ketoconazole, erythromycin, itraconazole) may decrease cinacalcet clearance
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Serum calcium reduction may cause lowered seizure threshold, paresthesia, myalgia, cramping, and tetany; monitor calcium and phosphorus levels closely within 1 wk following initial dose or dose changes, and then monthly (secondary hyperparathyroidism) and q2mo (parathyroid carcinoma); do not initiate treatment if serum calcium below 8.4 mg/dL; a dynamic bone disease may occur if iPTH levels suppressed below 100 pg/mL; caution with hepatic impairment; common adverse effects include nausea and vomiting
More on Hypercalcemia |
| Overview: Hypercalcemia |
| Differential Diagnoses & Workup: Hypercalcemia |
 Treatment & Medication: Hypercalcemia |
| Follow-up: Hypercalcemia |
| References |
| Further Reading |
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References
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Bilezikian JP. Management of acute hypercalcemia. N Engl J Med. Apr 30 1992;326(18):1196-203. [Medline].
Kiang DT, Loken MK, Kennedy BJ. Mechanism of the hypocalcemic effect of mithramycin. J Clin Endocrinol Metab. Feb 1979;48(2):341-4. [Medline].
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Keywords
elevated calcium level, elevated calcium, increased calcium level, high calcium, malignancy, hyperparathyroidism, primary hyperparathyroidism, parathyroid disease, calcium metabolism, excess calcium, vitamin D, bony metastases, serum calcium, plasma calcium, calcium regulation, calcitriol, 1, 25- dihydroxyvitamin D, calcitonin
parathyroid hormone, PTH, PTH-mediated hypercalcemia, non–PTH-mediated hypercalcemia, band keratopathy, sarcoidosis, granulomatous disease, multiple myeloma, hematologic malignancy, lymphoproliferative disease, multiple endocrine neoplasia, pheochromocytoma,hepatoma, adrenal insufficiency, hypophosphatasia, chronic hemodialysis, primary infantile hyperparathyroidism
