What is the treatment for hypercalcemia (elevated calcium levels)?

From the Guidelines

Hypercalcemia should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate 1.

Treatment Approach

The treatment of hypercalcemia depends on its severity and underlying cause. For mild cases, addressing the root cause may be sufficient.

• Initial management includes aggressive IV fluid rehydration with normal saline to increase calcium excretion.
• Loop diuretics like furosemide can be used after adequate hydration to enhance calcium elimination.
• Bisphosphonates, such as zoledronic acid, are first-line medications for severe hypercalcemia.
• Calcitonin provides rapid but short-term calcium reduction.
• Denosumab can be used for refractory cases.
• Dialysis is reserved for life-threatening hypercalcemia or patients with renal failure.
• Glucocorticoids like prednisone are helpful for hypercalcemia caused by certain conditions.

Key Considerations

• Treating hypercalcemia is crucial because elevated calcium levels can cause cardiac arrhythmias, kidney stones, neurological symptoms, and in severe cases, coma or death.
• Definitive treatment always requires addressing the underlying cause, commonly hyperparathyroidism, malignancy, or medication effects.
• The NCCN MM Panel members prefer zoledronic acid for treatment of hypercalcemia 1.
• Plasmapheresis should be used as adjunctive therapy for symptomatic hyperviscosity, and institutions may differ in their use of plasmapheresis for adjunctive treatment of renal dysfunction 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Hypercalcemia of Malignancy Consideration should be given to the severity of as well as the symptoms of hypercalcemia. Vigorous saline hydration alone may be sufficient for treating mild, asymptomatic hypercalcemia. Moderate Hypercalcemia The recommended dose of pamidronate disodium in moderate hypercalcemia (corrected serum calcium* of approximately 12 to 13.5 mg/dL) is 60 to 90 mg given as a SINGLE-DOSE, intravenous infusion over 2 to 24 hours. Severe Hypercalcemia The recommended dose of pamidronate disodium in severe hypercalcemia (corrected serum calcium* >13.5 mg/dL) is 90 mg given as a SINGLE-DOSE, intravenous infusion over 2 to 24 hours.

The treatment for hypercalcemia includes:

• Vigorous saline hydration for mild, asymptomatic cases
• Pamidronate disodium for moderate to severe cases, with doses of:
  • 60 to 90 mg for moderate hypercalcemia (corrected serum calcium of approximately 12 to 13.5 mg/dL)
  • 90 mg for severe hypercalcemia (corrected serum calcium >13.5 mg/dL) Given as a single-dose, intravenous infusion over 2 to 24 hours 2.

From the Research

Treatment of Hypercalcemia

The treatment of hypercalcemia depends on the underlying cause and severity of the condition.

• For mild hypercalcemia, treatment may not be necessary, but monitoring of serum calcium levels is recommended 3.
• For symptomatic or severe hypercalcemia, initial therapy consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate 3, 4, 5, 6.
• In patients with kidney failure, denosumab and dialysis may be indicated 3, 7.
• Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas) 3, 6, 7.
• Loop diuretics may be required in individuals with renal insufficiency or heart failure to prevent fluid overload 6.
• Calcitonin is administered for the immediate short-term management of severe symptomatic hypercalcemia 6, 7.

Specific Treatment Approaches

• For primary hyperparathyroidism (PHPT), parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement 3.
• For hypercalcemia of malignancy, treatment options include volume expansion with normal saline solution, intravenous bisphosphonates, calcitonin, gallium nitrate, and corticosteroids 7.
• Denosumab is an attractive therapeutic option for refractory cases of hypercalcemia, although more data are required before this therapy can be recommended 7.

Management of Severe Hypercalcemia

• Severe hypercalcemia is a life-threatening condition that should be managed urgently 5.
• The efficacy of saline hydration, furosemide, and zoledronic acid in the management of severe hypercalcemia secondary to primary hyperparathyroidism has been assessed, with zoledronic acid being more potent 5.
• Appropriate normal saline hydration with immediate intravenous bisphosphonates infusion should be considered in the management of severe hypercalcemia in patients with PHPT 5.