What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

The treatment of hypercalcemia requires aggressive IV fluid resuscitation with normal saline as the first step, followed by bisphosphonates (preferably zoledronic acid 4 mg IV over 15 minutes) as the first-line pharmacological intervention. 1, 2

Step-wise Treatment Approach

1. Initial Management

• Aggressive IV fluid resuscitation with normal saline
  • Correct hypercalcemia-associated hypovolemia
  • Promote calciuresis
  • Aim to restore urine output to about 2 L/day 2
  • Avoid overhydration, especially in patients with cardiac failure 2

2. Pharmacological Interventions

• Bisphosphonates

  • First-line for moderate to severe hypercalcemia (calcium ≥12 mg/dL) 1, 2
  • Zoledronic acid 4 mg IV over no less than 15 minutes is preferred 3, 1, 2
  • Normalizes calcium levels in 50% of patients by day 4 (compared to 33% with pamidronate) 1
  • Assess renal function before administration 2
  • Consider retreatment if calcium doesn't normalize; wait minimum 7 days between doses 2

• Denosumab

  • For hypercalcemia refractory to bisphosphonates
  • Alternative for patients with severe renal impairment 1
  • Dosing: 120 mg subcutaneously every 4 weeks with additional doses on days 8 and 15 of first month 1

• Calcitonin

  • For immediate short-term management of severe symptomatic hypercalcemia 1, 4
  • Rapid but modest effect 5
  • Can be combined with bisphosphonates for enhanced rate of calcium reduction 5

• Glucocorticoids

  • Effective for hypercalcemia due to:
    • Vitamin D toxicity
    • Granulomatous disorders (e.g., sarcoidosis)
    • Some lymphomas 1, 5, 4

• Loop diuretics (e.g., furosemide)

  • Use only after adequate hydration 3, 1
  • Enhances calcium excretion
  • Never use before correcting hypovolemia 2

3. Special Considerations

For Malignancy-Related Hypercalcemia

• Zoledronic acid is superior to other bisphosphonates 1, 6
• Consider plasmapheresis for symptomatic hyperviscosity in multiple myeloma 3

For Renal Impairment

• Adjust zoledronic acid dosing based on creatinine clearance 2:
  • CrCl >60 mL/min: 4 mg
  • CrCl 50-60 mL/min: 3.5 mg
  • CrCl 40-49 mL/min: 3.3 mg
  • CrCl 30-39 mL/min: 3 mg
• Consider denosumab for severe renal impairment 1
• Consider dialysis for severe hypercalcemia with renal failure 4

Monitoring and Follow-up

• Measure serum creatinine before each bisphosphonate treatment 1, 2
• Monitor calcium levels every 1-2 weeks initially, then monthly after stabilization 1
• Administer oral calcium supplement (500 mg) and vitamin D (400 IU) daily during treatment 2
• Monitor for hypocalcemia, especially with denosumab treatment 1

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia 1, 2
• Failing to correct calcium for albumin 1
• Inadequate hydration before bisphosphonate administration 1, 2
• Treating laboratory values without addressing the underlying cause 1
• Delaying treatment of severe hypercalcemia 1
• Administering bisphosphonates too rapidly (minimum 15 minutes) 2

Remember that the prognosis for hypercalcemia varies based on the underlying cause. While primary hyperparathyroidism has an excellent prognosis, malignancy-associated hypercalcemia indicates poor survival, with median survival of about 1 month in lung cancer patients 1, 7.