What medications are used to treat hypercalcemia?

Medications for Hypercalcemia Management

The first-line pharmacological treatment for hypercalcemia is aggressive IV fluid resuscitation with normal saline followed by bisphosphonates, with zoledronic acid 4 mg IV over 15 minutes being the preferred option. 1

Initial Treatment Approach

Fluid Resuscitation

• Begin with aggressive IV fluid resuscitation using normal saline (200-300 mL/hour initially)
• Target urine output greater than 3 L/day
• Ensure adequate hydration before administering bisphosphonates
• Avoid overhydration in patients with potential for cardiac failure

First-Line Medications

Bisphosphonates

1. Zoledronic acid (preferred first-line):

   • Dosage: 4 mg IV over 15 minutes
   • More effective than pamidronate with higher rates of calcium normalization (88.4% vs 69.7%) 2
   • Faster onset of action and longer time to relapse compared to pamidronate

2. Pamidronate:

   • For moderate hypercalcemia (corrected calcium 12-13.5 mg/dL): 60-90 mg IV over 2-24 hours
   • For severe hypercalcemia (corrected calcium >13.5 mg/dL): 90 mg IV over 2-24 hours
   • Longer infusions (>2 hours) recommended for patients with renal insufficiency 3

Second-Line and Adjunctive Medications

Denosumab

• Indicated for hypercalcemia refractory to bisphosphonates
• Preferred in patients with severe renal impairment
• Fully humanized anti-RANKL antibody that suppresses bone resorption 1, 4

Calcitonin

• For immediate short-term management of severe symptomatic hypercalcemia
• Rapid onset but modest and short-lived effect
• Can be combined with bisphosphonates for faster calcium reduction 1, 5

Glucocorticoids

• Indicated for specific causes of hypercalcemia:
  • Vitamin D toxicity
  • Granulomatous disorders (e.g., sarcoidosis)
  • Some lymphomas 1, 6

Loop Diuretics

• Use only after adequate hydration is achieved
• Enhances calcium excretion
• Never use before correcting hypovolemia 1

Treatment Based on Severity

Mild Hypercalcemia (< 12 mg/dL)

• Usually asymptomatic and may not require acute intervention
• Treat underlying cause
• Ensure adequate hydration

Moderate Hypercalcemia (12-13.5 mg/dL)

• IV fluid resuscitation
• Bisphosphonates (zoledronic acid 4 mg IV or pamidronate 60-90 mg IV)

Severe Hypercalcemia (> 13.5 mg/dL)

• Aggressive IV fluid resuscitation
• Bisphosphonates (zoledronic acid 4 mg IV or pamidronate 90 mg IV)
• Consider adding calcitonin for rapid initial response

Monitoring and Follow-up

• Regular monitoring of serum calcium, phosphate, magnesium
• Monitor renal function and electrolytes
• Watch for hypocalcemia after treatment, especially with denosumab
• Retreatment with bisphosphonates may be considered if serum calcium rises again (minimum 7 days between treatments) 3

Common Pitfalls to Avoid

• Using diuretics before correcting hypovolemia
• Failing to correct calcium for albumin
• Inadequate hydration before bisphosphonate administration
• Treating laboratory values without addressing the underlying cause
• Delaying treatment of severe hypercalcemia
• Administering bisphosphonates too rapidly
• Failing to monitor for hypocalcemia after treatment 1

Remember that while treating hypercalcemia is important, identifying and addressing the underlying cause (most commonly primary hyperparathyroidism or malignancy) is essential for long-term management.