How to treat hypercalcemia?

Treatment of Hypercalcemia

The first-line 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 pharmacological agent for moderate to severe cases. 1

Assessment and Classification

Hypercalcemia is classified based on severity:

• Mild: Total calcium <12 mg/dL
• Moderate: Total calcium 12.0-13.5 mg/dL
• Severe: Total calcium ≥14 mg/dL or ≥12 mg/dL with symptoms

Before initiating treatment, confirm hypercalcemia using the corrected calcium formula:

• Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1

Step-wise Treatment Approach

1. Aggressive IV Fluid Resuscitation

• First step for all moderate to severe cases
• Administer normal saline (0.9% NaCl) to:
  • Correct hypovolemia
  • Promote calciuresis
  • Restore urine output to approximately 2 L/day 1, 2
• Important: Avoid overhydration in patients with cardiac failure 2

2. Bisphosphonates

• First-line pharmacological treatment
• Zoledronic acid 4 mg IV over 15 minutes is preferred due to:
  • Higher complete response rate (50% by day 4 vs. 33% with pamidronate)
  • Longer response duration
  • Longer time to relapse 3, 1
• Dose adjustments not necessary for mild-to-moderate renal impairment (serum creatinine <4.5 mg/dL) 2
• Monitor renal function before each treatment 2
• For relapsed or refractory cases, zoledronic acid 8 mg may be considered 3, 1

3. Denosumab

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

4. Additional Therapies

• Calcitonin: For immediate short-term management of severe symptomatic hypercalcemia while waiting for bisphosphonates to take effect 1, 5
• Loop diuretics: Only after adequate hydration to enhance calcium excretion 1
• Glucocorticoids: For hypercalcemia due to vitamin D toxicity, granulomatous disorders, or lymphomas 1, 5
• Dialysis: For severe hypercalcemia complicated with kidney failure 5

Special Considerations

Malignancy-Associated Hypercalcemia

• Zoledronic acid has been proven more effective than pamidronate with:
  • Higher complete response rate
  • Longer response duration
  • Longer time to relapse 3
• A minimum of 7 days should elapse before retreatment with zoledronic acid to allow for full response to the initial dose 2

Renal Impairment

• Monitor serum creatinine before each treatment with bisphosphonates 2
• For patients with renal failure, denosumab or dialysis may be indicated 1, 6

Monitoring During Treatment

• Serum calcium, phosphate, magnesium
• Renal function
• Electrolytes
• Monitor for hypocalcemia, especially with denosumab 1

Common Pitfalls to Avoid

1. Using diuretics before correcting hypovolemia
2. Failing to correct calcium for albumin
3. Inadequate hydration before bisphosphonate administration
4. Treating laboratory values without addressing the underlying cause
5. Delaying treatment of severe hypercalcemia
6. Administering bisphosphonates too rapidly 1

Remember that while treating the hypercalcemia is important, identifying and addressing the underlying cause is essential for long-term management. Primary hyperparathyroidism and malignancy account for over 90% of hypercalcemia cases 6, 5.