What is the treatment for hypercalcemia?

Treatment of Hypercalcemia

Aggressive IV fluid resuscitation with normal saline and bisphosphonates (e.g., zoledronic acid 4 mg IV) are the first-line treatments for severe symptomatic hypercalcemia. 1

Step-wise Treatment Approach

Initial Assessment and Classification

• Confirm hypercalcemia with albumin-corrected calcium calculation:
  • Corrected calcium (mg/dL) = Total calcium (mg/dL) + 0.8 × [4 - Serum albumin (g/dL)] 1
• Classify severity:
  • Mild: total calcium <12 mg/dL
  • Severe: total calcium ≥14 mg/dL 1

Treatment Algorithm

1. Aggressive IV Fluid Resuscitation

   • Normal saline to correct hypovolemia and promote calciuresis
   • Target adequate hydration throughout treatment 1

2. Pharmacological Interventions

   • First-line: Bisphosphonates

     • Zoledronic acid 4 mg IV over 15 minutes (preferred agent) 1, 2
     • Maximum recommended dose for hypercalcemia of malignancy is 4 mg as a single-dose IV infusion 2
     • Zoledronic acid normalizes calcium levels in 50% of patients by day 4 (vs 33% with pamidronate) 1

   • For refractory cases or severe renal impairment:

     • Denosumab 1
     • Consider zoledronic acid 8 mg dose for relapsed/refractory cases 1

   • For specific causes:

     • Glucocorticoids: For vitamin D toxicity, granulomatous disorders, or lymphomas 1, 3
     • Calcitonin: For immediate short-term management of severe symptomatic hypercalcemia 1, 3

   • After adequate hydration:

     • Loop diuretics to enhance calcium excretion 1

3. Monitoring

   • Regular assessment of serum calcium, phosphate, magnesium, renal function, and electrolytes 1
   • Serum creatinine should be assessed prior to each treatment 2

Special Considerations

Renal Impairment

• Assess renal function before treatment 2
• For patients with reduced renal function and multiple myeloma or bone metastases:
  • CrCl >60 mL/min: 4 mg zoledronic acid
  • CrCl 50-60 mL/min: 3.5 mg
  • CrCl 40-49 mL/min: 3.3 mg
  • CrCl 30-39 mL/min: 3 mg 2
• Consider denosumab for patients with severe renal impairment 1

Retreatment

• May consider retreatment with zoledronic acid 4 mg if serum calcium doesn't normalize
• Allow minimum 7 days between treatments for full response 2
• Monitor renal function before retreatment 2

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, especially with denosumab 1

Cause-Specific Considerations

• Primary hyperparathyroidism: Parathyroidectomy may be considered depending on age, calcium level, and organ involvement 4
• Malignancy-associated hypercalcemia: Treat underlying malignancy; has poorer prognosis with median survival of about 1 month in lung cancer patients 1
• Vitamin D toxicity or granulomatous disease: Glucocorticoids are effective 3

Remember that while treating the acute hypercalcemia is critical, identifying and addressing the underlying cause is essential for long-term management.