What medications can be used to lower calcium levels in cases of hypercalcemia?

Medications to Lower Calcium Levels in Hypercalcemia

Bisphosphonates, particularly zoledronic acid, are the first-line treatment for hypercalcemia, with aggressive hydration as an essential initial step. 1, 2

First-Line Treatment Approach

Initial Management

1. Hydration

   • Intravenous crystalloid fluids (normal saline) to restore intravascular volume
   • Goal: Urine output of 100-150 mL/hour 1
   • Caution: Avoid overhydration in patients with oliguria or heart failure

2. Bisphosphonates

   • Zoledronic acid (preferred): 4 mg as a single dose infused over 15 minutes 1, 2

     • More effective than pamidronate with higher complete response rate, longer response duration, and longer time to relapse 1
     • Infusion volume of 100 mL to limit renal complications

   • Pamidronate: Alternative option 3

     • Moderate hypercalcemia (12-13.5 mg/dL): 60-90 mg as single-dose IV infusion over 2-24 hours
     • Severe hypercalcemia (>13.5 mg/dL): 90 mg as single-dose IV infusion over 2-24 hours
     • Longer infusion times (>2 hours) recommended for patients with renal insufficiency

3. Denosumab

   • Alternative for patients with renal impairment 1
   • Preferred over bisphosphonates in patients with renal disease
   • Note: May cause higher rates of hypocalcemia compared to bisphosphonates

Additional Treatment Options

1. Calcitonin

   • Rapid onset but less potent effect 4, 5
   • Useful when rapid calcium reduction is needed
   • Can be combined with bisphosphonates for faster initial response
   • May be effective in cases resistant to bisphosphonates 6

2. Loop Diuretics (e.g., furosemide)

   • Use only after adequate hydration is achieved 1
   • Helps with calcium excretion
   • Not recommended as initial therapy before volume restoration

3. Glucocorticoids

   • Effective primarily in hypercalcemia due to:
     • Vitamin D intoxication
     • Granulomatous disorders
     • Some lymphomas 1, 5
   • Not first-line for most malignancy-related hypercalcemia

Special Considerations

Renal Impairment

• Monitor renal function before and during treatment with bisphosphonates 1
• Dose adjustments or alternative agents may be needed:
  • For patients with renal failure, denosumab is preferred 1
  • Consider hemodialysis for severe cases with renal failure 1

Monitoring

• Monitor serum calcium, creatinine, and albumin levels regularly
• Watch for hypocalcemia with bisphosphonate or denosumab therapy
• For patients on bisphosphonates: monitor for osteonecrosis of jaw

Retreatment Considerations

• For pamidronate: minimum 7-day interval before retreatment 3
• For zoledronic acid: retreatment with higher doses (8 mg) may be considered for relapsed or refractory hypercalcemia 1

Common Pitfalls

1. Failing to adequately hydrate before administering bisphosphonates
2. Using loop diuretics before volume restoration
3. Not monitoring for renal dysfunction during bisphosphonate therapy
4. Overlooking the need for albumin correction when interpreting calcium levels
5. Delaying bisphosphonate administration (should be started early due to delayed onset of action)

The management of hypercalcemia requires prompt intervention, especially in severe cases, with hydration and bisphosphonates forming the cornerstone of therapy. The choice between agents should consider the severity of hypercalcemia, renal function, and underlying cause.