From the Guidelines
Hypercalcemia should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate option. Management of hypercalcemia requires a stepwise approach based on severity and underlying cause. For mild hypercalcemia (calcium <12 mg/dL), addressing the underlying cause may be sufficient. For moderate to severe hypercalcemia (calcium >12 mg/dL) or symptomatic patients, immediate treatment is necessary. Initial management includes aggressive intravenous fluid rehydration with normal saline at 200-300 mL/hour to restore intravascular volume and enhance renal calcium excretion. Once adequately hydrated, loop diuretics like furosemide 20-40 mg IV every 12 hours can be added to prevent fluid overload and further increase calcium excretion.
- Bisphosphonates are the mainstay for hypercalcemia of malignancy, with zoledronic acid 4 mg IV over 15 minutes or pamidronate 60-90 mg IV over 2-4 hours being first-line options, as recommended by the NCCN guidelines 1.
- Calcitonin 4-8 IU/kg SC/IM every 12 hours provides rapid but short-term calcium reduction and works well as bridge therapy.
- For refractory cases, cinacalcet 30-90 mg orally daily may help in hyperparathyroidism, while denosumab 120 mg SC can be used when bisphosphonates fail.
- Glucocorticoids like prednisone 40-60 mg daily benefit patients with vitamin D-mediated hypercalcemia or certain malignancies.
- Hemodialysis remains an option for severe, life-threatening hypercalcemia unresponsive to other measures, especially in patients with renal failure, as suggested by the NCCN guidelines 1. Throughout treatment, frequent monitoring of serum calcium, renal function, and electrolytes is essential to guide therapy adjustments, as emphasized in the NCCN guidelines 1.
From the FDA Drug Label
Reducing excessive bone resorption and maintaining adequate fluid administration are, therefore, essential to the management of hypercalcemia of malignancy Correction of excessive bone resorption and adequate fluid administration to correct volume deficits are therefore essential to the management of hypercalcemia
The management of hypercalcemia involves:
- Reducing excessive bone resorption
- Maintaining adequate fluid administration to correct volume deficits 2 3
From the Research
Management of Hypercalcemia
The management of hypercalcemia involves several approaches, including:
- Hydration: Treatment of hypercalcemia should be started with hydration 4, 5, 6, 7, 8
- Loop diuretics: May be required in individuals with renal insufficiency or heart failure to prevent fluid overload 4, 7
- Calcitonin: Administered for the immediate short-term management of severe symptomatic hypercalcemia 4
- Bisphosphonates: For long-term control of severe or symptomatic hypercalcemia, the addition of bisphosphonate is typically required 4, 5, 6, 7, 8
- Glucocorticoids: Effective in hypercalcemia due to lymphoma or granulomatous diseases 4, 5, 7
- Dialysis: Generally reserved for those with severe hypercalcemia complicated with kidney failure 4, 5, 7
- Parathyroidectomy: May be considered depending on age, serum calcium level, and kidney or skeletal involvement in patients with primary hyperparathyroidism 5, 8
Treatment Options
Treatment options for hypercalcemia include:
- Zoledronic acid or pamidronate: Intravenous bisphosphonates of choice for the management of severe hypercalcemia 4, 5, 6
- Denosumab: May be indicated in patients with kidney failure 5, 8
- Furosemide: May be prescribed in some cases, but its effectiveness is limited 6
- Normal saline hydration: Effective in reducing serum calcium levels, but may not lead to normalization of calcium levels 6
Underlying Cause
The underlying cause of hypercalcemia should be identified and treated, including: