What medications lower calcium levels in hypercalcemia?

From the Guidelines

Hypercalcemia should be treated with hydration, bisphosphonates, denosumab, steroids, and/or calcitonin, with zoledronic acid being the preferred bisphosphonate for treatment of hypercalcemia. The most commonly used medications to lower calcium levels in the body include bisphosphonates (like zoledronic acid, pamidronate, and alendronate), calcitonin, loop diuretics (particularly furosemide), corticosteroids, and calcimimetics (cinacalcet) 1. For acute severe hypercalcemia, intravenous fluids with normal saline are often the first-line treatment, followed by bisphosphonates which typically work within 2-4 days and can maintain effect for weeks. Calcitonin works quickly (within hours) but its effect diminishes after 2-3 days. Denosumab is useful for hypercalcemia caused by bone metastases. Loop diuretics help increase calcium excretion through the kidneys after adequate hydration. These medications work through different mechanisms: bisphosphonates inhibit bone resorption, calcitonin blocks calcium release from bone, diuretics increase urinary calcium excretion, and calcimimetics reduce parathyroid hormone production. The choice of medication depends on the cause and severity of hypercalcemia, with combination therapy often used in severe cases.

Some key points to consider when treating hypercalcemia include:

• The importance of hydration in the initial treatment of hypercalcemia
• The use of bisphosphonates, such as zoledronic acid, as a first-line treatment for hypercalcemia
• The role of calcitonin and denosumab in the treatment of hypercalcemia, particularly in cases caused by bone metastases
• The use of loop diuretics to increase calcium excretion through the kidneys
• The potential benefits and risks of using calcimimetics, such as cinacalcet, in the treatment of hypercalcemia

It's also important to note that the treatment of hypercalcemia should be individualized based on the underlying cause and severity of the condition, as well as the patient's overall health status and medical history. Additionally, regular monitoring of calcium levels and adjustment of treatment as needed is crucial to ensure effective management of hypercalcemia. According to the most recent guidelines, bisphosphonates, denosumab, steroids, and/or calcitonin are recommended for the treatment of hypercalcemia 1.

From the FDA Drug Label

The principal pharmacologic action of zoledronic acid is inhibition of bone resorption. Zoledronic acid inhibits the increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors released by tumors. Clinical studies in patients with hypercalcemia of malignancy (HCM) showed that single-dose infusions of zoledronic acid injection are associated with decreases in serum calcium and phosphorus

• Zoledronic acid is a medication that lowers calcium levels in hypercalcemia by inhibiting bone resorption and osteoclastic activity.
• It is used to treat hypercalcemia of malignancy (HCM) and has been shown to decrease serum calcium levels in clinical studies 2.

From the Research

Medications for Lowering Calcium Levels in Hypercalcemia

The following medications have been found to be effective in lowering calcium levels in hypercalcemia:

• Bisphosphonates, such as pamidronate 3, 4, 5, 6, ibandronate 4, 5, and zoledronic acid 4, 5, 7
• Calcitonin, which is characterized by good tolerability but poor efficacy in normalizing the serum calcium level 5, 7
• Glucocorticoids, which are effective in hypercalcemia due to lymphoma or granulomatous diseases 7
• Gallium nitrate, which may be a valuable treatment for hypercalcemia of malignancy, but data are limited and further trials are necessary 5

Administration and Efficacy

• Intravenous bisphosphonates, such as pamidronate and zoledronic acid, are the agents of choice for long-term control of severe or symptomatic hypercalcemia 7
• The efficacy of bisphosphonates depends on the dose administered and the initial serum calcium concentration 5
• Pamidronate has been studied in the greatest number of investigations and in the largest number of patients, with efficacy in restoring normocalcemia ranging from 40% to 100% 5
• The optimal frequency of administration of pamidronate is every 2 weeks, which can maintain normocalcemia in the vast majority of patients with hypercalcemia of malignancy 6

Adverse Events

• The most serious adverse events of bisphosphonates concern renal function, with increases in serum creatinine levels more frequently reported following treatment with etidronate and clodronate than with pamidronate and ibandronate 5
• Transient fever, lymphocytopenia, malaise, and myalgias are common adverse events associated with the administration of nitrogen-containing bisphosphonates, such as pamidronate and zoledronic acid 5
• Hypocalcemia occurs in up to 50% of patients treated with bisphosphonates for hypercalcemia of malignancy, although symptomatic hypocalcemia is rare 5