What medications can cause hypercalcemia, specifically elevated ionized calcium levels?

From the Guidelines

Thiazide diuretics, such as hydrochlorothiazide and chlorthalidone, are the most commonly used medications to elevate ionized calcium levels in the blood, as they decrease urinary calcium excretion, and their use is supported by the American Urological Association guideline 1.

Mechanisms of Action

These medications work by:

• Decreasing urinary calcium excretion
• Increasing parathyroid hormone secretion (lithium)
• Enhancing intestinal calcium absorption (vitamin D supplements)
• Increasing bone resorption (vitamin A derivatives)
• Directly increasing blood calcium (calcium-containing medications)

Medications that Elevate Ionized Calcium

Some of the medications that can elevate ionized calcium levels include:

• Thiazide diuretics (hydrochlorothiazide, chlorthalidone)
• Lithium
• Vitamin D supplements (ergocalciferol, cholecalciferol)
• Vitamin A derivatives (retinoids) such as isotretinoin
• Calcium-containing medications (calcium carbonate, calcium citrate)
• Hormone therapies (estrogens, tamoxifen, androgens)
• Antacids containing calcium
• Theophylline and some antipsychotics

Important Considerations

It is essential to monitor calcium levels periodically in patients taking these medications, especially those with risk factors for hypercalcemia, such as hyperparathyroidism, malignancy, or immobilization, as supported by the Kidney Disease: Improving Global Outcomes clinical practice guideline update 1.

Dosage and Administration

The dosage and administration of these medications vary, and it is crucial to follow the recommended guidelines, such as those provided by the American Academy of Pediatrics 1 and the American Heart Association 1.

From the FDA Drug Label

In clinical trials, the frequency of at least 1 episode of transient hypercalcemia in the 4 to 6 hours after teriparatide administration was 11% of women and 6% of men treated with teriparatide compared to 2% of women and 0% of the men treated with placebo Thiazides are known to induce hypercalcemia by the reduction of calcium excretion in urine. Hypercalcemia greater than 13 mg/dL has been reported with teriparatide use

• Medications that can elevate ionized calcium include:
  • Teriparatide 2
  • Thiazides 3
  • Calcitriol 3
  • Vitamin D supplements 3
  • Calcium supplements 3
  • Magnesium-containing preparations 3
  • Digitalis 3
  • Ketoconazole 3
  • Corticosteroids 3
  • Phosphate-Binding Agents 3

From the Research

Medications that Can Elevate Ionized Calcium

• The following medications can cause an increase in ionized calcium levels:
  • Vitamin D supplements and 1α-hydroxylated vitamin D analogues, which increase intestinal calcium absorption, renal calcium reabsorption, and bone resorption 4
  • Recombinant human PTH, which can cause transient hypercalcemia in patients with hypoparathyroidism, especially during acute illness 4
  • Thiazide diuretics, which enhance renal proximal calcium reabsorption and can unmask asymptomatic normocalcemic or intermittently hypercalcemic hyperparathyroidism 4, 5, 6
  • Lithium, which causes hypercalcemia mainly by inducing hyperparathyroidism 4, 7
• It is essential to note that these medications can have varying effects on calcium levels, and their use should be carefully monitored to avoid hypercalcemia or other complications 7, 8
• Additionally, other factors such as vitamin D deficiency or excessive intake can also impact calcium levels, highlighting the need for careful management and monitoring 7, 8