From the Guidelines
Thiazide diuretics, such as hydrochlorothiazide and chlorthalidone, are the most notable medications that can elevate serum ionized calcium levels by reducing urinary calcium excretion, as evidenced by the 2014 AUA guideline 1. Several medications can elevate serum ionized calcium levels in the body, including:
- Vitamin D supplements (calcitriol, ergocalciferol, cholecalciferol), which enhance intestinal calcium absorption and bone resorption
- Calcium supplements themselves, such as calcium carbonate or calcium citrate, directly increase serum calcium levels
- Thiazide diuretics like hydrochlorothiazide and chlorthalidone, which reduce urinary calcium excretion, leading to increased serum calcium, with dosages including hydrochlorothiazide (25 mg orally, twice daily; 50 mg orally, once daily), chlorthalidone (25 mg orally, once daily), and indapamide (2.5 mg orally, once daily) 1
- Lithium, used for bipolar disorder, can cause hyperparathyroidism and subsequent hypercalcemia
- Certain antiresorptive therapies paradoxically cause transient hypercalcemia, including teriparatide (Forteo)
- Vitamin A derivatives and excessive vitamin A supplementation can increase bone resorption and calcium release
- Theophylline, used for respiratory conditions, may elevate calcium levels through increased bone resorption
- Milk-alkali syndrome can occur with excessive intake of calcium-containing antacids These medications affect calcium homeostasis through various mechanisms including altered intestinal absorption, decreased renal excretion, or increased bone resorption, which is why monitoring calcium levels is important when using these medications, especially in patients with pre-existing calcium disorders or kidney dysfunction, as highlighted in the 2017 KDIGO CKD-MBD guideline update 1.
From the FDA Drug Label
Administration of calcitriol to patients in excess of their daily requirements can cause hypercalcemia, hypercalciuria, and hyperphosphatemia. High intake of calcium and phosphate concomitant with calcitriol may lead to similar abnormalities. Excessive dosage of calcitriol induces hypercalcemia and in some instances hypercalciuria; therefore, early in treatment during dosage adjustment, serum calcium should be determined twice weekly. An abrupt increase in calcium intake as a result of changes in diet (e. g., increased consumption of dairy products) or uncontrolled intake of calcium preparations may trigger hypercalcemia. Thiazides are known to induce hypercalcemia by the reduction of calcium excretion in urine. Uncontrolled intake of additional calcium-containing preparations should be avoided
The medications that can elevate serum ionized calcium are:
- Calcitriol: can cause hypercalcemia if taken in excess of daily requirements
- Thiazides: can induce hypercalcemia by reducing calcium excretion in urine
- Calcium supplements: uncontrolled intake can lead to hypercalcemia
- Vitamin D: pharmacological doses should be withheld during treatment with calcitriol to avoid possible additive effects and hypercalcemia 2, 2, 2
From the Research
Medications that Elevate Serum Ionized Calcium
The following medications can contribute to elevated serum ionized calcium levels:
- Calcium supplements, such as calcium carbonate 3
- Vitamin D supplements, including calcitriol and cholecalciferol (vitamin D3) 3, 4
- Thiazide diuretics, which can increase renal calcium resorption and contribute to hypercalcemia, particularly in patients taking calcium and vitamin D supplements 3
Mechanisms of Action
These medications can affect serum calcium concentrations by:
- Influencing intestinal calcium absorption
- Altering renal calcium resorption
- Modulating bone remodeling
- Interacting with parathyroid hormone (PTH) or 1,25-dihydroxyvitamin D-mediated regulation 5
Clinical Implications
Elevated serum ionized calcium levels can lead to hypercalcemia, which can cause symptoms such as nausea, vomiting, confusion, and difficulty walking 3. It is essential to monitor serum calcium levels and adjust medications accordingly to prevent hypercalcemia and its associated complications.