Famotidine Does Not Cause Hypercalcemia—It Actually Causes Hypocalcemia
Famotidine (an H2 blocker) does not cause high calcium levels; in fact, it can lead to low calcium (hypocalcemia) through magnesium depletion. 1
Mechanism of Calcium-Lowering Effect
Famotidine can induce hypomagnesemia, which subsequently leads to hypocalcemia through suppression of parathyroid hormone (PTH) secretion. 1 This is the opposite of hypercalcemia.
- A documented case report describes a patient on famotidine 20 mg twice daily for 2 years who developed severe hypocalcemia (5.7 mg/dL) with hypomagnesemia (0.55 mg/dL) and low PTH levels. 1
- The hypocalcemia and hypomagnesemia resolved completely after discontinuation of famotidine, confirming the drug as the causative agent. 1
Effect on Calcium-Phosphate Balance in Dialysis Patients
In hemodialysis patients taking calcium carbonate as a phosphate binder, famotidine has a neutral to slightly negative effect on serum calcium:
- Famotidine at the recommended dose (10 mg/day) did not significantly change serum calcium levels in hemodialysis patients on calcium carbonate. 2
- However, famotidine reduced the phosphate-binding effectiveness of calcium carbonate, leading to increased serum phosphate without increasing calcium absorption. 2, 3
- This suggests famotidine may actually impair calcium absorption from calcium carbonate by raising gastric pH, preventing the drug from causing hypercalcemia. 3
Clinical Use in Hypercalcemia Management
Famotidine is actually used as supportive therapy in treating hypercalcemia, not as a cause of it:
- H2 blockers like famotidine are recommended as adjunctive medications when managing severe drug reactions in cancer patients, alongside antihistamines and corticosteroids. 4
- In cardiovascular settings, famotidine (20 mg twice daily) is used to prevent peptic ulcers in patients on antiplatelet therapy without interfering with drug efficacy. 4
Key Clinical Pitfall to Avoid
Do not confuse famotidine with thiazide diuretics, which are a well-established cause of hypercalcemia through increased renal calcium reabsorption. 5 Famotidine works through a completely different mechanism (gastric acid suppression) and does not affect renal calcium handling in a way that would cause hypercalcemia.
Bottom Line
- Famotidine lowers, not raises, calcium levels when it causes electrolyte disturbances. 1
- The primary concern with famotidine is hypocalcemia secondary to hypomagnesemia, particularly with chronic use. 1
- Monitor magnesium and calcium levels in patients on long-term famotidine therapy, especially if they develop neuromuscular symptoms (Chvostek's sign, Trousseau's sign, muscle cramps, confusion). 1