Can famotidine (histamine-2 (H2) blocker) cause hypomagnesemia (low magnesium levels)?

Famotidine and Hypomagnesemia: Clinical Implications

Famotidine can cause hypomagnesemia in rare cases, particularly with long-term use, and should be considered as a potential cause when patients present with unexplained low magnesium levels. 1

Mechanism and Evidence

Histamine-2 receptor antagonists (H2 blockers) like famotidine have been documented to cause electrolyte disturbances, though less commonly than proton pump inhibitors (PPIs). The evidence specifically for famotidine-induced hypomagnesemia is limited but significant:

• A case report documented a 55-year-old female who developed severe hypomagnesemia (0.55 mg/dL) and associated hypocalcemia after taking famotidine 20 mg twice daily for 2 years 1
• The patient's electrolyte abnormalities normalized after discontinuation of famotidine, strongly suggesting a causal relationship 1

While PPIs are more frequently associated with hypomagnesemia, the mechanism may be similar, involving interference with intestinal magnesium absorption through:

• Inhibition of active magnesium transport via TRPM6/7 channels 2
• Possible interference with passive magnesium absorption 2

Clinical Presentation

Hypomagnesemia can present with various symptoms depending on severity:

• Neuromuscular manifestations: tremors, muscle cramps, tetany, positive Chvostek's and Trousseau's signs 1
• Neurological symptoms: confusion, altered mental status 1
• Cardiovascular effects: arrhythmias, including atrial fibrillation 3
• Secondary electrolyte abnormalities: hypocalcemia, hypokalemia 1, 4

Risk Factors

Factors that may increase the risk of developing famotidine-induced hypomagnesemia include:

• Long-term use (typically years rather than months) 1
• Concomitant use of other medications that can deplete magnesium (diuretics, certain antibiotics) 4, 5
• Advanced age 3
• Malnutrition or poor dietary magnesium intake 3
• Alcohol use 3
• Pre-existing renal impairment 4

Monitoring and Management

For patients on long-term famotidine therapy:

1. Monitor serum magnesium levels:

   • Before initiating therapy in high-risk patients
   • Periodically during long-term treatment (every 6-12 months)
   • When patients develop symptoms suggestive of hypomagnesemia

2. Management of hypomagnesemia:

   • Discontinue famotidine if hypomagnesemia is detected 1
   • Provide magnesium supplementation for symptomatic or severe cases 1
   • Consider switching to an alternative acid-suppressing medication with lower risk of hypomagnesemia
   • Monitor until magnesium levels normalize 1

3. Target magnesium levels:

   • Aim for serum magnesium >0.6 mmol/L (>1.5 mg/dL) 6
   • Monitor for improvement in secondary electrolyte abnormalities (potassium, calcium) 6

Prevention

For patients requiring long-term acid suppression therapy:

• Use the lowest effective dose of famotidine
• Consider periodic "drug holidays" if clinically appropriate
• Ensure adequate dietary magnesium intake (whole grains, nuts, leafy greens) 6
• Consider alternative acid-suppressing medications in high-risk patients

Clinical Pearls and Pitfalls

• Hypomagnesemia can persist for weeks after discontinuing the causative medication due to depleted body stores 1
• Serum magnesium levels may not accurately reflect total body magnesium stores 6
• Hypomagnesemia can cause refractory hypokalemia and hypocalcemia that won't correct until magnesium is repleted 4
• Consider famotidine as a potential cause when patients present with unexplained electrolyte abnormalities, particularly if they've been on long-term therapy

While famotidine-induced hypomagnesemia is less common than with PPIs, clinicians should maintain awareness of this potential adverse effect, especially in patients on long-term therapy who develop unexplained neurological, cardiovascular, or musculoskeletal symptoms.