H2 Receptor Antagonists (H2 Blockers)
The four H2 receptor antagonists available are famotidine, ranitidine, cimetidine, and nizatidine, with typical dosing as follows: famotidine 20 mg twice daily, ranitidine 150 mg twice daily, cimetidine 300 mg three to four times daily, and nizatidine 150 mg twice daily 1.
Complete List of H2 Blockers with Standard Dosing
Adult Dosing
- Famotidine: 20 mg twice daily (standard dose equivalent)
- Ranitidine: 150 mg twice daily (note: withdrawn from many markets due to NDMA contamination concerns)
- Cimetidine: 300 mg three to four times daily
- Nizatidine: 150 mg twice daily
These doses shown above are considered therapeutically equivalent to each other 1.
Pediatric Dosing
For children, weight-based dosing is required 2:
- Cimetidine: 30-40 mg/kg/day divided in 4 doses (FDA approved ≥16 years)
- Ranitidine: 5-10 mg/kg/day divided in 2-3 doses (FDA approved 1 month-16 years)
- Famotidine: 1 mg/kg/day divided in 2 doses (FDA approved 1-16 years)
- Nizatidine: 10 mg/kg/day divided in 2 doses (FDA approved ≥12 years)
Clinical Context and Mechanism
H2 receptor antagonists work by blocking histamine-2 receptors on gastric parietal cells, thereby reducing acid secretion 2. They are effective for treating gastroesophageal reflux disease, peptic ulcer disease, and preventing stress-related gastrointestinal bleeding in critically ill patients 3.
Important Dosing Considerations
For stress ulcer prophylaxis in critically ill adults, low-dose therapy is recommended: daily doses ≤40 mg famotidine, ≤150 mg IV ranitidine, ≤300 mg enteral ranitidine, or ≤1200 mg cimetidine 3.
For high fecal output/short bowel syndrome, ranitidine can be administered as continuous infusion at lower dosages (10-15 mg/kg/day), which is more efficient than intermittent dosing and can be added to parenteral nutrition bags 4.
Key Clinical Pearls
- All four H2 blockers are equally effective at standard doses for most indications 5
- Ranitidine has approximately 7 times more potent effect than cimetidine with longer duration of action 4
- Cimetidine specifically carries risk of liver disease and gynecomastia due to antiandrogenic activity, which other H2RAs do not share 2
- Tachyphylaxis develops within 6 weeks of continuous use, limiting long-term effectiveness 2
- H2RAs with anticholinergic effects can cause cognitive decline, particularly concerning in elderly patients 6