Omeprazole Dosage for H. pylori Treatment
For H. pylori eradication, omeprazole should be dosed at 20 mg twice daily when used in triple therapy regimens, or 40 mg once daily when used in dual therapy with clarithromycin. 1
FDA-Approved Dosing Regimens
Triple Therapy (Preferred)
- Omeprazole 20 mg twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily for 10 days 1
- If an ulcer is present at treatment initiation, continue omeprazole 20 mg once daily for an additional 18 days for ulcer healing 1
- This regimen achieves 69-83% eradication rates by intent-to-treat analysis and 78-90% by per-protocol analysis 1, 2
Dual Therapy (Alternative)
- Omeprazole 40 mg once daily + clarithromycin 500 mg three times daily for 14 days 1
- If an ulcer is present, continue omeprazole 20 mg once daily for an additional 14 days 1
- This regimen achieves 64-83% eradication rates per-protocol 1
Critical Optimization Factors
High-dose PPI twice daily is superior to standard dosing. The Maastricht IV/Florence consensus demonstrates that high-dose PPIs increase cure rates by 6-10% compared to standard doses 3. More potent second-generation PPIs like esomeprazole or rabeprazole at 40 mg twice daily can increase cure rates by an additional 8-12% compared to omeprazole 3, 4.
Treatment Duration
- 14-day regimens are superior to 7-10 day courses, improving eradication success by approximately 5% 3, 4
- The FDA label specifies 10 days for triple therapy, but current guidelines recommend extending to 14 days for optimal outcomes 1, 3
Administration Timing
- Take omeprazole 30 minutes before meals on an empty stomach 4, 5
- Avoid concomitant use with other antacids like H2-receptor antagonists 4, 5
Important Caveats
Triple therapy with omeprazole-clarithromycin should only be used in areas with documented clarithromycin resistance below 15%. 3, 4 Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 4. When clarithromycin-resistant strains are present, eradication rates drop from 90% to approximately 20% 4.
Bismuth quadruple therapy is now the preferred first-line treatment in most regions due to rising clarithromycin resistance, achieving 80-90% eradication rates even with dual resistance to clarithromycin and metronidazole 4.
Genetic Considerations
- The efficacy of omeprazole depends on CYP2C19 polymorphisms, with extensive metabolizers having lower eradication rates 3
- This difference is only observed with omeprazole, not with more potent PPIs like esomeprazole or rabeprazole 3
Alternative Regimens When Omeprazole Triple Therapy Fails
After failure of omeprazole-clarithromycin triple therapy, use bismuth quadruple therapy or levofloxacin triple therapy as second-line options. 3, 4 Never repeat clarithromycin if it was in the failed regimen, as resistance develops rapidly after exposure 4.