Bismuth Subsalicylate Dosing for H. pylori Eradication
For treatment of peptic ulcer disease associated with Helicobacter pylori, bismuth subsalicylate should be dosed at 262 mg (2 tablets) four times daily for 14 days as part of quadruple therapy with tetracycline 500 mg four times daily, metronidazole 500 mg three to four times daily, and a proton pump inhibitor twice daily. 1, 2
Standard Bismuth Quadruple Therapy Regimen
The complete regimen consists of four components taken for 14 days 1, 2:
- Bismuth subsalicylate: 262 mg (2 tablets or 2 capsules) four times daily, taken 30 minutes before meals 1, 2
- Tetracycline HCl: 500 mg four times daily, taken 30 minutes after meals 1, 2
- Metronidazole: 500 mg three to four times daily (or 400 mg four times daily), taken 30 minutes after meals 1, 2
- Proton pump inhibitor: High-dose PPI (esomeprazole 20 mg or rabeprazole 20 mg preferred) twice daily, taken 30 minutes before meals and at bedtime 1, 3
Alternative Bismuth Formulations
Some formulations use bismuth subcitrate at 120-140 mg three to four times daily, which is equivalent dosing 3, 2. The key is ensuring adequate bismuth exposure throughout the day with the four-times-daily dosing schedule 1, 2.
Duration of Treatment
All major guidelines converge on 14 days as the optimal duration 1, 2:
- The Toronto Consensus firmly recommends 14 days for all first-line treatments to maximize eradication rates 1, 2
- The Maastricht V/Florence Consensus agrees with 14 days unless 10 days has been proven locally to be equally effective 1, 2
- The American College of Gastroenterology considers 10-14 days adequate, though 14 days is preferred 1, 2
The 14-day duration is particularly important in areas with high metronidazole resistance, as longer treatment can partially overcome this resistance 3, 2.
Clinical Context and Rationale
Bismuth quadruple therapy is recommended as first-line treatment in areas with high clarithromycin resistance (>15-20%) 3, 2. This regimen is favored because it achieves acceptable success even against strains displaying in vitro metronidazole resistance 1, 4. The addition of bismuth significantly improves treatment efficacy, especially when metronidazole resistance is present 3, 4.
Critical Administration Details
Timing is essential for optimal efficacy 1:
- Take bismuth 30 minutes before meals
- Take tetracycline and metronidazole 30 minutes after meals
- Take PPI 30 minutes before meals on an empty stomach 2
Important Caveats
Do not substitute doxycycline for tetracycline, as multiple studies demonstrate significantly inferior results 3, 2. This is a common pitfall that must be avoided.
Avoid pantoprazole as the PPI choice 1, 3. Rabeprazole and esomeprazole are preferred due to higher potency (20 mg rabeprazole = 36 mg omeprazole; 20 mg esomeprazole = 32 mg omeprazole; 40 mg pantoprazole = only 9 mg omeprazole) 1.
The bismuth quadruple regimen is considered one of the least tolerable H. pylori therapies due to side effects including black stools, nausea, headache, and dizziness 3, 5. However, these adverse effects are generally manageable and should not prevent use of this highly effective regimen when indicated.