What is the recommended dosage and dosing schedule for Bismuth (Bismuth) Quadruple Therapy, including Proton Pump Inhibitor (PPI), Bismuth subsalicylate, Tetracycline, and Metronidazole?

Bismuth Quadruple Therapy Dosage and Dosing Schedule

The recommended dosage for bismuth quadruple therapy consists of a PPI twice daily, bismuth subsalicylate 2 tablets (262 mg each) four times daily, tetracycline 500 mg four times daily, and metronidazole 500 mg three to four times daily for 14 days. 1

Detailed Dosing Regimen

Proton Pump Inhibitor (PPI)

• Standard dose twice daily (30 minutes before morning and evening meals)
• Recommended PPIs and doses:
  • Esomeprazole 20 mg
  • Rabeprazole 20 mg
  • Lansoprazole 30 mg
  • Omeprazole 20 mg
  • Pantoprazole 40 mg
  • Dexlansoprazole 30 mg
• Higher potency PPIs (esomeprazole, rabeprazole) are preferred as they may increase eradication rates by 8-12% 2

Bismuth

• Bismuth subsalicylate (Pepto-Bismol®) 2 tablets (262 mg each) four times daily, 30 minutes before meals 1
• Alternative: Colloidal bismuth subcitrate 120 mg, 1 tablet four times daily 1

Tetracycline

• 500 mg four times daily 1
• Should be taken 30 minutes after meals 1

Metronidazole

• 500 mg three to four times daily 1
• Alternative: 400 mg four times daily 1
• Can be substituted with tinidazole at equivalent doses 1

Duration of Treatment

All major guidelines (Toronto Consensus, Maastricht V/Florence, and American College of Gastroenterology) recommend a 14-day treatment duration for bismuth quadruple therapy, although 10 days may be acceptable in areas where it has been proven locally to be equally effective 1.

Research evidence suggests that 14-day therapy is preferred, particularly in areas with high metronidazole resistance 1. A 14-day regimen helps overcome potential metronidazole resistance and improves eradication rates 1.

Administration Timing

• PPI: Take 30 minutes before morning and evening meals 1
• Bismuth: Take 30 minutes before meals, four times daily 1
• Tetracycline and Metronidazole: Take 30 minutes after meals 1

Special Considerations

Metronidazole Resistance

• In areas with high metronidazole resistance, 14-day therapy is strongly recommended 1
• Increasing the dose and duration of metronidazole therapy can help overcome resistance 1

Alternative Dosing Schedules

Some studies have explored twice-daily dosing regimens:

• A randomized trial showed that twice-daily bismuth quadruple therapy (pantoprazole 20 mg, tetracycline 500 mg, metronidazole 500 mg, and bismuth subcitrate 240 mg, all twice daily) was effective for both 10 and 14 days, with per-protocol eradication rates of 95% and 96%, respectively 3

Common Pitfalls and Caveats

1. Inadequate PPI dosing: Using standard-dose PPI once daily instead of twice daily can reduce eradication rates by 6-10% 2

2. Substituting tetracycline with doxycycline: Doxycycline cannot be substituted for tetracycline as the results are significantly inferior 1

3. Insufficient treatment duration: Using shorter durations (7 days) may lead to treatment failure, especially in areas with high metronidazole resistance 1

4. Poor adherence due to side effects: Bismuth quadruple therapy has more side effects than some other regimens, which may affect compliance 1, 4

5. Not adjusting for local resistance patterns: Treatment should be tailored based on local antibiotic resistance patterns, especially for metronidazole 1

6. Failure to confirm eradication: Eradication should be confirmed 4 weeks after completing treatment using urea breath test or monoclonal stool antigen test 2

Commercially Available Formulation

Pylera® is a commercially available 3-in-1 formulation containing bismuth subcitrate potassium 140 mg, tetracycline hydrochloride 125 mg, and metronidazole 125 mg per capsule. The recommended dosage is three capsules four times daily with meals, plus a PPI twice daily for 10 days 1, 5. However, this 10-day regimen was primarily developed for marketing purposes, and most guidelines still recommend 14-day therapy for optimal eradication 1.

Bismuth quadruple therapy remains a highly effective first-line and rescue therapy for H. pylori eradication, particularly in areas with high clarithromycin and metronidazole resistance 1, 2.