Vonaprazan Plus Amoxicillin for H. pylori Eradication
Vonaprazan 20 mg twice daily plus amoxicillin 1000 mg twice daily for 14 days is an FDA-approved, highly effective dual therapy regimen for H. pylori eradication, achieving 85-95% cure rates without requiring additional antibiotics. 1, 2
FDA-Approved Dosing Regimen
The FDA-approved dual therapy regimen consists of vonaprazan 20 mg twice daily (morning and evening, 12 hours apart) plus amoxicillin 1000 mg three times daily (morning, mid-day, and evening) for 14 days. 1
However, recent high-quality evidence demonstrates that twice-daily amoxicillin (1000 mg bid) is non-inferior to three-times-daily dosing (1000 mg tid), achieving 89-94% eradication rates with similar safety profiles. 3, 2 This simplified regimen improves adherence while maintaining excellent efficacy. 3
Optimal Amoxicillin Dosing Strategy
The total daily amoxicillin dose of 2000 mg (1000 mg bid) is non-inferior to 3000 mg (1000 mg tid) for first-line H. pylori treatment, with eradication rates of 85-89% versus 87-92% respectively. 2 The higher dose does not significantly improve outcomes but may increase adverse events. 2
For patients with BMI ≥24 kg/m², consider amoxicillin 750 mg four times daily instead of three times daily, as this achieves 100% eradication versus 85% with standard dosing in this population. 4 Higher BMI reduces drug concentrations at the gastric mucosal level, necessitating more frequent dosing. 5
Clinical Efficacy Data
Vonaprazan-amoxicillin dual therapy achieves 89-95% eradication rates by per-protocol analysis and 85-93% by intention-to-treat analysis as first-line treatment. 3, 2, 4 This matches or exceeds the efficacy of traditional triple therapy with clarithromycin. 6
As rescue therapy after 1-7 previous treatment failures, vonaprazan-amoxicillin dual therapy achieves 92.5% eradication rates, making it an excellent "simplified rescue therapy" option. 7 This is particularly valuable given that amoxicillin resistance remains extremely rare (<5%). 5, 2
Dosage Adjustments for Renal Impairment
For patients with estimated GFR ≥30 mL/minute, use the standard dose of vonaprazan 20 mg twice daily. 1
For patients with estimated GFR <30 mL/minute, vonaprazan-amoxicillin dual therapy is not recommended. 1 Consider alternative regimens such as bismuth quadruple therapy in this population. 5
Treatment Duration
The mandatory treatment duration is 14 days—shorter durations of 7-10 days are inadequate and reduce eradication rates by approximately 5%. 5, 8, 3 All studies demonstrating >90% efficacy used 14-day regimens. 7, 3, 2
Advantages Over Traditional Regimens
Vonaprazan-amoxicillin dual therapy eliminates the need for clarithromycin, avoiding the global crisis of clarithromycin resistance (>15-20% in most regions). 5, 8 This makes it effective regardless of local resistance patterns. 6
The regimen avoids metronidazole and tetracycline, reducing pill burden from 12-16 pills daily (bismuth quadruple therapy) to 4-6 pills daily. 5 This improves adherence, which is critical since >10% of patients are poor compliers. 5
Vonaprazan provides more potent and consistent acid suppression than PPIs, maintaining intragastric pH >4 for longer periods, which enhances amoxicillin stability and activity. 6, 3
Safety Profile
Adverse events occur in 7.5-17% of patients, primarily mild symptoms including skin rash, abdominal pain, diarrhea, and headache that resolve spontaneously without treatment discontinuation. 7, 4 The safety profile is comparable to or better than traditional triple therapy. 6, 3
The regimen has minimal impact on gut microbiota diversity, with restoration to baseline levels by 8-10 weeks post-treatment. 2 Beta-lactam resistance genes increase transiently at week 2 but return to baseline by week 8-10, particularly with the lower 2g daily amoxicillin dose. 2
Confirmation of Eradication
Perform ¹³C-urea breath test or validated monoclonal stool antigen test at least 4 weeks after completing therapy to confirm eradication. 5, 8, 3
Discontinue vonaprazan at least 2 weeks before testing to avoid false-negative results. 5, 8 Never use serology to confirm eradication, as antibodies persist long after successful treatment. 5
Clinical Positioning
Vonaprazan-amoxicillin dual therapy is appropriate as first-line treatment for H. pylori infection, particularly in regions with high clarithromycin resistance or when simplifying regimens to improve adherence. 1, 6, 3, 2
It is also highly effective as rescue therapy after multiple treatment failures, achieving 92.5% eradication regardless of previous regimens used. 7 This makes it valuable when bismuth quadruple therapy or levofloxacin-based regimens have failed. 5
Critical Pitfalls to Avoid
Do not use 7-day or 10-day treatment durations—these achieve suboptimal eradication rates of 70-80% compared to 90-95% with 14 days. 3
Do not reduce the vonaprazan dose below 20 mg twice daily, as adequate acid suppression is mandatory for amoxicillin efficacy. 1, 6
Do not assume treatment success without confirmation testing—always verify eradication with breath test or stool antigen at least 4 weeks post-treatment. 5, 8, 3
For patients with penicillin allergy, this regimen is contraindicated—use bismuth quadruple therapy instead. 5, 8