How is vonoprazan (vonoprazone) dosed for GERD and Helicobacter pylori eradication, and what are its contraindications, precautions, adverse effects, and alternatives?

Vonoprazan: Dosing, Indications, and Clinical Considerations

Dosing Regimens

For GERD and Erosive Esophagitis

Vonoprazan 20 mg once daily for 8 weeks is the standard dose for healing erosive esophagitis, followed by 10 mg once daily for maintenance therapy. 1, 2

• Healing phase: Vonoprazan 20 mg once daily achieves approximately 94% healing rates for erosive esophagitis 2
• Maintenance phase: Vonoprazan 10 mg once daily for long-term maintenance, particularly effective for severe erosive esophagitis (LA grade C/D) with maintenance rates of 75-77% versus 62% for lansoprazole 15 mg 1
• Dosing flexibility: Unlike PPIs, vonoprazan can be taken with or without food due to its acid-stable formulation 3

For Helicobacter pylori Eradication

Vonoprazan-based regimens should be used for 14 days as first-line therapy for H. pylori, with vonoprazan 20 mg twice daily combined with appropriate antibiotics. 1, 4

• Standard triple therapy: Vonoprazan 20 mg twice daily + clarithromycin + amoxicillin for 14 days achieves 92% eradication rates versus 80% with PPI-based regimens 1
• Dual therapy option: Vonoprazan 20 mg + amoxicillin 750 mg twice daily for 7 days achieves 85-95% eradication, particularly useful in clarithromycin-resistant strains 1
• Quadruple therapy: Vonoprazan 40 mg once daily + clarithromycin-MR 1 g + levofloxacin 500 mg + bismuth subsalicylate 1,048 mg for 14 days achieves >90% eradication in high-resistance regions 4

Clinical Positioning Algorithm

When to Use Vonoprazan as First-Line

Use vonoprazan as first-line therapy for H. pylori eradication in all patients, as recommended by the 2024 AGA guidelines. 1

• H. pylori eradication regimens benefit from vonoprazan's superior acid suppression, with 10-20% higher eradication rates, especially for clarithromycin-resistant strains (66-70% vs 32%) 1, 2
• The short-term duration of H. pylori treatment (14 days) reduces cost concerns compared to chronic GERD therapy 1

When to Reserve Vonoprazan as Second-Line

For GERD and peptic ulcer disease, reserve vonoprazan for patients who fail twice-daily PPI therapy, as the AGA does not recommend it as first-line due to significantly higher costs without clear superiority in mild-moderate disease. 1, 2

• Start with standard PPI therapy for LA grade A/B erosive esophagitis or non-erosive GERD 1
• Escalate to twice-daily PPI if inadequate response 2
• Consider vonoprazan 20 mg daily only after documented failure of twice-daily PPI therapy with confirmatory evidence (LA grade B or greater erosive esophagitis, Barrett's esophagus, peptic stricture, or ambulatory reflux monitoring showing distal esophageal acid exposure >6%) 1

When Vonoprazan is Particularly Beneficial

Vonoprazan should be prioritized for severe erosive esophagitis (LA grade C/D) and maintenance of healing in these patients, where it demonstrates clear superiority over PPIs. 1, 2

• For LA grade C/D erosive esophagitis, vonoprazan shows superior maintenance of healing (75-77% vs 62%) and lower recurrence rates (5-13% vs 39%) compared to lansoprazole 1, 2
• For PPI-resistant GERD with objective evidence of inadequate acid suppression on pH monitoring 2, 5
• For patients with documented PPI allergy, as vonoprazan has a distinct mechanism and no immunologic cross-reactivity 3

Contraindications and Precautions

Absolute Contraindication

Avoid concurrent use of vonoprazan with rilpivirine-containing products, as this is an FDA-mandated absolute contraindication. 3

Metabolic Considerations

Vonoprazan is not metabolized by CYP2C19, providing consistent therapeutic outcomes across all patient populations regardless of genetic polymorphisms, unlike PPIs. 1, 3, 2

• This eliminates the inter-individual pharmacokinetic variation seen with PPIs 1
• Particularly advantageous in populations with high prevalence of CYP2C19 poor metabolizers 2

Safety Monitoring

Monitor serum gastrin levels during long-term therapy, as vonoprazan elevates gastrin higher than PPIs, though levels return toward baseline within weeks after discontinuation. 3, 2

• Both vonoprazan and PPIs share similar risks of enteric infections including C. difficile (relative risk 1.89 for community-acquired pneumonia) 2
• Short-term and medium-term safety profiles are comparable to PPIs 3, 2
• Long-term safety data for vonoprazan are more limited than for PPIs 2

Adverse Effects

Vonoprazan is generally well-tolerated with adverse effects similar to PPIs, including mild-to-moderate gastrointestinal symptoms. 3, 6

• Most common adverse events: abdominal pain, constipation, diarrhea, nausea, dyspepsia 6
• In H. pylori eradication regimens: black stool (35-39%), nausea/vomiting (16-23%), bitter taste (18%), dizziness (6-8%) 4
• All adverse events typically resolve spontaneously without medical intervention 4
• Adverse event rates comparable to PPIs (risk ratio 1.08,95% CI 0.96-1.22) 7

Alternatives to Vonoprazan

For GERD and Peptic Ulcer Disease

Standard-dose PPIs remain the appropriate first-line therapy for most acid-related disorders due to established efficacy, extensive safety data, and significantly lower cost. 3, 2

• Lansoprazole 30 mg, omeprazole 20 mg, esomeprazole 20 mg, or rabeprazole 20 mg once daily 1
• Double-dose PPIs (e.g., lansoprazole 30 mg twice daily) for PPI-resistant cases before considering vonoprazan 1, 2
• H2 receptor antagonists for mild symptoms or as adjunct therapy, though less effective than PPIs or vonoprazan 3

For H. pylori Eradication

If vonoprazan is unavailable or cost-prohibitive, use high-dose PPI-based triple or quadruple therapy, though eradication rates will be 10-20% lower, particularly for resistant strains. 1

• PPI-based triple therapy: PPI twice daily + clarithromycin + amoxicillin for 14 days 1
• Bismuth quadruple therapy: PPI + bismuth + tetracycline + metronidazole for 14 days 1
• Note that PPI efficacy is affected by CYP2C19 polymorphisms, potentially requiring dose adjustments 1, 3

Common Pitfalls and Caveats

Do not prescribe vonoprazan as first-line therapy for mild GERD, non-erosive reflux disease, or peptic ulcer disease where PPIs are equally effective but significantly less expensive. 2, 8

Do not combine vonoprazan with PPIs, as vonoprazan already provides more potent acid suppression than PPIs, making additional acid suppression unnecessary and potentially increasing adverse effects. 8

Do not fail to obtain objective evidence (endoscopy showing LA grade B or greater erosive esophagitis, or pH monitoring showing acid exposure >6%) before escalating from twice-daily PPIs to vonoprazan. 1, 2

For H. pylori eradication, vonoprazan's superiority over PPIs is most pronounced in clarithromycin-resistant strains, where dual therapy with vonoprazan + amoxicillin achieves 92% eradication versus 76% with triple therapy. 1