When should Vonoprazan be considered over Proton Pump Inhibitors (PPIs)?

When to Consider Vonoprazan Over PPIs

Vonoprazan should be reserved for patients who have failed twice-daily PPI therapy, particularly those with severe erosive esophagitis (LA grade C/D) or documented PPI-resistant GERD, rather than as first-line therapy. 1

Clinical Scenarios Where Vonoprazan is Justified

PPI-Resistant GERD

• The strongest indication for vonoprazan is documented failure of twice-daily PPI therapy, as recommended by the American Gastroenterological Association 1, 2
• For PPI-resistant erosive esophagitis, vonoprazan 20 mg achieves healing rates of 91.7% at 4 weeks and 88.5% at 8 weeks 3
• For PPI-resistant NERD, vonoprazan improves symptom scores in 74.6% of patients at 4 weeks 3

Severe Erosive Esophagitis (LA Grade C/D)

• Vonoprazan demonstrates superior maintenance of healing in severe erosive esophagitis compared to lansoprazole, with recurrence rates of only 5-13% versus 39% 1
• Maintenance healing rates at 24 weeks for LA grade C/D are 75-77% with vonoprazan versus 62% with lansoprazole 1
• For mild erosive esophagitis (LA grade A/B), vonoprazan offers no significant advantage over PPIs, with similar healing rates of 94% vs 91% 1

H. pylori Eradication in Clarithromycin-Resistant Strains

• Vonoprazan provides 10-20% higher eradication rates when used in clarithromycin-based triple therapy, with superiority confined to clarithromycin-resistant strains 4
• Dual therapy with vonoprazan and amoxicillin achieves eradication rates approaching 95% for first-line and 90% for second-line treatment, potentially eliminating the need for clarithromycin 4

Peptic Ulcer Disease After PPI Failure

• For standard peptic ulcer disease, vonoprazan 20 mg is comparable to lansoprazole 30 mg, with healing rates of 94% vs 94% for gastric ulcers and 96% vs 98% for duodenal ulcers 1, 5
• Vonoprazan should only be considered for peptic ulcer disease after documented PPI treatment failure, not as first-line therapy 1

Key Advantages Supporting the Switch

Pharmacologic Superiority

• Vonoprazan provides more rapid onset of action (within 2-3 hours) and maintains intragastric pH >4 for 85% of the 24-hour period at 20 mg dosing, compared to 60% with standard PPIs 6, 7
• Unlike PPIs, vonoprazan is not affected by CYP2C19 polymorphisms, resulting in more consistent acid suppression across different patient populations 4, 2
• Vonoprazan can be taken with or without food, offering greater dosing flexibility than PPIs which require administration 30-60 minutes before meals 2

Critical Limitations and Caveats

Cost Considerations

• Vonoprazan is significantly more expensive than both standard and double-dose PPIs in the United States, which limits its use as first-line therapy 1, 2
• The American Gastroenterological Association explicitly recommends against using vonoprazan as first-line therapy where clinical superiority has not been clearly demonstrated 1, 2

Safety Concerns Requiring Monitoring

• Vonoprazan elevates serum gastrin levels higher than PPIs, though levels return to baseline within weeks after discontinuation 2, 8, 6
• Long-term use increases risk of fundic gland polyps, especially beyond one year of treatment 6
• Monitor magnesium and calcium levels prior to initiation and periodically during prolonged treatment, particularly in patients at risk for hypocalcemia 6
• Temporarily discontinue vonoprazan at least 4 weeks before assessing chromogranin A levels to avoid false positive results for neuroendocrine tumors 6
• Severe cutaneous adverse reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported 6

Contraindications

• Do not use vonoprazan for H. pylori treatment in patients with severe renal impairment (eGFR <30 mL/min) or moderate to severe hepatic impairment (Child-Pugh B or C) 6
• For healing erosive esophagitis in moderate to severe hepatic impairment, dosage reduction is required 6

Algorithmic Approach to Justify Vonoprazan

Step 1: Document adequate PPI trial

• Standard-dose PPI for 8 weeks for erosive esophagitis or 4 weeks for NERD 1
• If inadequate response, escalate to twice-daily PPI for additional 8 weeks 1

Step 2: Confirm PPI failure with objective evidence

• Persistent symptoms on twice-daily PPI therapy 1
• Endoscopic documentation of persistent erosive esophagitis, particularly LA grade C/D 1
• pH monitoring showing inadequate acid suppression if available

Step 3: Consider vonoprazan 20 mg daily

• For healing of PPI-resistant erosive esophagitis 1, 3
• For high-risk ulcer bleeding cases requiring rapid and potent acid inhibition 1

Step 4: Transition to maintenance therapy

• After healing, use vonoprazan 10 mg daily for maintenance of healed erosive esophagitis 1
• Use shortest duration appropriate to minimize long-term risks 6

Common Pitfalls to Avoid

• Do not prescribe vonoprazan as first-line therapy for mild GERD or peptic ulcer disease when PPIs would be more cost-effective 1, 2
• Do not assume vonoprazan is superior for all acid-related conditions—its advantage is primarily in PPI-resistant cases and severe erosive esophagitis 1, 3
• Do not overlook the need for monitoring gastrin levels, magnesium, calcium, and vitamin B12 with long-term use 6
• Do not continue vonoprazan indefinitely without reassessing the need for ongoing therapy 6