What is the recommended use and dosage of Fexuprazan (potassium-competitive acid blocker) for treating gastroesophageal reflux disease (GERD) and peptic ulcer disease?

Fexuprazan: Recommended Use and Dosing for GERD and Peptic Ulcer Disease

Fexuprazan should not be used as first-line therapy for GERD or peptic ulcer disease; reserve it for patients who fail twice-daily PPI therapy, with the exception of severe erosive esophagitis (LA grade C/D) where it may be considered earlier in the treatment algorithm. 1, 2

Clinical Positioning and Treatment Algorithm

For GERD Management

Initial Approach:

• Start with standard once-daily PPI therapy for 4-8 weeks 2
• If inadequate response, escalate to twice-daily PPI 2
• Consider fexuprazan 40 mg once daily only after documented failure of twice-daily PPI therapy 2

When to Consider Fexuprazan Earlier:

• Patients with severe erosive esophagitis (LA grade C/D) who have failed standard PPI therapy 2
• Confirmed acid-related reflux with objective evidence: LA grade B or greater erosive esophagitis, biopsy-proven Barrett's esophagus, peptic stricture, or ambulatory reflux monitoring showing distal esophageal acid exposure >6% 2

For Peptic Ulcer Disease

Standard Approach:

• Begin with standard PPI therapy as first-line treatment 1, 2
• Reserve fexuprazan for PPI treatment failures 1
• Fexuprazan may be useful when ulcers are not secondary to non-acid processes (cancer, opportunistic infections, vasculitis, ischemia) 1

Dosing Recommendations

FDA-Approved Dosing (from drug label):

• Adults and children ≥12 years: 10 mL every 12 hours; maximum 20 mL in 24 hours 3
• Children 2 to <12 years: 5 mL every 12 hours; maximum 10 mL in 24 hours 3
• Adults ≥65 years: consult physician 3
• Patients with kidney disease: consult physician 3

Clinical Trial Dosing:

• Erosive esophagitis healing: 40 mg once daily for 4-8 weeks 4, 5
• Maintenance therapy: 10 mg once daily for long-term use 2

Efficacy Data

GERD Treatment:

• Fexuprazan 40 mg demonstrates non-inferior efficacy to esomeprazole 40 mg for erosive esophagitis healing at 8 weeks (97-99% healing rates for both) 4, 5
• Similar symptom response and quality of life improvements compared to PPIs 4, 5
• Comparable efficacy for GERD-related chronic cough 6

Peptic Ulcer Disease:

• While other P-CABs (vonoprazan, tegoprazan) show non-inferior healing rates to PPIs for gastric and duodenal ulcers, fexuprazan-specific data for PUD are limited 1
• P-CABs generally achieve 94-96% healing rates for gastric ulcers at 8 weeks and 96-98% for duodenal ulcers at 6 weeks 1

Pharmacologic Advantages Over PPIs

Fexuprazan offers several theoretical benefits:

• Acid-stable formulation requiring no enteric coating 2
• Not a prodrug, allowing immediate action 2, 7
• Longer half-life with sustained acid suppression 2, 7
• Can be taken regardless of meal timing 2, 7
• Reaches maximal acid suppression within 1 day 2
• Not affected by CYP2C19 genetic polymorphisms, providing consistent efficacy across populations 2, 7

Critical Cost and Safety Considerations

Cost Barriers:

• Fexuprazan is significantly more expensive than both standard and double-dose PPIs 1, 2
• Even modest clinical superiority does not justify the higher cost as first-line therapy 2
• Cost-effectiveness is the primary reason for reserving P-CABs as second-line therapy 1, 2

Safety Profile:

• Short-term safety appears comparable to PPIs with similar adverse event rates (approximately 19-20%) 4, 5
• Long-term safety data are more limited than for PPIs 2
• Serum gastrin levels may be elevated higher than with PPIs, though clinical significance remains unclear 2
• Most adverse events are mild 6

Common Pitfalls to Avoid

• Do not prescribe fexuprazan as first-line therapy for mild GERD (non-erosive or LA grade A/B erosive esophagitis) or peptic ulcer disease when PPIs are equally effective and far less expensive 1, 2
• Do not use for uninvestigated heartburn without first attempting standard PPI therapy 2
• Do not overlook cost implications when making treatment decisions, as this significantly impacts healthcare resource utilization 1, 2
• Do not assume superiority over double-dose PPIs for severe erosive esophagitis; efficacy is comparable, not superior 2

Special Clinical Scenarios

H. pylori Eradication:

• While P-CABs (particularly vonoprazan) show superior eradication rates compared to PPIs (92% vs 80%), especially for clarithromycin-resistant strains, fexuprazan-specific data for H. pylori treatment are not yet established 1

High-Risk Ulcer Bleeding:

• P-CABs may have utility in high-risk ulcer bleeding due to rapid and potent acid inhibition, though fexuprazan-specific evidence is lacking 1