Can fexuprazan (potassium-competitive acid blocker) oral be used to treat Gastroesophageal Reflux Disease (GERD)?

Can Fexuprazan Be Used to Treat GERD?

Fexuprazan can be used to treat GERD, but it should generally not be used as first-line therapy; reserve it for patients who fail twice-daily PPI therapy or those with severe erosive esophagitis (LA grade C/D). 1, 2

First-Line Treatment Recommendations

• Start with standard PPI therapy for 4-8 weeks as the initial approach for GERD patients with heartburn, regurgitation, or non-cardiac chest pain without alarm symptoms 1
• PPIs remain the preferred first-line treatment due to their proven efficacy and significantly lower cost compared to potassium-competitive acid blockers (P-CABs) like fexuprazan 1, 2
• Any commercially available PPI can be used initially, with choice guided by insurance coverage and out-of-pocket costs 1

When to Consider Fexuprazan

Second-Line Therapy Algorithm

• Escalate to twice-daily PPI if inadequate response to once-daily dosing 1
• Consider fexuprazan only after documented failure of twice-daily PPI therapy in patients with confirmed acid-related reflux 1, 2
• Fexuprazan may be particularly useful in patients with documented severe erosive esophagitis (LA grade C/D) who have failed standard PPI therapy 1

Specific Clinical Scenarios Where Fexuprazan May Be Appropriate

• Severe erosive esophagitis (LA grade C/D): Fexuprazan can be used as a therapeutic option for healing and maintenance, though it's not clearly superior to double-dose PPIs 1
• PPI treatment failures with confirmatory GERD evidence: This includes LA grade B or greater erosive esophagitis, biopsy-proven Barrett's esophagus, peptic stricture, or ambulatory reflux monitoring showing distal esophageal acid exposure >6% 1

When NOT to Use Fexuprazan as First-Line

• Non-erosive reflux disease (NERD): Do not use fexuprazan as first-line therapy; clinical trials show inconsistent results with minimal difference from placebo in some studies 1, 2
• Mild erosive esophagitis (LA grade A/B): Fexuprazan has similar efficacy to PPIs (94-96% vs 93% healing rates), making the higher cost unjustifiable as first-line therapy 1, 2
• Uninvestigated heartburn symptoms: Reserve fexuprazan for documented cases that fail PPI therapy 1, 2

Pharmacological Advantages of Fexuprazan

While these advantages exist, they don't justify routine first-line use given cost considerations:

• Rapid onset: Reaches maximal acid suppression within 1 day versus 3-5 days for PPIs 1, 2
• Longer half-life: 5-7 hours compared to 1-2 hours for PPIs, allowing once-daily dosing independent of meal timing 1, 2
• No CYP2C19 variability: Not affected by genetic polymorphisms, providing more consistent acid suppression across patient populations 2, 3
• Acid-stable formulation: Does not require enteric coating and is not a prodrug requiring acid-mediated activation 1, 2

Efficacy Data for Fexuprazan

• Erosive esophagitis healing: Fexuprazan demonstrates comparable efficacy to esomeprazole with no significant differences in healing rates at 4 and 8 weeks 4
• Safety profile: Appears comparable to PPIs in short-term studies, though long-term safety data are more limited 2, 5
• Laryngopharyngeal reflux: In patients with severe symptoms (RSI ≥18), fexuprazan showed faster symptom improvement than PPIs at 4 weeks, particularly for hoarseness and cough 6

Critical Cost Considerations

• Significantly higher cost: P-CABs like fexuprazan are markedly more expensive than both standard and double-dose PPIs in the United States 1, 2
• Cost-effectiveness concerns: Even modest clinical superiority may not justify the higher cost as first-line therapy 1
• This cost differential is the primary reason guidelines recommend reserving fexuprazan for PPI failures rather than first-line use 1, 2

Common Pitfalls to Avoid

• Do not prescribe fexuprazan as first-line therapy for mild GERD or peptic ulcer disease when PPIs would be more cost-effective 2
• Do not use in unconfirmed GERD: Ensure objective documentation of acid-related disease (endoscopy showing LA grade B or greater erosive esophagitis, or pH monitoring showing acid exposure >6%) before escalating to fexuprazan 1
• Monitor serum gastrin levels: P-CABs may elevate gastrin to higher levels than PPIs, though clinical significance remains unclear 2
• Consider insurance coverage: Payor authorization and coverage issues may limit access to fexuprazan 1

Safety Monitoring

• Short-term safety appears comparable to PPIs with similar adverse event profiles 2, 4, 5
• Long-term safety data are more limited than for PPIs, warranting ongoing pharmacovigilance 2, 5
• No serious adverse events were reported in clinical trials for GERD treatment 4, 6