What is Fexuprazan (Potassium-Competitive Acid Blocker)?

What is Fexuprazan?

Fexuprazan is a potassium-competitive acid blocker (P-CAB) that reversibly inhibits the gastric H+/K+-ATPase enzyme, providing rapid and potent acid suppression for treating acid-related disorders such as erosive esophagitis. 1

Mechanism of Action

• Fexuprazan competitively and reversibly blocks the H+/K+-ATPase enzyme (proton pump) in gastric parietal cells, directly inhibiting acid secretion 1
• Unlike proton pump inhibitors (PPIs), fexuprazan does not require acid-mediated activation to become effective 1
• The drug is not metabolized by CYP2C19, eliminating the genetic polymorphism variability seen with PPIs 2
• Acid suppression is maintained for 24 hours in a dose-dependent manner 3

Pharmacokinetic Properties

• Fexuprazan demonstrates rapid onset of action without requiring conversion to an active form 1
• The drug has an estimated oral bioavailability of 38.4-38.6% with minimal urinary excretion (0.29-2.02%), being eliminated primarily through hepatic metabolism 4
• Food intake does not significantly affect absorption, unlike many PPIs 1
• At steady state with twice-daily dosing, the maximum plasma concentration and area under the curve approximately double compared to single-dose administration 5

Clinical Efficacy

• For erosive esophagitis: Fexuprazan 40 mg demonstrates non-inferiority to esomeprazole 40 mg, with healing rates of 99.1% at 8 weeks 3
• At 4 weeks, healing rates are 90.3% for fexuprazan versus 88.5% for esomeprazole 3
• Based on pharmacodynamic studies, fexuprazan 40 mg provides intragastric acid inhibition similar to standard PPI doses rather than more potent suppression 2

Safety Profile

• Fexuprazan shows comparable safety to PPIs in clinical trials, with no concerning safety signals identified 1
• Serum gastrin levels at weeks 4 and 8 do not significantly differ from esomeprazole 3
• Drug-related adverse events are similar between fexuprazan and comparator PPIs 3
• Like all potent acid suppressors, P-CABs including fexuprazan may be associated with increased risks of enteric infections, though this risk appears comparable to PPIs 2

Clinical Positioning

• Fexuprazan should generally not be used as first-line therapy for acid-related conditions where clinical superiority over PPIs has not been demonstrated 2
• The primary barriers to first-line use include higher costs compared to PPIs, less availability (PPIs are available over-the-counter), higher likelihood of requiring prior authorization, and less robust long-term safety data 2
• Fexuprazan may be considered in selected patients with documented acid-related reflux who fail twice-daily PPI therapy 2

Approved Indications and Ongoing Studies

• Fexuprazan is approved in South Korea for treatment of erosive esophagitis 1
• Ongoing clinical trials are evaluating fexuprazan for prevention of NSAID-induced peptic ulcer disease, non-erosive GERD, acute and chronic gastritis, and maintenance therapy for erosive esophagitis 1

Common Pitfalls to Avoid

• Do not prescribe fexuprazan as first-line therapy when standard PPIs would be more cost-effective, particularly for mild erosive esophagitis (LA grade A/B) or non-erosive reflux disease 2
• Avoid assuming that more potent acid inhibition automatically translates to superior clinical outcomes across all foregut disorders 2
• Do not overlook the need to demonstrate superiority over both standard-dose and double-dose PPIs before selecting fexuprazan, given the substantial cost differential 2