Rebamipide in Upper Gastrointestinal Bleeding
Rebamipide is not recommended as a standard treatment for acute upper gastrointestinal bleeding (UGIB) from peptic ulcer disease, as it is not mentioned in any major international guidelines for UGIB management, and proton pump inhibitors (PPIs) remain the evidence-based pharmacological therapy of choice.
Current Guideline-Based Management of UGIB
The 2020 World Society of Emergency Surgery (WSES) guidelines and 2019 International Consensus Group guidelines establish the standard pharmacological approach for bleeding peptic ulcers, which does not include rebamipide 1:
Acute Phase Management
- Start high-dose PPI therapy immediately upon presentation, before endoscopy (weak recommendation, moderate-quality evidence) 1
- After successful endoscopic hemostasis, administer high-dose PPI as continuous infusion for 72 hours (80 mg esomeprazole bolus plus 8 mg/h infusion), which reduces rebleeding from 10.3% to 5.9% 1
- Continue PPI therapy for 6-8 weeks following endoscopic treatment to allow mucosal healing 1
Adjunctive Therapies Recommended by Guidelines
- Pre-endoscopy erythromycin to improve visualization (weak recommendation) 1
- H. pylori testing and eradication therapy for all patients with bleeding peptic ulcer 1
Why Rebamipide Is Not Standard Therapy
Despite rebamipide's documented mechanisms of action—including prostaglandin stimulation, free radical scavenging, and improved quality of ulcer healing 2, 3—it is conspicuously absent from all major UGIB management guidelines 1.
Evidence Limitations
- The available evidence for rebamipide consists primarily of mechanistic studies and small trials focused on ulcer prevention and recurrence, not acute bleeding management 2, 3, 4
- One 1998 study showed rebamipide reduced ulcer recurrence rates comparable to H. pylori eradication, but this was in the post-healing maintenance phase, not during active bleeding 4
- No randomized controlled trials have evaluated rebamipide's efficacy in reducing mortality, rebleeding rates, or need for surgery in acute UGIB—the outcomes that matter most 1
Potential Role in Secondary Prevention
Rebamipide may have a limited role after the acute bleeding episode has resolved for specific indications:
Post-Healing Maintenance
- Rebamipide improved quality of ulcer healing and reduced recurrence in H. pylori-positive patients who did not receive eradication therapy 4
- It reduces inflammatory cell infiltration in ulcer scars, potentially improving healing quality 4
NSAID-Related Injury Prevention
- Rebamipide attenuates neutrophil activity and inflammatory cytokine production stimulated by NSAIDs 2, 3
- However, guidelines recommend PPI plus COX-2 inhibitor as the evidence-based approach for patients requiring continued NSAIDs after ulcer bleeding 5
Clinical Bottom Line
For acute UGIB management, adhere strictly to guideline-based therapy: high-dose PPI therapy, early endoscopy within 24 hours, endoscopic hemostasis for high-risk stigmata, and H. pylori eradication 1.
Rebamipide lacks the robust clinical trial evidence demonstrating impact on mortality, rebleeding, or surgical intervention that would justify its inclusion in acute UGIB protocols 2, 3, 4, 6, 7. While it has interesting gastroprotective mechanisms including COX-2 induction via AMPK activation 6, mechanism of action does not substitute for clinical outcomes data in life-threatening conditions like UGIB.
If considering rebamipide at all, reserve it for secondary prevention in the maintenance phase after ulcer healing in patients who cannot receive H. pylori eradication or require ongoing NSAID therapy, recognizing this represents off-guideline use with limited supporting evidence 4, 7.