Is Rebamipide Routinely Used in GERD?
No, rebamipide is not routinely used as first-line treatment for GERD in clinical practice, as it is not recommended in any major gastroenterology guidelines and lacks the evidence base supporting proton pump inhibitors (PPIs), which remain the cornerstone of GERD therapy.
Standard First-Line Treatment for GERD
The established first-line pharmacological treatment for GERD is proton pump inhibitors, not mucoprotective agents like rebamipide 1, 2. PPIs provide superior symptomatic relief and healing of erosive esophagitis compared to all other medication classes 2, 3. The American Gastroenterological Association explicitly recommends:
- Standard-dose PPI once daily (e.g., omeprazole 20 mg) taken 30-60 minutes before breakfast for 4-8 weeks as initial therapy 2, 3
- Escalation to twice-daily PPI dosing if symptoms persist after 4 weeks 2, 3
- H2-receptor antagonists as an alternative for mild disease, though less effective than PPIs 2, 4
Rebamipide's Limited Role in GERD
While rebamipide is a mucoprotective agent with anti-inflammatory properties that works through cyclooxygenase-2 induction and prostaglandin enhancement 5, its clinical utility in GERD is extremely limited:
Evidence for Rebamipide
- One small study (n=41) showed combination therapy with rebamipide 300 mg daily plus lansoprazole 15 mg reduced symptom recurrence compared to lansoprazole alone (20% vs 52.4% recurrence rate) over 12 months 6
- However, rebamipide failed to control reflux symptoms in PPI-refractory NERD patients in a randomized placebo-controlled trial (n=60) 7
Why Rebamipide Is Not Routinely Used
Rebamipide is absent from all major North American and European GERD guidelines 1, 2. The 2024 AGA Clinical Practice Update on acid suppression therapy makes no mention of mucoprotective agents as treatment options 1. Instead, guidelines focus on:
- PPIs as first-line therapy 2, 3
- Potassium-competitive acid blockers (P-CABs) as alternatives in specific situations, though generally not recommended as first-line due to cost 1
- Alginates as adjunctive therapy for breakthrough symptoms 1, 4
Practical Treatment Algorithm
Step 1: Initiate lifestyle modifications (weight loss if BMI ≥25, elevate head of bed, avoid lying down 2-3 hours after meals) 2, 3, 4
Step 2: Start PPI therapy at standard dose once daily before breakfast 2, 3
Step 3: If inadequate response after 4-8 weeks, escalate to twice-daily PPI dosing 2, 3
Step 4: If symptoms persist on twice-daily PPI, consider endoscopy to confirm diagnosis and rule out complications 2, 3
Step 5: For confirmed PPI-refractory GERD, consider P-CABs (vonoprazan) in selected patients, though cost may be prohibitive 1
Common Pitfalls
- Do not use metoclopramide routinely due to unfavorable risk-benefit profile, including tardive dyskinesia risk 2, 4
- Do not add H2-receptor antagonists to twice-daily PPI as standard practice, as evidence does not support improved efficacy 2, 4
- Do not pursue experimental or off-guideline therapies like rebamipide when standard PPI therapy has not been optimized 2
Geographic Considerations
Rebamipide was developed in Japan and appears primarily in Asian medical literature 5, 6. Its use may be more common in East Asian countries where it is approved and available, but it has not gained acceptance in Western clinical practice guidelines 1, 2. The limited evidence base (small studies, lack of large randomized controlled trials, absence from systematic reviews) and unavailability in most Western markets explain why it is not part of routine GERD management 5, 6, 7.