What is the recommended maintenance dose and regimen of rebamipide for patients with prior peptic ulcer disease, chronic gastritis, or chronic NSAID use, and what alternative maintenance therapies are available?

Rebamipide for Maintenance Therapy

Rebamipide 100 mg three times daily is an effective maintenance option for patients with chronic gastritis, prior peptic ulcer disease, or chronic NSAID use, particularly when standard PPI therapy is insufficient or when mucosal quality improvement is desired. However, PPIs remain the first-line standard for maintenance therapy in most clinical scenarios.

Primary Maintenance Therapy Recommendations

Standard First-Line Approach

• PPIs are the gold standard for maintenance therapy in patients with healed peptic ulcers, with continuous daily dosing strongly recommended to prevent recurrence 1
• Long-term PPI therapy should be titrated to the lowest effective dose based on symptom control 1
• For patients with prior erosive esophagitis or peptic ulcer disease, continuous (not on-demand) PPI therapy is essential to maintain healing 1

When to Consider Rebamipide

For NSAID-Associated Ulcers:

• Rebamipide 100 mg three times daily prevents NSAID-induced peptic ulcers as effectively as misoprostol, with significantly better tolerability 2
• In the STORM study, rebamipide showed comparable efficacy to misoprostol for preventing NSAID-induced complications (4.5% vs 4.4% peptic ulcer prevalence) over 12 weeks 2
• Rebamipide is particularly effective for gastric ulcers caused by NSAIDs, promoting improvement in gastric inflammation scores and ulcer healing 3

For Chronic Gastritis:

• Rebamipide 100 mg three times daily for 26 weeks significantly improved clinical symptoms, gastric mucosal lesions, and reduced progression to intestinal metaplasia and low-grade intraepithelial neoplasia 4
• This is the only mucosal-protective drug proven to improve histological gastritis in vivo, whereas PPIs have lesser effects on gastritis quality 5

For H. pylori-Related Disease:

• Rebamipide attenuates inflammatory responses in H. pylori-infected patients and may prevent gastritis progression and ulcer recurrence 6
• It can be used as adjunctive therapy alongside standard H. pylori eradication regimens 6

Dosing and Duration

Rebamipide Regimen

• Standard dose: 100 mg three times daily 3, 2, 4
• Treatment duration: 8-26 weeks depending on indication 3, 4
• Well-tolerated with minimal adverse effects compared to misoprostol 2

Alternative Maintenance Options

For High-Risk NSAID Users:

• If NSAIDs cannot be discontinued: PPI 40 mg once daily indefinitely plus consider COX-2 selective inhibitor 7, 8
• Misoprostol 200 mcg four times daily is effective but limited by side effects (diarrhea, abdominal cramping in ~20% of patients) 9

For Patients Requiring Continued Antiplatelet/Anticoagulation:

• Continue PPI therapy indefinitely in patients with history of ulcer bleeding on dual antiplatelet therapy or multiple antithrombotic agents 7

Clinical Algorithm for Maintenance Selection

Step 1: Assess Primary Risk Factor

• NSAID-induced ulcer → Discontinue NSAIDs if possible; if continued, use PPI indefinitely 7, 8
• H. pylori-positive → Eradicate first with triple therapy (PPI + amoxicillin 1000mg BID + clarithromycin 500mg BID for 14 days); maintenance PPI generally not needed after successful eradication 7
• Chronic gastritis with atrophy/metaplasia → Consider rebamipide 100mg TID for mucosal quality improvement 4

Step 2: Consider Rebamipide When:

• Patient requires continued NSAID use and cannot tolerate misoprostol side effects 2
• Histological gastritis improvement is desired (Asian populations with glandular atrophy and low acid output) 5
• Prevention of premalignant progression in chronic gastritis is a concern 4
• Adjunctive therapy needed alongside standard ulcer treatment 6

Step 3: Monitor and Adjust

• For gastric ulcers: Repeat endoscopy at 6 weeks to confirm healing and exclude malignancy 7
• For duodenal ulcers: Routine endoscopic confirmation not necessary unless NSAIDs must be continued 7
• Confirm H. pylori eradication 4-6 weeks after therapy completion using non-serological testing 9

Critical Pitfalls and Caveats

Common Errors to Avoid:

• Do not use H2-receptor antagonists as maintenance therapy for gastric ulcers—they only protect against duodenal ulcers, not gastric ulcers 9
• Never use less than daily PPI dosing as maintenance in patients with prior erosive esophagitis—recurrence rates are unacceptably high 1
• Poor compliance with gastroprotective therapy increases NSAID-induced adverse events 4-6 fold 8, 9

Important Warnings:

• Rebamipide is not widely available outside Asian countries and lacks the extensive long-term safety data of PPIs 5
• Testing for H. pylori during acute bleeding may yield false-negatives; repeat testing if initially negative 7, 9
• Long-term PPI use carries potential risks (pneumonia, hip fracture, C. difficile infection), requiring risk-benefit assessment 9

When Rebamipide is Insufficient:

• If alarm symptoms develop (hematemesis, melena, significant weight loss, dysphagia, recurrent vomiting), urgent endoscopy is required 7, 8
• Patients with very high risk (prior ulcer bleeding, multiple antithrombotic agents) require intensive gastroprotection with PPI plus COX-2 inhibitor 9