Rebamipide for Oral Ulcers: Dose and Mechanism of Action
Rebamipide 100 mg three times daily (300 mg/day total) is the recommended dose for treating oral ulcers, particularly in recurrent aphthous stomatitis and Behçet's disease, though this medication is not included in current Western clinical practice guidelines for oral ulcer management. 1
Recommended Dosing
- Administer rebamipide 100 mg orally three times daily (total daily dose 300 mg) for 12-24 weeks for treatment of recurrent oral aphthous ulcers 1
- The medication is available as both 100 mg tablets and 20% granules (0.5g), which are bioequivalent and can be used interchangeably 2
- Granule formulation may be preferred for patients with difficulty swallowing, as it provides equivalent pharmacokinetic parameters to tablets 2
Mechanism of Action
Rebamipide works through multiple protective mechanisms:
- Inhibits neutrophil activation, which is the primary mechanism preventing ulcer formation by reducing inflammatory cell-mediated tissue damage 3
- Reduces lipid peroxidation in gastric and oral mucosa, providing antioxidant protection against oxidative stress 3
- Inhibits both luminol- and lucigenin-dependent chemiluminescence of activated neutrophils, demonstrating broad anti-inflammatory effects 3
- Acts as a mucosal protective agent by enhancing local defense mechanisms 4
Clinical Evidence and Efficacy
- In a randomized, double-blind, placebo-controlled trial of Behçet's disease patients, 65% of rebamipide-treated patients showed moderate to marked improvement in aphthae count and pain compared to 36% with placebo 1
- Aphthae count decreased progressively over 6 months with rebamipide, while placebo-treated patients showed increased ulcer counts peaking at month 4 1
- In patients with severe symptoms (monthly aphthae pain score >28), rebamipide demonstrated statistically significant superiority over placebo (p < 0.01) during months 4-6 of treatment 1
- A comparative study showed that 5% amlexanox paste combined with rebamipide tablets healed ulcers at a more accelerated pace than standard topical treatments 5
Important Clinical Context
Rebamipide is not mentioned in current Western guidelines for oral ulcer management 6, 7, 8. The British Society of Gastroenterology, American College of Physicians, and European League Against Rheumatism guidelines all recommend topical corticosteroids as first-line therapy for oral ulcers 6, 7, 8.
Standard first-line treatment remains topical corticosteroids (betamethasone sodium phosphate 0.5 mg in 10 mL water as rinse four times daily, or clobetasol 0.05% for localized lesions) 6, 7
Practical Advantages
- Well-tolerated with no specific adverse drug reactions reported in clinical trials 1
- Administration is not cumbersome and does not cause discomfort unlike corticosteroid ointments 1
- Suitable for long-term treatment of recurrent oral aphthous ulcers due to favorable safety profile 1
- Oral bioavailability is approximately 10%, though lipid nanoemulsion formulations can improve this by 4.32-fold 4
Clinical Positioning
While rebamipide shows promise based on research evidence, current clinical practice guidelines prioritize topical corticosteroids, followed by systemic corticosteroids (prednisolone 30-60 mg or 1 mg/kg) for refractory cases 6, 7. Rebamipide may be considered as an adjunctive or alternative therapy, particularly in patients requiring long-term management or those wishing to avoid corticosteroids 1.