Rebamipide is a quinolone derivative, first developed in Japan, that functions as a mucosal protective and ulcer-healing drug. Unlike standard acid-reducing medications such as proton pump inhibitors (PPIs) and H2-receptor antagonists, rebamipide primarily works by strengthening the body's natural defense mechanisms. This unique approach makes it a valuable therapeutic option, particularly in Asian countries where it is widely used, though it has not been approved in the United States and Europe for gastrointestinal conditions. Its applications span multiple systems, from gastrointestinal disorders to ophthalmology, reflecting its versatile pharmacological properties.
Primary Gastrointestinal Uses
Gastric Ulcers and Gastritis
Rebamipide is a cornerstone treatment for gastric ulcers and gastritis, including both acute flare-ups and chronic conditions. It addresses the fundamental cause of mucosal damage by enhancing the intrinsic protective factors of the gastric lining rather than simply inhibiting acid production. This process involves several key actions:
- Increasing the production and secretion of gastric mucus, a protective barrier.
- Stimulating the synthesis of endogenous prostaglandins, which are crucial for maintaining mucosal integrity and blood flow.
- Improving blood flow to the gastric mucosa, which accelerates the healing process of damaged tissue.
Clinical studies have shown that rebamipide promotes high-quality ulcer healing and reduces the rate of recurrence. For cases of more severe ulcers, especially those induced by endoscopic submucosal dissection (ESD), rebamipide is often combined with PPIs for superior healing outcomes.
Nonsteroidal Anti-Inflammatory Drug (NSAID) Induced Gastrointestinal Injury
Long-term use of NSAIDs is a common cause of gastrointestinal bleeding and mucosal damage. Rebamipide effectively counteracts this damage by stabilizing the gastric mucosal blood flow and inhibiting the inflammatory response triggered by NSAIDs. A meta-analysis published in May 2025 indicated that rebamipide is effective in preventing NSAID-induced mucosal breaks and is comparable in efficacy to standard PPIs, making it a promising alternative for patients who have contraindications for prolonged PPI use.
Adjunct to Helicobacter pylori Eradication
Rebamipide has shown a synergistic effect when used in combination with standard antibiotic and acid-suppressive therapies for eradicating H. pylori infection. While it does not directly kill the bacteria, it helps by inhibiting the adhesion of H. pylori to gastric epithelial cells and suppressing the associated inflammatory responses. A meta-analysis found that adding rebamipide significantly increased the effectiveness of H. pylori eradication, particularly within certain treatment regimens.
Mechanism of Action and Multifaceted Effects
Rebamipide's therapeutic effects are derived from its diverse and powerful mechanisms at the molecular level, which include:
- Prostaglandin Induction: Upregulates the synthesis of prostaglandin E2 (PGE2), which plays a protective role in the gastrointestinal mucosa.
- Mucus Secretion Enhancement: Stimulates the production of thick, protective mucin glycoproteins that act as a physical barrier against gastric acid.
- Free Radical Scavenging: Acts as an antioxidant by scavenging reactive oxygen radicals, reducing oxidative stress and inflammation.
- Anti-inflammatory Properties: Attenuates the activity of neutrophils and suppresses the production of pro-inflammatory cytokines like interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α).
- Angiogenesis Promotion: Increases the expression of growth factors like epidermal growth factor (EGF) and vascular endothelial growth factor (VEGF), which promotes new blood vessel formation and accelerates ulcer healing.
Other Therapeutic Applications
Dry Eye Disease (Ophthalmic Solution)
Topical rebamipide has emerged as an effective treatment for dry eye disease. It increases the production of mucin-like substances from conjunctival goblet cells, improving tear film stability and alleviating symptoms such as foreign body sensation and eye pain. It also promotes the regeneration of corneal and conjunctival epithelia.
Oral and Oral Mucosal Disorders
Rebamipide can also be used as a treatment for recurrent oral aphthous ulcers and as part of the regimen for Behçet's disease. Its anti-inflammatory and cytoprotective actions help reduce pain and accelerate the healing of these painful oral lesions.
Rebamipide vs. Other Gastrointestinal Medications
| Feature | Rebamipide (Cytoprotective) | PPIs (Acid Suppressive) | H2RAs (Acid Suppressive) |
|---|---|---|---|
| Mechanism | Boosts mucosal defense, increases prostaglandin synthesis, scavenges free radicals. | Inhibit the H+/K+ ATPase pump, blocking gastric acid secretion. | Block histamine H2 receptors, reducing gastric acid secretion. |
| Primary Action | Protects and repairs gastrointestinal mucosa. | Suppresses gastric acid production. | Reduces gastric acid production. |
| Healing Quality | Promotes high-quality ulcer healing with reduced recurrence rates. | Effective at healing ulcers, but may not address mucosal quality as comprehensively. | Less potent than PPIs for acid suppression; promotes ulcer healing but less effectively than PPIs. |
| GI Target Area | Protects both upper and lower GI tracts, particularly against NSAID damage. | Primarily effective in the upper GI tract; less protection in the small intestine. | Primarily effective in the upper GI tract. |
| Side Effects | Generally mild; GI upset, taste disturbance. Fewer systemic side effects compared to PPIs. | Associated with long-term risks like C. difficile infection, fractures, and kidney disease. | Generally well-tolerated, but can cause headaches, dizziness, and GI issues. |
| Availability | Widely used in Asia; not FDA-approved in the US for GI conditions. | Widely available globally. | Widely available globally. |
Conclusion
Rebamipide is a powerful and versatile medication that enhances the body’s innate defense and healing mechanisms, offering significant therapeutic benefits beyond simple acid suppression. It is primarily utilized for treating and preventing gastrointestinal conditions like gastritis, peptic ulcers, and NSAID-induced injury, either alone or as an adjunct to other therapies. Its proven efficacy in healing, promoting mucosal repair, and its use in dry eye disease highlight its diverse applications. Given its favorable side effect profile and superior mucosal healing properties compared to some alternatives, particularly for specific GI injuries, rebamipide represents an important treatment option, especially for patients where long-term use of acid suppressants is a concern.
For more in-depth information on the mechanism of action, efficacy, and safety of rebamipide, an extensive literature review is available from a recent publication from the World Journal of Gastroenterology.
