Usage
Rebamipide is prescribed for the treatment of gastric ulcers and to improve gastric mucosal lesions (e.g., erosion, bleeding, redness, edema) in acute gastritis and acute exacerbations of chronic gastritis. It is also used in the treatment of recurrent aphthous ulcers and Behçet’s syndrome. It is classified as a gastroprotective agent or mucoprotectant.
Rebamipide’s mechanism of action involves increasing prostaglandin E2 in the gastric mucosa, which leads to several beneficial effects, including increased gastric mucus production, improved gastric mucosal blood flow, enhanced secretion of gastric alkaline, stimulation of gastric mucosal cell growth, and reduced gastric mucosa injury. It also exhibits antioxidant and anti-inflammatory properties.
Alternate Names
While “rebamipide” is the generic name, brand names include Mucosta, Mucopid, Mucopro, Mucoprotec, and Ramiper, among others. There are no widely recognized alternate names for this drug.
How It Works
Pharmacodynamics: Rebamipide exerts its therapeutic effects by increasing mucosal prostaglandin E2, protecting the gastric mucosa, suppressing gastric mucosal damage, and increasing gastric mucus secretion and mucosal blood flow. This helps improve hemodynamic impairment, suppress inflammation, and promote mucosal repair. It has also been shown to have free radical scavenging effects.
Pharmacokinetics:
- Absorption: Rebamipide is absorbed from the proximal portion of the small intestine, reaching peak plasma concentration in approximately 2 hours.
- Distribution: It is highly protein-bound (98.4-98.6%).
- Metabolism: Rebamipide is minimally metabolized in the liver, primarily by cytochrome P450 enzymes via hydroxylation and glucuronidation, forming 6-hydroxy and 8-hydroxyrebamipide.
- Elimination: Primarily excreted via urine (approximately 10% as unchanged drug) with an elimination half-life of approximately 1.5 hours.
Mode of Action: Rebamipide’s mode of action is multifactorial, enhancing the preservation of existing epithelial cells and replacing lost tissue. This involves increasing soluble mucus content, increasing gastric concentrations of PGE2 and PGI2, downregulating 15-hydroxyprostaglandin dehydrogenase, increasing mucosal blood flow via enhanced nitric oxide synthase activity, decreasing the expression of neutrophil adhesion molecules (CD11b/CD18), inhibiting the secretion of TNF-α, and scavenging reactive oxygen species. Additionally, it promotes tissue replacement by increasing the expression of epidermal growth factor (EGF) and EGF receptors.
Dosage
Standard Dosage
Special Cases:
- Elderly Patients: Start with a lower dose and monitor closely for adverse effects due to potential age-related physiological changes.
- Patients with Renal Impairment: Dosage adjustment may be necessary depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Dose adjustment may be required due to potential changes in metabolism.
- Patients with Comorbid Conditions: Careful consideration should be given to patients with diabetes, cardiovascular disease, or other conditions, as drug interactions may occur.
Clinical Use Cases
Dosage recommendations for specific clinical use cases like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations haven’t been clearly established. The standard dosage regimen is generally followed unless contraindicated by the patient’s condition.
Dosage Adjustments
Dose modifications should be made based on patient-specific factors such as renal or hepatic dysfunction, metabolic disorders, or genetic polymorphisms affecting drug metabolism. Consult specialized literature or expert opinion for guidance on these specific dosage adjustments.
Side Effects
Common Side Effects:
Nausea, vomiting, dry mouth, constipation, diarrhea, abdominal pain, abdominal enlargement sensation, belching, heartburn, and taste abnormalities. Dizziness, drowsiness, and numbness can also occur.
Rare but Serious Side Effects:
Anaphylactoid reactions, shock, thrombocytopenia, leukopenia, jaundice, and hepatic dysfunction.
Long-Term Effects:
Limited information is available on potential long-term complications of prolonged use. Regular monitoring of liver function and blood counts is advised during prolonged therapy.
Adverse Drug Reactions (ADR):
Clinically significant ADRs include anaphylactoid reactions, shock, severe blood dyscrasias (thrombocytopenia, leukopenia), and acute liver injury. These reactions require immediate medical intervention.
Contraindications
Rebamipide is contraindicated in patients with a known hypersensitivity to the drug.
Drug Interactions
Clinically significant drug interactions may occur with celecoxib and diclofenac. The potential for interactions with other medications metabolized by CYP450 enzymes should be considered. Closely monitor patients taking concomitant medications for any signs of adverse reactions or altered drug efficacy. Be mindful of potential interactions with commonly prescribed drugs, OTC medications, and lifestyle factors like alcohol and smoking.
Pregnancy and Breastfeeding
Information regarding the safety of rebamipide during pregnancy and breastfeeding is limited. Use with caution and only if the potential benefit outweighs the potential risk to the fetus or infant. Consult specialized resources or expert opinion for guidance in these situations.
Drug Profile Summary
- Mechanism of Action: Enhances mucosal protection, increases mucus secretion, improves blood flow, suppresses inflammation, and promotes mucosal repair in the gastrointestinal tract.
- Side Effects: Common: Nausea, vomiting, constipation, diarrhea. Serious: Anaphylaxis, blood dyscrasias, liver dysfunction.
- Contraindications: Hypersensitivity to rebamipide.
- Drug Interactions: Celecoxib, diclofenac, and potential interactions with other drugs metabolized by CYP450 enzymes.
- Pregnancy & Breastfeeding: Use with caution; safety not fully established.
- Dosage: Adults: 100 mg TID. Pediatric and special population dosing requires individualization.
- Monitoring Parameters: Liver function tests, complete blood count, and clinical response.
Popular Combinations
Rebamipide is frequently used in combination with proton pump inhibitors (PPIs) or H2 receptor antagonists for treating gastritis and peptic ulcers. It can also be combined with NSAIDs, but careful monitoring is required.
Precautions
- General Precautions: Pre-screening for allergies and organ dysfunction is recommended. Monitor for adverse events, especially during long-term therapy.
- Specific Populations: Exercise caution when prescribing to pregnant or breastfeeding women, children, and the elderly.
- Lifestyle Considerations: Advise patients to avoid alcohol and smoking as these may exacerbate underlying gastrointestinal conditions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Rebamipide?
A: The standard adult dosage is 100 mg orally three times a day. Pediatric and special populations (elderly, renal/hepatic impairment) require individualized dosing. Some formulations allow for twice-daily dosing.
Q2: What are the common side effects of Rebamipide?
A: Common side effects include nausea, vomiting, constipation, diarrhea, dry mouth, abdominal pain, and taste disturbances.
Q3: What are the serious side effects of Rebamipide?
A: Rare but serious side effects include anaphylactoid reactions, shock, thrombocytopenia, leukopenia, jaundice, and hepatic dysfunction.
Q4: Is Rebamipide safe during pregnancy and breastfeeding?
A: Limited data is available. Use with caution and only if the potential benefit outweighs the potential risk to the fetus or infant.
Q5: How does Rebamipide interact with other drugs?
A: Potential interactions exist with NSAIDs like celecoxib and diclofenac. Consider potential CYP450 interactions with other medications.
Q6: What is the mechanism of action of Rebamipide?
A: Rebamipide increases prostaglandin E2, promotes mucus secretion, improves blood flow, and suppresses inflammation in the gastric mucosa.
Q7: What conditions is Rebamipide used to treat?
A: Gastric ulcers, acute gastritis, acute exacerbations of chronic gastritis, recurrent aphthous ulcers, and Behçet’s syndrome.
Q8: Can Rebamipide be used with NSAIDs?
A: While it can be used concurrently with NSAIDs to mitigate gastrointestinal risks, close monitoring for adverse events is essential.
A: Yes, standard tablets and some sustained-release formulations are available. The dosing frequency may differ depending on the formulation.
