Concurrent Use of Rebamipide and Lansoprazole
Yes, rebamipide and lansoprazole can be given together, and this combination is actually more effective than lansoprazole alone for certain gastric conditions, particularly for healing post-endoscopic ulcers and preventing GERD symptom recurrence. 1, 2, 3, 4
Evidence for Combined Therapy
The research evidence consistently demonstrates synergistic benefits when these medications are used together:
For GERD maintenance therapy, combining rebamipide 300 mg daily with lansoprazole 15 mg daily significantly reduced symptom recurrence compared to lansoprazole alone (20% vs 52.4% recurrence rate over 12 months, P < 0.05). 1
For post-endoscopic ulcer healing, the combination of rebamipide with a PPI achieved superior healing rates compared to PPI monotherapy, with complete healing (S-stage) occurring in 86.7% vs 54.8% of patients at 8 weeks (odds ratio 5.3, P = 0.006). 3
In patients with severe atrophic gastritis (a particularly challenging population), the combination therapy was dramatically more effective, achieving 92.9% complete healing vs only 30.0% with PPI alone (odds ratio 30.3, P = 0.0023). 3
Mechanism of Synergy
The two medications work through complementary mechanisms without pharmacological interference:
Lansoprazole suppresses gastric acid production by inhibiting the proton pump in parietal cells, with bioavailability of 85% and duration of action exceeding 24 hours. 5
Rebamipide provides mucosal protection through a different pathway—it concentrates in esophageal and gastric mucosa 90-180 minutes after oral administration and significantly decreases IL-8 mRNA expression, reducing mucosal inflammation. 1
Important Caveat Regarding Lansoprazole
While rebamipide and lansoprazole can be safely combined, you should be aware that lansoprazole inhibits CYP450 2C19, which has clinical implications if your patient is taking clopidogrel for cardiovascular protection. 6
Lansoprazole reduces the antiplatelet effect of clopidogrel by interfering with its conversion to the active metabolite. 6
If your patient requires both gastric protection and clopidogrel, pantoprazole is the preferred PPI because it has minimal CYP450 2C19 inhibition. 7, 8, 9
The combination of clopidogrel and lansoprazole was specifically studied and showed reduced platelet inhibition, whereas prasugrel was unaffected by lansoprazole co-administration. 6
Clinical Dosing Recommendations
Based on the research evidence:
Standard combination regimen: Lansoprazole 15-30 mg daily plus rebamipide 300 mg daily (100 mg three times daily). 1, 2, 3, 4
For large post-procedural ulcers (>20 mm): This combination is particularly beneficial and more cost-effective than PPI monotherapy. 2, 4
Duration: Treatment for 4-8 weeks is typically sufficient for ulcer healing, while maintenance therapy for GERD can extend to 12 months. 1, 3, 4
Additional Benefits of Combination Therapy
Reduced granulation lesions: Rebamipide treatment resulted in 0% granulation lesions following ulcer healing compared to 13.6% with PPI alone (P = 0.0103). 2
Cost-effectiveness: Eight weeks of rebamipide treatment costs approximately 4,889 yen versus 10,945 yen for PPI therapy in the Japanese healthcare system. 2
No additional adverse effects: The combination therapy showed no increase in ulcer bleeding or drug-related complications compared to monotherapy. 2, 3, 4