What is the recommended management of drug‑induced gastropathy and what role does rebamipide play in its treatment?

Management of Drug-Induced Gastropathy and the Role of Rebamipide

Immediate First Step: Withdraw Offending Medications

The cornerstone of managing drug-induced gastropathy is immediate withdrawal of the causative agent, particularly opioids, anticholinergics, tricyclic antidepressants, GLP-1 receptor agonists, and pramlintide. 1

• Opioids directly impair gastrointestinal motility and are specifically contraindicated in gastroparesis patients 1
• This withdrawal should occur before initiating any pharmacologic gastroprotective therapy 2

Gastroprotective Pharmacotherapy Algorithm

First-Line: Proton Pump Inhibitors

Proton pump inhibitors are the gastroprotective comedication of choice for NSAID-induced gastropathy, as they effectively reduce gastrointestinal adverse events and are safe even in long-term use. 3

• Initiate PPI therapy 30-60 minutes prior to meals 4
• Continue for 4-8 weeks initially, then reassess 4
• PPIs can be combined with metoclopramide (10-20 mg every 6 hours) for medication-induced gastropathy 4

Rebamipide as an Alternative or Adjunctive Agent

Rebamipide (100 mg three times daily) represents a clinically effective and safe alternative to traditional gastroprotective strategies, with particular advantages in patient tolerability and compliance. 5

Mechanism and Efficacy

• Rebamipide increases mucosal prostaglandin generation and eliminates free oxygen radicals, enhancing gastric mucosal protection 5, 6
• In head-to-head comparison with misoprostol (200 μg three times daily), rebamipide showed equivalent efficacy in preventing gastric ulcers (20.3% vs 21.9%, p=0.6497) after 12 weeks of NSAID therapy 5
• Rebamipide demonstrated significantly lower gastrointestinal symptom severity scores compared to misoprostol (p=0.0002) 5
• The withdrawal rate was significantly lower with rebamipide (10.3%) versus misoprostol (18.6%, p=0.0103), indicating superior tolerability 5

Specific Advantages of Rebamipide

• Rebamipide provides protection against both upper and lower gastrointestinal NSAID-induced injury, showing particular benefit for small bowel damage (RR=2.70,95% CI=1.02-7.16, p=0.045) compared to placebo. 7
• Patients required significantly less antacid rescue medication with rebamipide versus misoprostol (p=0.0258) 5
• Average adverse event incidence is approximately 36.1% with no serious events recorded 7
• Rebamipide is equivalent to famotidine (10 mg twice daily) in preventing acute NSAID-induced gastric injury in patients without particular risk factors 8

Clinical Decision Algorithm

When to Choose Rebamipide Over PPIs

1. Patient requires NSAID therapy with concern for both upper and lower GI toxicity - rebamipide offers broader protection 7
2. Patient has poor compliance with misoprostol - rebamipide has superior tolerability profile 5
3. Patient experiences significant GI symptoms despite PPI therapy - rebamipide reduces symptom severity more effectively than misoprostol 5
4. Patient is in a region where rebamipide is available (primarily Japan and some Asian countries) - consider as first-line gastroprotective agent 6

Combination Strategies

• Rebamipide can be combined with PPIs for enhanced mucosal protection, though specific combination trial data are limited 6
• For medication-induced gastropathy, combine gastroprotective therapy (PPI or rebamipide) with metoclopramide (10-20 mg every 6 hours) 4

Management of Persistent Symptoms Despite Gastroprotection

Antiemetic Therapy

• Add 5-HT3 antagonists (ondansetron 4-8 mg twice or three times daily, or granisetron 1 mg twice daily) for persistent nausea and vomiting 4
• Consider dopamine receptor antagonists (prochlorperazine 5-10 mg four times daily or haloperidol) if symptoms persist 4
• Transdermal granisetron (3.1 mg/24 hours) decreases symptom scores by 50% in refractory cases 4

Pain Management Without Opioids

For visceral pain in drug-induced gastropathy, use tricyclic antidepressants or SNRIs as first-line agents, never opioids. 1

• Tricyclic antidepressants: amitriptyline, imipramine, desipramine, or nortriptyline (25-100 mg/day) 1
• SNRIs: duloxetine (60-120 mg/day) for visceral pain 1
• Anticonvulsants: gabapentin (>1200 mg/day) or pregabalin (100-300 mg/day) for neuropathic pain component 1
• Avoid tertiary amine TCAs in patients ≥65 years due to anticholinergic side effects 1

Critical Pitfalls to Avoid

• Never use opioid analgesics for chronic visceral abdominal pain - they further delay gastric emptying, increase risk of narcotic bowel syndrome, and create potential for addiction 4
• Do not continue causative medications while attempting gastroprotective therapy - withdrawal is mandatory 1
• Avoid assuming all gastroprotective agents are equivalent - rebamipide offers unique advantages for small bowel protection not provided by PPIs 7
• Do not overlook the importance of patient compliance - rebamipide's superior tolerability profile translates to better real-world outcomes 5

Monitoring and Reassessment

• Reassess symptoms after 4-8 weeks of gastroprotective therapy 4
• Monitor for adequate symptom control, reduction of patient distress, and optimization of quality of life 4
• If symptoms persist despite optimal gastroprotective therapy and medication withdrawal, consider endoscopic evaluation to rule out structural pathology 4