What is the initial treatment for peptic ulcer disease?

Initial Treatment for Peptic Ulcer Disease

Start proton pump inhibitor (PPI) therapy immediately at standard doses (omeprazole 20-40mg or equivalent once daily) for 6-8 weeks, test all patients for H. pylori infection, and initiate eradication therapy with 14-day triple therapy (PPI + clarithromycin 500mg + amoxicillin 1000mg, all twice daily) if positive. 1, 2

Immediate Pharmacological Management

PPI Therapy - The Foundation

• Initiate PPI therapy as soon as peptic ulcer disease is diagnosed, even before endoscopy if clinically indicated 2, 1
• Standard dosing: PPI standard dose (omeprazole 20-40mg or equivalent) once daily for uncomplicated ulcers 1, 3
• Duration: 6-8 weeks for duodenal ulcers (most heal within 4 weeks) and 6-8 weeks for gastric ulcers (most heal within 6 weeks), with gastric ulcers >2cm potentially requiring 8 weeks 1, 3
• PPIs heal 80-100% of peptic ulcers within this timeframe 3

For Bleeding Peptic Ulcers - Escalate Immediately

• High-dose PPI regimen: 80mg IV bolus followed by 8mg/hour continuous infusion for 72 hours after successful endoscopic hemostasis 2, 1, 4
• This high-dose regimen significantly reduces rebleeding (5.9% vs 10.3%), need for endoscopic retreatment, and mortality 2
• Pre-endoscopy erythromycin (250mg IV) improves gastric visualization and reduces need for repeat endoscopy 2, 1, 4
• Critical caveat: PPI therapy should not replace urgent endoscopy in patients with active bleeding 2, 1, 4

H. pylori Testing and Eradication - Essential for Prevention

Universal Testing Required

• Test ALL patients with peptic ulcer disease for H. pylori infection using urea breath test (sensitivity 88-95%, specificity 95-100%) or stool antigen testing (sensitivity 94%, specificity 92%) 2, 1
• For bleeding ulcers, H. pylori testing can be performed on endoscopic tissue biopsy 2
• Failure to test and eradicate H. pylori leads to recurrence rates of 40-50% over 10 years, compared to 0-2% with successful eradication 1, 3

First-Line Eradication: Standard Triple Therapy

For areas with low clarithromycin resistance (<15%):

• PPI standard dose twice daily + clarithromycin 500mg twice daily + amoxicillin 1000mg twice daily (or metronidazole 500mg twice daily if penicillin allergic) 2, 1
• Duration: 14 days (start after 72-96 hours of IV PPI if bleeding ulcer) 2
• This regimen is strongly recommended based on moderate-quality evidence 2

Alternative Regimens for High Clarithromycin Resistance

Sequential therapy (10 days total):

• Days 1-5: PPI standard dose twice daily + amoxicillin 1000mg twice daily 2, 1
• Days 6-10: PPI standard dose twice daily + clarithromycin 500mg twice daily + metronidazole 500mg twice daily 2, 1
• Use when clarithromycin resistance is high and patient compliance can be ensured 2

Second-Line Therapy if First-Line Fails

• Levofloxacin-based triple therapy for 10 days: PPI standard dose twice daily + levofloxacin 500mg once daily (or 250mg twice daily) + amoxicillin 1000mg twice daily 2, 1

NSAID-Associated Ulcers - Address the Cause

Discontinue NSAIDs When Possible

• Discontinuing NSAIDs heals 95% of ulcers and reduces recurrence from 40% to 9% 3
• If NSAID discontinuation is not feasible, consider switching to a less ulcerogenic NSAID (e.g., from ketorolac to ibuprofen) 3

Long-Term PPI for Ongoing NSAID Use

• Continue PPI therapy long-term only if NSAIDs cannot be discontinued 2, 1
• Omeprazole 20mg once daily is the optimal dose for healing NSAID-associated ulcers, with superior efficacy (77-83% healing at 8 weeks) compared to ranitidine (63-64%) or misoprostol (71-74%) 5
• For patients requiring continuous NSAID therapy, maintenance PPI therapy significantly reduces ulcer recurrence 6

Treatment Algorithm Summary

1. Immediate: Start standard-dose PPI (omeprazole 20-40mg daily)
2. Day 1-3: Test for H. pylori (urea breath test or stool antigen)
3. If bleeding: Escalate to high-dose IV PPI (80mg bolus + 8mg/hour × 72 hours) + urgent endoscopy 2, 4
4. If H. pylori positive: Add 14-day triple therapy (PPI + clarithromycin + amoxicillin) after initial stabilization 2, 1
5. If NSAID-associated: Discontinue NSAID if possible; if not, continue long-term PPI 1, 3
6. Duration: Continue PPI for 6-8 weeks total for uncomplicated ulcers 1, 3
7. Follow-up: Confirm H. pylori eradication if treated; repeat endoscopy for gastric ulcers to exclude malignancy 2

Common Pitfalls to Avoid

• Do not discontinue PPI therapy before 6-8 weeks, as this prevents adequate mucosal healing 1, 4
• Do not use long-term PPI therapy indiscriminately—only continue beyond 8 weeks for chronic NSAID users or recurrent ulcers despite H. pylori eradication 2, 1
• Do not rely solely on PPI therapy in active bleeding—urgent endoscopy remains first-line treatment 2, 1, 4
• Do not forget to confirm H. pylori eradication after treatment completion, as failure to do so perpetuates high recurrence rates 2, 1