Which PPI is Best?
Esomeprazole 20-40 mg twice daily or rabeprazole 20-40 mg twice daily are the preferred PPIs due to their superior potency, with pantoprazole specifically recommended to be avoided. 1
Relative Potency Rankings
PPIs vary remarkably in acid suppression capability, and this directly impacts clinical outcomes, particularly in amoxicillin-containing H. pylori regimens 1:
- Rabeprazole 20 mg = 36 mg omeprazole equivalent 1
- Esomeprazole 20 mg = 32 mg omeprazole equivalent 1
- Lansoprazole 30 mg = 27 mg omeprazole equivalent 1
- Pantoprazole 40 mg = 9 mg omeprazole equivalent (weakest, should be avoided) 1
Clinical Application by Indication
H. pylori Eradication
Use esomeprazole 40 mg twice daily or rabeprazole 40 mg twice daily in combination regimens 1. Higher-potency PPIs utilized twice daily produce optimal outcomes, especially with amoxicillin-containing regimens 1. If cost is equivalent, esomeprazole or rabeprazole are explicitly recommended over other agents 1.
Eosinophilic Esophagitis (EoE)
Omeprazole 20 mg twice daily is the only PPI formally assessed for EoE treatment 1. High-dose PPI (omeprazole 20 mg twice daily) achieved 50.8% clinicopathological response versus 35.8% with standard/low-dose regimens 1. Treatment should continue for 8-12 weeks before assessing histological response 1.
GERD and Erosive Esophagitis
For mild erosive esophagitis (LA grade A/B), standard once-daily dosing of any PPI is generally adequate 1. For severe erosive esophagitis (LA grade C/D), higher potency PPIs (esomeprazole or rabeprazole) may be considered 1, though the 2024 AGA guidance notes that cost considerations may outweigh modest clinical superiority over double-dose standard PPIs 1.
Peptic Ulcer Disease
Standard doses heal >90% of duodenal ulcers in 4 weeks and gastric ulcers in 6-8 weeks across all PPIs 2, 3. Omeprazole 20 mg daily, lansoprazole 30 mg daily, pantoprazole 40 mg daily, or rabeprazole 20 mg daily are all effective 2, though given the potency data, esomeprazole or rabeprazole would be preferred when cost is equivalent 1.
Dosing Strategy
Twice-daily dosing is superior to increasing once-daily dose strength 4. Increasing once-daily PPI strength (9-64 mg omeprazole equivalents) increases pH>4 time from 10.0 to 15.6 hours, but higher doses produce no further benefit 4. Twice-daily dosing increases pH>4 time linearly from 15.8 to 21.0 hours 4. Three-times daily dosing offers no advantage over twice-daily 4.
Important Caveats
Pantoprazole should be avoided when higher acid suppression is needed 1. Its dramatically lower potency (40 mg pantoprazole = only 9 mg omeprazole) makes it the least effective option 1.
The 2024 AGA guidance emphasizes that potassium-competitive acid blockers (P-CABs) should generally not be used as first-line therapy due to cost, access barriers, and limited long-term safety data, despite modest clinical advantages 1. P-CABs are recommended specifically for H. pylori eradication regimens 1.
All PPIs have excellent long-term safety profiles 5. Serious adverse events are extremely rare, with no convincing evidence of increased risk for gastric atrophy, carcinoid tumors, or vitamin B12 deficiency in most patients 5.
Cost Considerations
When cost is equivalent between agents, esomeprazole 20-40 mg twice daily or rabeprazole 20-40 mg twice daily should be selected 1. Cost variation among PPIs is substantial but not directly related to potency 4. Generic omeprazole remains widely used and effective, though less potent than esomeprazole or rabeprazole 1, 4.