What is the recommended treatment regimen for a patient with gastroesophageal reflux disease (GERD) or peptic ulcer disease using Vonoprazan (potassium-competitive acid blocker)?

Vonoprazan Treatment Regimens for GERD and Peptic Ulcer Disease

Vonoprazan should not be used as first-line therapy for GERD or peptic ulcer disease, but is reserved for patients who fail twice-daily PPI therapy, with the exception of severe erosive esophagitis (LA grade C/D) where earlier use may be warranted. 1

Standard Dosing by Indication

Erosive Esophagitis (Healing Phase)

• 20 mg once daily for 8 weeks achieves approximately 94% healing rates 1, 2
• Can be taken with or without food, and does not require timing with meals 3, 2
• For patients with renal impairment (eGFR <30 mL/min): reduce to 10 mg once daily 2
• For patients with hepatic impairment (Child-Pugh B or C): reduce to 10 mg once daily 2

Maintenance of Healed Erosive Esophagitis

• 10 mg once daily for long-term maintenance 1, 2
• Particularly effective for severe erosive esophagitis (LA grade C/D), with recurrence rates of only 5-13% compared to 39% with lansoprazole 1
• No dose adjustment needed for renal or hepatic impairment in maintenance therapy 2

Non-Erosive Reflux Disease (NERD)

• 10 mg once daily is the recommended dose, though clinical trial data show inconsistent results 1
• The American Gastroenterological Association does not recommend vonoprazan as first-line therapy for NERD due to minimal difference from placebo in some studies 1

Peptic Ulcer Disease

• 20 mg once daily for gastric ulcers (8 weeks) or duodenal ulcers (6 weeks) 1
• Healing rates: 94% for gastric ulcers and 96% for duodenal ulcers 1
• Reserve for PPI treatment failures, not first-line therapy 1

Ulcer Prophylaxis (Aspirin/NSAID Users)

• 10-20 mg once daily for patients on low-dose aspirin or NSAIDs with history of peptic ulcer disease 1
• Non-inferior to lansoprazole 15 mg for this indication 1

H. pylori Eradication

• 20 mg twice daily in combination with antibiotics (amoxicillin and clarithromycin) 1, 2
• Achieves 10-20% higher eradication rates than PPI-based triple therapy, particularly for clarithromycin-resistant strains 1
• Dual therapy with vonoprazan and amoxicillin alone achieves ~95% first-line and ~90% second-line eradication rates 1
• Not recommended in patients with eGFR <30 mL/min or Child-Pugh Class B or C hepatic impairment 2

Treatment Algorithm

For GERD Management

1. Start with standard once-daily PPI for 4-8 weeks 1
2. Escalate to twice-daily PPI if inadequate response 1
3. Consider vonoprazan 20 mg daily only after documented failure of twice-daily PPI therapy 1
4. Exception: May consider vonoprazan earlier for severe erosive esophagitis (LA grade C/D) after standard PPI failure 1

For Peptic Ulcer Disease

1. Begin with standard PPI therapy as first-line 1
2. Reserve vonoprazan 20 mg daily for PPI treatment failures 1
3. Consider vonoprazan for high-risk ulcer bleeding cases due to rapid and potent acid inhibition 1

Key Pharmacologic Advantages

• Rapid onset: Maximal acid suppression achieved by Day 4 (vs. 3-5 days for PPIs) 3
• Superior nighttime acid control: Maintains target intragastric pH for longer periods than PPIs 3
• No CYP2C19 variability: More consistent therapeutic outcomes across different patient populations 3
• Meal-independent dosing: Unlike PPIs which require dosing 30-60 minutes before meals 3

Critical Clinical Considerations

Cost-Effectiveness

• Vonoprazan is significantly more expensive than both standard and double-dose PPIs in the United States 1
• This cost differential is the primary reason for reserving vonoprazan as second-line therapy 1

Safety Profile

• Short-term safety comparable to PPIs with similar adverse event rates 1, 4
• Long-term safety data more limited than for PPIs 1
• Risk of acute tubulointerstitial nephritis has been reported 2
• May increase risk of Clostridioides difficile-associated diarrhea (similar to PPIs) 2
• Bone fracture risk with long-term use (similar to PPIs) 2
• Vitamin B12 deficiency possible with prolonged use 2

Gastrin Elevation

• Mean fasting gastrin levels increase during treatment but return to normal within 4 weeks of discontinuation 2
• Increased gastrin causes enterochromaffin-like cell hyperplasia and elevated serum chromogranin A (CgA) levels 2
• Elevated CgA may cause false-positive results in diagnostic investigations for neuroendocrine tumors 2

Common Pitfalls to Avoid

• Do not prescribe vonoprazan as first-line therapy for mild GERD or peptic ulcer disease when PPIs would be more cost-effective 1
• Do not assume superior acid suppression automatically translates to superior clinical outcomes in all acid-related conditions 3
• Always consider the higher cost of vonoprazan compared to PPIs when making treatment decisions 1
• Rule out gastric malignancy in patients with suboptimal response or early symptomatic relapse, particularly in older patients 2
• Ensure ulcers are not secondary to non-acid processes (cancer, opportunistic infections, vasculitis, ischemia) before initiating therapy 1

Administration Instructions

• Swallow tablets whole; do not chew or crush 2
• Missed dose (GERD/maintenance): Take within 12 hours; if >12 hours passed, skip and resume normal schedule 2
• Missed dose (H. pylori): Take within 4 hours; if >4 hours passed, skip and resume normal schedule 2