When to Trial Vonoprazan (Voquenza) After PPI Failure
Switch to vonoprazan only after documented failure of twice-daily PPI therapy in patients with objectively confirmed acid-related GERD, not as a first-line agent. 1, 2
Step 1: Optimize Current PPI Therapy First
Before considering vonoprazan, you must escalate and optimize standard PPI management:
- Increase to twice-daily dosing if the patient is currently on once-daily PPI 1, 2, 3
- Verify proper timing: PPIs should be taken 30-60 minutes before meals for optimal efficacy 3
- Continue optimized therapy for 4-8 weeks to assess response 1, 2
- If symptoms persist despite twice-daily PPI, the patient is considered a therapeutic failure and requires objective testing 3
Step 2: Obtain Objective Confirmation of GERD
Do not escalate to vonoprazan without documented GERD. This is a critical pitfall that leads to inappropriate long-term use of expensive medications. 1, 2
Required Testing Off PPI:
- Perform upper endoscopy to identify erosive esophagitis (Los Angeles grade B or higher), Barrett's esophagus, or hiatal hernia 1, 3
- Conduct prolonged wireless pH monitoring (96 hours preferred) after stopping PPI for 7 days 1, 3
Step 3: Consider Vonoprazan in Appropriate Candidates
Vonoprazan may be used in selected patients with documented acid-related reflux who fail twice-daily PPI therapy. 1, 2
Evidence Supporting This Approach:
- Vonoprazan achieves 91.7% healing rates at 4 weeks and 88.5% at 8 weeks in PPI-resistant erosive esophagitis 4
- Maintenance rates with vonoprazan 10 mg are 82.6% at 8 weeks and 93.8% at 48 weeks for healed PPI-resistant erosive esophagitis 4
- Vonoprazan shows particular superiority in severe erosive esophagitis (Los Angeles grade C/D), with a risk ratio of 1.14 compared to lansoprazole 5
- Long-term vonoprazan therapy effectively controls symptoms in both erosive and non-erosive PPI-resistant GERD over 1 year 6
When Vonoprazan Is NOT Appropriate:
- Do not use as first-line therapy for uninvestigated heartburn or mild erosive esophagitis (LA grade A/B) 1
- Do not use without objective GERD confirmation – higher cost, limited availability, and less long-term safety data make empiric use unjustified 1, 2
- Do not use if pH monitoring shows no acid reflux (functional heartburn) 1, 2
Step 4: Alternative Adjunctive Therapies Before Vonoprazan
If twice-daily PPI fails but you are awaiting testing or vonoprazan is unavailable, consider:
- Alginate-antacids for breakthrough symptoms 2, 3
- Nighttime H2-receptor antagonists for nocturnal symptoms (note: tachyphylaxis develops) 2, 3
- Baclofen if regurgitation or belching predominates 2, 3
- Prokinetics only if gastroparesis is documented by gastric emptying study 2, 3
Critical Pitfalls to Avoid
- Never escalate beyond twice-daily PPI without objective GERD confirmation – this leads to inappropriate long-term medication use 1, 2
- Do not continue vonoprazan indefinitely without reassessing indication within 12 months if GERD was never objectively proven 2
- Recognize that a European phase 2 trial showed no statistical difference between vonoprazan 20 mg, 40 mg, and esomeprazole 40 mg in PPI partial responders, though Asian studies show better results 7 – this suggests patient selection and objective confirmation are crucial
- Cost considerations: Vonoprazan is markedly more expensive than double-dose PPIs in the United States, making objective confirmation of need essential 1
Timeline Summary
- Weeks 0-8: Optimize to twice-daily PPI with proper timing
- Week 8+: If failure, stop PPI for 7 days and perform endoscopy + pH monitoring
- After confirmation: Switch to vonoprazan 20 mg once daily if objective GERD is documented
- Month 12: Reassess need for continued therapy 2