Vonoprazan (Voquezna): Clinical Guide
Primary Recommendation
Vonoprazan should NOT be used as first-line therapy for most acid-related disorders; reserve it for H. pylori eradication (where it is superior) and for severe erosive esophagitis or GERD that fails twice-daily PPI therapy. 1, 2, 3
FDA-Approved Indications
Vonoprazan is approved for the following in adults: 4
- Healing of all grades of erosive esophagitis and relief of associated heartburn
- Maintenance of healed erosive esophagitis and relief of associated heartburn
- Relief of heartburn in non-erosive GERD
- H. pylori eradication in combination with amoxicillin and clarithromycin (triple therapy)
- H. pylori eradication in combination with amoxicillin alone (dual therapy)
Dosing Regimens
Erosive Esophagitis 4
- Healing: 20 mg once daily for 8 weeks
- Maintenance: 10 mg once daily for up to 6 months
Non-Erosive GERD 4
- Heartburn relief: 10 mg once daily for 4 weeks
H. pylori Eradication 4
- Triple therapy: Vonoprazan 20 mg + amoxicillin 1000 mg + clarithromycin 500 mg, all twice daily for 14 days
- Dual therapy: Vonoprazan 20 mg twice daily + amoxicillin 1000 mg three times daily for 14 days
Renal Impairment Adjustments 4
- eGFR ≥30 mL/min: Standard dosing (20 mg for healing, 10 mg for maintenance/NERD)
- eGFR <30 mL/min: 10 mg once daily for erosive esophagitis healing; H. pylori treatment NOT recommended
Hepatic Impairment Adjustments 4
- Child-Pugh A: Standard dosing
- Child-Pugh B: 10 mg once daily for erosive esophagitis; H. pylori treatment NOT recommended
- Child-Pugh C: 10 mg once daily for erosive esophagitis; H. pylori treatment NOT recommended
Administration 4
- Take with or without food (no food effect) 5
- Swallow whole; do NOT crush or chew
- Missed dose: Take within 12 hours for GERD indications, within 4 hours for H. pylori treatment
Clinical Positioning Algorithm
For H. pylori Eradication: USE VONOPRAZAN FIRST-LINE 3
Vonoprazan achieves 10-20% higher eradication rates than PPI-based regimens, particularly for clarithromycin-resistant strains (92% vs 76% with PPIs). 1, 3
- Vonoprazan-based triple therapy: ~92% eradication vs 80% with PPI-based therapy 3
- Vonoprazan-amoxicillin dual therapy: ~95% first-line, ~90% second-line eradication 2
- Superiority is most pronounced in clarithromycin-resistant infections (66-70% success vs 32% with PPIs) 3
- Confirm eradication with urea breath test or stool antigen after treatment 3
For GERD and Erosive Esophagitis: Stepwise Escalation 2, 3
Step 1: Start with standard-dose PPI once daily 2
Step 2: If inadequate response, escalate to PPI twice daily 2, 3
Step 3: Consider vonoprazan ONLY after documented failure of twice-daily PPI 1, 2, 3
Specific GERD Scenarios:
Non-erosive GERD (NERD): Do NOT use vonoprazan first-line; clinical trials show inconsistent results with minimal difference vs placebo 2, 3
Mild erosive esophagitis (LA Grade A/B): Do NOT use vonoprazan first-line; healing rates are similar to PPIs (94% vs 91%) and do not justify the higher cost 2, 3
Severe erosive esophagitis (LA Grade C/D): Start with twice-daily PPI; if this fails, vonoprazan shows superior maintenance of healing (75-77% vs 62% with lansoprazole) and lower recurrence rates (5-13% vs 39%) 2, 3
For Peptic Ulcer Disease: Reserve for PPI Failures 1
Do NOT use vonoprazan as first-line therapy for PUD treatment or prophylaxis. 1
- Vonoprazan 20 mg is non-inferior to lansoprazole 30 mg for gastric ulcer healing (94% vs 94%) and duodenal ulcers (96% vs 98%) 1, 2
- For secondary prophylaxis in high-risk patients (aspirin/NSAID users with PUD history), vonoprazan 10-20 mg is non-inferior to lansoprazole 15 mg 1, 2
- Consider vonoprazan for PPI-refractory ulcers (excluding ulcers from cancer, infections, vasculitis, or ischemia) 1
- Potential role in high-risk ulcer bleeding after endoscopic hemostasis due to rapid acid suppression 1
Pharmacologic Advantages Over PPIs
Vonoprazan offers several mechanistic benefits: 1, 5
- Rapid onset: Achieves pH >4 within 4 hours (vs delayed onset with PPIs) 5
- Prolonged duration: Maintains pH >4 for 63% of 24 hours on day 1,83% by day 7 5
- No CYP2C19 polymorphism effect: Only 15-29% variation in exposure across genetic variants (vs significant PPI variability) 3, 5
- Acid-stable: Does NOT require conversion to active form; works immediately 1
- No meal timing required: Can be taken with or without food 4, 5
Safety Considerations
Short-Term Safety 1, 2
- Generally well-tolerated with safety profile comparable to PPIs 1
- Most common adverse events: abdominal pain, constipation, diarrhea, nausea, dyspepsia 6
- Nasopharyngitis, flatulence, and headache also reported 7
Long-Term Safety Concerns 1, 2
- Limited long-term data compared to PPIs 2, 3
- Higher serum gastrin elevation than PPIs (2-3 times higher), though levels normalize within weeks after discontinuation 1, 5
- Potential infection risk: Similar to PPIs, may increase enteric infections (relative risk 1.89 for community-acquired pneumonia) 2
- C. difficile risk: Comparable to PPIs 1
- Gastric cancer risk: Japanese data suggest hazard ratio <2, similar to PPIs 1
- Five-year maintenance data show comparable rates of enterochromaffin-like cell hyperplasia to lansoprazole 1
Contraindications 4
- Known hypersensitivity to vonoprazan (including anaphylactic shock)
- Concurrent use with rilpivirine-containing products
Drug Interactions 5
- Clarithromycin: Mutual metabolic inhibition increases vonoprazan AUC by 1.8-fold and clarithromycin by 1.5-fold 5
- Metabolized primarily by CYP3A4, with minor contributions from CYP2B6, CYP2C19, CYP2D6, and SULT2A1 5
Cost Considerations: The Critical Limiting Factor
Vonoprazan is markedly more expensive than both standard-dose and double-dose PPIs in the United States, which fundamentally limits its appropriate use. 1, 2, 3
- Do NOT prescribe vonoprazan when PPIs are equally effective 3
- Cost does NOT justify use in mild GERD, NERD, or routine PUD where clinical superiority is absent 2, 3
- The exception is H. pylori eradication, where superior efficacy justifies cost 3
Common Pitfalls to Avoid
- Do NOT assume greater acid suppression equals better outcomes across all conditions 3
- Do NOT use vonoprazan first-line for mild erosive esophagitis or NERD 2, 3
- Do NOT skip the twice-daily PPI trial before escalating to vonoprazan 2, 3
- Do NOT use vonoprazan for PUD prophylaxis as first-line therapy 1
- Do NOT forget to adjust dosing in severe renal (eGFR <30) or hepatic impairment (Child-Pugh B/C) 4
- Do NOT prescribe vonoprazan without considering the significant cost differential 1, 3