What are the adult indications, dosing schedules, contraindications, drug interactions, adverse effects, monitoring recommendations, and proton‑pump inhibitor alternatives for vonoprazan (Voquezna)?

Vonoprazan (Voquezna): Clinical Overview

Adult Indications

Vonoprazan is FDA-approved for four specific indications in adults: healing erosive esophagitis, maintaining healed erosive esophagitis, relieving heartburn in non-erosive GERD, and eradicating H. pylori infection. 1

• Healing of erosive esophagitis: 20 mg once daily for 8 weeks 1
• Maintenance of healed erosive esophagitis: 10 mg once daily for up to 6 months 1
• Relief of heartburn in non-erosive GERD: 10 mg once daily for 4 weeks 1
• H. pylori eradication (triple therapy): 20 mg twice daily + amoxicillin 1,000 mg twice daily + clarithromycin 500 mg twice daily for 14 days 1
• H. pylori eradication (dual therapy): 20 mg twice daily + amoxicillin 1,000 mg three times daily for 14 days 1

Dosing Schedules

Standard Dosing

• Take vonoprazan with or without food; swallow tablets whole without chewing or crushing 1
• For missed doses in GERD/erosive esophagitis: administer within 12 hours of the missed dose; if >12 hours have passed, skip and resume normal schedule 1
• For missed doses in H. pylori treatment: administer within 4 hours of the missed dose; if >4 hours have passed, skip and continue normal schedule 1

Renal Impairment Dosing

• eGFR ≥30 mL/min: Standard dosing for all indications 1
• eGFR <30 mL/min for erosive esophagitis healing: Reduce to 10 mg once daily 1
• eGFR <30 mL/min for H. pylori treatment: Use is not recommended 1
• eGFR <30 mL/min for maintenance therapy or non-erosive GERD: No dose adjustment needed 1

Hepatic Impairment Dosing

• Child-Pugh Class A: Standard dosing for all indications 1
• Child-Pugh Class B for erosive esophagitis healing: Reduce to 10 mg once daily 1
• Child-Pugh Class B for H. pylori treatment: Use is not recommended 1
• Child-Pugh Class C for erosive esophagitis healing: Reduce to 10 mg once daily 1
• Child-Pugh Class C for H. pylori treatment: Use is not recommended 1

Contraindications

Vonoprazan is absolutely contraindicated in patients with known hypersensitivity to vonoprazan (including anaphylactic shock) and in those taking rilpivirine-containing products. 1

• Known hypersensitivity to vonoprazan or any component of the formulation 1
• Concurrent use with rilpivirine-containing products 1
• Refer to amoxicillin and clarithromycin prescribing information for additional contraindications when using combination therapy 1

Drug Interactions

• Rilpivirine: Absolute contraindication due to reduced rilpivirine efficacy from increased gastric pH 1
• Clarithromycin: Mutual metabolic inhibition increases vonoprazan AUC by 1.8-fold and clarithromycin AUC by 1.5-fold 2
• CYP3A4 substrates: Vonoprazan is primarily metabolized by CYP3A4, with minor contributions from CYP2B6, CYP2C19, CYP2D6, and SULT2A1 2
• CYP2C19 polymorphisms: Unlike PPIs, vonoprazan exposure is minimally affected by CYP2C19 genetic variants (only 15-29% variation), providing more consistent acid suppression across populations 2, 3

Adverse Effects

The most common adverse effects include abdominal pain, constipation, diarrhea, nausea, and dyspepsia, occurring in 8-17% of patients. 4, 2

• Common (8-17%): Constipation, diarrhea, abdominal pain, dyspepsia, flatulence, nasopharyngitis, headache 5, 2
• Serious: Acute tubulointerstitial nephritis (TIN), anaphylactic shock 1
• Infection risk: Increased risk of Clostridioides difficile-associated diarrhea (CDAD), similar to PPIs 1
• Endocrine effects: Vonoprazan produces 2-3 times greater serum gastrin elevations compared to lansoprazole due to more extensive acid suppression 2

Monitoring Recommendations

Pre-Treatment Assessment

• Rule out gastric malignancy: Symptomatic response does not exclude gastric cancer; consider endoscopy in older patients or those with suboptimal response or early relapse 1
• Baseline renal and hepatic function: Required for appropriate dose adjustment 1

During Treatment

• Monitor for acute TIN: Discontinue immediately if suspected 1
• Monitor for CDAD: Evaluate patients with diarrhea that does not improve; use shortest treatment duration appropriate 1
• Assess treatment response: For H. pylori eradication, confirm eradication after completion of therapy 3

Long-Term Considerations

• Gastrin levels: Expect elevation 2-3 times higher than with PPIs 2
• Long-term safety: Data are more limited than for PPIs, though short-term safety appears comparable 6

Clinical Positioning Algorithm

When to Use Vonoprazan as First-Line Therapy

Use vonoprazan as first-line therapy ONLY for H. pylori eradication, where it demonstrates clear superiority over PPIs with 10-20% higher eradication rates, particularly in clarithromycin-resistant strains (66-70% vs 32%). 3, 7

• H. pylori eradication: Vonoprazan-based regimens achieve 92% eradication rates vs 80% with PPIs in first-line treatment 3
• Clarithromycin-resistant H. pylori: Vonoprazan dual therapy achieves 92% eradication vs 76% with triple therapy 3

When to Reserve Vonoprazan as Second-Line Therapy

For erosive esophagitis and non-erosive GERD, do NOT use vonoprazan as first-line therapy; reserve it for patients who fail twice-daily PPI therapy. 3, 6

• Mild erosive esophagitis (LA Grade A/B): Start with standard PPI; vonoprazan shows similar efficacy (94% vs 91%) but at significantly higher cost 6
• Non-erosive GERD: Start with standard PPI; clinical trials show inconsistent results for vonoprazan vs placebo 6
• Severe erosive esophagitis (LA Grade C/D): Start with standard PPI twice daily; escalate to vonoprazan only after PPI failure, where it demonstrates superior maintenance (75-77% vs 62%) 3, 6

When Vonoprazan Provides Clear Benefit

Vonoprazan is superior for maintaining healing in severe erosive esophagitis (LA Grade C/D), with recurrence rates of 5-13% vs 39% with lansoprazole. 3, 6

• Severe EE maintenance: Vonoprazan 10-20 mg once daily prevents recurrence better than lansoprazole 15 mg 3
• PPI-refractory GERD: Consider vonoprazan 20 mg daily after documented failure of twice-daily PPI therapy 6

Proton Pump Inhibitor Alternatives

Standard PPIs

• Omeprazole, esomeprazole, lansoprazole, pantoprazole, rabeprazole: Remain first-line for most acid-related disorders due to lower cost and extensive safety data 3, 6
• Double-dose PPI therapy: Should be attempted before escalating to vonoprazan for GERD 6

Other P-CABs

• Tegoprazan: Demonstrates noninferiority to lansoprazole for gastric ulcer healing (95% vs 96%) 3
• Fexuprazan: Provides acid inhibition similar to standard PPI doses rather than more potent suppression; should not be used as first-line therapy 8

Common Pitfalls and Caveats

Cost Considerations

Do not prescribe vonoprazan as first-line therapy for conditions where PPIs are equally effective, as vonoprazan is markedly more expensive than both standard and double-dose PPIs in the United States. 3, 6

Inappropriate First-Line Use

• Avoid using vonoprazan for mild GERD or peptic ulcer disease where clinical superiority has not been demonstrated 3, 6
• Do not assume more potent acid inhibition automatically translates to superior clinical outcomes across all foregut disorders 8

Infection Risk Management

• Use the shortest duration appropriate to minimize CDAD risk 1
• Consider CDAD in any patient with diarrhea that does not improve during or after vonoprazan therapy 1

Renal and Hepatic Dosing Errors

• Do not use vonoprazan for H. pylori eradication in patients with eGFR <30 mL/min or Child-Pugh Class B/C 1
• Remember to reduce dosing to 10 mg for erosive esophagitis healing in severe renal or hepatic impairment 1