What is the recommended dosing for Vonoprazan (Vonoprazan) for acid-related diseases?

Vonoprazan Dosing for Acid-Related Diseases

Standard Dosing by Indication

Vonoprazan dosing varies by indication: 20 mg once daily for erosive esophagitis healing and peptic ulcers, 10 mg once daily for maintenance therapy and ulcer prophylaxis, and 20 mg twice daily for H. pylori eradication. 1, 2

Erosive Esophagitis (EE)

• Treatment (healing): 20 mg once daily for 8 weeks achieves healing rates of approximately 94% 3, 1
• Maintenance (prevention of recurrence): 10 mg once daily for long-term maintenance, particularly effective for severe EE (LA grade C/D) with recurrence rates of only 5-13% compared to 39% with lansoprazole 4, 5
• Steady-state plasma concentrations are achieved by Day 3-4, with pH >4 holding time ratios of 63% on Day 1 and 83% on Day 7 1

Peptic Ulcer Disease

• Gastric ulcers: 20 mg once daily for 8 weeks achieves 94% healing rates 4, 6
• Duodenal ulcers: 20 mg once daily for 6 weeks achieves 96-98% healing rates 4, 6
• Ulcer prophylaxis (in patients on low-dose aspirin or NSAIDs with history of PUD): 10 mg once daily 4

H. pylori Eradication

• 20 mg twice daily in combination with clarithromycin and amoxicillin for 14 days 6, 1, 2
• This regimen provides 10-20% higher eradication rates than PPI-based triple therapy, with superiority particularly evident for clarithromycin-resistant strains 4
• Dual therapy with vonoprazan and amoxicillin achieves eradication rates approaching 95% for first-line treatment 4

Non-Erosive Reflux Disease (NERD)

• 10 mg once daily for symptom relief, though clinical trial data show inconsistent results 3, 4, 1
• Mean fasting gastrin levels increase from baseline but return to normal within 4 weeks of discontinuation 1

Pharmacokinetic Considerations

• Time to peak concentration (Tmax): 1.5-2.0 hours after oral administration 1, 2
• Elimination half-life: Approximately 7.7-7.9 hours 1, 2
• Food effect: High-fat meals cause only a 5% increase in Cmax and 15% increase in AUC with a 2-hour delay in Tmax—not clinically significant, so vonoprazan can be taken without regard to meals 1
• Steady state: Achieved by Day 3-4 with minimal accumulation (accumulation index <1.2) 1

Special Populations

Renal Impairment

• Mild to moderate renal impairment: No dose adjustment required 1
• Severe renal impairment (eGFR 15 to <30 mL/min/1.73 m²): Systemic exposure increases 2.4-fold, but no specific dose adjustment is recommended in the FDA label 1
• Dialysis patients: Exposure increases 1.3-fold; only 0.94% of the dose is removed by dialysis 1

Hepatic Impairment

• Severe hepatic impairment (Child-Pugh Class C): Systemic exposure increases 2.6-fold compared to normal hepatic function 1, 2
• Despite increased exposure, no specific dose adjustments are provided in the FDA label 1

CYP2C19 Polymorphisms

• No dose adjustment needed based on CYP2C19 metabolizer status, as genetic polymorphism influences drug exposure by only 15-29%—clinically insignificant 1, 2
• This represents a major advantage over PPIs, which show significant variability based on CYP2C19 status 4

Clinical Positioning Algorithm

First-Line Therapy (Generally NOT Recommended)

• Do not use vonoprazan as first-line therapy for mild EE (LA grade A/B), NERD, or peptic ulcer disease where PPIs are equally effective but significantly less expensive 3, 4, 5
• Cost considerations are paramount: vonoprazan is markedly more expensive than both standard-dose and double-dose PPIs in the United States 3, 4, 5

First-Line Therapy (Recommended)

• H. pylori eradication: Use vonoprazan 20 mg twice daily as first-line therapy due to superior eradication rates (92% vs 80% with PPIs) 4, 5
• Severe erosive esophagitis (LA grade C/D): Consider vonoprazan 20 mg once daily for initial treatment and 10 mg once daily for maintenance due to superior healing maintenance 4, 5

Second-Line Therapy (After PPI Failure)

• PPI-resistant GERD: Use vonoprazan 20 mg once daily for healing, then 10 mg once daily for maintenance in patients who fail twice-daily PPI therapy 3, 4, 5
• Real-world data shows 88% improvement and 42% resolution rates in PPI-resistant GERD patients treated with vonoprazan 10 mg daily 7
• Patients with erosive disease achieve higher resolution rates (83%) compared to those without erosions (28%) 7

Common Pitfalls to Avoid

• Avoid prescribing vonoprazan as first-line therapy for conditions where clinical superiority over PPIs has not been demonstrated, as cost-effectiveness is poor 3, 5
• Do not assume all GERD patients need vonoprazan: Ensure proper PPI dosing (30-60 minutes before meals) and consider twice-daily PPI dosing before switching 5
• Remember that long-term safety data are more limited for vonoprazan compared to PPIs, though short-term safety appears comparable 4
• Be aware of increased serum gastrin levels during treatment, which return to normal within 4 weeks of discontinuation 1
• Consider that vonoprazan may be particularly effective for H. pylori-associated ulcers compared to idiopathic or NSAID-related ulcers 4, 6

Drug Interactions

• Clarithromycin co-administration increases vonoprazan AUC by 1.8-fold and clarithromycin AUC by 1.5-fold due to mutual metabolic inhibition 2
• Vonoprazan is metabolized primarily by CYP3A4, with contributions from CYP2B6, CYP2C19, CYP2D6, and SULT2A1 1, 2