What is the recommended use and dosage of Vonoprazan (Vonoprazan) for treating acid-related diseases such as Gastroesophageal Reflux Disease (GERD) and Peptic Ulcer Disease (PUD)?

Vonoprazan for Acid-Related Diseases

Vonoprazan should generally not be used as first-line therapy for GERD or peptic ulcer disease but may be considered in patients who fail twice-daily PPI therapy. 1

Recommended Dosages

• For erosive esophagitis (EE): Vonoprazan 20 mg once daily for initial treatment (healing phase), with dosage reduction to 10 mg once daily for maintenance therapy 2
• For non-erosive GERD: Vonoprazan 10 mg once daily 2
• For peptic ulcer disease: Vonoprazan 20 mg once daily for 6-8 weeks 1
• For patients with severe renal impairment (eGFR 15 to <30 mL/min/1.73 m²): Consider dose reduction due to 2.4-fold greater systemic exposure 2
• For patients with moderate to severe hepatic impairment: Consider dose reduction due to 2.4-2.6 times greater systemic exposure 2

Clinical Efficacy by Condition

Erosive Esophagitis (EE)

• For mild EE (LA grade A/B): Vonoprazan and PPIs have similar healing efficacy (92-99% vs 96-100%), so vonoprazan is generally not recommended as first-line therapy 1
• For severe EE (LA grade C/D): Vonoprazan may be more effective than PPIs, making it a potential option for these patients 3
• For PPI-resistant EE: Vonoprazan 20 mg shows high healing rates of 91.7% at 4 weeks and 88.5% at 8 weeks 4

Non-Erosive Reflux Disease (NERD)

• Vonoprazan should generally not be used as first-line therapy for NERD or uninvestigated heartburn symptoms 1
• For PPI-resistant NERD: Vonoprazan improves symptoms in approximately 74.6% of patients at 4 weeks 4
• On-demand vonoprazan provides complete relief within 3 hours for 56-70% of heartburn episodes versus 27% with placebo 1

Peptic Ulcer Disease (PUD)

• Vonoprazan 20 mg is comparable to lansoprazole 30 mg for gastric ulcer healing (94% vs 94% at 8 weeks) and duodenal ulcers (96% vs 98% at 6 weeks) 1
• For ulcer prophylaxis in patients on low-dose aspirin or NSAIDs with history of PUD, vonoprazan 10-20 mg is non-inferior to lansoprazole 15 mg 1
• Vonoprazan may be particularly effective for H. pylori-associated ulcers compared to idiopathic or NSAID-related ulcers 1

Pharmacological Advantages Over PPIs

• Rapid onset of action: Vonoprazan reaches maximal acid suppression within 1 day versus 3-5 days for PPIs 5, 2
• No meal timing requirement: Vonoprazan can be taken regardless of meals, with minimal food effect (only 15% increase in AUC with high-fat meal) 2
• Consistent efficacy: Not affected by CYP2C19 genetic polymorphisms that impact PPI effectiveness 2
• Longer duration of effect: Elimination half-life of approximately 7-8 hours 2
• Steady state achieved by day 3-4 with minimal accumulation (accumulation index <1.2) 2

Clinical Considerations and Limitations

• Cost considerations: Vonoprazan is significantly more expensive than standard and double-dose PPIs in the United States, which may limit its use as first-line therapy 1
• Safety profile: While short-term safety appears comparable to PPIs, long-term safety data are more limited 1, 6
• Gastrin elevation: Vonoprazan increases serum gastrin levels more than PPIs, which return to normal within 4 weeks of discontinuation 2
• ECL cell effects: Increased incidence of hyperplasia of parietal cells and G-cells observed with long-term use, though no neoplastic changes were observed in biopsies from patients treated for up to 260 weeks 2

Algorithm for Vonoprazan Use

1. For GERD patients:

   • Start with standard PPI therapy
   • If inadequate response, escalate to twice-daily PPI
   • Consider vonoprazan 20 mg daily only after failure of twice-daily PPI therapy 1, 4

2. For Peptic Ulcer Disease:

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

3. For patients with severe renal or hepatic impairment:

   • Consider dose reduction due to increased systemic exposure 2

Common Pitfalls to Avoid

• Prescribing vonoprazan as first-line therapy for mild GERD or PUD when PPIs would be more cost-effective 1
• Failing to consider the higher cost of vonoprazan compared to PPIs when making treatment decisions 1
• Overlooking the need for dose adjustments in patients with severe renal impairment or moderate-to-severe hepatic impairment 2
• Neglecting to monitor for potential long-term effects of sustained gastrin elevation 2