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: Recommended Use and Dosage

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

Dosage Recommendations

• For erosive esophagitis treatment: Vonoprazan 20 mg once daily 1, 2
• For maintenance of healed erosive esophagitis: Vonoprazan 10 mg once daily 1, 2
• For non-erosive GERD: Vonoprazan 10 mg once daily 2
• For peptic ulcer disease: Vonoprazan 20 mg daily (after PPI failure) 1
• For ulcer prophylaxis in patients on low-dose aspirin or NSAIDs with history of PUD: Vonoprazan 10-20 mg daily 1

Treatment Algorithm for GERD

1. First-line therapy: Standard PPI therapy 1
2. Second-line therapy: Escalate to twice-daily PPI if inadequate response 1
3. Third-line therapy: Consider vonoprazan 20 mg daily only after failure of twice-daily PPI therapy 1

Treatment Algorithm for Peptic Ulcer Disease

1. First-line therapy: Standard PPI therapy 1
2. Second-line therapy: Vonoprazan 20 mg daily for PPI treatment failures 1
3. Special consideration: Consider vonoprazan for high-risk ulcer bleeding cases due to rapid and potent acid inhibition 1

Clinical Efficacy

• For peptic ulcer disease, 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
• Vonoprazan demonstrates superior efficacy for maintenance of healing in severe erosive esophagitis (LA grade C/D) compared to lansoprazole, with healing rates of 75-77% vs 62% 1
• For PPI-resistant erosive esophagitis, vonoprazan 20 mg shows healing rates of 91.7% at 4 weeks and 88.5% at 8 weeks 3
• Maintenance rates for healed PPI-resistant erosive esophagitis with vonoprazan 10 mg are 82.6% at week 8,86.0% at week 24, and 93.8% at week 48 3

Pharmacokinetic Considerations

• Vonoprazan reaches steady state concentrations by Day 3-4 2
• Food has minimal effect on absorption (5% increase in Cmax, 15% increase in AUC) 2
• Dose adjustments are recommended for patients with:
  • Severe renal impairment (eGFR 15 to <30 mL/min/1.73 m²): AUC is 2.4 times greater 2
  • Moderate hepatic impairment (Child-Pugh B): AUC is 2.4 times greater 2
  • Severe hepatic impairment (Child-Pugh C): AUC is 2.6 times greater 2

Advantages Over Traditional PPIs

• Vonoprazan provides more consistent acid suppression than PPIs, resulting in rapid and sustained symptom relief and mucosal healing 4, 5
• It is particularly effective for H. pylori-associated ulcers compared to idiopathic or NSAID-related ulcers 1
• Vonoprazan may be effective in curing PPI-resistant GERD 6, 3, 5

Common Pitfalls and Caveats

• Cost considerations: Vonoprazan is significantly more expensive than standard and double-dose PPIs in the United States, which limits its use as first-line therapy 1
• Limited long-term safety data: While short-term safety appears comparable to PPIs, long-term safety data are more limited 1
• Increased gastrin levels: Vonoprazan increases gastrin levels during treatment, which return to normal within 4 weeks of discontinuation 2
• Potential false positive results: Increased CgA levels may cause false positive results in diagnostic investigations for neuroendocrine tumors 2
• Enterochromaffin-like cell effects: An increase in the incidence of hyperplasia of the parietal cells and G-cells has been observed with vonoprazan treatment 2

Special Populations

• Erosive vs. non-erosive GERD: Vonoprazan achieves 100% improvement in erosive GERD and 83% in non-erosive GERD, with significantly higher resolution rates in erosive GERD (83% vs 28%) 6
• Elderly patients: No clinically meaningful differences in pharmacokinetics are predicted in patients 65 years of age and older compared to younger adults 2
• Sex, race, or ethnicity: No clinically significant differences in pharmacokinetics based on these factors 2