What is vonoprazan (proton pump inhibitor, PPI)?

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From the Guidelines

Vonoprazan should be used as a first-line treatment for Helicobacter pylori infections, particularly in cases where clarithromycin resistance is suspected, due to its superior eradication rates compared to traditional proton pump inhibitors (PPIs) 1.

Key Points

  • Vonoprazan is a potassium-competitive acid blocker (PCAB) that offers more rapid and profound acid suppression than PPIs.
  • Its efficacy is not altered by CYP2C19 polymorphisms, reducing inter-individual pharmacokinetic variation.
  • In clinical trials, vonoprazan has demonstrated 10%–20% higher eradication rates when used in first-line clarithromycin-based triple therapy for H. pylori infections, particularly in clarithromycin-resistant strains 1.
  • Preliminary evidence also suggests benefits in first- and second-line dual therapy with amoxicillin, with successful eradication approaching 95% and 90%, respectively, in a small study 1.

Clinical Use

  • The typical dosage of vonoprazan for H. pylori eradication is 20mg twice daily, combined with amoxicillin (1g twice daily) and clarithromycin (500mg twice daily) for 7-14 days.
  • Vonoprazan maintains consistent acid suppression throughout the day, making it effective regardless of meal timing.
  • Common side effects include headache, diarrhea, and nausea.

Recommendations

  • Vonoprazan should be considered as a first-line treatment option for H. pylori infections, especially in cases where clarithromycin resistance is suspected or confirmed 1.
  • Clinicians may also use vonoprazan in selected patients with documented acid-related reflux who fail therapy with twice-daily PPIs 1.
  • However, due to current costs and limited long-term safety data, vonoprazan should not be used as initial therapy for acid-related conditions in which clinical superiority has not been shown 1.

From the FDA Drug Label

12 CLINICAL PHARMACOLOGY

  1. 1 Mechanism of Action Vonoprazan suppresses basal and stimulated gastric acid secretion at the secretory surface of the gastric parietal cell through inhibition of the H+, K+-ATPase enzyme system in a potassium-competitive manner Because this enzyme is regarded as the acid (proton) pump within the parietal cell, vonoprazan has been characterized as a type of gastric proton-pump inhibitor, in that it blocks the final step of acid production. Vonoprazan does not require activation by acid. Vonoprazan may selectively concentrate in the parietal cells in both the resting and stimulated states. Vonoprazan binds to the active pumps in a noncovalent and reversible manner.
  • Mechanism of Action: Vonoprazan is a gastric proton-pump inhibitor that suppresses basal and stimulated gastric acid secretion by inhibiting the H+, K+-ATPase enzyme system in a potassium-competitive manner.
  • Key Characteristics:
    • Does not require activation by acid
    • May selectively concentrate in parietal cells
    • Binds to active pumps in a noncovalent and reversible manner
  • Clinical Implication: Vonoprazan's mechanism of action allows it to effectively block the final step of acid production, making it a potent inhibitor of gastric acid secretion 2.

From the Research

Vonoprazan Efficacy

  • Vonoprazan has been shown to be effective in treating patients with proton pump inhibitor (PPI)-refractory gastroesophageal reflux disease (GERD) 3.
  • It provides more potent gastric acid suppression, more effective esophageal acid exposure control, enhanced symptom improvement, and better esophagitis healing than PPIs 3.
  • The healing rate of GERD and gastric ulcers by vonoprazan is more than 95 and 90%, respectively 4.
  • Vonoprazan is also effective in curing PPI-resistant GERD and increases H. pylori eradication rate to more than 88% as part of both first-line and second-line therapy 4.

Vonoprazan Safety

  • Vonoprazan has been found to have a favorable safety profile, with adverse event rates similar to those of PPIs 5.
  • It is a safe option for the management of erosive oesophagitis, gastric/peptic ulcers, or peptic ulcers induced by chronic use of aspirin or NSAIDs 5.
  • Vonoprazan may also be considered for preventing aspirin- or non-steroidal anti-inflammatory drug-related peptic ulcer recurrence 6.
  • However, the use of vonoprazan is associated with more pronounced hypergastrinemia 7.

Vonoprazan Compared to PPIs

  • Vonoprazan has several advantages over conventional PPIs, including rapid onset of action, long duration of acid suppression, fewer interindividual variations in terms of acid suppression, and minimum dietary influence on its action 7.
  • Vonoprazan has been shown to be non-inferior to PPIs in healing and maintaining healed reflux oesophagitis, leading to faster symptom relief 6.
  • Vonoprazan may provide an excellent option for fulfilling some of the unmet needs for current GERD therapy 7.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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