Vonoprazan - Drug Monograph

Introduction

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) that represents a significant advancement in acid suppression therapy. Approved in Japan in 2015 and subsequently in other countries, it offers a distinct mechanism from traditional proton pump inhibitors (PPIs) with potentially superior acid control characteristics. This first-in-class medication provides rapid, potent, and sustained suppression of gastric acid secretion.

Mechanism of Action

Vonoprazan exerts its therapeutic effect through competitive inhibition of the H+/K+-ATPase (proton pump) in gastric parietal cells. Unlike PPIs that require acid activation and covalent binding to the proton pump, vonoprazan is acid-stable and reversibly binds to the potassium site of the proton pump. This mechanism allows for:

• Rapid onset of action (within hours)
• Consistent acid suppression regardless of food intake
• Sustained 24-hour acid control due to its long half-life
• More complete and predictable inhibition of both basal and stimulated acid secretion

Indications

Vonoprazan is approved for:

• Healing of gastric ulcers
• Healing of duodenal ulcers
• Eradication of Helicobacter pylori (in combination with antibiotics)
• Treatment and maintenance of erosive esophagitis
• Prevention of recurrence of gastric and duodenal ulcers
• Treatment of gastric hypersecretory conditions including Zollinger-Ellison syndrome

Dosage and Administration

• Gastric/duodenal ulcer: 20 mg once daily
• H. pylori eradication: 20 mg twice daily with appropriate antibiotics
• Erosive esophagitis: 20 mg once daily
• Maintenance therapy: 10 mg once daily

• Oral administration with or without food
• Tablets should be swallowed whole with water

• Renal impairment: No dose adjustment required
• Hepatic impairment: Use with caution in severe impairment
• Elderly: No dose adjustment required
• Pediatrics: Safety and efficacy not established

Pharmacokinetics

Contraindications

• Hypersensitivity to vonoprazan or any component of the formulation
• Concomitant use with rilpivirine-containing products
• Patients taking atazanavir due to significant interaction potential

Warnings and Precautions

• Gastric malignancy: Exclude malignancy before treatment as symptom relief may delay diagnosis
• Clostridium difficile-associated diarrhea: Reported with acid-suppressing agents
• Bone fracture: Long-term therapy may be associated with increased risk of hip, wrist, and spine fractures
• Hypomagnesemia: Reported with prolonged treatment; monitor magnesium levels
• Acute interstitial nephritis: Has been observed with PPIs; monitor renal function
• Cutaneous and systemic lupus erythematosus: Exacerbations reported with acid suppressants
• Vitamin B12 deficiency: Long-term use may reduce absorption

Drug Interactions

• CYP3A4 substrates: May increase concentrations of drugs metabolized by CYP3A4 (e.g., atazanavir, rilpivirine, saquinavir)
• CYP2C19 substrates: Minimal effect due to non-CYP2C19 dependent metabolism
• Drugs requiring gastric acid for absorption: May reduce absorption (e.g., ketoconazole, iron salts, dabigatran)

• Methotrexate: May increase methotrexate levels
• Digoxin: May increase digoxin absorption
• Tacrolimus: Possible increased tacrolimus exposure

Adverse Effects

• Diarrhea (3.2%)
• Nausea (1.5%)
• Abdominal distension (1.2%)
• Constipation (1.1%)

• Headache
• Rash
• Increased liver enzymes
• Hypergastrinemia

• Acute interstitial nephritis
• Clostridium difficile infection
• Hypomagnesemia
• Severe cutaneous adverse reactions

Monitoring Parameters

• Efficacy: Symptom improvement, endoscopic healing when indicated
• Safety: Renal function (BUN, creatinine), magnesium levels with long-term use
• Periodic assessment: Need for continued therapy (lowest effective dose)
• Nutritional status: Vitamin B12 levels with prolonged therapy
• Bone health: Consider bone density monitoring with long-term use in at-risk patients

Patient Education

• Take medication as prescribed, typically once daily
• May take with or without food
• Report any signs of allergic reaction (rash, swelling, difficulty breathing)
• Inform healthcare providers of all medications being taken
• Report persistent diarrhea, abdominal pain, or bloody stools
• Long-term use may require periodic monitoring of magnesium and vitamin B12 levels
• Do not crush or chew tablets
• Report any new or worsening symptoms promptly

References

1. Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: Pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. 2016;55(4):409-418.

2. Kagami T, Sahara S, Ichikawa H, et al. Potent acid inhibition by vonoprazan in comparison with esomeprazole, with reference to CYP2C19 genotype. Aliment Pharmacol Ther. 2016;43(10):1048-1059.

3. Ashida K, Sakurai Y, Hori T, et al. Randomised clinical trial: vonoprazan, a novel potassium-competitive acid blocker, vs. lansoprazole for the healing of erosive oesophagitis. Aliment Pharmacol Ther. 2016;43(2):240-251.

4. Jenkins H, Sakurai Y, Nishimura A, et al. Randomised clinical trial: safety, tolerability, pharmacokinetics and pharmacodynamics of repeated doses of vonoprazan (TAK-438) in healthy male subjects. Aliment Pharmacol Ther. 2015;41(9):836-846.

5. Maruyama M, Tanaka T, So S, et al. Efficacy and safety of vonoprazan in patients with nonerosive gastroesophageal reflux disease: a randomized, placebo-controlled, phase 3 study. Clin Transl Gastroenterol. 2021;12(12):e00422.

6. vonoprazan prescribing information. Revised January 2023.