Introduction
Voquezna (vonoprazan) is a novel potassium-competitive acid blocker (P-CAB) approved for the treatment of acid-related disorders. Unlike traditional proton pump inhibitors (PPIs), which require acid activation and have delayed onset of action, Voquezna provides rapid, potent, and sustained acid suppression through a distinct mechanism of action.
Mechanism of Action
Voquezna exerts its pharmacological effects through competitive inhibition of the H+/K+-ATPase proton pump in gastric parietal cells. As a potassium-competitive acid blocker, it binds reversibly to the potassium-binding site of the proton pump, preventing the exchange of intracellular H+ ions for extracellular K+ ions. This mechanism allows for rapid inhibition of gastric acid secretion regardless of parietal cell activation status, providing more predictable acid suppression compared to PPIs.
Indications
- Erosive Esophagitis: Healing and maintenance of healing of erosive esophagitis
- Symptomatic Gastroesophageal Reflux Disease (GERD): Relief of heartburn symptoms
- Helicobacter pylori Eradication: Used in combination with antibiotics for H. pylori eradication therapy
Dosage and Administration
Standard Adult Dosing:- Erosive esophagitis healing: 20 mg orally once daily for up to 8 weeks
- Maintenance of healed erosive esophagitis: 10 mg orally once daily
- Symptomatic GERD: 10 mg orally once daily for 4 weeks
- H. pylori eradication: 20 mg orally twice daily with antibiotics (typically amoxicillin and clarithromycin) for 14 days
- Renal impairment: No dosage adjustment necessary
- Hepatic impairment: Use with caution in severe hepatic impairment
- Geriatric patients: No dosage adjustment required
- Pediatric patients: Safety and effectiveness not established
Pharmacokinetics
Absorption: Rapidly absorbed with peak plasma concentrations achieved within 1.5-2 hours. Bioavailability is approximately 85% and is not significantly affected by food. Distribution: Extensive protein binding (>99%), primarily to albumin. Volume of distribution is approximately 50 L. Metabolism: Primarily metabolized by CYP3A4 to inactive metabolites. Minor metabolism via CYP2B6, CYP2C19, and CYP2D6. Elimination: Primarily excreted in feces (∼60%) with renal excretion accounting for ∼40%. Elimination half-life is approximately 5-8 hours.Contraindications
- Hypersensitivity to vonoprazan or any component of the formulation
- Concomitant use with rilpivirine-containing products
- Patients taking drugs that are highly dependent on CYP3A4 for clearance and have narrow therapeutic indices
Warnings and Precautions
- Gastric Malignancy: Symptomatic response does not preclude presence of gastric malignancy
- Acute Tubulointerstitial Nephritis: May occur at any time during therapy; discontinue if diagnosed
- Clostridioides difficile-Associated Diarrhea: PPI therapy may increase risk
- Bone Fracture: Long-term therapy may be associated with increased risk of osteoporosis-related fractures
- Hypomagnesemia: Reported with prolonged PPI use; monitor magnesium levels
- Vitamin B12 Deficiency: Long-term use may reduce vitamin B12 absorption
Drug Interactions
Significant Interactions:- CYP3A4 Inhibitors (ketoconazole, clarithromycin): May increase vonoprazan exposure
- CYP3A4 Inducers (rifampin, St. John's wort): May decrease vonoprazan efficacy
- Drugs dependent on gastric pH for absorption (ketoconazole, iron salts, digoxin): May have reduced absorption
- Warfarin: Monitor INR due to potential interaction
- Methotrexate: May increase methotrexate levels
Adverse Effects
Common (≥2%):- Diarrhea (5%)
- Abdominal pain (3%)
- Nausea (2%)
- Flatulence (2%)
- Headache (2%)
- Acute tubulointerstitial nephritis
- Clostridioides difficile infection
- Severe cutaneous adverse reactions
- Hypomagnesemia
- Vitamin B12 deficiency
Monitoring Parameters
- Symptom improvement and resolution
- Endoscopic healing in erosive esophagitis (if indicated)
- Serum magnesium levels (with prolonged therapy)
- Vitamin B12 levels (with long-term use)
- Renal function tests
- Signs and symptoms of gastrointestinal infection
- Bone density assessment (with long-term therapy in at-risk patients)
Patient Education
- Take medication as prescribed, typically before a meal
- Do not crush or chew tablets; swallow whole
- Inform healthcare provider of all medications being taken, including over-the-counter products
- Report any signs of allergic reaction (rash, itching, swelling)
- Notify provider if symptoms do not improve or worsen
- Report persistent diarrhea, abdominal pain, or bloody stools
- Discuss duration of therapy with healthcare provider; do not use longer than recommended
- Maintain regular follow-up appointments for monitoring
References
1. Echizen H. The first-in-class potassium-competitive acid blocker, vonoprazan fumarate: Pharmacokinetic and pharmacodynamic considerations. Clin Pharmacokinet. 2018;57(4):409-418.
2. Graham DY, Dore MP. Update on the use of vonoprazan: a competitive acid blocker. Gastroenterology. 2018;154(3):462-466.
3. FDA Prescribing Information: Voquezna (vonoprazan). 2022.
4. Ashida K, Sakurai Y, Nishimura A, 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.
5. Maruyama M, Tanaka T, Fujisawa T, et al. Vonoprazan-based triple therapy is effective for Helicobacter pylori eradication irrespective of clarithromycin susceptibility. J Gastroenterol. 2020;55(11):1054-1061.
6. 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.
This monograph is for educational purposes only and should not replace professional medical advice. Always consult with a qualified healthcare provider for medical guidance.