VONOPRAZON

https://meditropics.com/1472-2/

*Prerna Nagare

*Post Graduate Resident, Department of Medicine, LHMC

 

INTRODUCTION
Gastro esophageal reflux diseases and H. Pylori-induced duodenal and gastric ulcers are some of the most prevalent medical conditions worldwide, with a prevalence rate reported to be 10–20%. Most of the patients affected with H. Pylori have no symptoms, but the infection can lead to peptic ulcers, MALToma and adenocarcinoma of the stomach. Chronic untreated reflux diseases can cause a variety of conditions including esophagitis, Barrett’s esophagus, esophageal carcinoma, gastric ulcers, and even life-threatening esophageal and gastric perforation. Studies have shown that these complications can be avoided or minimized by agents that work by neutralizing the acidic pH of the stomach.

Different classes of medications are used to decrease the gastric pH including Proton pump inhibitors (PPIs), H2 Histamine blockers, antacids etc. The most commonly used among these are PPIs, which are also a part of combination drugs used for H. Pylori eradication therapy. However, up to 40% of people with gastro esophageal reflux diseases have reported at least some resistance to conventional PPI therapy. The mechanisms of this resistance are thought to be poor control of gastric acid secretion, esophageal hypersensitivity, and changes in the esophageal epithelium. Recently, a new drug, Vonoprazan (aka TAK-438), has been approved for clinical use in Japan to reduce intragastric pH. VPZ is a potassium-competitive acid blocker (P-CAB) which works by inhibiting potassium ion binding to the H+/K + -ATPase channel in the gastric parietal cells. VPZ appears to be superior to PPIs in the sense that VPZ does not depend upon gastric acid activation to inhibit acid secretion and has a longer half-life.

Recent literature has reported that the rate of gastro esophageal reflux disease treatment and H. Pylori eradication is higher with VPZ as compared to conventional PPI therapy. So the use of vonoprazan should be preferred over conventional therapy of PPIs used in gastrointestinal reflux diseases and eradication of H. Pylori.

INDICATIONS AND USAGE

  1. For healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.
  2. To maintain healing of all grades of erosive esophagitis and relief of heartburn associated with erosive esophagitis in adults.
  3. For the relief of heartburn associated with non-erosive gastro esophageal reflux disease in adults.
  4. In combination with amoxicillin and clarithromycin for the treatment of Helicobacter pylori (H. pylori) infection in adults.

MECHANISM OF ACTION

  • Competitively inhibiting potassium channels in parietal cells ( potassium-competitive acid blocker (P-CAB)
  • Reducing gastric acid secretion thereby Increasing gastric pH

 This mechanism differs from:

  • Proton pump inhibitors (PPIs), which block the hydrogen-potassium ATPase enzyme
  • Histamine-2 receptor antagonists (H2RAs), which reduce histamine-stimulated acid secretion

 

PHARMACOKINETICS
Absorption: Rapidly absorbed, with peak plasma concentrations within 2-4 hours
Distribution: Extensive distribution, with high concentrations in gastric mucosa
Metabolism: Vonoprazan is metabolized to inactive metabolites via multiple pathways by a combination of cytochrome P450 (CYP) isoforms (CYP3A4/5, CYP2B6, CYP2C19, CYP2C9, and CYP2D6) along with sulfo- and glucuronosyl-transferases.
Elimination: Following oral administration of radiolabeled vonoprazan, approximately 67% of the radiolabeled dose (8% as unchanged vonoprazan) was recovered in urine, and 31% (1.4% as unchanged vonoprazan) was recovered in feces.

ADVERSE EFFECTS

  • Common Adverse Reactions : Abdominal pain, Diarrhea, Taste sense altered, headache, and Candida vaginitis.
  • Severe/rare adverse Reactions 

Cardiovascular: Prolonged QT interval, Torsades de pointes.

Dermatologic:  Stevens-Johnson syndrome, Toxic epidermal necrolysis.

Gastrointestinal: Clostridioides difficile infection.

Hepatic: Cholestatic hepatitis, Hepatocellular liver damage, Increased liver enzymes, Liver failure.

Immunologic:  Anaphylaxis, Drug reaction with eosinophilia and systemic symptoms, Hypersensitivity reaction.

Neurologic: Myasthenia gravis

CONTRAINDICATIONS

  • Hypersensitivity to vonoprazan or any component of formulation
  • Concomitant use with rilpivirine-containing products.
  • Concomitant use with the following lipid-lowering agents: Lomitapide, simvastatin, and lovastatin.
  • Concomitant use with colchicine in patients with renal or hepatic impairment. History of hepatic dysfunction associated with prior use of clarithromycin.
  • Cardiovascular: Avoid use in patients with known prolongation of QT interval, ventricular cardiac arrhythmia (including torsades de pointes)

DOSAGE AND ADMINISTRATION

Route of Administration: oral.

Dosage Forms: Oral tablet.

DOSING

  • Healing of Erosive Esophagitis: 20 mg once daily for 8 weeks.
  • Maintenance of Healed Erosive Esophagitis: 10 mg once daily for up to 6 months.
  • Relief of Heartburn Associated with Non-Erosive Gastroesophageal Reflux Disease: 10 mg once daily for 4 weeks.
  • Treatment of H. pylori Infection: 20 mg twise daily as part of appropriate regimen for 14 days.

References

  1. VOQUEZNA (Vonoprazan)[prescribing information]. Buffalo Grove, IL :Phathom Pharmaceuticals Inc;july 2024
  2. Shehryar M, Ahmad RU, Kareem HK, Khan L, Ashraf MF, Hassan A, Saeed S, Tareen HK, Nazir DA, Ashraf MA. Efficacy, safety and cost-effectiveness of vonoprazan vs Proton Pump Inhibitors in reflux disorders and H. pylori eradication: A literature review. Ann Med Surg (Lond). 2022 Sep 22; 82:104760. doi: 10.1016/j.amsu.2022.104760. PMID: 36268393; PMCID: PMC9577871.
  3. Akiyama J, Hosaka H, Kuribayashi S, Moriyasu S, Hisada Y, Okubo H, Watanabe K, Imbe K, Nagata N, Kojima Y, Yokoi C, Uemura N, Shimoyama Y, Kawamura O, Yamada M, Kusano M. Efficacy of Vonoprazan, a Novel Potassium-Competitive Acid Blocker, in Patients with Proton Pump Inhibitor-Refractory Acid Reflux. Digestion. 2020; 101(2):174-183. doi: 10.1159/000497775. Epub 2019 Mar 21. PMID: 30897577.
  4. Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomized, doubleblind study. Gut. 2016; 65(9):1439-46. doi: 10.1136/ gutjnl-2015-311304, PMID 26935876.
    5. Kondo, Y., et al. (2020). Vonoprazan, a novel potassium-competitive acid blocker, for the treatment of gastroesophageal reflux disease. Journal of Clinical Gastroenterology, 54(8), 553-562.
    6. Sakai, T., et al. (2020). Pharmacokinetics and pharmacodynamics of vonoprazan in healthy subjects. European Journal of Clinical Pharmacology, 76(11), 1531-1538.
    7. FDA. (2022). Vonoprazan. FDA Approval Package.