Vonoprazan

Vonoprazan is a Potassium- competitive acid blocker (PCAB) belonging toAnti-ulcer agent.

Vonoprazan is a potassium-competitive acid blocker used in the treatment of acid-related disorders and as an adjunct to Helicobacter pylori eradication.

Rapidly absorbed from the gastrointestinal tract. The Time to peak plasma concentration is about 1-3 hours (fasted state) and 1-4 hours (after meal).The Plasma protein-binding is about 85.2-88%.Vonoprazan metabolized in the liver mainly by CYP3A4 isoenzyme and partially by CYP2B6, CYP2C19 and CYP2D6 isoenzymes to inactive metabolites.Via urine (67.4%); faeces (31.1%). The Elimination half-life is about 7.7 ± 1 hours (fasted state); 7.7 ± 1.2 hours (after meal).

Vonoprazan shows common side effects like Diarrhea, stomach pain, change in ability to taste food, headache, sore throat, vaginal itching and/or discharge.

Vonoprazan is available in the form of Oral Tablet.

Vonoprazan is available in India, US, Europe, China, Switzerland, Malaysia, France, Russia, Japan.

Vonoprazan is an Anti-ulcer agent belonging to the class Potassium- competitive acid blocker (PCAB).

Vonoprazan is a potassium-competitive acid blocker (PCAB) that inhibits the H⁺, K⁺-ATPase enzyme system in a potassium-competitive manner. Through this mechanism, vonoprazan suppresses basal and stimulated gastric acid secretion at the secretory surface of gastric parietal cells.Although both classes of drugs inhibit the H⁺, K⁺-ATPase, the mechanism of action of PCABs differs from that of proton-pump inhibitors (PPIs). PPIs form a covalent disulphide bond with a cysteine residue on the H⁺, K⁺-ATPase, which leads to the inactivation of the enzyme, while PCABs interfere with the binding of K⁺ to the H⁺, K⁺-ATPase.

The Data of Onset and Duration of action of Vonoprazan clinically not established.

The Tmax was found to be approximately 1-3 hours (fasted state) and 1-4 hours (after meal).

Vonoprazan is available in the form of Oral Tablet.

Vonoprazan Tablet is taken orally usually, once, or twice a daily.

Vonoprazan, clarithromycin, and amoxicillin are used to treat and prevent the return of ulcers (sores in the lining of the stomach or intestine) caused by a certain type of bacteria (H. pylori). Vonoprazan is in a class of medications called potassium-competitive acid blockers (PCAB).

Vonoprazan is a Potassium- competitive acid blocker (PCAB) belonging to Anti-ulcer agent.

Vonoprazan is a potassium-competitive acid blocker (PCAB). It competitively inhibits the binding of K ions to hydrogen/potassium-adenosine triphosphate (H⁺/K⁺-ATPase) enzyme system that acts as the proton pump of the gastric parietal cell, thereby inhibiting gastric acid production.

Vonoprazan is approved for use in the following clinical indications

• Reflux oesophagitis
• Gastric ulcer
• Prophylaxis of NSAID-induced ulcers
• Duodenal ulcer
• Eradication of H. pylori associated with peptic ulcer disease

• Reflux oesophagitis

Adult: 20 mg once daily for 4 weeks, may be followed by a further 4 weeks if necessary. Maintenance therapy of healing in patients with repeat recurrence or relapse: 10 mg once daily, may be increased to 20 mg once daily if needed.

• Gastric ulcer

Adult: 20 mg once daily for 8 weeks.

• Prophylaxis of NSAID-induced ulcers

Adult: Including cases that occur during low-dose aspirin therapy: 10 mg once daily.

• Duodenal ulcer

Adult: 20 mg once daily for 6 weeks.

• Eradication of H. pylori associated with peptic ulcer disease

Adult: Adjunct in the triple therapy regimen with antibiotics: 20 mg twice a day for 7 days in combination with amoxicillin and clarithromycin. Alternatively, 20 mg twice a day may be given for 7 days in combination with amoxicillin and metronidazole.

Vonoprazan is available in various strengths as 10mg and 20mg.

Vonoprazan is available in the form of Oral Tablet.

Avoid High-fat meals, it may decrease the absorption of vonoprazan.

Vonoprazan is contraindicated in patients with

• Hypersensitivity

• Common

Clostridioides difficile-associated infection, pseudomembranous colitis, increased intragastric pH, benign gastric polyps (prolonged use); increased risk of hip, spine, or wrist osteoporosis-related fractures (long-term use or high doses); hepatic function abnormalities, including liver injury, hypomagnesaemia (prolonged use), Diarrhoea, constipation, nausea, abdominal distention or discomfort, stomatitis, taste abnormality, Jaundice, Hypersensitivity reactions (e.g. urticaria, anaphylactic shock), Increased AST, ALT, and gamma-glutamyl transferase, Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis, drug eruption.

• Vonoprazan may increase blood concentration with CYP3A4 inhibitors (e.g. clarithromycin) and amoxicillin in the triple treatment for H. pylori eradication.
• Vonoprazan enhances the effects of digoxin and methyldigoxin.
• Vonoprazan diminishes the effects of nelfinavir, itraconazole, and tyrosine kinase inhibitors (e.g. gefitinib, nilotinib).
• It significantly decreases the blood concentrations of atazanavir and rilpivirine.

The common side effectsof Vonoprazan include the following

• Common side effects

Diarrhea, stomach pain, change in ability to taste food, headache, sore throat, vaginal itching and/or discharge.

• Pregnancy

Pregnancy Category

No clinical studies have been conducted to date to evaluate vonoprazan in subjects who are pregnant. In a rat toxicology study, embryo-foetal toxicity was observed following exposure of more than approximately 28 times of the exposure (AUC) at the maximum clinical dose (40 mg/day) of vonoprazan. As a precaution, vonoprazan should not be administered to women who are or may be pregnant, unless the expected therapeutic benefit is thought to outweigh any possible risk.

• Nursing Mothers

No clinical studies have been conducted to date to evaluate vonoprazan in subjects who are lactating. It is unknown whether vonoprazan is excreted in human milk. In animal studies it has been shown that vonoprazan was excreted in milk. During treatment with vonoprazan, nursing should be avoided if the administration of this drug is necessary for the mother.

• Pediatric Use

Vonoprazan has not been studied in patients under 18 years of age.

There is no experience of overdose with vonoprazan. Vonoprazan is not removed from the circulation by hemodialysis. If overdose occurs, treatment should be symptomatic and supportive.

• Pharmacodynamic

The use of vonoprazan leads to an increase in intragastric pH. The inhibitory effect of vonoprazan on acid secretion increases with repeated daily dosing. Although the antisecretory effect of vonoprazan decreases after drug discontinuation, intragastric pH remains elevated for 24 to 48 hours. Vonoprazan does not have a clinically significant effect on QT prolongation. Compared to other potassium-competitive acid blockers (PCABs), vonoprazan has a higher point-positive charge (pKa of 9.06). This allows vonoprazan to accumulate at higher concentrations in the canalicular space of the gastric parietal cells, where it binds H⁺, K⁺-ATPase in a K⁺-competitive and reversible manner. Compared to other PCABs, such as SCH28080, or proton-pump inhibitors, such as lansoprazole, vonoprazan has a more potent H⁺, K⁺-ATPase inhibitory activity.

• Pharmacokinetics

Absorption

Rapidly absorbed from the gastrointestinal tract. The Time to peak plasma concentration is about 1-3 hours (fasted state) and 1-4 hours (after meal).

Distribution

The Plasma protein-binding is about 85.2-88%.

Metabolism and Excretion

Vonoprazan metabolized in the liver mainly by CYP3A4 isoenzyme and partially by CYP2B6, CYP2C19 and CYP2D6 isoenzymes to inactive metabolites. Via urine (67.4%); faeces (31.1%). Elimination half-life: 7.7 ± 1 hours (fasted state); 7.7 ± 1.2 hours (after meal).

• https://go.drugbank.com/drugs/DB11739
• https://www.mims.com/malaysia/drug/info/vonoprazan?mtype=generic
• https://medlineplus.gov/druginfo/meds/a622051.html#precautions
• https://www.drugs.com/history/vonoprazan.html
• https://www.mims.com/malaysia/drug/info/vocinti/contraindications
• https://www.webmd.com/drugs/2/drug-184084/vonoprazan-amoxicillin-oral/details