VONOCID-20

Indications

• Gastroesophageal reflux disease (GERD)
• Peptic ulcers
• Zollinger-Ellison syndrome
• H. pylori eradication therapy

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines for paediatric patients.

Adults: Refer to the BNF for specific dosing guidelines for adults.

Mechanism of action

Vonoprazan inhibits the H+, K+-ATPase enzyme system in a potassium-competitive manner, suppressing both basal and stimulated gastric acid secretion. Unlike PPIs that form a covalent bond with the enzyme, vonoprazan interferes with the binding of potassium, enabling a different approach to acid inhibition.

Pharmacodynamics

The use of vonoprazan results in an increased intragastric pH, enhancing the antisecretory effect with continued daily dosing. After discontinuation, intragastric pH remains elevated for 24 to 48 hours. Vonoprazan does not significantly affect QT prolongation and is more potent than other PCABs and PPIs in inhibiting H+, K+-ATPase due to its higher point-positive charge (pKa of 9.06), allowing for greater accumulation in the gastric canalicular space.

Pharmacokinetics

Vonoprazan is rapidly absorbed with peak plasma concentrations occurring within 1 to 2 hours post-dose. It is extensively metabolized in the liver, primarily via cytochrome P450 enzymes. The elimination half-life ranges from 5 to 10 hours, and the drug is primarily excreted in urine as metabolites.

Adverse effects

• Headache
• Diarrhea
• Nausea
• Vomiting
• Abdominal pain
• Fatigue
• Constipation

Precautions

• Use with caution in patients with hepatic impairment
• Monitor for potential interactions with other medications that affect gastric pH

Pregnancy

There is limited data on the use of vonoprazan in pregnancy. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

It is not known whether vonoprazan is excreted in human milk. Use caution when administering to nursing mothers.

Storage

Store in a cool, dry place, away from light. Keep out of reach of children.

Formulations

• Tablets

Mechanism of action

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.

Pharmacodynamics

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.