Vonoprazan

MECHANISM OF ACTION

Vonoprazan inhibits gastric acid secretion by working as a potassium-competitive acid blocker (P-CAB). It concentrates in gastric parietal cells and reversibly binds to the potassium-binding site of the H+/K+-ATPase (proton pump). This binding prevents potassium ions from interacting with the proton pump, thereby blocking the final step in gastric acid production and leading to reduced acid secretion. 

PHARMACOKINETICS

Absorption

Vonoprazan is rapidly absorbed orally, with peak plasma levels reached within 1.5 to 2 hours, and its absorption is not significantly affected by food intake, allowing it to be taken with or without meals. This rapid and consistent absorption, coupled with a long elimination half-life of approximately 7 to 9 hours, contributes to its potent and sustained acid-suppressive effect, enabling once-daily dosing. 

Distribution

Vonoprazan has a large apparent volume of distribution, with reported values around 1050 L after a single dose and 782.7 L at steady state.

Metabolism

Vonoprazan is metabolized in the liver by a combination of enzymes, primarily CYP3A4 and to a lesser extent CYP2B6, CYP2C19, CYP2D6, and sulfotransferase (SULT2A1). This complex metabolic pathway, which includes oxidation and non-oxidative processes forming inactive metabolites like M-I and M-II, results in less dependency on CYP2C19 polymorphisms compared to traditional proton pump inhibitors (PPIs). Vonoprazan is excreted in urine and feces. 

Excretion

The main pathways for drug elimination are urine about 67% of the administered dose and feces about 31%. 

PHARMACODYNAMICS

Vonoprazan is a potassium-competitive acid blocker (P-CAB) that inhibits gastric acid secretion by reversibly and competitively binding to the potassium-binding site of the H+/K+-ATPase (proton pump) in gastric parietal cells. Its distinct mechanism of action offers several advantages over traditional proton pump inhibitors (PPIs). 

ADMINISTRATION

Vonoprazan should be taken by mouth with a glass of water. You may take it with or without food. Swallow the tablet whole do not chew or crush it.

DOSAGE AND STRENGTH

• Strengths: 10 mg and 20 mg tablets.

• Erosive Esophagitis (healing): 20 mg once daily for 8 weeks.

• Maintenance: 10 mg once daily (up to 6 months).

• H. pylori infection: 20 mg twice daily with antibiotics for 14 days.

• Dose adjustment: In severe liver or kidney problems – 10 mg once daily.

• Administration: Swallow whole with water; with or without food.

DRUG INTERACTIONS

Vonoprazan can interact with several medications. Because it increases stomach pH, it may reduce the absorption of drugs that need an acidic environment, such as ketoconazole, itraconazole, atazanavir, and nelfinavir. It also affects liver enzymes (CYP3A4 and CYP2C19), which can change the levels of other drugs that use these pathways. For example, strong CYP3A4 inducers (like rifampicin or carbamazepine) can lower vonoprazan levels, while strong inhibitors can increase them. Vonoprazan may also reduce the effectiveness of clopidogrel by decreasing its active metabolite formation. Patients should always inform their doctor or pharmacist about all medications they are taking to avoid possible interactions and ensure proper dose adjustments if needed.

FOOD INTERACTIONS

Vonoprazan can be taken with or without food, as food does not significantly affect its absorption or effectiveness. There are no major food interactions reported. However, it is best to take it at the same time each day for consistency. Avoid excessive alcohol consumption, as it may irritate the stomach and worsen acid-related symptoms.

CONTRAINDICATIONS

Vonoprazan is contraindicated in patients with hypersensitivity to the drug or its components. It should not be used in severe liver impairment or with drugs that require an acidic environment for absorption, such as atazanavir or nelfinavir. Use during pregnancy or breastfeeding only if clearly needed and prescribed by a doctor.

SIDE EFFECTS

• Stomach pain, inflammation, or bloating

• Diarrhea or constipation

• Nausea and vomiting

• Headache

• Indigestion (dyspepsia)

• High blood pressure (hypertension)

• Urinary tract infection (UTI)

• Altered sense of taste

• Common cold-like symptoms (nasopharyngitis)

• Vaginal itching or discharge

• Painful urination 

OVERDOSE

• Severe headache

• Dizziness or confusion

• Nausea and vomiting

• Abdominal pain or discomfort

• Diarrhea

• Fatigue or weakness

• Rapid heartbeat or palpitations

TOXICITY

Vonoprazan has a low potential for toxicity. In humans, overdose typically causes mild to moderate symptoms such as nausea, headache, and dizziness. Severe toxic effects are rare but may include electrolyte imbalances, liver enzyme elevations, or cardiac effects with very high doses. Animal studies suggest that high doses can cause mild gastrointestinal irritation and reversible liver changes. There is no specific antidote for vonoprazan toxicity, so treatment is supportive and based on symptoms, with monitoring of vital signs and electrolytes in severe cases.