Usage
Vonoprazan is prescribed for the treatment of:
- Erosive esophagitis (damage to the esophagus caused by stomach acid)
- Gastroesophageal reflux disease (GERD)
- Gastric ulcer
- Duodenal ulcer
- Helicobacter pylori infection (in combination with antibiotics)
- Prevention of recurrence of gastric or duodenal ulcer during NSAID (including low-dose aspirin) administration.
It is classified as a potassium-competitive acid blocker (P-CAB). Vonoprazan works by blocking the H+, K+-ATPase enzyme system (proton pump) in the stomach, thereby reducing gastric acid production.
Alternate Names
Vonoprazan fumarate is the chemical name. It is marketed under various brand names including Voquezna, Takecab, Vonoprazan Fumarate, Vonozan and Vonospire.
How It Works
Pharmacodynamics: Vonoprazan competitively inhibits the binding of potassium ions to the H+, K+-ATPase enzyme on the secretory surface of gastric parietal cells. This action blocks the final step of acid secretion, effectively reducing both basal and stimulated gastric acid production. Unlike proton pump inhibitors (PPIs), vonoprazan doesn’t require acid activation and exhibits a rapid onset of action. This leads to faster and more sustained acid suppression.
Pharmacokinetics:
- Absorption: Well-absorbed orally.
- Metabolism: Primarily metabolized by CYP3A4, CYP2C19, and CYP2B6 enzymes in the liver.
- Elimination: Excreted through both renal and hepatic pathways (urine and bile). Steady state is reached by day 3 of administration.
Mode of Action: Vonoprazan is a potassium-competitive acid blocker. This means it binds directly to the potassium-binding site of the H+,K+-ATPase, inhibiting the enzyme’s ability to transport protons into the stomach lumen and thus reducing acid secretion. This binding is reversible, non-covalent and doesn’t require acid activation.
Dosage
Standard Dosage
Adults:
- Erosive Esophagitis: 20 mg once daily for up to 8 weeks for healing; 10 mg once daily for up to 6 months for maintenance.
- GERD (Non-Erosive): 10 mg once daily for up to 4 weeks.
- Gastric Ulcer: 20 mg once daily for 8 weeks.
- Duodenal Ulcer: 20 mg once daily for 6 weeks.
- H. pylori Eradication: 20 mg twice daily for 7 days, combined with amoxicillin (with or without clarithromycin or metronidazole).
- NSAID-induced Ulcer Prevention (including low-dose aspirin): 10 mg once daily.
Children:
Safety and effectiveness in children have not been established.
Special Cases:
- Elderly Patients: Administer with caution due to potential age-related decline in hepatic and renal function.
- Patients with Renal Impairment: Dose reduction to 10 mg once daily for severe renal impairment (eGFR < 30 mL/min) when treating erosive esophagitis. Not recommended for H. pylori treatment if eGFR < 30 mL/min.
- Patients with Hepatic Dysfunction: Dose reduction to 10 mg once daily is recommended in moderate to severe hepatic impairment (Child-Pugh B or C) when treating erosive esophagitis. Not recommended for H. pylori treatment if Child-Pugh B or C.
- Patients with Comorbid Conditions: Exercise caution in patients with a history of osteoporosis.
Clinical Use Cases
Dosage guidelines provided above generally apply to the listed clinical settings, including intubation, surgical procedures, mechanical ventilation, ICU use, and emergency situations. Dose adjustments may be necessary based on specific patient circumstances and concomitant medications.
Dosage Adjustments
See “Special Cases” section above.
Side Effects
Common Side Effects:
- Diarrhea
- Headache
- Nausea
- Abdominal pain
- Constipation
- Upper respiratory tract infection
Rare but Serious Side Effects:
- Severe allergic reactions (rash, hives, itching, swelling, difficulty breathing)
- Clostridium difficile-associated diarrhea
- Liver injury
- Hypomagnesemia
- Stevens-Johnson syndrome/toxic epidermal necrolysis
- Severe cutaneous adverse reactions (SCARs)
Long-Term Effects:
- Vitamin B12 deficiency
- Increased risk of infections (e.g., pneumonia)
- Increased risk of bone fractures (with prolonged use or high doses)
- Gastric polyps
Adverse Drug Reactions (ADR):
See “Rare but Serious Side Effects”
Contraindications
- Hypersensitivity to vonoprazan
- Concomitant use with rilpivirine, atazanavir, and nelfinavir
Drug Interactions
Vonoprazan is metabolized by CYP enzymes and can interact with numerous medications:
- CYP3A4 Inhibitors: (e.g., clarithromycin, ketoconazole, itraconazole) can increase vonoprazan levels.
- CYP3A4 Inducers: (e.g., rifampin, phenytoin, St. John’s wort) can decrease vonoprazan levels.
- Other: Metoclopramide may enhance vonoprazan absorption.
Consult a comprehensive drug interaction resource for detailed information.
Pregnancy and Breastfeeding
- Pregnancy: No adequate and well-controlled studies in pregnant women. Use only if potential benefit outweighs risk.
- Breastfeeding: Not recommended. Advise patients to discontinue breastfeeding or pump and discard milk during treatment and for 2 days after the final dose.
Drug Profile Summary
- Mechanism of Action: Potassium-competitive acid blocker (P-CAB), inhibits H+, K+-ATPase.
- Side Effects: Diarrhea, headache, nausea, abdominal pain, constipation; rarely liver injury, severe allergic reactions.
- Contraindications: Hypersensitivity, concomitant use with rilpivirine.
- Drug Interactions: CYP3A4 inhibitors/inducers, metoclopramide.
- Pregnancy & Breastfeeding: Not recommended for either.
- Dosage: Varies based on indication; usually 10-20 mg once or twice daily.
- Monitoring Parameters: Liver function tests, magnesium levels (for long-term use).
Popular Combinations
- Vonoprazan + amoxicillin
- Vonoprazan + amoxicillin + clarithromycin
- Vonoprazan + amoxicillin + metronidazole
Precautions
See “Special Cases,” “Drug Interactions,” and “Pregnancy and Breastfeeding” sections. Monitor for signs of liver injury, hypomagnesemia, and C. difficile infection. Screen patients for osteoporosis risk factors, especially with long-term use.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Vonoprazan?
A: It varies depending on the indication. See “Dosage” section above for detailed information.
Q2: How does Vonoprazan differ from PPIs?
A: Vonoprazan offers faster onset, longer duration of action, and doesn’t require acid activation, unlike PPIs.
Q3: What are the most serious side effects of Vonoprazan?
A: Severe allergic reactions, C. difficile infection, liver injury, hypomagnesemia, and severe cutaneous adverse reactions (SCARs).
Q4: Can Vonoprazan be used during pregnancy or breastfeeding?
A: It’s not recommended for either. Consult “Pregnancy and Breastfeeding” section.
Q5: What are the common drug interactions with Vonoprazan?
A: Mainly CYP3A4 inhibitors and inducers. Refer to “Drug Interactions” section and a comprehensive drug interaction checker.
Q6: What should I monitor in patients on long-term Vonoprazan therapy?
A: Monitor liver function, magnesium levels, and assess for signs of C. difficile infection and bone density changes.
Q7: Can Vonoprazan be crushed or chewed?
A: No, the tablets should be swallowed whole.
Q8: Does Vonoprazan interact with food?
A: No, it can be taken with or without food.
Q9: How long does it take for Vonoprazan to reach steady-state levels?
A: Approximately 3 days.
Q10: Can Vonoprazan be used in patients with renal impairment?
A: Use cautiously. Dose adjustments might be needed. See “Dosage - Special Cases.”
