Vonoprazan
Vonoprazan
Generic Name
Vonoprazan
Mechanism
- Potassium‑competitive ATPase inhibition:
- Binds the *cytoplasmic* H⁺/K⁺ ATPase (proton pump) in the gastric parietal cell, competing with K⁺ rather than proton, leading to rapid, reversible inhibition.
- Works in a *non‑acid‑dependent* fashion—effective even when luminal pH is low, unlike proton‑pump inhibitors (PPIs) that require activation in an acidic microenvironment.
- Superior pharmacodynamic profile:
- Achieves >99 % acid suppression within 1 h and maintains this suppression for >24 h, allowing once‑daily dosing.
- Maintains activity over a wide pH range (1–7), making it less susceptible to food‑related variations in absorption.
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Pharmacokinetics
| Parameter | Typical Value | Notes |
| Absorption | Rapid; Tmax 1.5 h (fasting) | F ~25 %; food delays but does not obstruct absorption. |
| Bioavailability | 20–25 % | Low, but clinically adequate due to high potency. |
| Protein binding | 94 % | Primarily albumin; little interaction with weakly bound drugs. |
| Metabolism | Cytochrome P450 3A4 (CYP3A4) path | Minor CYP2B6 contribution; reduced by strong CYP3A4 inhibitors. |
| Half‑life | 7–9 h (single‑dose) | 4–5 h in hepatically impaired patients. |
| Elimination | 67 % hepatic, 32 % renal | Urinary excretion largely of unchanged drug and metabolites. |
| Food effect | Minimal | Excellent for outpatient use. |
| Special populations |
• Elderly: no dose adjustment required. • Renal impairment: no dose adjustment. • Hepatic impairment: dose reduction 50 % when Child‑Pugh B, 40 % for C. |
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Indications
- GERD (moderate–severe symptomatic disease, erosive esophagitis, or refractory PPI use).
- Peptic ulcer disease (both gastric and duodenal ulcer healing and maintenance).
- Helicobacter pylori eradication
- Triple therapy (vonoprazan + clarithromycin + metronidazole) or quadruple therapy (versus standard PPI‑based regimens).
- Prevention of NSAID‑associated ulcers (especially in high‑risk patients).
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Contraindications
| Category | Key Points |
| Contraindications | • Known hypersensitivity to vonoprazan or its excipients. |
| Warnings |
• Use with caution in patients with severe hepatic impairment. • Drug interactions: potent CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin) may increase exposure; potent inducers (rifampin, carbamazepine) may reduce efficacy. • Clopidogrel: co‑administration may reduce clopidogrel's antiplatelet effect. • S-adenosylmethionine (SAMe) deficiency borderline risk—monitor for hepatic decompensation. |
| Not indicated | • Pediatric patients <18 yrs (insufficient data). |
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Dosing
- Adults
- *GERD, ulcer, and H. pylori*: 20 mg oral once daily (QD).
- *H. pylori combination therapy* (triple therapy): 20 mg QD + clarithromycin 500 mg BID + amoxicillin 1000 mg BID (or metronidazole 500 mg BID).
- *Quadruple therapy*: 20 mg QD + clarithromycin 500 mg BID + amoxicillin 1000 mg BID + bismuth subcitrate 240 mg QD.
- *Maintenance*: 10–20 mg QD depending on symptom control.
- Elderly / Renal impairment: no dose adjustment.
- Hepatic impairment: reduce to 10 mg QD for Child‑Pugh B, 7.5 mg QD for Child‑Pugh C.
- Administration: take on an empty stomach; however, food does not significantly alter bioavailability, providing flexibility.
- Switching from PPI: Start vonoprazan immediately; consider 24‑h washout if simultaneous use is required for coordination of care.
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Adverse Effects
| Category | Frequency / Comment |
| Common |
• Headache (5–7 %) • Flatulence (4‑5 %) • Diarrhea (3‑4 %) • Nausea/vomiting (3 %) • Abdominal pain (2‑3 %) |
| Serious |
• Hypomagnesemia (rare; significant in long‑term use >3 mo) • Clostridioides difficile colitis (immunomodulation potential) • Hepatotoxicity (mostly mild, ALT/AST ↑ <3× ULN; severe acute liver injury rare) • QTc prolongation (1‑2 % in susceptible patients) • Allopurinol‑induced hyperuricemia (unmasking) |
*Monitoring for magnesium and hepatic enzymes is recommended at baseline and at 4–6 weeks for patients on prolonged therapy.*
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Monitoring
- Baseline (newly started or at baseline for chronic use)
- Liver function tests (ALT, AST, ALP, bilirubin)
- Serum magnesium and electrolytes
- Renal function if combined with nephrotoxic drugs
- Periodic (every 4–8 weeks for >3 mo therapy)
- Repeat LFTs and Mg ²⁺ levels
- CBC if symptomatic malaise or unexplained fatigue
- During antibiotic therapy (H. pylori)
- Document adherence and monitor for antibiotic‑related GI events
- Drug‑interaction alerts
- Review concomitant CYP3A4 inhibitors/inducers; adjust dose if necessary
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Clinical Pearls
1. Fast‑acting advantage: Vonoprazan reaches peak acid inhibition within *1–2 h*, making it ideal for acute ulcer bleeding or rapid symptom relief when time is critical.
2. Lower food effect: Unlike PPIs, vonoprazan can be taken with or without meals, simplifying adherence in outpatient settings.
3. Superior H. pylori cure rate: In regions with high clarithromycin resistance, vonoprazan‑based triple therapy improves cure rates >90 % vs PPI regimens (~70‑80 %).
4. Precise dosing windows: A 10‑mg dose is effective for maintenance in GERD; 20‑mg QD provides maximum therapeutic coverage for ulcers and H. pylori.
5. Drug‑interaction roulette: Remember to cyclo‑cross‑check for CYP3A4 inhibitors before adding antifungals (ketoconazole) or antiretrovirals (ritonavir), as vonoprazan exposure rises up to 4‑fold.
6. No “acid rebound”: Vonoprazan does not cause the rebound acid hypersecretion phenomenon seen with abrupt PPI discontinuation.
7. Use in pregnancy: Classified Category B; limited case series suggest no teratogenicity, but still weigh risk vs benefit.
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