VOQUEZNA TRIPLE PAK
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VOQUEZNA TRIPLE PAK (VOQUEZNA TRIPLE PAK).
Vonoprazan is a potassium-competitive acid blocker (P-CAB) that reversibly inhibits gastric H+, K+-ATPase in a pH-independent manner. Amoxicillin and clarithromycin are antibiotics that inhibit bacterial cell wall synthesis and protein synthesis, respectively, to eradicate Helicobacter pylori.
| Metabolism | Vonoprazan: primarily metabolized by CYP3A4/5; Amoxicillin: renal elimination; Clarithromycin: primarily metabolized by CYP3A4. |
| Excretion | Amoxicillin: 60-80% excreted unchanged in urine via glomerular filtration and tubular secretion; Clarithromycin: 20-30% excreted unchanged in urine, remainder metabolized to 14-hydroxyclarithromycin (active) and other metabolites, with renal and biliary excretion; Vonoprazan: primarily metabolized, negligible unchanged drug in urine, with 1-3% excreted in feces as unchanged and metabolites. |
| Half-life | Amoxicillin: 1-1.5 hours (prolonged in renal impairment); Clarithromycin: 3-4 hours (up to 5-7 hours for 14-hydroxy metabolite); Vonoprazan: approximately 8 hours (range 6-10 hours), supporting once-daily dosing for acid suppression. |
| Protein binding | Amoxicillin: 17-20% bound to serum albumin; Clarithromycin: 70% bound to albumin and alpha-1-acid glycoprotein; Vonoprazan: 88-94% bound to albumin. |
| Volume of Distribution | Amoxicillin: 0.3-0.4 L/kg; distributes widely into body tissues and fluids; Clarithromycin: 3-5 L/kg; extensive tissue distribution exceeding plasma; Vonoprazan: 0.49 L/kg (approx. 35 L), indicating moderate distribution into total body water. |
| Bioavailability | Amoxicillin: 60-80% oral bioavailability; Clarithromycin: 50-55% oral bioavailability (reduces with high doses); Vonoprazan: 36-52% oral bioavailability (mean 39%), with high interindividual variability. |
| Onset of Action | Vonoprazan: acid suppression begins within 1 hour of oral administration; Amoxicillin and Clarithromycin achieve therapeutic plasma concentrations within 1-2 hours; clinical effect (symptom relief) may be seen within 1-3 days of triple therapy initiation. |
| Duration of Action | Vonoprazan: acid suppression persists for 24 hours; Clarithromycin: antibacterial effect requires twice-daily dosing to maintain levels; Amoxicillin: dosing every 12 hours maintains adequate levels; the triple pack is administered for 14 days for H. pylori eradication. |
Each carton contains a 14-day course: amoxicillin 1 g orally twice daily, clarithromycin 500 mg orally twice daily, and vonoprazan 20 mg orally twice daily, taken for 14 days.
| Dosage form | CAPSULE, TABLET, TABLET |
| Renal impairment | For CrCl 30-59 mL/min: reduce clarithromycin dose by 50% or use alternative; for CrCl <30 mL/min: avoid clarithromycin and vonoprazan not recommended. Amoxicillin: dose adjustment per guidelines for CrCl <30 mL/min (e.g., 250-500 mg every 12 hours). |
| Liver impairment | For severe hepatic impairment (Child-Pugh C): avoid clarithromycin; vonoprazan no dose adjustment recommended, amoxicillin use with caution. For moderate impairment (Child-Pugh B): clarithromycin no adjustment, monitor. |
| Pediatric use | Not established; safety and efficacy not studied in patients <18 years. |
| Geriatric use | No specific dose adjustment required; monitor renal function and consider age-related decline in CrCl; adjust clarithromycin and/or amoxicillin based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VOQUEZNA TRIPLE PAK (VOQUEZNA TRIPLE PAK).
| Breastfeeding | Omeprazole: Excreted in breast milk; relative infant dose estimated 1-3% of maternal weight-adjusted dose; M/P ratio approximately 0.2. Amoxicillin: Excreted in breast milk in low levels; M/P ratio about 0.01-0.05. Clarithromycin: Excreted in breast milk; infant exposure approximately 2-3% of maternal dose; M/P ratio not defined. Potential adverse effects in nursing infants include diarrhea, rash, and alteration of gut flora. Use with caution during breastfeeding; consider temporary discontinuation of breastfeeding during therapy. |
| Teratogenic Risk | VOQUEZNA TRIPLE PAK contains omeprazole, amoxicillin, and clarithromycin. Omeprazole: Animal studies showed no evidence of teratogenicity; human data from cohort studies suggest no major congenital malformations. Amoxicillin: Penicillins are considered low risk; no teratogenic effects in animal studies. Clarithromycin: Animal studies demonstrated embryotoxicity and malformations; human data limited but may increase risk of spontaneous abortion and malformations. FDA Pregnancy Category C for clarithromycin; category B for omeprazole and amoxicillin. First trimester: Potential risk with clarithromycin. Second and third trimesters: No known fetal risks from omeprazole or amoxicillin; clarithromycin should be avoided unless benefit outweighs risk. |
■ FDA Black Box Warning
None
| Serious Effects |
["Hypersensitivity to any component","Concomitant use with CYP3A4 substrates that have narrow therapeutic indices (e.g., cisapride, pimozide, ergotamine)","History of QT prolongation or torsades de pointes","Renal impairment (creatinine clearance <30 mL/min) for clarithromycin-containing regimen"]
| Precautions | ["Clostridioides difficile-associated diarrhea","Hypersensitivity reactions including anaphylaxis","Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome)","Acute interstitial nephritis","Clarithromycin increases risk of cardiac events (e.g., QT prolongation, arrhythmias) in patients with coronary artery disease","Potential for drug interactions with clarithromycin due to CYP3A4 inhibition"] |
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| Fetal Monitoring | Monitor for maternal adverse effects: allergic reactions (especially amoxicillin and clarithromycin), hepatotoxicity (clarithromycin), QT interval prolongation (clarithromycin). Fetal monitoring: ultrasound assessment for fetal growth and anatomy if used in second or third trimester. Assess for signs of fetal distress or preterm labor if prolonged use. Monitor infant for diarrhea, rash, or candidiasis if used near term. |
| Fertility Effects | Omeprazole: No known effect on human fertility. Amoxicillin: No known effect on fertility. Clarithromycin: Animal studies showed reduced fertility at high doses; human data lacking. Combination therapy may disrupt vaginal flora, potentially affecting fertility; no direct contraceptive effect. Based on available evidence, no significant impact on fertility is expected. |