AMOXICILLIN/ CLARITHROMYCIN/ VONOPRAZAN MISCELLANEOUS

Clinical Criteria Summary

VOQUEZNA Triple Pak: Vonoprazan 20 mg, amoxicillin 1,000 mg, clarithromycin 500 mg. Take 12 hours apart (morning and evening), with or without food. Duration: 14 days.
VOQUEZNA Dual Pak: Vonoprazan 20 mg twice daily plus amoxicillin 1,000 mg. Dosing schedule: Morning (1 vonoprazan tablet, 2 amoxicillin capsules), Mid-day (2 amoxicillin capsules), Evening (1 vonoprazan tablet, 2 amoxicillin capsules). Duration: 14 days.
Dosing can be administered without regard to food.

Hypersensitivity to any component, including hypersensitivity to drugs in the same class.
Contraindication to clarithromycin, including contraindicated concomitant medications or a history of cholestatic jaundice/hepatic dysfunction with prior clarithromycin.
Concomitant use with rilpivirine-containing products.

Hypersensitivity reactions (serious and fatal reactions reported).
Acute tubulointerstitial nephritis (reported with vonoprazan).
Severe cutaneous adverse reactions (e.g., Stevens-Johnson syndrome/toxic epidermal necrolysis).
Drug-induced enterocolitis syndrome (most commonly in pediatric patients, presenting as protracted vomiting 1–4 hours after drug injection).
Clostridioides difficile-associated diarrhea.
Rash with mononucleosis (due to amoxicillin component).
Interaction with diagnostic investigations for neuroendocrine tumors (can cause false positive results secondary to drug-induced decreases in gastric acidity).
Development of resistant bacteria.
Clarithromycin-specific warnings: QT prolongation (avoid in known prolonged QT, ventricular arrhythmia, or other drugs/conditions known to prolong QT interval), hepatotoxicity, serious adverse events with CYP3A4-metabolized drugs, embryofetal toxicity (increased risk of miscarriage and fetal malformations), infertility (may impair fertility in males of reproductive potential based on animal studies), exacerbation of myasthenia gravis.

Pregnancy: No adequate and well-controlled studies. Animal studies show possible harm. Clarithromycin is associated with increased miscarriage and possible major congenital malformations. VOQUEZNA Triple Pak is NOT recommended in pregnancy unless no alternative therapy is appropriate.
Renal impairment: No dose adjustment needed for estimated GFR ≥ 30 mL/min. Not recommended with GFR < 30 mL/min.
Hepatic impairment: Standard doses for patients with Child-Pugh A hepatic impairment. Not recommended in Child-Pugh B or C.

VOQUEZNA Dual Pak is a suggested first-line option for treatment-naïve patients based on demonstrated noninferiority to standard triple therapy, superiority in clarithromycin-resistant strains, and better tolerability compared to bismuth quadruple therapy.
VOQUEZNA Triple Pak is suggested as a salvage regimen when clarithromycin susceptibility can be documented.
Optimized bismuth quadruple therapy (BQT) for 14 days remains the only recommended first-line treatment option per updated ACG guidelines; Voquezna dual may be reserved for patients who cannot tolerate BQT.
Rifabutin-based triple therapy is suggested as a first-line treatment but may be more beneficial as a second-line empiric regimen if BQT cannot be used.
Other regimens (e.g., Voquezna triple, levofloxacin-based) require susceptibility testing.
PPI-based triple therapy with clarithromycin or levofloxacin is no longer recommended in the absence of susceptibility testing due to high resistance rates.
High-dose dual double-dose PPI plus amoxicillin is no longer recommended; vonoprazan dual therapy is preferred.

Pregnancy
Need for concomitant rilpivirine administration
Serious drug-drug interactions that cannot be managed (e.g., concomitant colchicine if renal or hepatic impairment, pimozide, lurasidone, lovastatin, simvastatin, strong CYP3A inducers)
Known prolongation of QT interval or ongoing proarrhythmic condition (e.g. uncorrected hypokalemia or hypomagnesemia, significant bradycardia, concomitant Class IA or III antiarrhythmics)

Documented H.pylori by laboratory test or pathology
Documented susceptibility to clarithromycin (If clarithromycin susceptibility cannot be documented by culture-based or molecular methods, exceptions to this criterion may be considered on a case-by-case basis with the guidance of a subject matter expert)
At least one prior course of first-line regimen: bismuth quadruple or vonoprazan dual therapy unless not tolerated or contraindicated
At least one course of salvage therapy with rifabutin triple therapy unless not tolerated or contraindicated