Amoxicillin/Vonoprazan Drug Interactions: What to Avoid and What to Tell Your Doctor

Before starting Amoxicillin/Vonoprazan (Voquezna Dual Pak), it's essential to review everything you're currently taking — including prescription medications, over-the-counter drugs, vitamins, and herbal supplements. Vonoprazan, in particular, affects stomach acid and certain liver enzymes, which can change how other drugs are absorbed or metabolized. Here is a complete guide to known interactions.

Always Tell Your Doctor About Your Current Medications

Before starting Voquezna Dual Pak, provide your prescriber and pharmacist with a complete list of:

• All prescription medications (including HIV medications, anticoagulants, immunosuppressants)
• Over-the-counter drugs (antacids, aspirin, NSAIDs)
• Vitamins and minerals (especially iron supplements)
• Herbal supplements (especially St. John's Wort)

Major Drug Interactions — Avoid These While on Amoxicillin/Vonoprazan

The following interactions are considered major and generally require avoiding the combination:

• Rilpivirine (Edurant, Complera, Juluca, Odefsey) — An HIV medication. Vonoprazan's acid suppression reduces rilpivirine absorption, potentially causing treatment failure. This combination is contraindicated. Tell your HIV provider before starting H. pylori treatment.
• St. John's Wort — This herbal supplement is a potent CYP3A4 inducer. It significantly reduces vonoprazan blood levels, potentially making the treatment less effective at suppressing acid and eradicating H. pylori. Avoid during the 14-day treatment course.
• Rifampin (Rifadin) — A strong CYP3A4 inducer used for tuberculosis and other infections. Like St. John's Wort, it can reduce vonoprazan exposure significantly.

Moderate Drug Interactions — May Require Monitoring or Dose Adjustment

• Probenecid — A gout medication that blocks the kidney from excreting amoxicillin. This increases amoxicillin blood levels, which may raise the risk of amoxicillin-related side effects. Your doctor may need to adjust dosing or monitor more closely.
• Warfarin (Coumadin) — Antibiotics can alter gut bacteria that produce vitamin K, potentially affecting anticoagulation. If you take warfarin, your INR should be monitored during and after treatment.
• Clopidogrel (Plavix) — Vonoprazan is a CYP2C19 inhibitor and may reduce the conversion of clopidogrel to its active form, potentially reducing antiplatelet effectiveness. If you are on clopidogrel for heart disease or stents, discuss this interaction with your cardiologist before starting treatment.
• Omeprazole and other PPIs — The prescribing information advises avoiding concomitant omeprazole use with vonoprazan. There is no benefit to combining two acid suppressants, and this combination is not part of any approved regimen.
• Iron salts (oral iron supplements) — Iron requires an acidic stomach environment for absorption. Vonoprazan raises stomach pH, which can reduce iron absorption. If you take iron supplements for anemia, discuss timing with your doctor.
• Ketoconazole, itraconazole (antifungals) — These antifungal medications require acidic gastric pH to be absorbed properly. Vonoprazan's acid suppression may reduce their effectiveness.
• Mycophenolate mofetil (CellCept) — An immunosuppressant used after organ transplant. Its absorption may be altered by vonoprazan's acid suppression.

Interactions Related to H. pylori Itself

One often-overlooked point: H. pylori infection itself can affect drug metabolism. Successfully treating H. pylori can change stomach pH back to normal, which in turn can alter the absorption of medications you take long-term. After completing H. pylori treatment, your doctor may want to reassess dosing for medications that are pH-sensitive.

Breastfeeding and Pregnancy

If you are pregnant, planning to become pregnant, or breastfeeding, tell your doctor before starting Voquezna Dual Pak. Vonoprazan has limited human pregnancy data. Because vonoprazan may pass into breast milk and animal studies showed potential liver effects at higher doses, breastfeeding is generally not recommended during treatment. Discuss alternatives with your provider if you are nursing.

The Bottom Line

The most important interactions to know about for Amoxicillin/Vonoprazan are rilpivirine (contraindicated), St. John's Wort (avoid), warfarin (monitor), clopidogrel (discuss with cardiologist), and iron supplements (timing adjustment). Always give your pharmacist a complete medication list before starting. See also: Amoxicillin/Vonoprazan Side Effects.