Drug Interaction Report

Neratinib and Rabeprazole: Interaction Details

A pharmacist-reviewed analysis of the Neratinib and Rabeprazole interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Neratinib

Nerlynx Nerlynx®
+

Rabeprazole

Aciphex AcipHex® AcipHex® Sprinkles
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
How we grade severity & evidence

Severity levels

  • Contraindicated: These should generally not be used together.
  • Major: Potentially serious — often needs a change or close monitoring.
  • Moderate: Can be significant — usually manageable with monitoring.
  • Minor: Usually limited clinical impact.

Evidence grades

  • Established: Well documented — supported by controlled studies or strong clinical data.
  • Probable: Good supporting evidence, though not definitively proven.
  • Suspected: Some evidence suggests this interaction, but it is not well established.
  • Possible: Limited or conflicting evidence; the interaction may occur.
  • Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.

Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.

Of 157 documented Neratinib interactions, 139 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
unspecified
Evidence
probable
Severity
Major

What happens

Decreased neratinib solubility, absorption, and exposure

Interaction Deep Dive

Coadministration of neratinib with agents that increase the gastric pH, such as a proton pump inhibitor, may result in a decrease in neratinib plasma concentration and AUC resulting in reduced efficacy. Avoid concomitant use of neratinib with proton pump inhibitors. A single dose of neratinib given concomitantly with lansoprazole decreased the neratinib Cmax by 71% and the AUC by 65%2.

Why it happens (mechanism)

Increased gastric pH by the proton pump inhibitor

Literature reports

1 report — tap to read

a) Coadministration of a single oral dose of neratinib 240 mg with lansoprazole 30 mg orally at steady state decreased the neratinib Cmax by 71% and the AUC by 65% in a drug interaction study in healthy subjects (N=15) 1.

Common questions

Can I take Neratinib and Rabeprazole together?

Decreased neratinib solubility, absorption, and exposure Always confirm with your pharmacist or prescriber before making any change.

How serious is the Neratinib and Rabeprazole interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "unspecified". The timing of this interaction is not well characterized.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Neratinib or Rabeprazole need adjusting while I take them together?
  • What symptoms should prompt me to call you or my prescriber right away?
  • Does the timing of my doses matter for this combination?
  • Is there a safer alternative to one of these medications for me?

References (2)

  1. Product Information: NERLYNX(TM) oral tablets, neratinib oral tablets. Puma Biotechnology, Inc (per FDA), Los Angeles, CA, 2017. DailyMed
  2. Product Information: NERLYNX(R) oral tablets, neratinib oral tablets. Puma Biotechnology Inc (per FDA), Los Angeles, CA, 2018. DailyMed
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Neratinib

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All Neratinib interactions (157) Neratinib drug information
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Rabeprazole

Keep reading about Rabeprazole

All Rabeprazole interactions (28) Rabeprazole drug information
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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Rabeprazole + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato American Elder Artichoke + 164 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.