Neratinib and Nirmatrelvir: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Neratinib
Nirmatrelvir
No brand names on record
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.
What happens
Increased neratinib exposure and risk of toxicity
Interaction Deep Dive
Avoid concomitant administration of neratinib with nirmatrelvir/ritonavir due to increased neratinib plasma concentrations and potential risk of serious adverse events2.
Why it happens (mechanism)
Inhibition of neratinib metabolism
Literature reports
1 report — tap to read
a) Coadministration of a single oral dose of neratinib 240 mg with ketoconazole 400 mg orally once daily for 5 days (a strong CYP3A4 inhibitor) increased the neratinib Cmax by 221% and the AUC by 381% in a drug interaction study in healthy subjects (N=24) 1.
Common questions
Can I take Neratinib and Nirmatrelvir together?
Increased neratinib exposure and risk of toxicity Always confirm with your pharmacist or prescriber before making any change.
How serious is the Neratinib and Nirmatrelvir 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Neratinib or Nirmatrelvir 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)
- Product Information: NERLYNX(R) oral tablets, neratinib oral tablets. Puma Biotechnology Inc (per manufacturer), Los Angeles, CA, 2020. DailyMed
- Pfizer Inc: Fact sheet for healthcare providers: Emergency Use Authorization for PAXLOVID(TM). US Food & Drug Administration (FDA). Silver Spring, MD. 2021.
Keep reading about Neratinib
Keep reading about Nirmatrelvir
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