Lorlatinib and Neratinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lorlatinib
Neratinib
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
Decreased exposure of neratinib and risk of reduced efficacy
Interaction Deep Dive
Coadministration of neratinib (a CYP3A4 substrate) with moderate CYP3A4 inducers may result in a decrease of neratinib exposure resulting in a risk of reduced efficacy. Avoid concomitant use based on reductions in neratinib exposure seen during simulations using physiologically based pharmacokinetic models1.
Why it happens (mechanism)
Induction of CYP3A4-mediated neratinib metabolism
Literature reports
1 report — tap to read
a) Concomitant use of neratinib (a CYP3A4 substrate) and efavirenz (a moderate CYP3A4 inducer) may decrease the neratinib Cmax by 36% and decrease AUC by 52% in simulations using physiologically based pharmacokinetic models 1.
Common questions
Can I take Lorlatinib and Neratinib together?
Decreased exposure of neratinib and risk of reduced efficacy Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lorlatinib and Neratinib 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 Lorlatinib or Neratinib 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 (1)
- Product Information: NERLYNX(R) oral tablets, neratinib oral tablets. Puma Biotechnology Inc (per manufacturer), Los Angeles, CA, 2020. DailyMed
Keep reading about Lorlatinib
Keep reading about Neratinib
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:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist