Methotrexate and Zongertinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methotrexate
Zongertinib
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 BCRP substrates exposure and an increased risk of BCRP substrates-related adverse reactions
Interaction Deep Dive
Concomitant use of zongertinib (BCRP inhibitor) with BCRP substrates may increase BCRP substrates exposure which may lead to serious adverse reactions related to BCRP substrates. Monitor for increased adverse reactions and adjust the dosages of BCRP substrates as clinically appropriate1.
Why it happens (mechanism)
Inhibition of BCRP-mediated efflux transport of zongertinib
Literature reports
1 report — tap to read
a) In the drug interaction studies, coadministration a single dose of zongertinib 120 mg daily for 12 days with rosuvastatin (BCRP substrate), resulted in increased Cmax and AUC by 3-fold and 2.3-fold, respectively 1.
Common questions
Can I take Methotrexate and Zongertinib together?
Increased BCRP substrates exposure and an increased risk of BCRP substrates-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Methotrexate and Zongertinib interaction?
It is rated moderate. Can be significant — usually manageable with 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Methotrexate or Zongertinib 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 anything you'd monitor while I'm on both?
References (1)
- Product Information: HERNEXEOS(R) oral tablets, zongertinib oral tablets. Boehringer Ingelheim Pharmaceuticals, Inc (per FDA), Ridgefield, CT, 2025. DailyMed
Keep reading about Methotrexate
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.
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