Drug Interaction Report

Methotrexate Injection and Encorafenib: Interaction Details

A pharmacist-reviewed analysis of the Methotrexate Injection and Encorafenib 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

Encorafenib

Braftovi Braftovi®
+

Methotrexate Injection

Abitrexate® Folex® Jylamvo Mexate® Otrexup Otrexup® Rasuvo Rasuvo®
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
Moderate
Can be significant — usually manageable with 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 354 documented Methotrexate Injection interactions, 13 are rated moderate — including this one.
Onset
unspecified
Evidence
theoretical
Severity
Moderate

What happens

Increased methotrexate exposure and an increased risk of methotrexate-related toxicities

Interaction Deep Dive

Concomitant administration of encorafenib (an inhibitor of BCRP and OATP1B1) with methotrexate (a sensitive substrate of BCRP and OATP1B1) may increase methotrexate exposure and may increase risk of methotrexate-related adverse reactions. Monitor patients closely for signs and symptoms of increased exposure and consider adjusting the dose of methotrexate. In a drug interaction study, repeated doses of encorafenib 450 mg once daily and binimetinib 45 mg twice daily with a single dose of rosuvastatin (a sensitive substrate of BCRP and OATP1B1) increased rosuvastatin Cmax by 2.7-fold and AUC by 1.6-fold1.

Why it happens (mechanism)

Inhibition of BCRP-mediated efflux transport of encorafenib; inhibition of OATP1B1-mediated efflux transport of encorafenib

Literature reports

1 report — tap to read

a) In a drug interaction study, repeated doses of encorafenib 450 mg once daily and binimetinib 45 mg twice daily with a single dose of rosuvastatin (a sensitive substrate of BCRP and OATP1B1) increased rosuvastatin Cmax by 2.7-fold and AUC by 1.6-fold 1.

Common questions

Can I take Methotrexate Injection and Encorafenib together?

Increased methotrexate exposure and an increased risk of methotrexate-related toxicities Always confirm with your pharmacist or prescriber before making any change.

How serious is the Methotrexate Injection and Encorafenib 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.

Questions for your pharmacist

  • Does my dose of Methotrexate Injection or Encorafenib 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)

  1. Product Information: BRAFTOVI(R) oral capsules, encorafenib oral capsules. Array BioPharma Inc (per FDA), Boulder, CO, 2024. DailyMed
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Encorafenib

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Methotrexate Injection

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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:

Encorafenib + Activated Charcoal American Hellebore Arsenic Cesium Ephedra Grapefruit Sida Cordifolia St. John's Wort + 143 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.