Drug Interaction Report

Encorafenib and Lorlatinib: Interaction Details

A pharmacist-reviewed analysis of the Encorafenib and Lorlatinib 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

Lorlatinib

Lorbrena
+

Encorafenib

Braftovi Braftovi®
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
Contraindicated
These should generally not be used together.
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 468 documented Encorafenib interactions, 36 are rated contraindicated — 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
theoretical
Severity
Contraindicated

What happens

Reduced encorafenib exposure, reduced lorlatinib exposure and an increased risk of serious hepatotoxicity

Interaction Deep Dive

Concomitant use of lorlatinib (a CYP3A substrate) with encorafenib (strong CYP3A inducer) is contraindicated due to the potential for serious hepatotoxicity. Coadministration may also reduce lorlatinib exposure. Prior to initiating lorlatinib, discontinue the strong CYP3A inducer for 3 plasma half-lives of the strong CYP3A inducer2. Concomitant use of encorafenib with lorlatinib (moderate CYP3A inducer) may reduce encorafenib exposure and may reduce efficacy 1.

Why it happens (mechanism)

Induction of CYP3A-mediated metabolism of encorafenib; induction of CYP3A-mediated metabolism of lorlatinib

Common questions

Can I take Encorafenib and Lorlatinib together?

Reduced encorafenib exposure, reduced lorlatinib exposure and an increased risk of serious hepatotoxicity Always confirm with your pharmacist or prescriber before making any change.

How serious is the Encorafenib and Lorlatinib interaction?

It is rated contraindicated. These should generally not be used together.

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 Encorafenib or Lorlatinib 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: BRAFTOVI(TM) oral capsules, encorafenib oral capsules. Array BioPharma Inc (per FDA), Boulder, CO, 2018. DailyMed
  2. Product Information: LORBRENA® oral tablets, lorlatinib oral tablets. Pfizer Labs (per FDA), New York, NY, 2026. DailyMed
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Lorlatinib

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All Lorlatinib interactions (69)
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Encorafenib

Keep reading about Encorafenib

All Encorafenib interactions (468) Encorafenib 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:

Lorlatinib + Activated Charcoal Grapefruit St. John's Wort Acacia Rigidula Adrafinil African Wild Potato Alkanna Alpine Ragwort + 145 more
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.