Lorlatinib and Mitapivat: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lorlatinib
Mitapivat
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
Reduced lorlatinib exposure, reduced efficacy of lorlatinib, reduced mitapivat exposure and reduced efficacy of mitapivat
Interaction Deep Dive
Avoid concomitant use of lorlatinib (CYP3A substrate) with mitapivat (moderate CYP3A inducer) as it may reduce lorlatinib exposure, which may reduce efficacy of lorlatinib. If concomitant use of a moderate CYP3A inducer cannot be avoided, increase the dose of lorlatinib to 125 mg orally once daily3. Coadministration of mitapivat (CYP3A substrate) and lorlatinib (moderate CYP3A inducer) reduces mitapivat exposure. Consider alternative therapy. If coadministration is required, monitor hemoglobin (Hb) and titrate beyond 50 mg twice daily if necessary 2, but do not exceed 100 mg twice daily 21.
Why it happens (mechanism)
Induction of CYP3A-mediated metabolism of lorlatinib; induction of CYP3A-mediated metabolism of mitapivat
Literature reports
2 reports — tap to read
a) Coadministration of mitapivat with efavirenz, a moderate CYP3A inducer, decreased mitapivat AUC (0 to 12) and Cmax by 60% and 30%, respectively, following mitapivat 5 or 20 mg twice daily. Additionally, efavirenz decreased mitapivat AUC (0 to 12) and Cmax by 55% and 24%, respectively, following administration of mitapivat 50 mg twice daily 2.
b) In a drug interaction study, coadministration of a single 100 mg dose of lorlatinib with modafinil (a moderate CYP3A inducer) decreased the AUC(infinity) of lorlatinib by 23% and decreased the Cmax by 22% 3.
Common questions
Can I take Lorlatinib and Mitapivat together?
Reduced lorlatinib exposure, reduced efficacy of lorlatinib, reduced mitapivat exposure and reduced efficacy of mitapivat Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lorlatinib and Mitapivat 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 Mitapivat 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 (3)
- Product Information: AQVESME™ oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: PYRUKYND(R) oral tablets, mitapivat oral tablets. Agios Pharmaceuticals Inc (per FDA), Cambridge, MA, 2025. DailyMed
- Product Information: LORBRENA® oral tablets, lorlatinib oral tablets. Pfizer Labs (per FDA), New York, NY, 2026. DailyMed
Keep reading about Lorlatinib
Keep reading about Mitapivat
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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