Lorlatinib and Everolimus: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lorlatinib
Everolimus
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 P-gp and CYP3A4 substrates exposure and reduced efficacy of P-gp and CYP3A4 substrates
Interaction Deep Dive
Avoid concomitant use of lorlatinib with P-gp and CYP3A4 substrates with NTI as it may reduce P-gp and CYP3A4 substrates with NTI exposure, which may reduce the efficacy of these substrates. If concomitant use is unavoidable, increasing the P-gp and CYP3A4 substrates dosage may be needed1.
Why it happens (mechanism)
Induction of CYP3A4-substrate metabolism by lorlatinib; induction of CYP3A4-substrate metabolism by lorlatinib
Literature reports
2 reports — tap to read
a) Coadministration of lorlatinib 100 mg orally once daily for 15 days and a single fexofenadine 60 mg dose (a P-gp substrate) decreased fexofenadine AUC(infinity) by 67% and Cmax by 63% 1.
b) Coadministration of lorlatinib, 150 mg orally once daily for 15 days with a single oral 2 mg dose of midazolam (a sensitive CYP3A substrate) decreased midazolam AUC by 64% and Cmax by 50% 1.
Common questions
Can I take Lorlatinib and Everolimus together?
Reduced P-gp and CYP3A4 substrates exposure and reduced efficacy of P-gp and CYP3A4 substrates Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lorlatinib and Everolimus 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 Everolimus 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: LORBRENA® oral tablets, lorlatinib oral tablets. Pfizer Labs (per FDA), New York, NY, 2026. DailyMed
Keep reading about Lorlatinib
Keep reading about Everolimus
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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