Mitotane and Cobimetinib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mitotane
Cobimetinib
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
Decreased cobimetinib plasma concentrations
Interaction Deep Dive
Avoid concomitant use of cobimetinib with strong or moderate CYP3A4 inducers. Simulations showed that cobimetinib exposures would decrease by 83% when a strong CYP3A inducer was coadministered and 73% when a moderate CYP3A inducer was coadministered1.
Why it happens (mechanism)
Induction of CYP3A4-mediated cobimetinib metabolism
Literature reports
1 report — tap to read
a) Simulations showed that cobimetinib exposures would decrease by 83% when a strong CYP3A inducer was coadministered and 73% when a moderate CYP3A inducer was coadministered 1.
Common questions
Can I take Mitotane and Cobimetinib together?
Decreased cobimetinib plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mitotane and Cobimetinib 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 Mitotane or Cobimetinib 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: COTELLIC(TM) oral tablets, cobimetinib oral tablets. Genentech USA, Inc.(per FDA), South San Francisco, CA, 2015. DailyMed
Keep reading about Mitotane
Keep reading about Cobimetinib
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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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