Mitotane and Belumosudil: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 15, 2026 · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Mitotane
Belumosudil
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.
These two medicines can work against each other. Mitotane (Lysodren) speeds up the liver enzyme that breaks down belumosudil (Rezurock). When that enzyme works faster, your body clears belumosudil more quickly, so there is less of it in your blood. That can make the belumosudil less effective at treating your condition.
The good news is this is a well-known, manageable situation. Your care team may raise your belumosudil dose or watch your response more closely. Please don't change anything on your own. Just talk with your pharmacist or doctor so they can adjust things safely.
Effect: Reduced belumosudil exposure and efficacy.
Mechanism: Mitotane is a strong CYP3A inducer; belumosudil is a CYP3A substrate. Induction accelerates belumosudil metabolism, lowering plasma concentrations. Neither drug is a prodrug, so the effect is straightforward loss of exposure.
Magnitude: With rifampin (strong inducer), belumosudil Cmax fell 59% and AUC fell 72%. Similar loss is expected with mitotane.
- Evidence: Probable; onset unspecified.
- Management: If coadministered, increase belumosudil to 200 mg twice daily. Monitor for reduced therapeutic response (e.g., chronic GVHD control).
What happens
Reduced belumosudil exposure and reduced efficacy of belumosudil
Interaction Deep Dive
When belumosudil (a CYP3A substrate) is given together with a strong CYP3A inducer, belumosudil exposure may fall, potentially lowering the drug's effectiveness. A drug interaction study conducted in healthy subjects showed that giving belumosudil alongside rifAMPin (a strong CYP3A inducer) reduced belumosudil Cmax by 59% and AUC by 72%. When belumosudil is combined with a strong CYP3A inducer, raise the belumosudil dose to 200 mg twice daily1.
Why it happens (mechanism)
Induction of CYP3A-mediated belumosudil metabolism
How to manage this interaction
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because mitotane can lower how well belumosudil works, your team has a clear way to handle this.
- Your prescriber may increase your belumosudil dose (the labeled adjustment is 200 mg twice daily) when it is taken with a strong enzyme-inducer like mitotane.
- Your team may monitor your response more closely to be sure the belumosudil is still working.
- Tell your pharmacist and doctor that you take both drugs, and mention any signs your condition is not well controlled.
Do not adjust doses yourself; let your care team individualize the plan.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) In a drug interaction study conducted in healthy subjects, giving belumosudil together with rifAMPin (a strong CYP3A inducer) reduced belumosudil Cmax by 59% and AUC by 72% 1.
Common questions
Can I take Mitotane and Belumosudil together?
Mitotane speeds up the breakdown of belumosudil, which can lower its levels and make it less effective; your doctor may raise the belumosudil dose (often to 200 mg twice daily) and monitor your response. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Mitotane and Belumosudil 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 is the Mitotane and Belumosudil interaction managed?
Keep taking both medicines as prescribed unless your care team tells you otherwise. Because mitotane can lower how well belumosudil works, your team has a clear way to handle this. Your prescriber may increase your belumosudil dose (the labeled adjustment is 200 mg twice daily) when it is taken with a strong enzyme-inducer like mitotane. Your team may monitor your response more closely to be sure… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
Questions for your pharmacist
- Does my dose of Mitotane or Belumosudil 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: REZUROCK(R) oral tablets, belumosudil oral tablets. Kadmon Pharmaceuticals LLC (per FDA), Bridgewater, NJ, 2024. DailyMed
Keep reading about Mitotane
Keep reading about Belumosudil
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