Midostaurin and Lonafarnib: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Lonafarnib
Midostaurin
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
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions
Interaction Deep Dive
Avoid concomitant use of lonafarnib (a CYP3A inhibitor) with sensitive CYP3A substrates with narrow therapeutic index (NTI) as it increases exposure of CYP3A substrates with NTI, which may increase the risk of adverse reactions related to these substrates. With coadministration of a single oral 2 mg dose of loperamide (CYP3A substrate) with multiple oral doses of lonafarnib 100 mg twice daily for 5 days in healthy subjects, the Cmax and AUC of loperamide were increased by 214% and 299%, respectively. And with coadministration of a single oral dose of 3 mg midazolam (CYP3A substrate) with multiple oral doses of 100 mg lonafarnib twice daily for 5 days in healthy subjects, the Cmax and AUC of midazolam were increased by 180% and 639%, respectively. If coadministration of other sensitive CYP3A substrates is unavoidable, monitor for adverse reactions and reduce the dosage of those sensitive CYP3A substrate with NTI, if needed1.
Why it happens (mechanism)
Inhibition of CYP3A-substrate metabolism by lonafarnib
Literature reports
2 reports — tap to read
a) In a clinical study, with coadministration of a single oral 2 mg dose of loperamide (CYP3A substrate) with multiple oral doses of lonafarnib 100 mg twice daily for 5 days in healthy subjects, the Cmax and AUC of loperamide were increased by 214% and 299%, respectively 1.
b) In a clinical study, with coadministration of a single oral dose of 3 mg midazolam (CYP3A substrate) with multiple oral doses of 100 mg lonafarnib twice daily for 5 days in healthy subjects, the Cmax and AUC of midazolam were increased by 180% and 639%, respectively 1.
Common questions
Can I take Midostaurin and Lonafarnib together?
Increased CYP3A substrate exposure and an increased risk of CYP3A substrate-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midostaurin and Lonafarnib 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 Midostaurin or Lonafarnib 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: ZOKINVY(TM) oral capsules, lonafarnib oral capsules. Eiger BioPharmaceuticals Inc (per FDA), Palo Alto, CA, 2024. DailyMed
Keep reading about Lonafarnib
Keep reading about Midostaurin
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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