Entrectinib and Primidone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Primidone
Entrectinib
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
An increased risk of QT interval prolongation, reduced entrectinib exposure and reduced efficacy of entrectinib
Interaction Deep Dive
Coadministration of entrectinib (CYP3A substrate) with a strong or moderate CYP3A inducer decreases entrectinib plasma concentrations, which may reduce entrectinib efficacy and therefore should be avoided. Coadministration of rifAMPin (a strong CYP3A inducer) with a single entrectinib 600 mg dose reduced entrectinib AUC(0 to infinity) by 77% and Cmax by 56%. Coadministration of a moderate CYP3A inducer with entrectinib is predicted to reduce entrectinib AUC (0 to Tau) by 56% and Cmax by 43%1. Also, concomitant use of PHENobarbital with other products that prolong the QTc interval may result in a greater increase in the QTc interval and adverse reactions associated with QTc interval prolongation. If concomitant use of entrectinib and PHENobarbital cannot be avoided, monitor patients for increased risk of QTc interval prolongation, closely monitor neonates and consider increasing the entrectinib dosage accordingly 2.
Why it happens (mechanism)
Additive QT interval prolongation; induction of CYP3A4-mediated metabolism of entrectinib
Literature reports
2 reports — tap to read
a) Coadministration of rifAMPin (a strong CYP3A inducer) with a single entrectinib 600 mg dose reduced entrectinib AUC(0 to infinity) by 77% and Cmax by 56% 1.
b) Coadministration of a moderate CYP3A inducer with entrectinib is predicted to reduce entrectinib AUC (0 to Tau) by 56% and Cmax by 43% 1.
Common questions
Can I take Entrectinib and Primidone together?
An increased risk of QT interval prolongation, reduced entrectinib exposure and reduced efficacy of entrectinib Always confirm with your pharmacist or prescriber before making any change.
How serious is the Entrectinib and Primidone 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 "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Entrectinib or Primidone 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 (2)
- Product Information: ROZLYTREK(R) oral capsules, pellets, entrectinib oral capsules, pellets. Genentech Inc (per FDA), South San Francisco, CA, 2023. DailyMed
- Product Information: SEZABY(TM) intravenous injection, phenobarbital sodium intravenous injection. Sun Pharmaceutical Industries Inc (per manufacturer), Cranbury, NJ, 2022. DailyMed
Keep reading about Primidone
Keep reading about Entrectinib
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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