Entrectinib and Cobicistat: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cobicistat
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
Increased entrectinib exposure and an increased frequency or severity of adverse reactions
Interaction Deep Dive
Avoid concomitant use of entrectinib (CYP3A substrate) with strong CYP3A inhibitors since coadministration increases entrectinib exposure, which could increase the frequency or severity of adverse reactions. When coadministered with itraconazole (a strong inhibitor) entrectinib's AUC was increased 6-fold and Cmax by 1.7 fold. If coadministration is unavoidable, in adults and pediatric patients 2 years or older reduce the 600 mg starting entrectinib dose to 100 mg orally once daily, 400 mg or 300 mg to 50 mg once daily, 200 mg to 50 mg on alternate days and limit coadministration to 14 days or less. After discontinuation of a strong CYP3A inhibitor for 3 to 5 elimination half-lives, resume the entrectinib dose that was taken prior to initiating the CYP3A inhibitor. For pediatric patients with a starting dose less than 200 mg avoid coadministration with strong CYP3A inhibitors1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of entrectinib
Literature reports
1 report — tap to read
a) Coadministration of itraconazole (a strong CYP3A inhibitor) with a single entrectinib dose of 100 mg increased entrectinib AUC(0 to infinity) by 6-fold and Cmax by 1.7-fold 1.
Common questions
Can I take Entrectinib and Cobicistat together?
Increased entrectinib exposure and an increased frequency or severity of adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Entrectinib and Cobicistat 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 Entrectinib or Cobicistat 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: ROZLYTREK(R) oral capsules, pellets, entrectinib oral capsules, pellets. Genentech Inc (per FDA), South San Francisco, CA, 2023. DailyMed
Keep reading about Cobicistat
Keep reading about Entrectinib
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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:
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