Entrectinib and Voriconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Voriconazole
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, an increased entrectinib exposure, an increased entrectinib-related adverse effects, an increased voriconazole exposure and an increased risk of voriconazole-related adverse reactions
Interaction Deep Dive
Avoid concomitant use of entrectinib (CYP3A4 substrate) with voriconazole (strong CYP3A4 inhibitor that prolong the QT-interval) since coadministration increases entrectinib exposure, which could increase the frequency or severity of adverse reactions, including risk of cardiac arrhythmias. 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 CYP3A4 inhibitor for 3 to 5 elimination half-lives, resume the entrectinib dose that was taken prior to initiating the CYP3A4 inhibitor. For pediatric patients with a starting dose less than 200 mg avoid coadministration with strong CYP3A4 inhibitors. Also, assess QT interval and electrolytes prior to initiation of entrectinib and periodically during treatment. Based on the severity of QTc interval prolongation, withhold entrectinib and then resume at same or reduced dose, or permanently discontinue1. Coadministration of voriconazole with entrectinib (CYP3A4 inhibitor) may also increase voriconazole exposure. Adjust voriconazole dosage and monitor for adverse reactions 2.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of entrectinib; inhibition of CYP3A4-mediated metabolism of voriconazole
Literature reports
5 reports — 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.
b) In an independent published study, concomitant use of voriconazole (400 mg every 12 hours on Day 1, then 200 mg every 12 hours on Day 2) with a single intravenous dose of fentaNYL (CYP3A4 substrate) (5 microgram/kg) resulted in an increase in the mean AUC (0 to inf) of fentaNYL by 1.4-fold (range 0.81- to 2.04-fold) 2.
c) In another independent published study, coadministration of multiple doses of oral voriconazole (400 mg every 12 hours, on Day 1 followed by five doses of 200 mg every 12 hours on Days 2 to 4) with a single 10 mg oral dose of oxyCODONE (CYP3A4 substrate) on Day 3 resulted in an increase in the mean Cmax and AUC (0 to inf) of oxyCODONE by 1.7-fold (range 1.4- to 2.2-fold) and 3.6- fold (range 2.7- to 5.6-fold), respectively. The mean elimination half-life of oxyCODONE was also increased by 2.0-fold (range 1.4- to 2.5-fold) 2.
d) In stable renal transplant recipients receiving chronic cycloSPORINE (CYP3A4 substrate) therapy, concomitant administration of oral voriconazole (200 mg every 12 hours for 8 days) increased cycloSPORINE Cmax and AUC (tau) an average of 1.1 times (90% CI: 0.9, 1.41) and 1.7 times (90% CI: 1.5, 2.0), respectively, as compared to when cycloSPORINE was administered without voriconazole 2.
e) In a drug interaction study, concurrent administration of oral voriconazole (400 mg every 12 hours for 1 day, then 200 mg every 12 hours for 2.5 days) and oral fluconazole (CYP3A4 inhibitor) (400 mg on day 1, then 200 mg every 24 hours for 4 days) to 6 healthy male subjects resulted in an increase in Cmax and AUC(tau) of voriconazole by an average of 57% (90% CI: 20%, 107%) and 79% (90% CI: 40%, 128%), respectively 2.
Common questions
Can I take Entrectinib and Voriconazole together?
An increased risk of QT interval prolongation, an increased entrectinib exposure, an increased entrectinib-related adverse effects, an increased voriconazole exposure and an increased risk of voriconazole-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.
How serious is the Entrectinib and Voriconazole 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 Voriconazole 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: VFEND(R) oral tablets, oral suspension, intravenous injection, voriconazole oral tablets, oral suspension, intravenous injection. Roerig (per FDA), New York, NY, 2025. DailyMed
Keep reading about Voriconazole
Keep reading about Entrectinib
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