Voriconazole and Sertraline: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Sertraline
No brand names on recordVoriconazole
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.
Sertraline (an antidepressant) and voriconazole (an antifungal) can affect each other in two ways. Voriconazole slows down a liver enzyme that clears sertraline, so more sertraline can build up in your body. That may lead to more side effects like nausea, jitteriness, or trouble sleeping.
Both drugs can also slightly affect your heart's rhythm (something called QT prolongation), and taking them together may add to that effect. This concern is mostly theoretical right now, so please don't panic. The good news is your care team can manage this safely by adjusting your sertraline dose and keeping a closer eye on you. Talk with your pharmacist or doctor before making any changes.
Mechanism: Voriconazole inhibits CYP3A4, a contributor to sertraline metabolism, increasing sertraline exposure. Both agents independently prolong the QT interval, giving an additive effect. Neither is a prodrug, so the effect is increased sertraline activity plus additive cardiac risk.
- Direction: Increased sertraline AUC/Cmax; heightened risk of QT prolongation and ventricular arrhythmias.
- Evidence: Theoretical; severity rated major.
- Onset: Unspecified.
- Management: Ideally avoid coadministration. If used together, reduce sertraline dose, individualize therapy, and monitor for serotonergic/sertraline adverse effects and consider ECG monitoring, especially with other QT-prolonging drugs or electrolyte abnormalities.
What happens
An increased risk of QT interval prolongation, an increased sertraline exposure and an increased risk of sertraline-related adverse reactions
Interaction Deep Dive
The combined use of sertraline and voriconazole should be avoided, because doing so can raise the likelihood of QT prolongation and/or ventricular arrhythmias1. Because sertraline is a CYP3A4 substrate, giving voriconazole together with it may also raise sertraline exposure. Lower the sertraline dose and watch for adverse reactions2.
Why it happens (mechanism)
Additive QT interval prolongation; inhibition of CYP3A4-mediated metabolism of sertraline
How to manage this interaction
Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own.
- Your care team may prefer to avoid using these two together when possible, or they may lower your sertraline dose and individualize it for you.
- They may monitor you more closely for sertraline side effects and, given the heart-rhythm concern, may check your heart rhythm.
- Tell your pharmacist or doctor about any other medicines you take that affect heart rhythm.
Report symptoms like fainting, palpitations, severe dizziness, or worsening nausea and restlessness to your care team.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) In a separately published study, giving voriconazole (400 mg every 12 hours on Day 1, followed by 200 mg every 12 hours on Day 2) together with a single intravenous dose of fentaNYL (a CYP3A4 substrate) (5 microgram/kg) produced a 1.4-fold rise in the mean AUC (0 to inf) of fentaNYL (range 0.81- to 2.04-fold) 2.
b) In a different independently published study, giving multiple doses of oral voriconazole (400 mg every 12 hours on Day 1, then five doses of 200 mg every 12 hours on Days 2 to 4) along with a single 10 mg oral dose of oxyCODONE (a CYP3A4 substrate) on Day 3 led to a rise 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 also rose by 2.0-fold (range 1.4- to 2.5-fold) 2.
c) In stable renal transplant recipients on ongoing cycloSPORINE (a CYP3A4 substrate) therapy, adding oral voriconazole (200 mg every 12 hours for 8 days) raised cycloSPORINE Cmax and AUC (tau) by an average of 1.1 times (90% CI: 0.9, 1.41) and 1.7 times (90% CI: 1.5, 2.0), respectively, compared with cycloSPORINE given without voriconazole 2.
Common questions
Can I take Voriconazole and Sertraline together?
Voriconazole can raise sertraline levels and both can affect heart rhythm, so this combination is usually avoided; if used together your team may lower the sertraline dose and monitor you more closely. Talk with your pharmacist or doctor before changing anything. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Voriconazole and Sertraline 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 Voriconazole and Sertraline interaction managed?
Keep taking both medications exactly as prescribed unless your prescriber tells you otherwise. Do not stop or change doses on your own. Your care team may prefer to avoid using these two together when possible, or they may lower your sertraline dose and individualize it for you. They may monitor you more closely for sertraline side effects and, given the heart-rhythm concern, may check your heart… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Voriconazole or Sertraline 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: ZOLOFT oral tablets, oral solution, sertraline hydrochloride oral tablets, oral solution. Viatris Specialty LLC (per FDA), Morgantown, WV, 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 Sertraline
Keep reading about Voriconazole
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