Voriconazole and Clindamycin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 1, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Voriconazole
Clindamycin
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.
Voriconazole (Vfend) is an antifungal that can slow down a liver enzyme called CYP3A4. Your body uses that enzyme to break down some other medicines, including clindamycin. When the enzyme is slowed, clindamycin can build up more than usual, which may make its effects and its side effects (like stomach upset or diarrhea) stronger.
The good news is that this is very manageable. Please don't stop or change either medicine on your own. Your doctor or pharmacist may lower the clindamycin dose or keep a closer eye on you for side effects. If you notice anything new or bothersome, just let your care team know.
Mechanism: Voriconazole is a potent CYP3A4 inhibitor. Clindamycin is partially metabolized by CYP3A4, so coadministration may reduce its clearance and increase systemic exposure (AUC/Cmax), with heightened pharmacologic effect and adverse reactions (GI effects, potential for C. difficile-associated diarrhea).
- Direction: increased clindamycin exposure and effect
- Onset: unspecified
- Evidence: probable (class effect for CYP3A4 substrates; documented fold-increases seen with fentanyl, oxycodone, cyclosporine)
- Management: consider reducing the CYP3A4-substrate dose and monitor for adverse reactions; individualize per patient
Neither agent's active moiety depends on CYP3A4 activation, so inhibition raises exposure rather than reducing efficacy.
What happens
Increased CYP3A4 substrates exposure and an increased efficacy of CYP3A4 substrates-related adverse effects
Interaction Deep Dive
When voriconazole is given together with CYP3A4 substrates, the exposure to those substrates may rise, potentially heightening their effectiveness. The dosage of such substrates should be lowered, and patients should be watched for adverse reactions. One independent published trial examined voriconazole (400 mg every 12 hours on Day 1, followed by 200 mg every 12 hours on Day 2) taken alongside a single intravenous fentaNYL dose (5 microgram/kg); the mean AUC (0 to inf) of fentaNYL rose 1.4-fold (range 0.81- to 2.04-fold). A separate independent published trial gave multiple oral voriconazole doses (400 mg every 12 hours on Day 1, then five doses of 200 mg every 12 hours across Days 2 to 4) together with a single 10 mg oral dose of oxyCODONE on Day 3; this produced increases in the mean Cmax and AUC (0 to inf) of oxyCODONE of 1.7-fold (range 1.4- to 2.2-fold) and 3.6-fold (range 2.7- to 5.6-fold), respectively. Additionally, the mean elimination half-life of oxyCODONE increased 2.0-fold (range 1.4- to 2.5-fold). Among stable renal transplant patients on ongoing cycloSPORINE therapy, adding oral voriconazole (200 mg every 12 hours over 8 days) raised the cycloSPORINE Cmax and AUC (tau) by averages of 1.1 times (90% CI: 0.9, 1.41) and 1.7 times (90% CI: 1.5, 2.0), respectively, relative to cycloSPORINE given without voriconazole1.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism by voriconazole
How to manage this interaction
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This interaction is manageable.
- Your prescriber may lower the clindamycin dose and tailor it to you.
- Your team may monitor you more closely for side effects such as stomach upset or diarrhea.
- Report any new or worsening symptoms, especially severe or persistent diarrhea, to your pharmacist or doctor promptly.
- Make sure both prescribers know you are taking these two medicines together.
The goal is simply to adjust and watch, not to alarm you. Your care team can handle this by individualizing your dose and monitoring.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
3 reports — tap to read
a) In a separate published investigation, the concurrent administration of 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) at 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) 1.
b) In a further independent published investigation, 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) alongside 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 of 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 likewise rose by 2.0-fold (range 1.4- to 2.5-fold) 1.
c) In stable renal transplant patients on long-term cycloSPORINE (a CYP3A4 substrate) treatment, adding oral voriconazole (200 mg every 12 hours for 8 days) raised the 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 in the absence of voriconazole 1.
Common questions
Can I take Voriconazole and Clindamycin together?
Voriconazole can raise clindamycin levels by slowing its breakdown, which may increase side effects; keep taking both as prescribed and let your care team adjust the dose and monitor you. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Voriconazole and Clindamycin 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 Clindamycin interaction managed?
Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. This interaction is manageable. Your prescriber may lower the clindamycin dose and tailor it to you. Your team may monitor you more closely for side effects such as stomach upset or diarrhea. Report any new or worsening symptoms, especially severe or persistent diarrhea, to your pharmacist or doctor promptl… Management is individual — always follow your own care team's guidance.
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 Voriconazole or Clindamycin 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: 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 Clindamycin
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