Naproxen and Voriconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Voriconazole
Naproxen
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 naproxen exposure and plasma concentration
Interaction Deep Dive
Concomitant administration of naproxen, a CYP2C9 substrate, together with voriconazole may result in increased naproxen exposure and plasma concentration due to inhibition of CYP2C9-mediated naproxen metabolism by voriconazole. Although no formal drug interaction studies have been performed with naproxen and voriconazole, two separate single-dose drug interaction studies involving coadministration of ibuprofen or diclofenac (both are CYP2C9 substrates) with voriconazole demonstrated significantly increased ibuprofen and diclofenac exposure and plasma concentration32. Frequent monitoring for NSAID toxicities is recommended during coadministration and dosage reduction of naproxen may be necessary 1.
Why it happens (mechanism)
Inhibition of CYP2C9-mediated naproxen metabolism
Literature reports
2 reports — tap to read
a) Voriconazole significantly increased exposure and plasma concentration of diclofenac in a two-way, crossover design study in 10 healthy male volunteers. Adults (age range, 20 to 31 yr) received a single oral dose of diclofenac 50 mg either alone (control phase) or 1 hour following receipt of the final dose of voriconazole on day 2 (400 mg orally twice daily on day 1, followed by 200 mg orally twice daily on day 2). The washout interval between phases was 2 weeks. During the voriconazole phase, the diclofenac AUC was 178% (95% confidence interval (CI), 143% to 212%); p less than 0.001) and the diclofenac Cmax was 214% (95% CI 128% to 300%; p less than 0.05) of their respective control value, representing an increase of 78% and 114% in AUC and Cmax, respectively. Concurrent administration of voriconazole also decreased the renal clearance of diclofenac by 47% (95% CI, -76% to -16%; p less than 0.01) compared with control; however, the amount of diclofenac excreted in the urine was only 0.7% and 0.6% of the total dose in the control and voriconazole phases, respectively. Voriconazole administration did not effect the elimination half-life of diclofenac. Inhibition of CYP2C9-mediated diclofenac metabolism by voriconazole was proposed as the most probable mechanism of this interaction 2.
b) Voriconazole significantly increased the exposure and plasma concentration of the pharmacologically active S-(+) enantiomer of ibuprofen in a two-way, crossover design study in 12 healthy male volunteers. Adults (age range, 19 to 23 yr) a single oral dose of ibuprofen 400 mg either alone (control phase) or 1 hour following receipt of the final dose of voriconazole on day 2 (400 mg orally twice daily on day 1, followed by 200 mg orally twice daily on day 2). The washout interval between phases was 2 weeks. During the voriconazole phase, the AUC of the S-(+) ibuprofen was 205% (p less than 0.001) and the Cmax 122% (p less than 0.01) of the respective control value, representing an increase of 105% and 22% in AUC and Cmax, respectively. The mean elimination half-life of S-(+) ibuprofen was prolonged by 43% (going from 2.4 hr to 3.2 hr) compared with control (p less than 0.01). The effect of voriconazole of the R-(-) enantiomer of ibuprofen was much less, with no effect observed in the Cmax and just a 20% increase in AUC (p less than 0.05). Inhibition of CYP2C9-mediated ibuprofen metabolism by voriconazole was proposed as the most probable mechanism of this interaction 3.
Common questions
Can I take Naproxen and Voriconazole together?
Increased naproxen exposure and plasma concentration Always confirm with your pharmacist or prescriber before making any change.
How serious is the Naproxen and Voriconazole interaction?
It is rated moderate. Can be significant — usually manageable with 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.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Naproxen 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 anything you'd monitor while I'm on both?
References (3)
- Product Information: VFEND(R) intravenous injection, oral tablets, oral suspension, voriconazole intravenous injection, oral tablets, oral suspension. Pfizer Inc. New York, NY, 2010. DailyMed
- Hynninen VV, Olkkola KT, Leino K, et al: Effect of voriconazole on the pharmacokinetics of diclofenac. Fundam Clin Pharmacol 2007; 21(6):651-656. PubMed
- Hynninen VV, Olkkola KT, Leino K, et al: Effects of the antifungals voriconazole and fluconazole on the pharmacokinetics of s-(+)- and R-(-)-Ibuprofen. Antimicrob Agents Chemother 2006; 50(6):1967-1972.
Keep reading about Voriconazole
Keep reading about Naproxen
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.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist