Drug Interaction Report

Fluconazole and Nevirapine: Interaction Details

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Nevirapine

Viramune Viramune® Viramune® XR
+

Fluconazole

Diflucan
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Updated Aug 8, 2026
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Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 166 documented Fluconazole interactions, 128 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
rapid
Evidence
established
Severity
Major

What happens

Increased nevirapine exposure and an increased risk of nevirapine-related adverse events

Interaction Deep Dive

Use caution with concomitant use of fluconazole and nevirapine as it may increase nevirapine exposure. Coadministration of nevirapine and fluconazole has resulted in an approximate 100% increase in nevirapine exposure. Monitor closely for nevirapine-associated adverse effects12. In a study of HIV-infected patients, nevirapine exposure (AUC (0 to 8 hr)) was increased by 29% in those receiving a nevirapine-containing regimen plus fluconazole. Despite the significant increase in nevirapine exposure, there was no evidence of increased nevirapine toxicity 3.

Why it happens (mechanism)

Inhibition of CYP3A-mediated metabolism of nevirapine

Literature reports

2 reports — tap to read

a) Concomitant use of fluconazole and nevirapine significantly increased nevirapine exposure in a subset of HIV-infected Uganda patients (n=49) from a placebo-controlled study. Patients were treated with an antiretroviral regimen, that contained nevirapine (200 mg twice daily), plus either fluconazole (n=27) or placebo (n=22) for a median of 55 weeks (range, 48 to 68 weeks). The fluconazole and placebo groups had geometric mean pre-dose nevirapine concentrations of 5141 nanogram/mL (ng/mL; 19,305 mcmol/L) and 3865 ng/mL (14,513 mcmol/L), respectively. Nevirapine Cmax was also higher with fluconazole (p=0.012). The nevirapine AUC (0 to 8 hr) was increased by 29% in the fluconazole group (geometric mean AUC, 46,135 ng x hr/mL vs 35,871 ng x hr/mL ). The nevirapine concentration at 8 hr was increased by 28% with concomitant fluconazole (p=0.02). Nevirapine clearance decreased with fluconazole (5.58 L/hr vs 4.34 L/hr; p=0.0172). There was no evidence of increased risk of hepatotoxicity with concomitant use of nevirapine and fluconazole despite the increased nevirapine exposure. In the study from which the subset was taken, elevated transaminases (greater than 5 times the ULN) resulted in trial withdrawal in 5.2% (27 of 522) and 6.3% (34 of 541) of patients being treated with fluconazole and placebo, respectively. A total of 1.3% (14 of 1063) had liver function tests greater than 5 times the ULN in the initial 6 to 12 weeks. Of these 14 patients, 5 and 9 received fluconazole and placebo, respectively (p=0.42) 3.

b) Administration of fluconazole resulted in an approximate 100% increase in nevirapine exposure 12.

Common questions

Can I take Fluconazole and Nevirapine together?

Increased nevirapine exposure and an increased risk of nevirapine-related adverse events Always confirm with your pharmacist or prescriber before making any change.

How serious is the Fluconazole and Nevirapine interaction?

It is rated major. Potentially serious — often needs a change or close monitoring.

How quickly could this interaction happen?

The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.

How strong is the evidence for this interaction?

The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.

From our Q&A

Real reader questions about these medications, each personally answered by our pharmacist:

Questions for your pharmacist

  • Does my dose of Fluconazole or Nevirapine 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 (3)

  1. Product Information: VIRAMUNE(R) oral suspension, nevirapine oral suspension. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2024. DailyMed
  2. Product Information: VIRAMUNE XR(R) oral extended-release tablets, nevirapine oral extended-release tablets. Boehringer Ingelheim Pharmaceuticals Inc (per FDA), Ridgefield, CT, 2024. DailyMed
  3. Wakeham K, Parkes-Ratanshi R, Watson V, et al: Co-administration of fluconazole increases nevirapine concentrations in HIV-infected Ugandans. J Antimicrob Chemother 2010; 65(2):316-319. PubMed
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Beyond drug–drug

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.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.