Fluticasone and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Fluticasone
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 fluticasone exposure and an increased risk of cardiovascular effects
Interaction Deep Dive
Concomitant use of fluticasone with strong CYP3A4 inhibitors is not recommended due to an increased risk of systemic corticosteroid adverse effects1 and increased cardiovascular effects may occur 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of fluticasone
Literature reports
7 reports — tap to read
a) In an observational study, 10 of 12 patients with cystic fibrosis who received concomitant inhaled fluticasone and oral itraconazole had evidence of hypothalamic-pituitary-adrenal (HPA) axis suppression, which was moderate or severe in 5 subjects. Clinical evidence of Cushing syndrome was present in 1 subject. All participants had reduced basal and peak serum cortisol levels and a blunted challenge response, particularly when compared with cystic fibrosis patients who received fluticasone but not itraconazole 3.
b) When orally inhaled fluticasone propionate (1000 mcg) was coadministered with ketoconazole 200 mg once daily (n=8), fluticasone AUC increased 1.9-fold and plasma cortisol AUC decreased 45%. There was no effect on urinary cortisol excretion 1.
c) In a drug interaction study, the fluticasone furoate AUC was increased by 36%, when coadministered with ketoconazole 400 mg compared with placebo. The increase in fluticasone furoate exposure was associated with a 27% reduction in weighted mean serum cortisol (0 to 24 hours) 2.
d) In a pharmacokinetic study (N=23), administration of a single midazolam 5 mg dose following multiple doses of idelalisib 150 mg orally twice daily resulted in significant increases in midazolam exposure (138% increase in Cmax and 437% increase in AUC) compared with midazolam alone 4.
e) Coadministration of a single dose of midazolam (a sensitive CYP3A4 substrate) following 3 weeks of ceritinib 750 mg daily under fasted conditions increased the midazolam AUC by 5.4-fold and Cmax by 1.8-fold compared to midazolam administered alone 5.
f) Coadministration of diazePAM and idelalisib for 10 days in a 71-year-old woman resulted in altered mental status and respiratory failure. She was receiving diazePAM 5 mg twice daily, venlafaxine XL 300 mg daily, and had initiated idelalisib 150 mg twice daily 10 days prior to presentation. The patient presented with lethargy, speaking difficulty, and progressive weakness inhibiting her ability to stand. Arterial blood gas analysis revealed respiratory acidosis and type II respiratory failure (pH 7.3, PO2 113 mmHg, PCO2 63 mmHg, and bicarbonate 31 mEq/L). Venlafaxine was reduced to 37.5 mg daily, diazePAM was changed to LORazepam 0.5 mg twice daily, and full-dose idelalisib was restarted with no further sequelae 6.
g) The strong CYP3A inhibitor conivaptan 40 mg/day IV increased the AUC of midazolam, a CYP3A4 substrate, by approximately 100% with a 1 mg IV dose and by 200% with a 2 mg oral dose. Conivaptan 30 mg/day IV tripled the AUC of simvastatin, a CYP3A4 substrate. And conivaptan 40 mg orally twice daily doubled the AUC and half-life of amLODIPine, a CYP3A4 substrate 7.
Common questions
Can I take Fluticasone and Ketoconazole Topical together?
Increased fluticasone exposure and an increased risk of cardiovascular effects Always confirm with your pharmacist or prescriber before making any change.
How serious is the Fluticasone and Ketoconazole Topical 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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Fluticasone or Ketoconazole Topical 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 (7)
- Product Information: AIRDUO(R) DIGIHALER(TM) inhalation powder, fluticasone propionate salmeterol inhalation powder. Teva Respiratory, LLC (per manufacturer), Frazer, PA, 2019.
- Product Information: BREO ELLIPTA inhalation powder, fluticasone furoate vilanterol inhalation powder. GlaxoSmithKline (per FDA), Research Triangle Park, NC, 2023. DailyMed
- Gilchrist FJ, Cox KJ, Rowe R, et al: Itraconazole and inhaled fluticasone causing hypothalamic-pituitary-adrenal axis suppression in adults with cystic fibrosis. J Cyst Fibros 2013; 12(4):399-402. PubMed
- Jin F, Robeson M, Zhou H, et al: Clinical drug interaction profile of idelalisib in healthy subjects. J Clin Pharmacol 2015; 55(8):909-919. DOI
- Product Information: ZYKADIA(R) oral capsules, ceritinib oral capsules. Novartis Pharmaceuticals Corporation (per FDA), East Hanover, NJ, 2019. DailyMed
- Bossaer JB & Chakraborty K: Drug interaction between idelalisib and diazepam resulting in altered mental status and respiratory failure. J Oncol Pharm Pract 2017; 23(6):470-472. PubMed
- Product Information: VAPRISOL(R) intravenous injection, conivaptan HCl intravenous injection. Cumberland Pharmaceuticals Inc (per FDA), Nashville, TN, 2016.
Keep reading about Ketoconazole Topical
Keep reading about Fluticasone
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