Ketoconazole Topical and Salmeterol: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Salmeterol
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 salmeterol exposure and an increased risk of salmeterol-related adverse effects (including cardiovascular adverse effects)
Interaction Deep Dive
Salmeterol exposure increased 16-fold when administered concomitantly with ketoconazole. Concomitant use of salmeterol with strong CYP3A inhibitors is not recommended due to an increased risk of systemic corticosteroid adverse effects2. Concomitant administration of salmeterol is not recommended during and 2 weeks after itraconazole treatment as it may result in increased salmeterol plasma concentrations resulting in more salmeterol-related adverse effects 1.
Why it happens (mechanism)
Inhibition of CYP3A-mediated metabolism of salmeterol
Literature reports
1 report — tap to read
a) In a placebo-controlled, crossover, drug interaction study of 20 healthy participants, coadministration of ketoconazole, a strong CYP3A4 inhibitor, at a dose of 400 mg/day with salmeterol at a dose of 50 mcg twice daily for 7 days led to a significant 16-fold increase in salmeterol AUC (ratio with and without ketoconazole 15.76; 90% confidence interval (CI), 10.66 to 23.31) and a significant 1.4-fold increase in salmeterol Cmax (90% CI, 1.23 to 1.68) compared with salmeterol plus placebo. These increases were mainly due to increased bioavailability of the swallowed portion of the dose. Out of the 20 participants, 3 discontinued the study due to beta-agonist-mediated systemic adverse effects; QTc prolongation occurred in 2 participants and palpitations with sinus tachycardia occurred in one. Concomitant use of ketoconazole and salmeterol did not significantly affect mean heart rate, mean blood potassium, mean blood glucose, or mean QTc. However, concomitant use was associated with a higher rate of increases in QTc duration compared with salmeterol and placebo 3.
Common questions
Can I take Ketoconazole Topical and Salmeterol together?
Increased salmeterol exposure and an increased risk of salmeterol-related adverse effects (including cardiovascular adverse effects) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Salmeterol 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Ketoconazole Topical or Salmeterol 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)
- Product Information: SPORANOX(R) oral capsules, itraconazole oral capsules. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2022. DailyMed
- Product Information: AIRDUO(R) DIGIHALER(TM) inhalation powder, fluticasone propionate salmeterol inhalation powder. Teva Respiratory, LLC (per manufacturer), Frazer, PA, 2019.
- Product Information: SEREVENT(R) DISKUS(R) oral inhalation powder, salmeterol xinafoate oral inhalation powder. GlaxoSmithKline LLC (per DailyMed), Research Triangle Park, NC, 2011. DailyMed
Keep reading about Ketoconazole Topical
Keep reading about Salmeterol
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