Ketoconazole Topical and Prednisolone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Ketoconazole Topical
Prednisolone
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
An increased risk of corticosteroid side effects (neuropsychiatric reactions, fluid and electrolyte disturbances, hypertension, hyperglycemia)
Interaction Deep Dive
Ketoconazole doses at greater than or equal to 200 mg daily for at least 5 to 7 days have been reported to decrease the metabolism of prednisoLONE, the active metabolite of prednisone, by about 50%2. However, other studies have failed to find a pharmacokinetic or pharmacodynamic interaction between ketoconazole and prednisoLONE 31.
Why it happens (mechanism)
Decreased prednisoLONE metabolism
Literature reports
3 reports — tap to read
a) Ten healthy volunteers who received an intravenous bolus of prednisoLONE 0.8 mg/kg and an oral dose of prednisone 0.8 mg/kg on two occasions were studied. The steroids were given once before and once with ketoconazole 200 mg after ketoconazole had been given for 6 to 7 days. After the administration of ketoconazole, the total body clearance of total prednisoLONE decreased in all subjects as a result of a decline in the nonrenal and renal clearance of prednisoLONE. The urinary excretion of 6-betahydroxyprednisolone, a metabolite of prednisoLONE, decreased by more than two-fold in all subjects. Similarly, the urinary excretion of 6-betahydroxy cortisol was also decreased after ketoconazole therapy, indicating that ketoconazole is a potent inhibitor of 6-betahydroxylase, a well-defined oxidase of the cytochrome P450 system 2.
b) No significant interaction between ketoconazole and prednisoLONE was observed in one study. Four healthy male volunteers were administered prednisone 20 mg alone and in combination with oral ketoconazole 200 mg, which had been initiated six days prior to prednisone treatment. PrednisoLONE clearance, mean residence time, terminal slope, and volume of distribution were not significantly altered by the presence of ketoconazole. Renal excretion of prednisone and prednisoLONE was also not significantly changed 1.
c) No significant pharmacokinetic or pharmacodynamic interaction between ketoconazole and prednisoLONE was found in one study. Six healthy volunteers received an intravenous prednisoLONE dose of 14.8 mg alone and on the sixth day of therapy with ketoconazole 200 mg. Coadministration with ketoconazole did not significantly affect the clearance, mean residence time, volume of distribution, or plasma protein binding characteristics of prednisoLONE. The authors concluded that when combined therapy with ketoconazole and a corticosteroid is necessary, prednisoLONE may be preferable to methylprednisolone, which has been demonstrated to be pharmacokinetically altered by the presence of ketoconazole 3.
Common questions
Can I take Ketoconazole Topical and Prednisolone together?
An increased risk of corticosteroid side effects (neuropsychiatric reactions, fluid and electrolyte disturbances, hypertension, hyperglycemia) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Ketoconazole Topical and Prednisolone interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "delayed". Effects tend to build up gradually over days to weeks.
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 Ketoconazole Topical or Prednisolone 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)
- Ludwig EA, Slaughter RL, Savliwala M, et al: Steroid-specific effects of ketoconazole on corticosteroid disposition: unaltered prednisolone elimination. DICP 1989; 23:858-861. PubMed
- Zurcher RM, Frey BM, & Frey FJ: Impact of ketoconazole on the metabolism of prednisolone. Clin Pharmacol Ther 1989; 45:366-372. DOI
- Yamashita SK, Ludwig EA, Middleton E Jr. et al: Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone. Clin Pharmacol Ther 1991; 49:558-570. PubMed
Keep reading about Ketoconazole Topical
Keep reading about Prednisolone
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