Methylprednisolone and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Methylprednisolone
Ketoconazole Topical
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 may inhibit the metabolism of methylPREDNISolone and thus decrease its clearance2. Caution is warranted with the concurrent use of methylPREDNISolone and ketoconazole, as it may increase methylPREDNISolone exposure. Upon coadministration, monitor patients closely for signs or symptoms of increased or prolonged effects or side effects of methylPREDNISolone, and reduce dosage of methylPREDNISolone as deemed necessary 1. Ketoconazole doses at greater than 200 mg daily for at least six to seven days have been reported to decrease the metabolism of methylPREDNISolone by about 50 to 60% 534.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of methylPREDNISolone
Literature reports
3 reports — tap to read
a) MethylPREDNISolone clearance was decreased by 50% to 60% following therapy with oral ketoconazole 200 mg daily for six to seven days in 14 healthy volunteers; the methylPREDNISolone-induced adrenal suppression was also enhanced. The patients were given single intravenous methylPREDNISolone doses of 15, 20, or 30 mg before and after the ketoconazole dosing period. A 50% reduction in the methylPREDNISolone dose is recommended 3.
b) Six healthy male volunteers were studied by in three phases to determine the effects of ketoconazole on the disposition of methylPREDNISolone. During Phase I, the 24-hour baseline cortisol concentration was determined in each subject. Phase II consisted of methylPREDNISolone 20 mg being administered by a rapid intravenous bolus, and blood samples were drawn to define the pharmacokinetic characteristics of methylPREDNISolone. After a two-week wash-out period, ketoconazole 200 mg daily was administered for six days, followed by methylPREDNISolone 20 mg intravenously to make up Phase III. Ketoconazole was found to raise the methylPREDNISolone area under the concentration-time curve (AUC) from 829 ng/hr/mL to 1953 ng/hr/mL, representing a 135% increase. The clearance of methylPREDNISolone decreased from 423 mL/hr/kg during monotherapy to 170 mL/hr/kg with ketoconazole coadministration. The cortisol AUC was lower during ketoconazole therapy (795 ng/hr/mL) as compared to baseline (2139 ng/hr/mL) and phase II (1189 ng/hr/mL) 4.
c) Ketoconazole doses at greater than 200 mg daily for at least six to seven days have been reported to decrease the metabolism of methylPREDNISolone by about 50 to 60% 5.
Common questions
Can I take Methylprednisolone and Ketoconazole Topical 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 Methylprednisolone 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 "delayed". Effects tend to build up gradually over days to weeks.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Methylprednisolone 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 (5)
- Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
- Product Information: MEDROL(R) oral tablets, methylprednisolone oral tablets. Pharmacia & Upjohn Co (per FDA), New York, NY, 2024. DailyMed
- Kandrotas RJ, Slaughter RL, Brass C, et al: Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous cortisol. Clin Pharmacol Ther 1987; 42:465-470. PubMed
- Glynn AM, Slaughter RL, Brass C, et al: Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion. Clin Pharmacol Ther 1986; 39:654-659. DOI
- 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
Keep reading about Methylprednisolone
Keep reading about Ketoconazole Topical
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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