Eplerenone and Ketoconazole Topical: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Eplerenone
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
Increased eplerenone exposure
Interaction Deep Dive
Concomitant use of eplerenone and a strong CYP3A4 inhibitor is contraindicated due to the potential for significantly elevated eplerenone plasma concentrations via inhibition of CYP3A4-mediated eplerenone metabolism1. In a clinical study, with coadministration of a single oral 2 mg dose of loperamide (CYP3A4 substrate) with multiple oral doses of lonafarnib (strong CYP3A4 inhibitor) 100 mg twice daily for 5 days in healthy subjects, the Cmax and AUC of loperamide were increased by 214% and 299%, respectively 2, and in a case report, hypotension occurred one day after the initiation of voriconazole therapy in a 48-year-old man who had been maintained on NIFEdipine, candesartan, and eplerenone for hypertension 3.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of eplerenone
Literature reports
2 reports — tap to read
a) In a clinical study, with coadministration of a single oral 2 mg dose of loperamide (CYP3A4 substrate) with multiple oral doses of lonafarnib (strong CYP3A4 inhibitor) 100 mg twice daily for 5 days in healthy subjects, the Cmax and AUC of loperamide were increased by 214% and 299%, respectively 2.
b) In a case report, hypotension occurred the day following initiation of voriconazole (strong CYP3A4 inhibitor) therapy in a 48-year-old man maintained on NIFEdipine, candesartan, and eplerenone for hypertension. The patient's medical history included myelodysplastic syndrome, bone marrow transplantation, acute graft-versus-host disease, and hypertension. Blood pressure had been maintained in a range of 130 to 146/70 to 88 mmHg with regular administration of candesartan 8 mg/day, NIFEdipine 40 mg/day, and eplerenone 50 mg/day. Voriconazole for the prophylaxis of fungal infection was initiated with 6 mg/kg IV every 12 hours for 2 doses, followed by 4 mg/kg IV every 12 hours. The following day, the patient's blood pressure fell to 76/48 mmHg with no signs of hypovolemia, blood loss, or septicemia. Five days following discontinuation of all antihypertensive therapies, blood pressure increased to 164 to 180/80 to 84 mmHg. Candesartan and NIFEdipine (dose reduced to 20 mg/day) were restarted, which continued to control hypertension without the need for eplerenone therapy 3.
Common questions
Can I take Eplerenone and Ketoconazole Topical together?
Increased eplerenone exposure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Eplerenone and Ketoconazole Topical interaction?
It is rated contraindicated. These should generally not be used together.
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 "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 Eplerenone 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 (3)
- Product Information: INSPRA(R) oral tablets, eplerenone oral tablets. GD Searle LLC (per DailyMed), New York, NY, 2020. DailyMed
- Product Information: ZOKINVY(TM) oral capsules, lonafarnib oral capsules. Eiger BioPharmaceuticals Inc (per FDA), Palo Alto, CA, 2024. DailyMed
- Kato J, Mori T, Nakamura Y, et al: Hypotension due to the drug interaction of voriconazole with eplerenone and nifedipine. Eur J Clin Pharmacol 2009; 65(3):323-324. PubMed
Keep reading about Eplerenone
Keep reading about Ketoconazole Topical
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