Drug Interaction Report

Ramelteon and Ketoconazole Topical: Interaction Details

A pharmacist-reviewed analysis of the Ramelteon and Ketoconazole Topical interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Ramelteon

Rozerem
+

Ketoconazole Topical

Extina® Foam Ketozole® Cream Kuric Nizoral AD® Shampoo Nizoral® Cream Nizoral® Shampoo Xolegel®
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
LinkedIn
Interaction severity
Major
Potentially serious — often needs a change or close monitoring.
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.

Of 23 documented Ramelteon interactions, 22 are rated major — including this one.
Worried about symptoms right now? Contact your pharmacist or prescriber, or call Poison Control at 1-800-222-1222 (US). Call 911 for an emergency.
Onset
delayed
Evidence
probable
Severity
Major

What happens

Increased ramelteon exposure and an increased risk of ramelteon-related adverse reactions

Interaction Deep Dive

Caution is warranted with the concurrent use of ramelteon and ketoconazole. Upon coadministration, monitor patients closely for signs or symptoms of increased or prolonged effects or side effects of ramelteon, and reduce ramelteon dose as deemed necessary1. Ketoconazole, a potent CYP3A4 inhibitor, may increase ramelteon exposure when used concurrently. Subjects of a study were administered ketoconazole 200 mg twice daily for four days, then administered a single dose of ramelteon 16 mg. The ramelteon AUC and Cmax increased 84% and 36%, respectively, compared to ramelteon alone 2.

Why it happens (mechanism)

Inhibition of CYP3A4-mediated metabolism of ramelteon

Literature reports

1 report — tap to read

a) Subjects of a study were administered ketoconazole 200 mg twice daily for four days, then administered a single dose of ramelteon 16 mg. The ramelteon AUC and Cmax increased 84% and 36%, respectively, compared to ramelteon alone 2.

Common questions

Can I take Ramelteon and Ketoconazole Topical together?

Increased ramelteon exposure and an increased risk of ramelteon-related adverse reactions Always confirm with your pharmacist or prescriber before making any change.

How serious is the Ramelteon 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 Ramelteon 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 (2)

  1. Product Information: Ketoconazole oral tablet, ketoconazole oral tablet. Taro Pharmaceuticals U.S.A. Inc. (per DailyMed), Hawthorne, NY, 2024. DailyMed
  2. Product Information: ROZEREM oral tablets, ramelteon oral tablets. Takeda Pharmaceuticals America Inc (per FDA), Deerfield, IL, 2018. DailyMed
Was this write-up helpful?
Ramelteon

Keep reading about Ramelteon

All Ramelteon interactions (23)
Also serious with: Lacosamide Injection Nalbuphine Injection Butorphanol Injection Butorphanol Nasal Spray
Ketoconazole Topical

Keep reading about Ketoconazole Topical

All Ketoconazole Topical interactions (546) Ketoconazole Topical drug information
Also serious with: Colchicine Conivaptan Crizotinib Dabrafenib
Beyond drug–drug

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:

Ramelteon + 1,4-butanediol Activated Charcoal Beer Gamma-hydroxybutyrate (ghb) Grapefruit Kava L-tryptophan St. John's Wort + 220 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

Check another combination

Our instant two-drug interaction checker is almost here.

Coming soon

The instant two-drug checker is on its way.

In the meantime, browse the directory below to look up any drug and see its documented interactions.

Still have questions about this combination?

Every question gets a real answer from a licensed pharmacist — free, and usually within a day.

Ask the pharmacist
This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.