Alitretinoin and Ketoconazole: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Alitretinoin
Ketoconazole
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 alitretinoin plasma concentrations
Interaction Deep Dive
The concomitant administration of alitretinoin (a CYP3A4 substrate) with a CYP3A4 inhibitor (such as ketoconazole) may result in increased alitretinoin plasma concentrations. An analysis of 16 patients in a drug interaction study demonstrated that concomitant administration of alitretinoin and ketoconazole increased the AUC and Cmax of alitretinoin by up to 40% and up to 60%, respectively. Reduction in the dose of alitretinoin may be required with concomitant use of ketoconazole or other CYP3A4 inhibitors1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of alitretinoin by ketoconazole
Literature reports
1 report — tap to read
a) In a randomized, crossover, drug interaction equivalence study comparing the pharmacokinetics (PK) of alitretinoin in the presence of simvastatin, ketoconazole, and cyclosporine (n=54; age range, 18 to 45 years), an analysis of 16 patients revealed alitretinoin AUC and Cmax fell outside the margin of equivalence and were significantly increased by up to 40% and up to 60%, respectively, in the presence of ketoconazole compared with administration of alitretinoin alone. The study also examined the effects of alitretinoin administration on ketoconazole pharmacokinetics. Subjects received single and multiple doses of alitretinoin 30 mg or ketoconazole 200 mg alone and in combination. To deem the PK parameters equivalent (showing no interaction), the 90% confidence interval (CI) around the geometric mean ratio (GMR) comparing alitretinoin and ketoconazole AUC and Cmax alone and with coadministration had to fall within 0.8 to 1.25. Following multiple doses, ketoconazole AUC (GMR, 1.054; 90% CI, 0.933 to 1.193) and Cmax (GMR, 1.031; 90% CI, 0.921 to 1.157) were equivalent when administered with alitretinoin and without; however, the alitretinoin AUC and Cmax fell outside the equivalence margins when given with ketoconazole compared with administration alone, showing a significant increase in AUC (GMR, 0.718; 90% CI, 0.628 to 0.823) and Cmax (GMR, 0.654; 90% CI, 0.521 to 0.822). Alitretinoin may require a dose reduction when given in combination with ketoconazole or other CYP3A4 inhibitors 1.
Common questions
Can I take Alitretinoin and Ketoconazole together?
Increased alitretinoin plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Alitretinoin and Ketoconazole interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Alitretinoin or Ketoconazole 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 (1)
- Schmitt-Hoffmann AH, Roos B, Sauer J, et al: Pharmacokinetic interactions between alitretinoin and ketoconazole or simvastatin or ciclosporin A. Clin Exp Dermatol 2011; 36 Suppl 2:24-28. PubMed
Keep reading about Ketoconazole
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.
Check another combination
Our instant two-drug interaction checker is almost here.
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