Alitretinoin and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 11, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Alitretinoin
Simvastatin
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
Decreased simvastatin plasma concentrations
Interaction Deep Dive
Concomitant use of alitretinoin and simvastatin may lead to a slight decrease in simvastatin plasma concentrations. An analysis of 18 patients in a drug interaction study demonstrated that concomitant administration of alitretinoin and simvastatin yielded a modest but statistically significant decrease in the AUC and Cmax of simvastatin by 16% and 23%, respectively1. Monitor patients for loss of simvastatin’s lipid-lowering effect, making dosage adjustments or therapy modifications as necessary.
Why it happens (mechanism)
Competitive inhibition of CYP3A4-mediated metabolism of simvastatin
Literature reports
1 report — tap to read
a) In a randomized, crossover, drug interaction equivalence study comparing the pharmacokinetics (PK) of simvastatin, ketoconazole, and cyclosporine in the presence of alitretinoin (n=54; age range, 18 to 45 years), an analysis of 18 patients revealed simvastatin AUC and Cmax fell outside the margin of equivalence, with a modest but statistically significant decrease by 16% and 23%, respectively, in the presence of alitretinoin compared with administration of simvastatin alone. The study also examined the effects of simvastatin, ketoconazole, and cyclosporine administration on alitretinoin pharmacokinetics. Subjects received single and multiple doses of alitretinoin 30 mg or simvastatin 40 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 simvastatin AUC and Cmax alone and with coadministration had to fall within 0.8 to 1.25. Following multiple doses, alitretinoin AUC (GMR, 1.071; 90% CI, 0.920 to 1.247) was equivalent when administered with simvastatin and without; however, the simvastatin AUC and Cmax fell outside the equivalence margins when given with alitretinoin compared with administration alone, showing a slight but significant decrease in AUC (GMR, 0.862; 90% CI, 0.782 to 0.952) and Cmax (GMR, 0.757; 90% CI, 0.643 to 0.890) 1.
Common questions
Can I take Alitretinoin and Simvastatin together?
Decreased simvastatin plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Alitretinoin and Simvastatin 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 "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Alitretinoin or Simvastatin 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 Simvastatin
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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