Roflumilast and Atorvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Jul 15, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Atorvastatin
Roflumilast
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 roflumilast exposure and an increased risk of roflumilast-related adverse events
Interaction Deep Dive
Coadministration of roflumilast with CYP3A4 inhibitors may increase roflumilast systemic exposure and may result in increased adverse reactions. Weigh the potential for increased adverse reactions against benefit. In an open-label crossover study of 16 healthy volunteers, concomitant oral administration of ketoconazole 200 mg twice daily for 13 days and a single dose of roflumilast 500 mcg resulted in increased roflumilast Cmax and AUC values of 23% and 99%, respectively, and a 38% reduction and 3% increase in the Cmax and AUC of roflumilast N-oxide (active metabolite), respectively12.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of roflumilast
Literature reports
4 reports — tap to read
a) In an open-label crossover study of 16 healthy volunteers, concomitant oral administration of ketoconazole 200 mg twice daily for 13 days and a single dose of roflumilast 500 mcg resulted in increased roflumilast Cmax and AUC values of 23% and 99%, respectively, and a 38% reduction and 3% increase in the Cmax and AUC of roflumilast N-oxide (active metabolite), respectively 12.
b) In an open-label crossover study in 16 healthy volunteers, the coadministration of CYP3A4 inhibitor erythromycin (500 mg 3 times daily for 13 days) with a single oral dose of 500 mcg roflumilast resulted in 40% and 70% increase in Cmax and AUC for roflumilast, respectively, and a 34% decrease and a 4% increase in Cmax and AUC for roflumilast N-oxide, respectively 2.
c) In an open-label crossover study in 16 healthy volunteers, the coadministration of CYP3A4 inhibitor, fluvoxaMINE (50 mg daily for 14 days) with a single oral dose of 500 mcg roflumilast showed a 12 % and 156% increase in roflumilast Cmax and AUC along with a 210% decrease and 52% increase in roflumilast N-oxide Cmax and AUC, respectively 2.
d) In an open-label crossover study in 16 healthy volunteers, the coadministration of CYP3A4 inhibitor enoxacin (400 mg twice daily for 12 days) with a single oral dose of 500 mcg roflumilast resulted in an increased Cmax and AUC of roflumilast by 20% and 56%, respectively. Roflumilast N-oxide Cmax was decreased by 14% while roflumilast N-oxide AUC was increased by 23% 2.
Common questions
Can I take Roflumilast and Atorvastatin together?
Increased roflumilast exposure and an increased risk of roflumilast-related adverse events Always confirm with your pharmacist or prescriber before making any change.
How serious is the Roflumilast and Atorvastatin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
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 Roflumilast or Atorvastatin 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)
- Product Information: DALIRESP(R) oral tablets, roflumilast oral tablets. AstraZeneca Pharmaceuticals LP (per FDA), Wilmington, DE, 2018. DailyMed
- Product Information: ZORYVE(R) topical foam, roflumilast topical foam. Arcutis Biotherapeutics Inc (per Manufacturer), Westlake Village, CA, 2025. DailyMed
Keep reading about Atorvastatin
Keep reading about Roflumilast
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