Roflumilast and Estradiol Transdermal Patch: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Estradiol Transdermal Patch
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 oral contraceptives containing gestodene and ethinyl estradiol (dual inhibitors that inhibit both CYP3A4 and CYP1A2) simultaneously 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 in 20 healthy adult volunteers, coadministration of a single oral dose of roflumilast with repeated doses of a fixed combination oral contraceptive containing 0.075 mg gestodene and 0.03 mg ethinyl estradiol to steady state caused a 38% increase and 12% decrease in Cmax of roflumilast and roflumilast N-oxide, respectively. Roflumilast and roflumilast N-oxide AUCs were increased by 51% and 14%, respectively1.
Why it happens (mechanism)
Inhibition of CYP1A2-mediated metabolism of roflumilast; inhibition of CYP3A4-mediated metabolism of roflumilast
Literature reports
4 reports — tap to read
a) In an open-label crossover study in 16 healthy volunteers, the coadministration of dual CYP3A4/CYP1A2 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 1.
b) In an open-label crossover study in 20 healthy adult volunteers, coadministration of a single oral dose of roflumilast with repeated doses of a fixed combination oral contraceptive containing 0.075 mg gestodene and 0.03 mg ethinyl estradiol to steady state caused a 38% increase and 12% decrease in Cmax of roflumilast and roflumilast N-oxide, respectively. Roflumilast and roflumilast N-oxide AUCs were increased by 51% and 14%, respectively 1.
c) In an open-label crossover study in 16 healthy volunteers, the coadministration of dual CYP3A4/1A2 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% 1.
d) In an open-label crossover study of 16 healthy volunteers, concomitant oral administration of erythromycin 500 mg 3 times daily for 13 days and a single dose of roflumilast 500 mcg increased Cmax and AUC values of roflumilast by 40% and 70%, respectively, with a 34% reduction and 4% increase in Cmax and AUC of roflumilast N-oxide (active metabolite), respectively 1.
Common questions
Can I take Roflumilast and Estradiol Transdermal Patch 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 Estradiol Transdermal Patch 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.
Questions for your pharmacist
- Does my dose of Roflumilast or Estradiol Transdermal Patch 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 (1)
- Product Information: ZORYVE(R) topical foam, roflumilast topical foam. Arcutis Biotherapeutics Inc (per Manufacturer), Westlake Village, CA, 2025. DailyMed
Keep reading about Estradiol Transdermal Patch
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