Estradiol and Phenylbutazone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Estradiol
Phenylbutazone
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
Reduced contraceptive exposure, reduced efficacy of hormonal contraceptives and an increased risk of breakthrough bleeding and/or contraceptive failure
Interaction Deep Dive
Contraceptive effectiveness may be reduced when hormonal contraceptives are coadministered with drugs that increase the metabolism of contraceptive steroids, such as phenylbutazone. This could result in unintended pregnancy or breakthrough bleeding12. In such cases, a back-up nonhormonal method of birth control should be considered 1.
Why it happens (mechanism)
Increased metabolism of contraceptive steroids
Literature reports
1 report — tap to read
a) No alterations were found in phenylbutazone serum concentrations when a single-dose of phenylbutazone was coadministered with low-estrogen combination contraceptives. Seven volunteers using oral contraceptives containing norethindrone 1 mg plus ethinyl estradiol 30 mcg received one dose of phenylbutazone 400 mg. Phenylbutazone serum levels were not affected (the same study reported that oral contraceptives lowered aspirin concentrations). Although phenylbutazone has been demonstrated to interact with oral contraceptives in animal studies, no interaction has been reported in humans 3.
Common questions
Can I take Estradiol and Phenylbutazone together?
Reduced contraceptive exposure, reduced efficacy of hormonal contraceptives and an increased risk of breakthrough bleeding and/or contraceptive failure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Estradiol and Phenylbutazone 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Estradiol or Phenylbutazone 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 (3)
- Product Information: ALESSE(R) 28 oral tablets, levonorgestrel ethinyl estradiol oral tablets. Cadence Health (per FDA), New York, NY, 2024.
- Product Information: Ortho Evra(TM), norelgestromin/ethinyl estradiol. Ortho McNeil Pharmaceutical, Inc. Raritan, NJ, 2001.
- Gupta KC, Joshi JV, Hazari K, et al: Effect of low estrogen combination oral contraceptive on metabolism of aspirin and phenylbutazone. Int J Clin Pharmacol 1982; 20:511-513.
Keep reading about Estradiol
Keep reading about Phenylbutazone
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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