Belzutifan and Medroxyprogesterone: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Belzutifan
Medroxyprogesterone
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
An increased belzutifan exposure, an increased risk of belzutifan-related adverse effects, reduced hormonal contraceptives exposure, reduced efficacy of hormonal contraceptive, and an increased risk of breakthrough bleeding/contraceptive failure
Interaction Deep Dive
Avoid concomitant use of belzutifan (CYP3A4 inducer) and a hormonal contraceptive1 as it may reduce the contraceptive leading to contraceptive failure or an increase in breakthrough bleeding. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with belzutifan and 2 to continue back-up non-hormonal contraception for 28 days after discontinuing the belzutifan to ensure contraceptive reliability 3. Additionally, concomitant use of belzutifan with inhibitors of CYP2C19, such as hormonal contraceptives may increase belzutifan exposure, which may increase the incidence and severity of adverse reactions. If used concomitantly, monitor for anemia and hypoxia and reduce the dose of belzutifan accordingly (first dose reduction, 80 mg once daily; second dose reduction, 40 mg once daily; third dose reduction, permanently discontinue) 2.
Why it happens (mechanism)
Inhibition of CYP2C19-mediated metabolism of belzutifan; induction of CYP3A4-mediated hormonal contraceptive metabolism by belzutifan
Common questions
Can I take Belzutifan and Medroxyprogesterone together?
An increased belzutifan exposure, an increased risk of belzutifan-related adverse effects, reduced hormonal contraceptives exposure, reduced efficacy of hormonal contraceptive, and an increased risk of breakthrough bleeding/contraceptive failure Always confirm with your pharmacist or prescriber before making any change.
How serious is the Belzutifan and Medroxyprogesterone 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.
Questions for your pharmacist
- Does my dose of Belzutifan or Medroxyprogesterone 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: FEMLYV orally disintegrating tablets, norethindrone acetate, ethinyl estradiol orally disintegrating tablets. Millicent U.S. Inc (per FDA), East Hanover, NJ, 2024. DailyMed
- Product Information: WELIREG(R) oral tablets, belzutifan oral tablets. Merck Sharp & Dohme LLC (per manufacturer), Rahway, NJ, 2025. DailyMed
- Product Information: NuvaRing(R) vaginal ring, etonogestrel ethinyl estradiol vaginal ring. Organon & Co. (per FDA), Jersey City, NJ, 2024.
Keep reading about Belzutifan
Keep reading about Medroxyprogesterone
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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