Estradiol and dienogest and Mifepristone interaction

Estradiol and dienogest and Mifepristone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Mifepristone label · effective 2025-09-25

Major

Hormonal contraceptives: Do not use with mifepristone ( 7.6 ).

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Moderate

…study has been conducted to evaluate the effect of mifepristone on substrates of CYP2B6, the concomitant use of bupropion and efavirenz should be undertaken with caution. [See Clinical Pharmacology ( 12.3 )] 7.6 Use of Hormonal Contraceptives Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives.

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Minor

Therefore, non-hormonal contraceptive methods should be used. [See Use In Specific Populations ( 8.3 )]

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From the Estradiol and dienogest (Natazia) label · effective 2024-06-26

Moderate

…exposure at steady state. [See Clinical Pharmacology (12.3).] Substances Increasing the Systemic Exposure of COCs (enzyme inhibitors): Concomitant administration of moderate or strong CYP3A4 inhibitors like azole antifungals (for example, ketoconazole, itraconazole, voriconazole, fluconazole), verapamil, macrolides (for example, clarithromycin, erythromycin), diltiazem,…

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Moderate

In a multiple dose study investigating the effect of CYP3A4 inhibitors (ketoconazole and erythromycin) on Natazia, steady state estradiol and dienogest exposures were increased when co-administered with ketoconazole or erythromycin [see Clinical Pharmacology ( 12.3 )] .

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Minor

Effects of Other Drugs on Combined Oral Contraceptives Substances diminishing the efficacy of COCs: Dienogest is a substrate of CYP3A4.

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.