Estradiol and norethindrone and Mifepristone interaction

Estradiol and norethindrone 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 Estradiol and norethindrone (Estradiol / Norethindrone Acetate) label · effective 2026-06-26

Major

Therefore, the relevance of the WHI findings regarding adverse cardiovascular events, dementia and breast cancer to lower CE plus other MPA doses, other routes of administration, or other estrogen plus progestogen products is not known.

Boxed warningby drug classView label on DailyMed
Moderate

Inducers and/or inhibitors of CYP3A4 may affect estrogen drug metabolism and decrease or increase the estrogen plasma concentration.

Drug interactionsby drug classView label on DailyMed
Moderate

Inhibitors of CYP3A4 such as erythromycin, clarithromycin, ketoconazole, itraconazole, ritonavir and grapefruit juice may increase plasma concentrations of estrogens and result in adverse reactions.

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Minor

Therefore, inducers or inhibitors of CYP3A4 may affect estrogen drug metabolism.

Drug interactionsby drug classView label on DailyMed

From the Mifepristone label · effective 2025-09-25

Major

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

Drug interactionsby drug classView label on DailyMed
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.

Drug interactionsby drug classView label on DailyMed
Minor

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

Drug interactionsby drug classView label on DailyMed

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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.