Estradiol and norethindrone and Medroxyprogesterone interaction

Estradiol and norethindrone and Medroxyprogesterone: 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

…vein thrombosis (DVT), pulmonary embolism (PE), stroke and myocardial infarction (MI) in postmenopausal women (50 to 79 years of age) during 5.6 years of treatment with daily oral conjugated estrogen (CE) [0.625 mg] combined with medroxyprogesterone acetate (MPA) [2.5 mg], relative to placebo [see Warnings and Precautions (5.1) , and Clinical Studies (14.5) ] .

Boxed warningnames MedroxyprogesteroneView label on DailyMed
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

From the Medroxyprogesterone (medroxyprogesterone acetate) label · effective 2026-02-23

Moderate

The following laboratory tests may be affected by progestins including MPA Injectable Suspension, USP: (a) Plasma and urinary steroid levels are decreased (e.g., progesterone, estradiol, pregnanediol, testosterone, cortisol).

Drug interactionsnames Estradiol and norethindroneView label on DailyMed
Moderate

Loss of Bone Mineral Density Use of MPA Injectable Suspension, USP reduces serum estrogen levels and is associated with significant loss of bone mineral density (BMD).

Warnings and precautionsby drug classView label on DailyMed
Moderate

Cancer Risks Breast Cancer Women who have or have had a history of breast cancer should not use hormonal contraceptives, including MPA Injectable Suspension, USP, because breast cancer may be hormonally sensitive [see Contraindications (4) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Monitoring A woman who is taking hormonal contraceptive should have a yearly visit with her healthcare professional for a blood pressure check and for other indicated healthcare.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Drugs or herbal products that induce such enzymes may decrease the plasma concentrations of contraceptive hormones, and may decrease the effectiveness of hormonal contraceptives.

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.