Levonorgestrel and Norethindrone and ethinyl estradiol interaction

Levonorgestrel and Norethindrone and ethinyl estradiol: 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 Levonorgestrel (Skyla) label · effective 2026-03-04

Major

…Precautions ( 5.4 )] • Postpartum endometritis or infected abortion in the past 3 months • Known or suspected uterine or cervical malignancy • Known or suspected breast cancer or other progestin-sensitive cancer, now or in the past • Uterine bleeding of unknown etiology • Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital…

Contraindicationsby drug classView label on DailyMed
Major

• Known or suspected breast cancer or other progestin-sensitive cancer ( 4 )

Contraindicationsby drug classView label on DailyMed
Moderate

• Uterine perforation may occur and may reduce contraceptive effectiveness or require surgery.

Warnings and precautionsby drug classView label on DailyMed
Moderate

In addition, perforation may reduce contraceptive efficacy and result in pregnancy.

Warnings and precautionsby drug classView label on DailyMed
Minor

• Partial or complete expulsion may occur, which can be unnoticed, leading to loss of contraceptive efficacy.

Warnings and precautionsby drug classView label on DailyMed

From the Norethindrone and ethinyl estradiol (Lo Loestrin Fe) label · effective 2025-03-07

Minor

Changes in Contraceptive Effectiveness Associated with Co-Administration of Other Products If a woman on hormonal contraceptives takes a drug or herbal product that induces enzymes, including CYP3A4, that metabolize contraceptive hormones, counsel her to use additional contraception or a different method of contraception.

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.