Norethindrone
AYGESTIN
Pronunciation: nor-eth-IN-droen
“Nora, Effin’ drone”
What it isProgesterone-receptor agonist; contraception, abnormal bleeding, and endometrial protection.
Why this oneIts traditional progestin-only pill has a narrower missed-dose window than newer drospirenone-only contraception.
What limits itIrregular bleeding is the usual reason for stopping; CYP3A4 inducers can cause contraceptive failure.
Norethindrone prescription history
Animated chart of estimated U.S. prescriptions per year, Menopausal hormones (1941–2026). Norethindrone enters in 1965 (estimated).
FDA-approved for
- contraception (~1962)
Principal riskA narrow three-hour dosing window for the progestin-only pill
Classes and tags
Clinical profile
Legacy pregnancy categoryX
Defining liabilityVenous thromboembolism and hormone-related adverse effects; estrogen also lowers lamotrigine exposure.
FDA label
Read the full label on DailyMed ↗
NO BOXED WARNINGS
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| Secondary amenorrhea; abnormal uterine bleeding due to hormonal imbalance (no organic pathology) | Women with estrogen-primed endometrium | 2.5–10 mg QD x5–10 days | 2.5–10 mg QD x5–10 days (withdrawal bleed usually 3–7 days after stopping) | Undefined (labeled range 2.5–10 mg QD x5–10 days) |
| Endometriosis | Women | 5 mg QD x2 weeks | Increase by 2.5 mg/day every 2 weeks to 15 mg QD; hold six to nine months or until breakthrough bleeding demands temporary termination | 15 mg QD |
Titration Endometriosis: every two weeks (+2.5 mg/day)
Renal Undefined
Hepatic Contraindicated in impaired liver function or liver disease
Not indicated in children
Instructions
- Adapt therapy to the specific indication and individual therapeutic response
- Recurrent abnormal uterine bleeding: planned menstrual cycling with norethindrone acetate may benefit
- Not for use with estrogen in postmenopausal women for endometrial protection
Available strengths
- tab 0.35, 5 mg
Contraindications
- Known or suspected pregnancy; use as a diagnostic test for pregnancy
- Undiagnosed vaginal bleeding
- Known, suspected or history of breast cancer
- Active DVT or PE, or history of these
- Active or recent (e.g. within past year) arterial thromboembolic disease (stroke, MI)
- Impaired liver function or liver disease
Cautions
- Cardiovascular disorders: manage arterial vascular and VTE risk factors appropriately
- Visual abnormalities: discontinue pending exam for sudden vision loss, proptosis, diplopia or migraine; discontinue if papilledema/retinal vascular lesions
- Fluid retention: observe epilepsy, migraine, cardiac or renal dysfunction
- Breakthrough/irregular bleeding: consider nonfunctional causes; diagnose undiagnosed bleeding
- History of depression: observe; discontinue if serious recurrence
- Lipid/carbohydrate metabolism effects: monitor hyperlipidemia and diabetes
- Advise the pathologist of progestin therapy
Adverse reactions
- Breakthrough bleeding, spotting, change in menstrual flow, amenorrhea
- Edema, weight changes
- Cholestatic jaundice, liver test abnormalities
- Rash with/without pruritus, urticaria, anaphylactic/anaphylactoid reactions
- Melasma/chloasma, acne
- Clinical depression, mood swings, insomnia
- Breast enlargement/tenderness
- Headache/migraine
- Nausea
- Decreased HDL, increased LDL/HDL ratio
- Thrombotic/thromboembolic events (DVT, PE, retinal/cerebral thrombosis)
- Optic neuritis
Pregnancy Contraindicated in pregnancy (may cause fetal harm); first-trimester progestin exposure associated with congenital abnormalities incl. mild virilization of female fetuses
Lactation Detectable amounts of progestins in breast milk; use caution in nursing women
Cost
Generic entry1987
Open Norethindrone in the interactive console ↗
Memory aids: interaction avatars
Open Norethindrone in the interactive console ↗
Self-check
- How does the traditional norethindrone-only pill’s missed-dose window compare with drospirenone-only contraception?
Narrower. - What CYP interaction can cause norethindrone contraceptive failure?
CYP3A4 induction.