NORETHINDRONE ACETATE
Clinical safety rating: avoid
CYP3A4 inducers can decrease efficacy Can cause thromboembolic disorders.
Progestin that suppresses gonadotropin secretion, inhibits ovulation, and induces endometrial thinning. Also binds to progesterone receptors, exerting antiestrogenic effects.
| Metabolism | Hepatic via reduction and conjugation; CYP3A4 is involved; also undergoes glucuronidation. |
| Excretion | Renal (39-61% as metabolites), biliary/fecal (35-49% as metabolites). Less than 1% excreted unchanged. |
| Half-life | Terminal elimination half-life is approximately 5-8 hours (mean 7.5 hours). Clinically, steady-state is achieved within 2-3 days of daily dosing. |
| Protein binding | Approximately 80-85% bound to albumin; weakly bound to sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Apparent volume of distribution is approximately 4 L/kg. This large Vd indicates extensive tissue distribution and binding. |
| Bioavailability | Oral: Approximately 64-70% (first-pass metabolism reduces bioavailability from 100% to ~60%). Not administered parenterally in the US. |
| Onset of Action | Oral: Onset of progestational effect within 2-4 hours. Depot injection (not available in US): Onset within 24 hours. |
| Duration of Action | Oral: Duration of progestational effect is approximately 24 hours with once-daily dosing. For contraceptive use, continuous daily administration is required to maintain effect. |
Oral, 5 mg once daily for 14 days per cycle, beginning on day 1 of menstrual cycle; for endometriosis, 5 mg daily for 14 days then 10 mg daily for 14 days, then 15 mg daily, or as tolerated up to 15 mg daily continuous.
| Dosage form | TABLET |
| Renal impairment | No adjustment recommended for mild to moderate impairment; insufficient data for severe impairment (CrCl <30 mL/min). Use with caution. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Use with caution, reduce dose by 50% or monitor for adverse effects. Child-Pugh C: Contraindicated. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; initiate at low end of dosing range due to potential for hepatic or renal impairment and increased sensitivity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CYP3A4 inducers can decrease efficacy Can cause thromboembolic disorders.
| FDA category | Positive |
| Breastfeeding | Small amounts of norethindrone acetate are excreted in breast milk (M/P ratio not well defined). Use with caution; may potentially affect infant development. Limited data, but generally considered compatible with breastfeeding at low doses. |
| Teratogenic Risk | First trimester: Exposure is associated with a slight increase in risk of cardiovascular defects and limb reduction defects. Second and third trimesters: Continued exposure may cause masculinization of female fetuses (clitoral enlargement, labial fusion) due to androgenic activity. Prolonged use in pregnancy is contraindicated. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Women over 35 who smoke should not use norethindrone acetate.
| Common Effects | abnormal uterine bleeding |
| Serious Effects |
Known or suspected pregnancy, undiagnosed abnormal genital bleeding, history of or current thromboembolic disorders, liver disease or tumors, known or suspected breast carcinoma.
| Precautions | Increased risk of thromboembolic disorders, hepatic disease, depression, fluid retention, breakthrough bleeding, and reduced glucose tolerance. Monitor for hypertension and lipid changes. |
Loading safety data…
| Fetal Monitoring | Monitor maternal blood pressure, liver function, and glucose tolerance. In cases of inadvertent use, fetal ultrasound for anatomical assessment and growth monitoring is recommended. |
| Fertility Effects | Norethindrone acetate inhibits ovulation and is used as a contraceptive; fertility returns upon discontinuation. No permanent adverse effects on fertility reported. |