NORETHINDRONE ACETATE AND ETHINYL ESTRADIOL AND FERROUS FUMARATE
Clinical safety rating: avoid
CYP3A4 inducers can decrease efficacy Can cause thromboembolic disorders.
Norethindrone acetate is a progestin that suppresses gonadotropin release, inhibiting ovulation and altering cervical mucus and endometrium. Ethinyl estradiol is an estrogen that provides cycle control and contributes to contraceptive efficacy. Ferrous fumarate provides iron supplementation.
| Metabolism | Norethindrone acetate is metabolized via reduction and conjugation; ethinyl estradiol is metabolized primarily by CYP3A4. |
| Excretion | Norethindrone acetate and ethinyl estradiol are primarily excreted in urine (40-60% as metabolites) and feces (20-40% as metabolites). Ferrous fumarate is absorbed and iron is utilized; unabsorbed iron is excreted in feces. |
| Half-life | Norethindrone: 8-11 hours (terminal). Ethinyl estradiol: 10-20 hours (terminal). Clinical context: Steady-state achieved after 5-7 days; half-life supports once-daily dosing. |
| Protein binding | Norethindrone: ~60-80% bound to albumin and SHBG. Ethinyl estradiol: ~95-98% bound to albumin. Ferrous fumarate: iron is bound to transferrin and ferritin. |
| Volume of Distribution | Norethindrone: 2-4 L/kg. Ethinyl estradiol: 3-5 L/kg. Clinical meaning: Large Vd indicates extensive tissue distribution, not limited to plasma. |
| Bioavailability | Oral: Norethindrone acetate is rapidly converted to norethindrone; bioavailability ~50-60% due to first-pass metabolism. Ethinyl estradiol: ~40-50% oral bioavailability. Ferrous fumarate: iron absorption is variable (10-35% depending on iron stores). |
| Onset of Action | Oral administration: Contraceptive effect begins within 7 days if started on day 1 of menstrual cycle; iron supplementation effect is gradual. |
| Duration of Action | Contraceptive effect lasts for the duration of daily dosing (24 hours). Iron supplementation effect persists with continued intake. |
One tablet (1 mg norethindrone acetate, 20 mcg ethinyl estradiol, and 75 mg ferrous fumarate) orally once daily for 28 days, without interruption. Take the first tablet on the first day of menstrual bleeding.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. Not recommended for use in patients with severe renal impairment or end-stage renal disease due to lack of safety data. |
| Liver impairment | Contraindicated in patients with severe hepatic impairment (Child-Pugh class C). Use with caution in mild to moderate impairment, with no specific dose adjustment recommended; monitor liver function. |
| Pediatric use | Safety and efficacy established in females of reproductive age (post-menarche). Dosing is same as adult (one tablet daily). Not indicated for pre-menarche use. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific studies in geriatric population; follow standard adult dosing in women of reproductive age. |
| 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 | Excreted into breast milk. Ethinyl estradiol and norethindrone acetate M/P ratio not well defined. May reduce milk production and quality due to estrogen content. Not recommended during breastfeeding. Use alternative contraception. |
| Teratogenic Risk | Pregnancy category X. Use contraindicated in pregnancy. First trimester: estrogen/progestin combination associated with fetal cardiovascular defects (e.g., VSD), limb reduction defects, and neural tube defects. Second/third trimester: increased risk of fetal genital abnormalities in females (e.g., vaginal adenosis, clear cell adenocarcinoma) and hypospadias in males. Postnatal: potential long-term neurodevelopmental effects. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular adverse events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use this product.
| Common Effects | abnormal uterine bleeding |
| Serious Effects |
Thrombophlebitis or thromboembolic disorders, cerebral vascular or coronary artery disease, known or suspected breast cancer, undiagnosed abnormal uterine bleeding, cholestatic jaundice of pregnancy or jaundice with prior pill use, hepatic adenoma or carcinoma, known or suspected pregnancy, heavy smoking in women over 35.
| Precautions | Risk of thromboembolic disorders, cardiovascular disease, liver disease, hypertension, gallbladder disease, carbohydrate and lipid effects, ocular lesions, irregular bleeding, ferrous fumarate interaction with other iron supplements, and need for regular medical monitoring. |
Loading safety data…
| Fetal Monitoring | Pregnancy test before initiation. Monitor for signs of thromboembolism (DVT, PE), hypertension, and hepatic dysfunction. Baseline and periodic liver function tests, blood pressure, and glucose. If pregnancy occurs, discontinue and consider fetal ultrasound for congenital anomalies. |
| Fertility Effects | Reversible inhibition of ovulation while taken. After discontinuation, return to normal fertility generally within 1-3 cycles. No permanent impairment. |