NORINYL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORINYL (NORINYL).
Combination of norethindrone (progestin) and ethinyl estradiol (estrogen) provides contraception by inhibiting gonadotropin secretion via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing ovulation, increasing cervical mucus viscosity, and altering endometrial receptivity.
| Metabolism | Norethindrone is metabolized primarily via reduction and conjugation; ethinyl estradiol is metabolized via CYP3A4 and undergoes glucuronidation. Both undergo enterohepatic circulation. |
| Excretion | Renal: ~60% as metabolites, biliary/fecal: ~40% as glucuronide conjugates |
| Half-life | Terminal half-life: norethindrone 7-8 hours, ethinyl estradiol 13-27 hours; clinical context: steady-state achieved in 3-5 half-lives |
| Protein binding | Norethindrone: 80% bound to albumin and SHBG; ethinyl estradiol: 97% bound to albumin |
| Volume of Distribution | Norethindrone: 4 L/kg, indicates extensive tissue distribution; ethinyl estradiol: 4-5 L/kg |
| Bioavailability | Oral: norethindrone ~65%, ethinyl estradiol ~40-45% due to first-pass metabolism |
| Onset of Action | Oral: contraceptive effect begins after 7 days of continuous dosing |
| Duration of Action | 24 hours; one tablet daily maintains contraceptive effect |
One tablet (norethindrone 1 mg/ethinyl estradiol 0.035 mg) orally once daily for 21 days, followed by 7 placebo tablets. For first cycle, start on first Sunday after menstruation begins or on day 1 of menstrual cycle.
| Dosage form | TABLET |
| Renal impairment | No specific GFR-based dose adjustments recommended; use with caution in renal impairment due to potential fluid retention. |
| Liver impairment | Contraindicated in Child-Pugh class B or C (severe hepatic impairment) or active liver disease. For mild impairment (Child-Pugh A), use with caution and monitor liver function. |
| Pediatric use | Not indicated for use before menarche; dosing for postmenarchal adolescents same as adult. |
| Geriatric use | Not indicated for use in postmenopausal women; no geriatric dosing established due to lack of indication. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORINYL (NORINYL).
| Breastfeeding | Norethindrone and ethinyl estradiol are excreted in breast milk in small amounts (M/P ratio approximately 0.5-1.0 for norethindrone). May reduce milk production and quality. Use only if clearly needed and with caution, as long-term effects on infant are unknown. Typically not recommended during breastfeeding. |
| Teratogenic Risk | Pregnancy category X. Contraindicated in pregnancy. First trimester: Increased risk of congenital anomalies, including cardiac and limb defects, due to progestin and estrogen exposure. Second and third trimesters: Risk of feminization of male fetus, urogenital sinus abnormalities, and clitoral hypertrophy from progestin (norethindrone). Post-fertilization: Disruption of fetal development. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. This risk increases with age and heavy smoking (≥15 cigarettes/day) and is significant in women over 35. Women over 35 who smoke should not use this product.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Undiagnosed abnormal genital bleeding","Pregnancy or suspected pregnancy","Benign or malignant liver tumors, or active liver disease","Hypersensitivity to any component","Women over 35 who smoke cigarettes"]
| Precautions | ["Thrombotic disorders (venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction)","Cerebrovascular disease","Hepatic neoplasia (benign and malignant)","Gallbladder disease","Hypertension","Carbohydrate and lipid metabolism effects","Ocular lesions (retinal thrombosis, optic neuritis)","Headache (including migraine)","Breakthrough bleeding and spotting","Depression","Malignant neoplasms (breast, cervical)","Effect on pregnancies (fetal harm if used during pregnancy)","Lactation (may decrease milk production)","Hereditary angioedema","Chloasma","Laboratory test interference"] |
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| Fetal Monitoring | If inadvertent exposure during pregnancy, monitor fetal growth and development via ultrasound. Maternal monitoring includes blood pressure, liver function, and signs of thromboembolism. No routine fetal monitoring required unless complications arise. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropins. Normal fertility typically returns within 1-3 cycles after discontinuation. No permanent adverse effects on fertility. |