NORINYL 1+35 28-DAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORINYL 1+35 28-DAY (NORINYL 1+35 28-DAY).
Norethindrone is a progestogen that suppresses gonadotropin release, inhibiting ovulation; ethinyl estradiol is an estrogen that provides negative feedback on the hypothalamic-pituitary-ovarian axis, further suppressing ovulation and altering cervical mucus and endometrial thickness.
| Metabolism | Norethindrone is primarily metabolized via reduction and conjugation; ethinyl estradiol is metabolized by CYP3A4 and undergoes conjugation. Both are hepatically eliminated. |
| Excretion | Renal: 50-60% (conjugates and metabolites), Fecal: 30-40% (biliary elimination of norethindrone and ethinyl estradiol conjugates); total clearance ~4-6 mL/min/kg. |
| Half-life | Norethindrone: 7-8 hours (terminal half-life); steady state achieved after 5 days. Ethinyl estradiol: biphasic with terminal half-life of 13-27 hours (mean ~17 hours). Clinical context: dosing interval of 24 hours allows stable hormone levels after first cycle. |
| Protein binding | Norethindrone: 80-85% bound to albumin and SHBG; Ethinyl estradiol: 95-98% bound to albumin (not strongly to SHBG). |
| Volume of Distribution | Norethindrone: 2-4 L/kg; Ethinyl estradiol: 2.5-5 L/kg; both indicate extensive tissue distribution. |
| Bioavailability | Norethindrone: 64-67% (oral, first-pass metabolism); Ethinyl estradiol: 38-48% (oral, extensive first-pass conjugation); food does not significantly alter bioavailability. |
| Onset of Action | Oral: Contraceptive effect requires 7 days of consecutive dosing to achieve ovulation suppression; therapeutic effect (cycle control) occurs within first cycle (typically 21 days). |
| Duration of Action | 24 hours (supports once-daily dosing); contraceptive efficacy maintained if no missed pills and consistent dosing; after discontinuation, ovulation may return within 1-2 weeks. |
One tablet orally once daily for 28 consecutive days (21 active tablets followed by 7 inert tablets).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl <30 mL/min); contraindicated in acute renal failure or significant renal disease due to potential fluid retention. |
| Liver impairment | Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). Use with caution in Child-Pugh class A (mild hepatic impairment) as metabolism may be reduced; monitor for adverse effects. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents, dose is same as adults: one tablet orally once daily for 28 days. |
| Geriatric use | Not indicated for use after menopause. In perimenopausal women, same adult dosing applies; monitor for increased risk of thromboembolism, hypertension, and carbohydrate intolerance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORINYL 1+35 28-DAY (NORINYL 1+35 28-DAY).
| Breastfeeding | Excreted in breast milk in small amounts; M/P ratio not established for norethindrone/ethinyl estradiol combination. Use with caution; may reduce milk production. Consider alternative contraception during breastfeeding. |
| Teratogenic Risk | First trimester: No increased risk of major birth defects from inadvertent exposure. Second and third trimesters: Avoid use due to risk of fetal harm from estrogen/progestin exposure; association with placental abruption, fetal growth restriction, and preterm delivery. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular adverse events from combined hormonal contraceptive use. This risk increases with age, especially in women over 35, and with the number of cigarettes smoked. Women who use combined hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; undiagnosed abnormal genital bleeding; pregnancy; liver tumors or active liver disease; known hypersensitivity; concomitant use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir.
| Precautions | Increased risk of thromboembolic disorders; liver disease; hypertension; gallbladder disease; carbohydrate and lipid effects; headache; irregular bleeding; ectopic pregnancy; depression; cervical cancer; hereditary angioedema; chloasma; retinal thrombosis; monitoring of blood pressure, glucose, lipids, liver function. |
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| Fetal Monitoring |
| Monitor blood pressure, liver function, and signs of thromboembolism. Perform fetal growth ultrasound if used inadvertently in later pregnancy. |
| Fertility Effects | Normal ovulation and fertility return promptly after discontinuation. No evidence of permanent impairment. |