NORINYL 1+80 21-DAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for NORINYL 1+80 21-DAY (NORINYL 1+80 21-DAY).
Combination oral contraceptive containing norethindrone (a progestin) and ethinyl estradiol (an estrogen). Inhibits ovulation by suppressing gonadotropin release (FSH and LH). Also increases cervical mucus viscosity and alters endometrial morphology.
| Metabolism | Ethinyl estradiol undergoes first-pass metabolism in the intestinal wall and liver via CYP3A4, with conjugation and enterohepatic recirculation. Norethindrone is metabolized in the liver primarily via reduction and conjugation, with CYP3A4 involvement. Both are excreted in urine and feces. |
| Excretion | Renal (40-60% as metabolites), fecal (20-30%) |
| Half-life | Norethindrone: 8-11 hours; Mestranol: 12-24 hours (metabolized to ethinyl estradiol with half-life 20-27 hours). Steady-state after 5-7 days. |
| Protein binding | Norethindrone: 61% bound to albumin and SHBG; Mestranol/ethinyl estradiol: 98% bound to albumin |
| Volume of Distribution | Norethindrone: 3.6 L/kg; Mestranol/ethinyl estradiol: 1.5-4.0 L/kg |
| Bioavailability | Oral: norethindrone ~64%; mestranol ~40-60% (prodrug, converted to ethinyl estradiol) |
| Onset of Action | Oral: 7 days for contraceptive effect |
| Duration of Action | 24 hours; requires daily dosing; withdrawal bleed within 2-3 days after last active pill |
One tablet orally once daily for 21 days, followed by 7 days of no active treatment.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment required for renal impairment. Use with caution in patients with renal dysfunction. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B), use only if benefits outweigh risks and monitor liver function closely. |
| Pediatric use | Not indicated for use before menarche. For adolescents post-menarche, same adult dosing: one tablet orally once daily for 21 days, then 7-day pill-free interval. |
| Geriatric use | Not indicated for use after menopause. No specific dose adjustments in elderly women of reproductive age; standard adult dosing applies. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for NORINYL 1+80 21-DAY (NORINYL 1+80 21-DAY).
| Breastfeeding | Small amounts of norethindrone and ethinyl estradiol excreted in breast milk; M/P ratio not established. Use is not recommended during breastfeeding as estrogen may reduce milk production and quality; progestin-only contraception preferred. |
| Teratogenic Risk | First trimester: No conclusive evidence of major malformations from combined hormonal contraceptives; however, data are limited. Second/third trimester: Use is contraindicated due to possible adverse effects on fetal development, including potential masculinization of female genitalia (androgenic progestin) and other hormonal effects, though the risk is low with norethindrone. Postnatal: No specific long-term effects documented. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Risk increases with age (especially >35 years) and heavy smoking (≥15 cigarettes/day). Women who use combination oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Carcinoma of endometrium or other estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenoma or carcinoma","Known or suspected pregnancy","Active liver disease with abnormal liver function","Hypersensitivity to any component","Diabetes with vascular involvement","Uncontrolled hypertension","Major surgery with prolonged immobilization","Migraine with focal aura or over age 35 with any migraine"]
| Precautions | ["Thrombotic events (venous thromboembolism, stroke, MI)","Cigarette smoking","Hypertension","Gallbladder disease","Hepatic neoplasia","Carbohydrate/lipid effects","Headache/migraine","Bleeding irregularities","Use in pregnancy","Diabetes","Depression","Hereditary angioedema","Chloasma","Hepatic impairment","Renal impairment","Breast cancer risk"] |
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| Fetal Monitoring | No standard monitoring required during pregnancy since drug is contraindicated. If exposure occurs, routine obstetric care and fetal ultrasound for anatomy assessment are recommended. |
| Fertility Effects | Temporary; after discontinuation, return to fertility may be delayed by a few months but no permanent effect on fertility. |