ORTHO-NOVUM 1/35-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/35-21 (ORTHO-NOVUM 1/35-21).
Combination estrogen-progestin contraceptive; suppresses gonadotropin (FSH and LH) secretion via negative feedback, inhibiting ovulation. Increases cervical mucus viscosity and alters endometrial lining, impairing sperm penetration and implantation.
| Metabolism | Norethindrone: primarily hepatic metabolism via reduction and sulfation, with CYP3A4 involvement. Ethinyl estradiol: hepatic metabolism via CYP3A4, also undergoes conjugation (glucuronidation and sulfation). Undergoes enterohepatic recirculation. |
| Excretion | Renal (approx. 40% as metabolites, <10% unchanged), fecal (approx. 60% as metabolites, primarily via bile). |
| Half-life | Norethindrone: 7-9 hours (terminal); Ethinyl estradiol: 13-27 hours (terminal). At steady state, clinical contraceptive efficacy is maintained with daily dosing. |
| Protein binding | Norethindrone: 61-77% bound, primarily to SHBG and albumin; Ethinyl estradiol: 97-98% bound, primarily to albumin. |
| Volume of Distribution | Norethindrone: 4-5 L/kg; Ethinyl estradiol: 2-5 L/kg. Indicates extensive tissue distribution exceeding total body water. |
| Bioavailability | Oral: Norethindrone 50-70%; Ethinyl estradiol 40-50% due to first-pass metabolism. |
| Onset of Action | Oral: Full contraceptive effect achieved after 7 consecutive days of dosing; immediate if started on day 1 of menstrual cycle. |
| Duration of Action | Contraceptive protection lasts 24 hours with daily dosing; withdrawal bleeding usually occurs within 2-3 days after last active tablet. |
One tablet orally once daily for 21 days, followed by 7 placebo tablets. Each tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe renal impairment (GFR <30 mL/min/1.73 m²); use caution and monitor for adverse effects. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For moderate impairment (Child-Pugh class B), avoid use as oral contraceptives may exacerbate liver dysfunction. Mild impairment (Child-Pugh class A): use with caution and monitor liver function. |
| Pediatric use | Safety and efficacy not established in premenarchal girls. Dosing for adolescents post-menarche is same as adults; use with caution and monitor for thromboembolic risk. |
| Geriatric use | Not indicated for postmenopausal women due to absence of ovulation. In perimenopausal women, use lowest effective dose; monitor cardiovascular risk and bone density. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/35-21 (ORTHO-NOVUM 1/35-21).
| Breastfeeding | Excreted in breast milk; may reduce milk production and quality. M/P ratio not established for this combination; progestin-only contraceptives preferred. Use only if benefits outweigh risks; monitor infant for jaundice or growth delay. |
| Teratogenic Risk | FDA Pregnancy Category X; contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects due to progestin component. Second/third trimesters: feminization of male fetus, potential for congenital anomalies, and possible long-term reproductive effects. No safe use in pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use (e.g., myocardial infarction, thromboembolism, stroke). Risk increases with age (>35 years) and number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; cerebral vascular or coronary artery disease; known or suspected pregnancy; undiagnosed abnormal genital bleeding; known/suspected breast cancer; estrogen-dependent neoplasia; benign/malignant liver tumor (active); known or suspected pregnancy; hypersensitivity to any component; smoking in women >35 years; uncontrolled hypertension; diabetes with vascular disease; migraines with focal aura; major surgery with prolonged immobilization.
| Precautions | Increased risk of thromboembolic disorders (venous and arterial), stroke, myocardial infarction; hepatic neoplasia; gallbladder disease; hypertension; carbohydrate/lipid effects; ocular lesions (retinal thrombosis); headache/migraine; breakthrough bleeding/spotting; depression; fluid retention; hereditary angioedema; chloasma; liver function impairment. |
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| Fetal Monitoring | Monitor blood pressure, liver function, glucose levels, and signs of thromboembolism. Fetal ultrasound for anomaly detection if unintended exposure occurs. Assess for cholestasis or hypertension. |
| Fertility Effects | Reversibly suppresses ovulation; fertility returns within 1-3 cycles post-discontinuation. No permanent negative impact on fertility. May cause transient menstrual irregularity upon cessation. |