ORTHO-NOVUM 1/50 28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/50 28 (ORTHO-NOVUM 1/50 28).
Combination oral contraceptive; suppresses gonadotropin secretion (FSH, LH) via estrogen and progestin, inhibiting ovulation, increasing cervical mucus viscosity, and altering endometrial structure.
| Metabolism | Ethinyl estradiol metabolized via CYP3A4; mestranol (prodrug converted to ethinyl estradiol) and norethindrone metabolized via hepatic reduction and conjugation. |
| Excretion | Renal: ~50-60% as metabolites; fecal: ~30-40% as metabolites; biliary: <10% |
| Half-life | Norethindrone: 5-12 h (mean 8 h); Mestranol: 12-24 h (mean 18 h); steady-state reached within 5-7 days |
| Protein binding | Norethindrone: 96-98% (SHBG, albumin); Mestranol: 97-99% (albumin, SHBG with lower affinity) |
| Volume of Distribution | Norethindrone: 1.5-2.5 L/kg; Mestranol: 0.9-1.5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: norethindrone ~64%; mestranol ~40-70% (first-pass metabolism) |
| Onset of Action | Oral: ovulation suppression begins within 2-3 days of continuous use; contraceptive effect requires 7 days of consistent dosing |
| Duration of Action | Contraceptive coverage persists for 24 h; missed pills reduce efficacy; withdrawal bleed occurs within 2-3 days after active pills |
One tablet (1 mg norethindrone/50 mcg mestranol) orally once daily for 21 days, followed by 7 days of placebo tablets (inactive) for a 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe impairment (CrCl <30 mL/min); avoid use due to potential for fluid retention and hypertension. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh C) or acute liver disease. For mild to moderate impairment (Child-Pugh A or B), use with caution; monitor liver function, no specific dose adjustment guidelines available. |
| Pediatric use | Not indicated in prepubertal girls. Postmenarchal adolescents: same as adult dosing; initiate after menarche and once growth complete. |
| Geriatric use | Not indicated for postmenopausal women; no geriatric-specific dosing. Use with caution in older women due to increased risk of thromboembolism and cardiovascular events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/50 28 (ORTHO-NOVUM 1/50 28).
| Breastfeeding | Contraindicated during breastfeeding. Norethindrone and mestranol/metabolites are excreted in breast milk; M/P ratio not established. May reduce milk production and quality, and expose infant to hormonal effects. Recommend alternative contraception. |
| Teratogenic Risk | Pregnancy category X. First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects due to progestin and estrogen exposure. Second and third trimesters: Risk of fetal genital abnormalities (e.g., hypospadias, clitoral hypertrophy), low birth weight, and potential long-term metabolic effects. Use contraindicated in pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Use is contraindicated in women over 35 years who smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; pregnancy; hepatic adenoma or carcinoma; jaundice with prior pill use; hypersensitivity to components; women over 35 who smoke.
| Precautions | Increased risk of thromboembolic disorders, venous thromboembolism (VTE), arterial thrombosis, myocardial infarction, stroke, hepatic neoplasia, and gallbladder disease. Regular monitoring of blood pressure, glucose, and lipid profiles recommended. |
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| Fetal Monitoring | Not applicable as contraindicated in pregnancy. For accidental exposure: monitor fetal growth via ultrasound, assess for congenital anomalies, and evaluate neonatal genital development. No specific maternal monitoring required outside of routine prenatal care. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropins. After discontinuation, normal fertility typically returns within 1-3 cycles. May cause transient irregular cycles or amenorrhea; no evidence of long-term fertility impairment. |