ORTHO-NOVUM 1/35-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/35-28 (ORTHO-NOVUM 1/35-28).
Combination oral contraceptive containing ethinyl estradiol and norethindrone. Inhibits ovulation by suppressing gonadotropin release (FSH and LH) from the pituitary; increases viscosity of cervical mucus, impeding sperm penetration; alters endometrial lining, reducing implantation likelihood.
| Metabolism | Ethinyl estradiol primarily metabolized via CYP3A4, with phase II conjugation (glucuronidation and sulfation). Norethindrone metabolized via reduction and conjugation, primarily as glucuronide conjugates. Both undergo enterohepatic recirculation. |
| Excretion | Renal 50-60% as metabolites; fecal 30-40% via biliary elimination; <1% unchanged in urine. |
| Half-life | Norethindrone: 5-14 hrs (terminal); ethinyl estradiol: 10-24 hrs. Steady-state achieved within 5-7 days; terminal half-life supports once-daily dosing. |
| Protein binding | Norethindrone: ~97% (mainly SHBG and albumin); ethinyl estradiol: ~98% (albumin and SHBG, induces SHBG synthesis). |
| Volume of Distribution | Norethindrone: 3-4 L/kg; ethinyl estradiol: 2-4 L/kg. Large Vd indicates extensive tissue distribution and binding. |
| Bioavailability | Oral: Norethindrone ~50-70% (first-pass metabolism); ethinyl estradiol ~40-50% (first-pass metabolism, variable). |
| Onset of Action | Oral: Onset of contraceptive effect within 7 days if started on day 1 of menses; 2-3 weeks if started at other times (requires backup contraception for 7 days). |
| Duration of Action | 24 hours (daily dosing); suppression of ovulation maintained with consistent daily use. Missed dose reduces efficacy. |
1 tablet (norethindrone 1 mg / ethinyl estradiol 35 mcg) orally once daily for 28 consecutive days. Placebo tablets on days 22-28 if included.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild-to-moderate renal impairment. Contraindicated in severe renal impairment or acute renal failure due to potential fluid retention and hyperkalemia. |
| Liver impairment | Contraindicated in acute hepatic disease, hepatocellular carcinoma, and Child-Pugh class C cirrhosis. Use with caution in Child-Pugh class A or B; no specific dose adjustment established, but reduced metabolism may increase estrogen exposure. |
| Pediatric use | Use after menarche. Same dosing as adults: 1 tablet daily for 28 days. Not indicated for use before menarche. |
| Geriatric use | Not indicated for postmenopausal women. In elderly reproductive-age women, same dosing as adults; consider increased risk of thromboembolic events and cardiovascular disease with age. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 1/35-28 (ORTHO-NOVUM 1/35-28).
| Breastfeeding | Excreted in breast milk in small amounts; no adverse effects reported in infants. M/P ratio not established. Use with caution; may reduce milk production. |
| Teratogenic Risk | First trimester: No increased risk of major birth defects based on large epidemiological studies. Second/third trimester: Exposure may increase risk of intrauterine growth restriction, preterm birth, and neonatal complications such as respiratory distress syndrome. Postnatal: May cause hormonal withdrawal effects in neonate. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from oral contraceptive use. Risk increases with age (especially in women over 35) and with heavy smoking (≥15 cigarettes/day). Women taking oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast carcinoma","Known or suspected estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Pregnancy (known or suspected)","Benign or malignant liver tumors (current or history)","Active liver disease or impaired liver function","Hypersensitivity to any component","Heavy smoking (≥15 cigarettes/day) in women over 35"]
| Precautions | ["Increased risk of thromboembolic disorders (venous and arterial), especially in smokers, obese, or hypertensive patients","Risk of myocardial infarction and stroke","Hepatic neoplasia (benign and malignant) reported","Increased risk of gallbladder disease","Elevated blood pressure","Carbohydrate and lipid metabolic effects","Ocular lesions (retinal thrombosis) reported","Headache including migraine","Uterine bleeding irregularities","Depression","Discontinue if jaundice, visual disturbances, or thromboembolic symptoms occur"] |
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| Fetal Monitoring |
| Monitor maternal blood pressure, glucose, and liver function. Fetal ultrasound for growth assessment if used beyond first trimester. |
| Fertility Effects | No long-term effects on fertility; normal fertility returns after discontinuation. |