ORTHO-NOVUM 10/11-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO-NOVUM 10/11-28 (ORTHO-NOVUM 10/11-28).
Combination estrogen-progestin contraceptive; suppresses gonadotropins (FSH, LH) via negative feedback inhibition of hypothalamic-pituitary axis, preventing ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes first-pass metabolism with extensive conjugation (glucuronidation and sulfation). Norethindrone: metabolized via reduction, conjugation (glucuronidation), and hydroxylation; also involves CYP3A4 to a lesser extent. |
| Excretion | Renal (50-60% as metabolites, <10% unchanged); fecal (30-40%) with biliary elimination of conjugates. |
| Half-life | Norethindrone: 5-14 hours; Ethinyl estradiol: 8-20 hours. Steady state reached within 5 days. Clinical significance: missed doses may increase pregnancy risk due to rapid decline. |
| Protein binding | Norethindrone: 61% bound to albumin and 36% to SHBG; Ethinyl estradiol: 98% bound to albumin. |
| Volume of Distribution | Norethindrone: 4 L/kg; Ethinyl estradiol: 4-5 L/kg. Indicates extensive tissue distribution. |
| Bioavailability | Oral: Norethindrone ~64%; Ethinyl estradiol ~45% (due to first-pass metabolism). |
| Onset of Action | Oral: 7 days of continuous dosing to achieve contraceptive effect; immediate if started on day 1 of menses. |
| Duration of Action | Contraceptive effect lasts 24 hours; requires daily dosing. Missed pills reduce duration; backup contraception needed if >2 pills missed. |
One tablet daily for 28 days, starting on day 1 of menstrual cycle. Each tablet contains 1 mg norethindrone and 10 mcg ethinyl estradiol for first 10 tablets, then 1 mg norethindrone and 35 mcg ethinyl estradiol for next 11 tablets, followed by 7 placebo tablets.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment guidelines for renal impairment. Use with caution in patients with renal impairment, as ethinyl estradiol and norethindrone may accumulate. Monitor for fluid retention and hypertension. |
| Liver impairment | Contraindicated in patients with severe hepatic disease (Child-Pugh class C) due to potential accumulation and hepatotoxicity. For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose adjustment, but monitor liver function tests. |
| Pediatric use | Not indicated for use before menarche. Post-menarche: same dosing as adults (one tablet daily for 28 days). Safety and efficacy in adolescents have not been specifically established; however, use is common off-label. |
| Geriatric use | Not indicated for use after menopause. No specific geriatric dosing; however, elderly women should not use combination hormonal contraceptives due to increased risk of thromboembolic events and cardiovascular disease. Use alternative contraception if needed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 10/11-28 (ORTHO-NOVUM 10/11-28).
| Breastfeeding | Excreted in breast milk in small amounts; M/P ratio approximately 0.4. May reduce milk production and quality. Use alternative contraception during breastfeeding. |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects and cardiovascular malformations; second and third trimesters: Risk of fetal growth restriction, preterm birth, and transient metabolic disturbances. Contraindicated during pregnancy (FDA Category X). |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events (myocardial infarction, thromboembolism, stroke) from combination hormonal contraceptive use. Risk increases with age and with smoking intensity (especially >15 cigarettes/day). Women >35 years who smoke should not use this medication.
| Serious Effects |
["Known or suspected pregnancy","Current or past thromboembolic disorders (DVT, PE, stroke, MI)","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Estrogen-dependent neoplasia","Hepatic adenomas or carcinomas, or active liver disease (e.g., acute hepatitis)","Undiagnosed abnormal uterine bleeding","Heavy smoking (>15 cigarettes/day) in women ≥35 years"]
| Precautions | ["Thromboembolic disorders (DVT, PE, arterial thrombosis, stroke, MI) – increased risk especially in smokers >35 years, obese, or with hypertension","Cerebrovascular disease","Hepatic disease (including hepatic adenoma or impaired liver function)","Gallbladder disease","Hypertension","Glucose intolerance/diabetes mellitus","Headache (including migraine with or without aura)","Uterine bleeding irregularities","Depression","Possible increased risk of cervical cancer with long-term use"] |
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| Monitor blood pressure, glucose levels, liver function, and signs of thromboembolism. In pregnancy, discontinue immediately and monitor for fetal anomalies via ultrasound. |
| Fertility Effects | No significant long-term effects on fertility; return to ovulation may be delayed briefly after discontinuation. Use in early pregnancy may be teratogenic. |