ORTHO-NOVUM 10-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO-NOVUM 10-21 (ORTHO-NOVUM 10-21).
Combination estrogen-progestin contraceptive; suppresses gonadotropin release (FSH, LH) from pituitary, inhibiting ovulation; increases viscosity of cervical mucus and alters endometrial lining, reducing sperm penetration and implantation.
| Metabolism | Hepatic via cytochrome P450 3A4 (CYP3A4) for norethindrone and ethinyl estradiol; first-pass metabolism; enterohepatic recirculation; elimination as glucuronide and sulfate conjugates in urine and feces. |
| Excretion | Renal approximately 50-60% as metabolites, biliary/fecal approximately 30-40% as metabolites and unchanged drug. |
| Half-life | Norethindrone 5-14 hours (mean 8 hours), ethinyl estradiol 7-20 hours (mean 13 hours). Steady-state achieved in 5-10 days. |
| Protein binding | Norethindrone: 90-95% bound to albumin and SHBG; ethinyl estradiol: 97-98% bound to albumin. |
| Volume of Distribution | Norethindrone: 4 L/kg; ethinyl estradiol: 2-4 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: norethindrone 50-80%, ethinyl estradiol 40-60% due to first-pass metabolism. |
| Onset of Action | Oral: 1-2 hours for serum hormone levels to reach contraceptive range. |
| Duration of Action | 24 hours for contraceptive effect; required daily dosing. |
1 tablet (1 mg norethindrone, 0.035 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 days of no tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment (GFR <30 mL/min) due to lack of safety data. |
| Liver impairment | Contraindicated in Child-Pugh class B or C hepatic impairment. For Child-Pugh class A, use with caution and monitor liver function; no specific dose adjustment established. |
| Pediatric use | Not indicated for use in pediatric patients before menarche. Post-menarche: same adult dosing, 1 tablet orally once daily for 21 days, then 7 days off. |
| Geriatric use | Not indicated for use in postmenopausal women. Not recommended for elderly patients due to lack of efficacy and increased thrombotic risk. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 10-21 (ORTHO-NOVUM 10-21).
| Breastfeeding | Excreted into breast milk in small amounts (M/P ratio approximately 0.5). May reduce milk production and composition. Use during breastfeeding not recommended; alternative contraception advised. |
| Teratogenic Risk | Pregnancy category X. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects. Second and third trimesters: associated with fetal adrenal suppression, virilization of female fetuses, and potential for long-term neurodevelopmental effects. Use contraindicated in pregnant women. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially in women >35 years) and with number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
| Serious Effects |
Thrombophlebitis or thromboembolic disorders; history of DVT or PE; cerebrovascular or coronary artery disease; known or suspected breast cancer; endometrial cancer or other estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; known or suspected pregnancy; liver tumors (benign or malignant) or active liver disease; hypersensitivity to any component; age >35 years and smoking cigarettes; uncontrolled hypertension; diabetes with vascular involvement; migraine with focal aura; major surgery with prolonged immobilization.
| Precautions | Increased risk of thromboembolic disorders (e.g., DVT, pulmonary embolism), myocardial infarction, stroke; hepatic neoplasia (benign and malignant); gallbladder disease; hypertension; glucose intolerance; elevated triglyceride levels; exacerbation of depression; fluid retention; headache; irregular bleeding; potential for decreased efficacy with concomitant enzyme-inducing drugs; instruct to report visual disturbances or migraine; discontinue if jaundice occurs; monitor for signs of thrombosis. |
Loading safety data…
| Fetal Monitoring |
| During inadvertent exposure, monitor fetal growth via ultrasound, assess for congenital anomalies. Maternal monitoring includes blood pressure, liver function, and glucose tolerance. Evaluate for thromboembolic events. |
| Fertility Effects | Suppresses ovulation via combined hormonal effects. Return to baseline fertility may be delayed up to 3 months after discontinuation. No permanent impairment. |