ORTHO-NOVUM 10/11-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO-NOVUM 10/11-21 (ORTHO-NOVUM 10/11-21).
Combination oral contraceptive consisting of norethindrone (progestin) and ethinyl estradiol (estrogen). Prevents ovulation primarily by suppressing gonadotropin release, including FSH and LH. Also increases cervical mucus viscosity, impeding sperm penetration, and alters endometrial structure, reducing implantation likelihood.
| Metabolism | Norethindrone undergoes extensive first-pass metabolism in the liver via reduction and conjugation, primarily by CYP3A4. Ethinyl estradiol is metabolized by hydroxylation and conjugation, involving CYP3A4 and sulfate conjugation. Both undergo enterohepatic recirculation. |
| Excretion | Renal: ~50% (metabolites as glucuronide and sulfate conjugates); Fecal: ~30% (via bile); Urinary unchanged: <1%. |
| Half-life | Norethindrone: 7-8 hours (terminal); Ethinyl estradiol: 10-20 hours (terminal). Clinically, steady state reached within 5-7 days. |
| Protein binding | Norethindrone: ~97% bound to albumin and SHBG; Ethinyl estradiol: ~98% bound to albumin (not SHBG). |
| Volume of Distribution | Norethindrone: ~2-4 L/kg; Ethinyl estradiol: ~2-3 L/kg; indicates extensive tissue distribution and binding. |
| Bioavailability | Oral: Norethindrone ~60-70% (first-pass metabolism); Ethinyl estradiol ~40-50% (first-pass metabolism). |
| Onset of Action | Oral: Maximal contraceptive effect after 7 days of consistent daily dosing; ovulation inhibition begins within 2-3 days. |
| Duration of Action | 24 hours with daily dosing; missed pills >12 hours compromise contraceptive efficacy; withdrawal bleed occurs during 7-day pill-free interval. |
One tablet (10 mg norethindrone/0.035 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 placebo days. Start on first Sunday after menstrual period begins or on day 1 of cycle.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment recommended. Use with caution in patients with severe renal impairment; monitor for fluid retention. |
| Liver impairment | Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B): use only if benefits outweigh risks, as hormonal contraceptives may worsen cholestasis. |
| Pediatric use | Not indicated for use before menarche. For postmenarchal adolescents: same dosing as adults (one tablet daily for 21 days, then 7 placebo). Regular menstrual cycles should be established before initiation. |
| Geriatric use | Not indicated for use after menopause. No specific dosing studies in elderly; estrogen-containing contraceptives are contraindicated in women over 35 who smoke or have cardiovascular risk factors. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO-NOVUM 10/11-21 (ORTHO-NOVUM 10/11-21).
| Breastfeeding | Excretion into breast milk minimal; estimated relative infant dose <1% of maternal weight-adjusted dose; M/P ratio not reported. American Academy of Pediatrics compatible with breastfeeding; avoid high-dose formulations. |
| Teratogenic Risk | First trimester: Increased risk of neural tube defects (OR 1.2-1.4), cardiovascular malformations (OR 1.1-1.3). Second/third trimester: No significant increase in major malformations; possible association with low birth weight, preterm delivery. Postnatal: No known long-term effects. |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 years old who smoke should not use this product.
| Serious Effects |
["Known or suspected pregnancy","Current or history of thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Estrogen-dependent neoplasia (e.g., endometrial cancer)","Undiagnosed abnormal genital bleeding","Acute liver disease, hepatic adenoma, or impaired liver function","History of cholestatic jaundice with prior OC use","Age >35 years and smoking","Known hypersensitivity to any component"]
| Precautions | ["Increased risk of thromboembolic disorders (e.g., venous thrombosis, stroke, MI); discontinue if symptoms occur","Elevated blood pressure; monitor regularly","Hepatic neoplasia risk (benign and malignant); discontinue if jaundice or liver abnormalities","Cholestatic jaundice; caution in patients with history","Risk of retinal thrombosis; discontinue if unexplained vision loss","Altered glucose tolerance; caution in diabetics","Depression; discontinue if severe","Headache (including migraine); discontinue if new pattern or worsening","Breakthrough bleeding and spotting; rule out pregnancy if persistent","Gallbladder disease risk"] |
Loading safety data…
| Fetal Monitoring |
| Maternal: Blood pressure, glucose tolerance, lipid profile, liver function. Fetal: Ultrasound for growth and anatomy; consider amniocentesis if high risk. |
| Fertility Effects | Transient anovulation after discontinuation (up to 3 months); no permanent effect on fertility. May mask early pregnancy; discontinue prior to conception. |