Comparative Pharmacology
Head-to-head clinical analysis: ORTHO NOVUM 10 21 versus ORTHO NOVUM 10 11 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO NOVUM 10 21 versus ORTHO NOVUM 10 11 21.
ORTHO-NOVUM 10-21 vs ORTHO-NOVUM 10/11-21
Head-to-head clinical comparison of therapeutic indices and safety profiles.
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.
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.
Prevention of pregnancyTreatment of menorrhagiaTreatment of dysmenorrheaRegulation of menstrual cyclesEmergency contraception (off-label)
Prevention of pregnancyTreatment of moderate acne vulgaris in females ≥15 years of ageOral contraception with a biphasic hormone regimen providing a low-dose alternative
1 tablet (1 mg norethindrone, 0.035 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 days of no tablets.
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.
None Documented
None Documented
Norethindrone 5-14 hours (mean 8 hours), ethinyl estradiol 7-20 hours (mean 13 hours). Steady-state achieved in 5-10 days.
Norethindrone: 7-8 hours (terminal); Ethinyl estradiol: 10-20 hours (terminal). Clinically, steady state reached within 5-7 days.
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.
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.
Renal approximately 50-60% as metabolites, biliary/fecal approximately 30-40% as metabolites and unchanged drug.
Renal: ~50% (metabolites as glucuronide and sulfate conjugates); Fecal: ~30% (via bile); Urinary unchanged: <1%.
Norethindrone: 90-95% bound to albumin and SHBG; ethinyl estradiol: 97-98% bound to albumin.
Norethindrone: ~97% bound to albumin and SHBG; Ethinyl estradiol: ~98% bound to albumin (not SHBG).
Norethindrone: 4 L/kg; ethinyl estradiol: 2-4 L/kg; indicates extensive tissue distribution.
Norethindrone: ~2-4 L/kg; Ethinyl estradiol: ~2-3 L/kg; indicates extensive tissue distribution and binding.
Oral: norethindrone 50-80%, ethinyl estradiol 40-60% due to first-pass metabolism.
Oral: Norethindrone ~60-70% (first-pass metabolism); Ethinyl estradiol ~40-50% (first-pass metabolism).
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.
No specific dose adjustment recommended. Use with caution in patients with severe renal impairment; monitor for fluid retention.
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.
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.
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.
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.
Not indicated for use in postmenopausal women. Not recommended for elderly patients due to lack of efficacy and increased thrombotic risk.
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.
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.
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.
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.
["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"]
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.
["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"]
Data Pending Review
Data Pending Review
No significant food interactions. Grapefruit juice may increase estrogen levels but clinical relevance is minimal. Avoid excessive alcohol consumption due to potential liver strain. Maintain consistent dietary habits to reduce gastrointestinal side effects.
No clinically significant food interactions. However, grapefruit juice may increase ethinyl estradiol levels by inhibiting CYP3A4; avoid large amounts. Take with food if gastrointestinal upset occurs.
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.
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.
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.
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.
Contraindicated in pregnancy; no dosing adjustments are applicable. Discontinue immediately if pregnancy occurs.
No dose adjustment recommended during pregnancy; drug should be discontinued as soon as pregnancy is detected. No pharmacokinetic studies indicating need for change.
Category C
Category C
ORTHO-NOVUM 10-21 (norethindrone 10 mg with ethinyl estradiol 21 mcg) 21-day regimen: breakthrough bleeding/spotting is common during first 3 cycles; encourage continuation. If a dose is missed, take as soon as remembered and use backup contraception for 7 days. Higher estrogen content increases thromboembolic risk; avoid in smokers >35 years. Monitor blood pressure and liver function at baseline and periodically.
For ORTHO-NOVUM 10/11-21 (norethindrone/ethinyl estradiol), a biphasic oral contraceptive, patients must take the 10 white tablets (0.5 mg norethindrone, 35 mcg ethinyl estradiol) for 10 days, followed by 11 peach tablets (1 mg norethindrone, 35 mcg ethinyl estradiol) for 11 days. Missed pills increase breakthrough bleeding and pregnancy risk; if one pill missed, take as soon as remembered, next at regular time. If two consecutive pills missed, take two pills for two days and use backup contraception for 7 days. Advise about increased thromboembolic risk, especially in smokers over 35. Prescribe only after thorough medical history and blood pressure measurement.
Take one tablet daily at the same time for 21 days, then 7 pill-free days.Use backup contraception (e.g., condoms) for the first 7 days of the first pack.If you miss a pill, take it as soon as you remember; if more than 24 hours, take last missed and use backup for 7 days.Common side effects include nausea, breast tenderness, spotting, and mood changes; they often improve within 3 months.Seek medical attention for severe leg pain, chest pain, shortness of breath, or severe headache.Do not smoke while taking this medication, especially if over 35 years old.
Take the pills exactly as directed: white pills for 10 days, then peach pills for 11 days, followed by 7 placebo days.Use backup contraception (e.g., condoms) if you miss any pills, especially during the first week of a new pack.Smoking while on this pill increases risk of serious cardiovascular side effects; avoid smoking, especially if over 35 years old.Contact your doctor immediately if you experience severe leg pain, chest pain, shortness of breath, severe headache, or vision changes.Notify all healthcare providers that you are taking this medication before any surgery or prolonged immobility.This prescription does not protect against HIV or other sexually transmitted infections.