Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN versus ORTHO NOVUM 10 11 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN versus ORTHO NOVUM 10 11 21.
ORTHO TRI-CYCLEN vs ORTHO-NOVUM 10/11-21
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Combined estrogen-progestin oral contraceptive; suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity and alters endometrial lining.
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.
FDA-approved: Prevention of pregnancyOff-label: Treatment of acne vulgaris, management of menstrual disorders
Prevention of pregnancyTreatment of moderate acne vulgaris in females ≥15 years of ageOral contraception with a biphasic hormone regimen providing a low-dose alternative
One tablet (norgestimate 0.180-0.215-0.250 mg/ethinyl estradiol 0.035 mg) orally once daily for 21 days, followed by 7 days of placebo or 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: ~8 hours (terminal). Ethinyl estradiol: ~12-15 hours (terminal). Clinical context: Steady-state achieved within 5-7 days; contraceptive efficacy maintained with daily dosing.
Norethindrone: 7-8 hours (terminal); Ethinyl estradiol: 10-20 hours (terminal). Clinically, steady state reached within 5-7 days.
Ethinyl estradiol: primarily metabolized by CYP3A4; norgestimate: rapidly hydrolyzed to norelgestromin (active) then levonorgestrel, metabolized by CYP3A4 and CYP2C9.
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.
Norethindrone: 60-80% renal (as metabolites), 20-40% fecal. Ethinyl estradiol: ~40% renal, ~60% fecal. Biliary excretion contributes to fecal elimination.
Renal: ~50% (metabolites as glucuronide and sulfate conjugates); Fecal: ~30% (via bile); Urinary unchanged: <1%.
Norethindrone: ~97% bound to albumin and SHBG. Ethinyl estradiol: ~98% bound to albumin.
Norethindrone: ~97% bound to albumin and SHBG; Ethinyl estradiol: ~98% bound to albumin (not SHBG).
Norethindrone: 3-4 L/kg (large distribution into tissues, including breast and reproductive tissues). Ethinyl estradiol: 2-3 L/kg (distributes widely).
Norethindrone: ~2-4 L/kg; Ethinyl estradiol: ~2-3 L/kg; indicates extensive tissue distribution and binding.
Norethindrone: ~65% (oral). Ethinyl estradiol: ~40-45% (oral) 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. Insufficient data for severe impairment (GFR <30 mL/min); use alternative contraception.
No specific dose adjustment recommended. Use with caution in patients with severe renal impairment; monitor for fluid retention.
Contraindicated in patients with acute hepatitis, cholestatic jaundice of pregnancy or prior OCP use, or severe cirrhosis (Child-Pugh C). Use with caution in Child-Pugh A/B; dose adjustment not defined but consider lower estrogen options.
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 in prepubertal children. Postmenarchal adolescents: same dosing as adults. Safety and efficacy not established in children <18 years.
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 after menopause. No specific geriatric dosing; contraindicated in postmenopausal women.
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 combined hormonal contraceptive use. Risk increases with age and number of cigarettes smoked, especially in women over 35.
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.
["Thrombotic disorders (venous thromboembolism, stroke, myocardial infarction)","Hepatic neoplasia (benign/malignant)","Gallbladder disease","Hypertension","Carbohydrate/lipid effects","Hereditary angioedema","Chloasma","Retinal thrombosis","Depression"]
["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","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Undiagnosed abnormal genital bleeding","Pregnancy","Active liver disease or benign/malignant liver tumors","Hypersensitivity to any component","Heavy smoking in women over 35"]
["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 specific food restrictions. Grapefruit may slightly increase estrogen levels; avoid large amounts. Alcohol consumption may increase hepatic toxicity risk; limit to moderate intake.
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.
Contraindicated in pregnancy. First trimester: associated with cardiovascular defects and limb reduction defects. Second and third trimesters: no increased risk of major malformations, but may cause fetal harm due to hormonal effects; use only if clearly needed.
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.
Small amounts of ethinyl estradiol and norgestimate pass into breast milk; may reduce milk production and composition. M/P ratio not established. Generally avoided during breastfeeding; alternative contraception recommended.
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.
No dosing adjustments applicable; drug is contraindicated during pregnancy. If used inadvertently, discontinue immediately.
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
Contains norgestimate 0.180/0.215/0.250 mg and ethinyl estradiol 0.035 mg. Triphasic regimen mimics natural cycle. Monitor for breakthrough bleeding, especially during first 3 cycles. Use with caution in patients with migraine with aura, hypertension, or history of VTE. Effective for acne vulgaris (FDA-approved indication). Counsel that efficacy may be reduced with concurrent rifampin, certain anticonvulsants, and St. John's wort. Consider switching to monophasic pill if persistent breakthrough bleeding after 3 months.
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 pill daily at the same time for 21 days, then placebo pills for 7 days.If you miss a pill within 12 hours, take it as soon as remembered. If more than 12 hours late, use backup contraception (e.g., condoms) for 7 days.Do not smoke while taking this medication; smoking increases risk of blood clots and stroke, especially if over 35.Common side effects: spotting between periods, nausea, breast tenderness, headache. These often improve after a few cycles.Seek emergency medical attention for signs of blood clot: leg pain/swelling, sudden chest pain, difficulty breathing, severe headache, vision changes.This medication does not protect against HIV or other sexually transmitted infections.
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.