Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN versus ORTHO NOVUM 1 80 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN versus ORTHO NOVUM 1 80 28.
ORTHO TRI-CYCLEN vs ORTHO-NOVUM 1/80 28
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 estrogen-progestin contraceptive; primarily inhibits ovulation by suppressing gonadotropin release (FSH and LH). Also increases cervical mucus viscosity and alters endometrial receptivity.
FDA-approved: Prevention of pregnancyOff-label: Treatment of acne vulgaris, management of menstrual disorders
Prevention of pregnancy
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 orally once daily at the same time each day for 28 days (21 active tablets containing norethindrone 1 mg and ethinyl estradiol 80 mcg, followed by 7 placebo tablets).
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; mestranol: 10-13 hours (terminal). Steady-state achieved in 5-7 days.
Ethinyl estradiol: primarily metabolized by CYP3A4; norgestimate: rapidly hydrolyzed to norelgestromin (active) then levonorgestrel, metabolized by CYP3A4 and CYP2C9.
Ethinyl estradiol is metabolized primarily via CYP3A4 and undergoes glucuronidation; norethindrone is metabolized via reduction and conjugation.
Norethindrone: 60-80% renal (as metabolites), 20-40% fecal. Ethinyl estradiol: ~40% renal, ~60% fecal. Biliary excretion contributes to fecal elimination.
Norethindrone: 50-60% renal, 20-30% fecal; mestranol: 30-40% renal, 60-70% fecal.
Norethindrone: ~97% bound to albumin and SHBG. Ethinyl estradiol: ~98% bound to albumin.
Norethindrone: 60-80% bound to albumin and SHBG; mestranol: 90-95% bound to albumin and 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; mestranol: 1-3 L/kg. Indicates extensive tissue distribution.
Norethindrone: ~65% (oral). Ethinyl estradiol: ~40-45% (oral) due to first-pass metabolism.
Oral: norethindrone 50-65%, mestranol 40-60% due to 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 renal impairment due to potential fluid retention. GFR-based modifications not established.
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 patients with Child-Pugh class C cirrhosis. Use with caution in Child-Pugh class A or B; consider alternative contraception due to risk of decreased hormone clearance.
Not indicated in prepubertal children. Postmenarchal adolescents: same dosing as adults. Safety and efficacy not established in children <18 years.
Not indicated for premenarchal girls. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 28 days.
Not indicated for use after menopause. No specific geriatric dosing; contraindicated in postmenopausal women.
Not indicated for use in postmenopausal women. No geriatric dosing established; use not recommended in women over 50 years due to increased risk of thromboembolism and lack of efficacy for contraception.
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 risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age and smoking intensity, especially in women over 35 years of age. Women using oral contraceptives should be strongly advised not to smoke.
["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","Cerebrovascular disease","Myocardial infarction","Breast cancer risk","Hepatic neoplasia","Elevated blood pressure","Gallbladder disease","Glucose intolerance","Ocular lesions","Headache","Menstrual irregularities","Depression","Contact lens intolerance","Fluid retention","Lipid effects"]
["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 past thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Known or suspected estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use","Hepatic adenoma or carcinoma","Known or suspected 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 significant food interactions; however, high-fat meals may delay absorption. Avoid grapefruit juice as it may increase estrogen levels via CYP3A4 inhibition.
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: No consistent evidence of major malformations, but oral contraceptives are not recommended due to potential risk. Second/third trimester: No specific fetal risks; exposure is not advised due to hormonal 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.
Excreted in breast milk; may reduce milk production and affect infant. M/P ratio not well established. Avoid use during breastfeeding.
No dosing adjustments applicable; drug is contraindicated during pregnancy. If used inadvertently, discontinue immediately.
No dose adjustment applicable; drug is contraindicated in pregnancy. Pharmacokinetic changes in pregnancy may alter efficacy but no standard dose modification exists.
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.
1. If a dose is missed, take it as soon as remembered; if more than 24 hours late, use backup contraception for 7 days. 2. Monitor blood pressure within 3 months of initiation due to potential hypertensive effects. 3. Caution in patients with migraine with aura due to increased stroke risk. 4. The estrogen component (mestranol) is a prodrug of ethinyl estradiol; bioavailability considerations influence dosing. 5. 21 active pills followed by 7 placebo pills; ensure patient understands the tricycle regimen.
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 one pill at the same time daily, preferably after dinner to reduce nausea.If you miss a pill, consult the package insert for instructions; use backup contraception as needed.Report unusual symptoms: leg pain/swelling (DVT), chest pain/shortness of breath (pulmonary embolism), severe headache, vision changes.This does not protect against STIs; use condoms for additional protection.Expect breakthrough bleeding or spotting in the first few months; persistent bleeding requires evaluation.Smoking increases risk of serious cardiovascular side effects, especially in women over 35.