Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN 28 versus ORTHO NOVUM 1 50 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN 28 versus ORTHO NOVUM 1 50 28.
ORTHO TRI-CYCLEN 28 vs ORTHO-NOVUM 1/50 28
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Combination of ethinyl estradiol and norgestimate primarily suppresses gonadotropin (FSH and LH) secretion via negative feedback on the hypothalamic-pituitary-ovarian axis, inhibiting ovulation. Additionally, it increases cervical mucus viscosity and alters endometrial structure to impede fertilization and implantation.
Combination oral contraceptive; suppresses gonadotropin secretion (FSH, LH) via estrogen and progestin, inhibiting ovulation, increasing cervical mucus viscosity, and altering endometrial structure.
FDA-approved: Prevention of pregnancyOff-label: Treatment of moderate acne vulgaris in females ≥15 years of age who have no known contraindications and desire oral contraception
Prevention of pregnancy
One tablet daily for 28 days: 21 active tablets (norgestimate 0.180 mg/ethinyl estradiol 0.035 mg, norgestimate 0.215 mg/ethinyl estradiol 0.035 mg, norgestimate 0.250 mg/ethinyl estradiol 0.035 mg) followed by 7 inert tablets. Route: oral.
One tablet (1 mg norethindrone/50 mcg mestranol) orally once daily for 21 days, followed by 7 days of placebo tablets (inactive) for a 28-day cycle.
None Documented
None Documented
Norethindrone: ~8 hours; Ethinyl estradiol: ~15 hours (biphasic, terminal: 15-20 hours). Steady-state achieved within 7-14 days.
Norethindrone: 5-12 h (mean 8 h); Mestranol: 12-24 h (mean 18 h); steady-state reached within 5-7 days
Ethinyl estradiol undergoes oxidative metabolism primarily via CYP3A4 and undergoes conjugation (glucuronidation and sulfation). Norgestimate is extensively metabolized to its active metabolite norelgestromin via first-pass hepatic (hydrolysis) and further to levonorgestrel; norelgestromin is metabolized by CYP3A4 and CYP2C9.
Ethinyl estradiol metabolized via CYP3A4; mestranol (prodrug converted to ethinyl estradiol) and norethindrone metabolized via hepatic reduction and conjugation.
Renal: ~60% (metabolites); Fecal: ~40% (metabolites); unchanged drug <1%
Renal: ~50-60% as metabolites; fecal: ~30-40% as metabolites; biliary: <10%
Norethindrone: ~97% (albumin, SHBG); Ethinyl estradiol: ~98% (albumin, SHBG).
Norethindrone: 96-98% (SHBG, albumin); Mestranol: 97-99% (albumin, SHBG with lower affinity)
Norethindrone: 3-4 L/kg; Ethinyl estradiol: 2-3 L/kg. Indicates extensive tissue distribution.
Norethindrone: 1.5-2.5 L/kg; Mestranol: 0.9-1.5 L/kg; indicates extensive tissue distribution
Norethindrone: ~65% (first-pass metabolism); Ethinyl estradiol: ~45% (first-pass metabolism).
Oral: norethindrone ~64%; mestranol ~40-70% (first-pass metabolism)
No specific GFR-based dose adjustments established. Use with caution in severe renal impairment (GFR <30 mL/min) due to potential fluid retention and electrolyte disturbances.
No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Insufficient data for severe impairment (CrCl <30 mL/min); avoid use due to potential for fluid retention and hypertension.
Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). No data for Child-Pugh A; use with caution.
Contraindicated in severe hepatic disease (Child-Pugh C) or acute liver disease. For mild to moderate impairment (Child-Pugh A or B), use with caution; monitor liver function, no specific dose adjustment guidelines available.
Not indicated for use before menarche. For postmenarchal adolescents, same dosing as adults. Safety and efficacy not established in pediatric patients under 18 years for contraception.
Not indicated in prepubertal girls. Postmenarchal adolescents: same as adult dosing; initiate after menarche and once growth complete.
Not indicated for use in postmenopausal women. No specific dosing adjustments; risks of thromboembolic events outweigh benefits in women over 35 who smoke or have cardiovascular risk factors.
Not indicated for postmenopausal women; no geriatric-specific dosing. Use with caution in older women due to increased risk of thromboembolism and cardiovascular events.
Cigarette smoking increases the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age (especially in women over 35 years) and with the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Use is contraindicated in women over 35 years who smoke.
["Thromboembolic disorders: increased risk of venous thromboembolism and arterial thrombosis","Cigarette smoking increases cardiovascular risk","Hypertension: may cause or worsen hypertension","Gallbladder disease: increased risk of gallbladder disease","Hepatic tumors: risk of hepatic adenomas (rare) and possible hepatocellular carcinoma","Carbohydrate and lipid effects: may affect glucose tolerance and lipid profile","Ocular lesions: retinal thrombosis (discontinue if unexplained vision loss occurs)","Depression: may precipitate or worsen depression","Bleeding irregularities: breakthrough bleeding and spotting common","Hereditary angioedema: may exacerbate symptoms"]
Increased risk of thromboembolic disorders, venous thromboembolism (VTE), arterial thrombosis, myocardial infarction, stroke, hepatic neoplasia, and gallbladder disease. Regular monitoring of blood pressure, glucose, and lipid profiles recommended.
["Known or suspected pregnancy","Current or past thrombophlebitis or thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism)","Current or past arterial thromboembolic disease (e.g., stroke, myocardial infarction)","Cerebrovascular disease","Known or suspected breast carcinoma or other estrogen- or progestin-sensitive cancer","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenomas or carcinomas","Known liver disease or impaired liver function, including active viral hepatitis","Uncontrolled hypertension (>160/100 mmHg)","Diabetes with vascular involvement","Headaches with focal neurological symptoms (e.g., migraine with aura)","Major surgery with prolonged immobilization","Smoking in women over 35 years","Hypersensitivity to any component of the product"]
Thrombophlebitis or thromboembolic disorders; cerebrovascular or coronary artery disease; known or suspected breast carcinoma; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; pregnancy; hepatic adenoma or carcinoma; jaundice with prior pill use; hypersensitivity to components; women over 35 who smoke.
Data Pending Review
Data Pending Review
No significant food interactions. Grapefruit juice may slightly increase ethinyl estradiol levels but not clinically relevant. Maintain consistent dietary habits to avoid variability in absorption.
No significant food interactions. Grapefruit juice may slightly increase estrogen exposure; avoid excessive intake. Taking with food may reduce nausea.
Pregnancy category X. Contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and oral clefts. Second and third trimesters: association with fetal genital abnormalities (e.g., hypospadias in males, virilization of female fetuses). No safe use established.
Pregnancy category X. First trimester: Increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects due to progestin and estrogen exposure. Second and third trimesters: Risk of fetal genital abnormalities (e.g., hypospadias, clitoral hypertrophy), low birth weight, and potential long-term metabolic effects. Use contraindicated in pregnancy.
Not recommended during breastfeeding. Combined hormonal contraceptives reduce milk production and nutrient content. Limited ethinyl estradiol and norgestimate transfer into breast milk; M/P ratio not well defined. Use alternative contraception.
Contraindicated during breastfeeding. Norethindrone and mestranol/metabolites are excreted in breast milk; M/P ratio not established. May reduce milk production and quality, and expose infant to hormonal effects. Recommend alternative contraception.
No dose adjustment applicable; contraindicated in pregnancy. If exposure occurs, discontinue immediately. No pharmacokinetic data indicate safe use or dose modifications during pregnancy.
No indication for use in pregnancy; contraindicated. If inadvertent use occurs, discontinue immediately. No pharmacokinetic data to support dose adjustments as drug should not be administered during pregnancy.
Category C
Category C
Ortho Tri-Cyclen 28 is a triphasic oral contraceptive containing norgestimate and ethinyl estradiol. The triphasic dosing mimics natural hormonal fluctuations and may reduce breakthrough bleeding. It is also FDA-approved for moderate acne vulgaris in women at least 15 years old who desire contraception. Monitor for thromboembolic events, especially in smokers over 35. CYP3A4 inducers (e.g., rifampin, carbamazepine) may reduce efficacy. Advise backup contraception during concurrent antibiotic use.
ORTHO-NOVUM 1/50 28 is a monophasic oral contraceptive containing mestranol 50 µg (a prodrug of ethinyl estradiol) and norethindrone 1 mg. Due to higher estrogen dose, it poses increased risk of venous thromboembolism, especially in smokers over 35. It may reduce the efficacy of lamotrigine. Use with caution in patients with hypertension or liver disease.
Take one pill daily at the same time, preferably after a meal.The 28-day pack has 21 active pills and 7 placebo pills; always start a new pack immediately after finishing the previous one.If you miss a pill, check the package insert: take missed pill as soon as remembered and use backup contraception.Common side effects include nausea, breast tenderness, and breakthrough bleeding; these often improve after 3 months.Seek medical attention for severe headache, vision changes, leg pain, or shortness of breath (thrombosis symptoms).Do not smoke while taking this medication, as it increases risk of blood clots and stroke.This pill does not protect against sexually transmitted infections (STIs).
Take one tablet daily at the same time, following the package directions for the 28-day regimen.If you miss a pill, follow the instructions in the package insert; use backup contraception if needed.Common side effects include nausea, breast tenderness, and breakthrough bleeding; these often resolve after a few cycles.This medication does not protect against HIV or other sexually transmitted infections.Smoking while using this pill increases your risk of serious cardiovascular side effects; do not smoke.Contact your provider if you experience leg pain, chest pain, shortness of breath, severe headache, or vision changes.