Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN 28 versus ORTHO NOVUM 1 80 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN 28 versus ORTHO NOVUM 1 80 28.
ORTHO TRI-CYCLEN 28 vs ORTHO-NOVUM 1/80 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 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 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 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; Ethinyl estradiol: ~15 hours (biphasic, terminal: 15-20 hours). Steady-state achieved within 7-14 days.
Norethindrone: 7-8 hours; mestranol: 10-13 hours (terminal). Steady-state achieved in 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 is metabolized primarily via CYP3A4 and undergoes glucuronidation; norethindrone is metabolized via reduction and conjugation.
Renal: ~60% (metabolites); Fecal: ~40% (metabolites); unchanged drug <1%
Norethindrone: 50-60% renal, 20-30% fecal; mestranol: 30-40% renal, 60-70% fecal.
Norethindrone: ~97% (albumin, SHBG); Ethinyl estradiol: ~98% (albumin, SHBG).
Norethindrone: 60-80% bound to albumin and SHBG; mestranol: 90-95% bound to albumin and SHBG.
Norethindrone: 3-4 L/kg; Ethinyl estradiol: 2-3 L/kg. Indicates extensive tissue distribution.
Norethindrone: 2-4 L/kg; mestranol: 1-3 L/kg. Indicates extensive tissue distribution.
Norethindrone: ~65% (first-pass metabolism); Ethinyl estradiol: ~45% (first-pass metabolism).
Oral: norethindrone 50-65%, mestranol 40-60% due to 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 specific dose adjustment recommended; use with caution in patients with renal impairment due to potential fluid retention. GFR-based modifications not established.
Contraindicated in Child-Pugh class B and C (moderate to severe hepatic impairment). No data for Child-Pugh A; use with caution.
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 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 for premenarchal girls. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 28 days.
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 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 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. 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.
["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","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"]
["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"]
["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 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; however, high-fat meals may delay absorption. Avoid grapefruit juice as it may increase estrogen levels via CYP3A4 inhibition.
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.
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.
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.
Excreted in breast milk; may reduce milk production and affect infant. M/P ratio not well established. Avoid use during breastfeeding.
No dose adjustment applicable; contraindicated in pregnancy. If exposure occurs, discontinue immediately. No pharmacokinetic data indicate safe use or dose modifications during pregnancy.
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
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.
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, 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 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.