Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 50 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 50 28.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 1/50 28
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Combination estrogen (ethinyl estradiol) and progestin (norgestimate) oral contraceptive. Suppresses gonadotropin release, inhibiting ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial lining, reducing implantation likelihood.
Combination oral contraceptive; suppresses gonadotropin secretion (FSH, LH) via estrogen and progestin, inhibiting ovulation, increasing cervical mucus viscosity, and altering endometrial structure.
Prevention of pregnancyAcne vulgaris (for women aged ≥15 who desire contraception)
Prevention of pregnancy
One tablet daily orally for 21 days, followed by 7 placebo tablets. Each active tablet contains 0.025 mg ethinyl estradiol and 0.18 mg norelgestromin (days 1-7), 0.215 mg norelgestromin (days 8-14), 0.25 mg norelgestromin (days 15-21).
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
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: 5-12 h (mean 8 h); Mestranol: 12-24 h (mean 18 h); steady-state reached within 5-7 days
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Ethinyl estradiol metabolized via CYP3A4; mestranol (prodrug converted to ethinyl estradiol) and norethindrone metabolized via hepatic reduction and conjugation.
Renal (∼40% as metabolites, <10% unchanged) and fecal (∼30% as metabolites); conjugated metabolites excreted in bile and undergo enterohepatic circulation.
Renal: ~50-60% as metabolites; fecal: ~30-40% as metabolites; biliary: <10%
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: 96-98% (SHBG, albumin); Mestranol: 97-99% (albumin, SHBG with lower affinity)
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: 1.5-2.5 L/kg; Mestranol: 0.9-1.5 L/kg; indicates extensive tissue distribution
Oral: Norelgestromin ~100% (after first-pass conversion from norgestimate); Ethinyl estradiol ~45% (due to first-pass metabolism).
Oral: norethindrone ~64%; mestranol ~40-70% (first-pass metabolism)
No dose adjustment recommended for mild to moderate renal impairment. Not studied in severe renal impairment (GFR <30 mL/min); use contraindicated in patients with renal disease.
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 or C (moderate to severe hepatic impairment). Not studied in Child-Pugh Class A; use 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.
No specific weight-based dosing; use only after menarche. Dose same as adult: one active tablet daily for 21 days then 7 placebo. Safety and efficacy established in females of reproductive age.
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 geriatric dosing studies conducted.
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 risk of serious cardiovascular events (e.g., thromboembolism, stroke, myocardial infarction). Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 who smoke should not use combination oral contraceptives.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Use is contraindicated in women over 35 years who smoke.
["Thromboembolic disorders: Discontinue if thrombotic event occurs or is suspected.","Cerebrovascular disease: Increased risk of stroke.","Cardiovascular disease: Increased risk of MI, especially in smokers.","Hepatic neoplasia: Associated with hepatic adenoma or carcinoma.","Gallbladder disease: Increased risk of gallstones.","Hypertension: Monitor blood pressure; discontinue if hypertension develops.","Carbohydrate/lipid effects: May impair glucose tolerance and alter lipid profiles.","Headache: Discontinue if new or worsening migraine occurs.","Bleeding irregularities: Amenorrhea or breakthrough bleeding may occur.","Depression: May worsen or trigger depression.","Hereditary angioedema: May exacerbate symptoms.","Chloasma: May cause facial hyperpigmentation."]
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.
["Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast cancer","Estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Hepatic adenoma or carcinoma (current or history)","Active liver disease with abnormal liver function","Known or suspected pregnancy","Heavy smoking (≥15 cigarettes/day) in women over 35","Hypersensitivity to any component","Use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir (with or without dasabuvir)"]
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 known food interactions. Grapefruit juice may increase estrogen levels, but effect is not clinically significant with low-dose pills. Maintain a consistent diet to avoid gastrointestinal disturbances that could affect 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 cardiovascular defects, neural tube defects, and oral clefts. Second and third trimesters: Not indicated; no specific fetal risks documented due to contraindication.
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.
Small amounts of estrogen and progestin are excreted in breast milk (M/P ratio not available). May reduce milk production and quality. Not recommended during breastfeeding.
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.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
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
Lower estrogen dose (0.025 mg ethinyl estradiol) may cause more breakthrough bleeding, especially in the first few cycles. Counsel patients that unscheduled bleeding is common and usually improves after 3-6 months. The 91-day extended regimen (7 days placebo) reduces number of withdrawal bleeds but may increase spotting. Contraceptive efficacy may be reduced in patients with BMI > 30; consider alternative methods. Monitor blood pressure after starting, as estrogen can elevate BP. Absolute contraindication in migraine with aura, history of thromboembolism, or smoking >35 years old.
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 each day, even if you do not have intercourse regularly.If you miss a pill, refer to the package insert for specific instructions based on how many pills you missed and the week of the cycle.Breakthrough bleeding or spotting is common in the first 3-6 months; contact your healthcare provider if bleeding is heavy or prolonged.This product does not protect against HIV or other sexually transmitted infections; use condoms for infection prevention.Tell your healthcare provider if you start smoking, as smoking increases the risk of serious cardiovascular side effects.Seek emergency medical attention if you experience sudden chest pain, shortness of breath, leg pain or swelling, severe headache, or vision changes.Store at room temperature (20-25°C); keep in original blister pack until use.If you have vomiting or diarrhea for more than 24 hours, use backup contraception until you have taken 7 consecutive active pills.
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.