Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 35 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 35 21.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 1/35-21
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 estrogen-progestin contraceptive; suppresses gonadotropin (FSH and LH) secretion via negative feedback, inhibiting ovulation. Increases cervical mucus viscosity and alters endometrial lining, impairing sperm penetration and implantation.
Prevention of pregnancyAcne vulgaris (for women aged ≥15 who desire contraception)
Prevention of pregnancyOral contraception
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 orally once daily for 21 days, followed by 7 placebo tablets. Each tablet contains 1 mg norethindrone and 0.035 mg ethinyl estradiol.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: 7-9 hours (terminal); Ethinyl estradiol: 13-27 hours (terminal). At steady state, clinical contraceptive efficacy is maintained with daily dosing.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Norethindrone: primarily hepatic metabolism via reduction and sulfation, with CYP3A4 involvement. Ethinyl estradiol: hepatic metabolism via CYP3A4, also undergoes conjugation (glucuronidation and sulfation). Undergoes enterohepatic recirculation.
Renal (∼40% as metabolites, <10% unchanged) and fecal (∼30% as metabolites); conjugated metabolites excreted in bile and undergo enterohepatic circulation.
Renal (approx. 40% as metabolites, <10% unchanged), fecal (approx. 60% as metabolites, primarily via bile).
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: 61-77% bound, primarily to SHBG and albumin; Ethinyl estradiol: 97-98% bound, primarily to albumin.
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: 4-5 L/kg; Ethinyl estradiol: 2-5 L/kg. Indicates extensive tissue distribution exceeding total body water.
Oral: Norelgestromin ~100% (after first-pass conversion from norgestimate); Ethinyl estradiol ~45% (due to first-pass metabolism).
Oral: Norethindrone 50-70%; Ethinyl estradiol 40-50% due to 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. Insufficient data for severe renal impairment (GFR <30 mL/min/1.73 m²); use caution and monitor for adverse effects.
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 class C). For moderate impairment (Child-Pugh class B), avoid use as oral contraceptives may exacerbate liver dysfunction. Mild impairment (Child-Pugh class A): use with caution and monitor liver function.
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.
Safety and efficacy not established in premenarchal girls. Dosing for adolescents post-menarche is same as adults; use with caution and monitor for thromboembolic risk.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for postmenopausal women due to absence of ovulation. In perimenopausal women, use lowest effective dose; monitor cardiovascular risk and bone density.
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 contraceptive use (e.g., myocardial infarction, thromboembolism, stroke). Risk increases with age (>35 years) and number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to 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 and arterial), stroke, myocardial infarction; hepatic neoplasia; gallbladder disease; hypertension; carbohydrate/lipid effects; ocular lesions (retinal thrombosis); headache/migraine; breakthrough bleeding/spotting; depression; fluid retention; hereditary angioedema; chloasma; liver function impairment.
["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; cerebral vascular or coronary artery disease; known or suspected pregnancy; undiagnosed abnormal genital bleeding; known/suspected breast cancer; estrogen-dependent neoplasia; benign/malignant liver tumor (active); known or suspected pregnancy; hypersensitivity to any component; smoking in women >35 years; uncontrolled hypertension; diabetes with vascular disease; migraines with focal aura; major surgery with prolonged immobilization.
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.
Grapefruit and grapefruit juice may increase estrogen levels; avoid excessive consumption. No specific food restrictions; maintain consistent dietary habits to avoid fluctuations in absorption.
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.
FDA Pregnancy Category X; contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and limb reduction defects due to progestin component. Second/third trimesters: feminization of male fetus, potential for congenital anomalies, and possible long-term reproductive effects. No safe use 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.
Excreted in breast milk; may reduce milk production and quality. M/P ratio not established for this combination; progestin-only contraceptives preferred. Use only if benefits outweigh risks; monitor infant for jaundice or growth delay.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
Discontinue immediately if pregnancy suspected or confirmed. No dose adjustment is recommended as drug is contraindicated. Pharmacokinetic changes in pregnancy (increased clearance) are not applicable for a contraindicated drug.
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.
Contains 1 mg norethindrone and 0.035 mg ethinyl estradiol. Monophasic combination oral contraceptive. Risk of venous thromboembolism is dose-dependent; use lowest effective estrogen dose. CYP3A4 inducers (e.g., rifampin, anticonvulsants) may reduce efficacy. Prescribe for cycle control and contraception. Monitor blood pressure at baseline and follow-up. Avoid in smokers over 35 and those with migraine with aura.
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 pill daily at the same time for 21 days, then none for 7 days.Use backup contraception (e.g., condoms) if you miss a pill or start late.Common side effects include nausea, breast tenderness, and breakthrough bleeding.Seek emergency care for severe leg pain, chest pain, sudden severe headache, or vision changes.Do not smoke while taking this medication, especially if over 35.Notify your doctor if you develop jaundice, depression, or unexplained weight gain.This medication does not protect against HIV or other sexually transmitted infections.