Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 35 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 35 28.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 1/35-28
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 containing ethinyl estradiol and norethindrone. Inhibits ovulation by suppressing gonadotropin release (FSH and LH) from the pituitary; increases viscosity of cervical mucus, impeding sperm penetration; alters endometrial lining, reducing implantation likelihood.
Prevention of pregnancyAcne vulgaris (for women aged ≥15 who desire contraception)
Prevention of pregnancy (FDA-approved)Treatment of acne (off-label)
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).
1 tablet (norethindrone 1 mg / ethinyl estradiol 35 mcg) orally once daily for 28 consecutive days. Placebo tablets on days 22-28 if included.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: 5-14 hrs (terminal); ethinyl estradiol: 10-24 hrs. Steady-state achieved within 5-7 days; terminal half-life supports once-daily dosing.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Ethinyl estradiol primarily metabolized via CYP3A4, with phase II conjugation (glucuronidation and sulfation). Norethindrone metabolized via reduction and conjugation, primarily as glucuronide conjugates. Both undergo enterohepatic recirculation.
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% via biliary elimination; <1% unchanged in urine.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: ~97% (mainly SHBG and albumin); ethinyl estradiol: ~98% (albumin and SHBG, induces SHBG synthesis).
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: 3-4 L/kg; ethinyl estradiol: 2-4 L/kg. Large Vd indicates extensive tissue distribution and binding.
Oral: Norelgestromin ~100% (after first-pass conversion from norgestimate); Ethinyl estradiol ~45% (due to first-pass metabolism).
Oral: Norethindrone ~50-70% (first-pass metabolism); ethinyl estradiol ~40-50% (first-pass metabolism, variable).
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. Contraindicated in severe renal impairment or acute renal failure due to potential fluid retention and hyperkalemia.
Contraindicated in Child-Pugh Class B or C (moderate to severe hepatic impairment). Not studied in Child-Pugh Class A; use caution.
Contraindicated in acute hepatic disease, hepatocellular carcinoma, and Child-Pugh class C cirrhosis. Use with caution in Child-Pugh class A or B; no specific dose adjustment established, but reduced metabolism may increase estrogen exposure.
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.
Use after menarche. Same dosing as adults: 1 tablet daily for 28 days. Not indicated for use before menarche.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for postmenopausal women. In elderly reproductive-age women, same dosing as adults; consider increased risk of thromboembolic events and cardiovascular disease with age.
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 oral contraceptive use. Risk increases with age (especially in women over 35) and with heavy smoking (≥15 cigarettes/day). Women taking oral 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), especially in smokers, obese, or hypertensive patients","Risk of myocardial infarction and stroke","Hepatic neoplasia (benign and malignant) reported","Increased risk of gallbladder disease","Elevated blood pressure","Carbohydrate and lipid metabolic effects","Ocular lesions (retinal thrombosis) reported","Headache including migraine","Uterine bleeding irregularities","Depression","Discontinue if jaundice, visual disturbances, or thromboembolic symptoms occur"]
["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 (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast carcinoma","Known or suspected estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Pregnancy (known or suspected)","Benign or malignant liver tumors (current or history)","Active liver disease or impaired liver function","Hypersensitivity to any component","Heavy smoking (≥15 cigarettes/day) in women over 35"]
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 increase estrogen levels slightly but not clinically relevant. Taking with food can 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.
First trimester: No increased risk of major birth defects based on large epidemiological studies. Second/third trimester: Exposure may increase risk of intrauterine growth restriction, preterm birth, and neonatal complications such as respiratory distress syndrome. Postnatal: May cause hormonal withdrawal effects in neonate.
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 in small amounts; no adverse effects reported in infants. M/P ratio not established. Use with caution; may reduce milk production.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
Contraindicated in pregnancy; no dose adjustment applicable as drug is discontinued.
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 1/35-28 is a monophasic oral contraceptive containing 1 mg norethindrone and 35 mcg ethinyl estradiol. Use 28-day packs with 21 active pills and 7 placebos. Counsel patients to take at same time daily to maintain hormone levels. Missed pill management: if missed one active pill, take as soon as remembered; if missed two or more, use backup contraception for 7 days. Consider drug interactions with rifampin, certain anticonvulsants, and St. John's wort.
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, preferably after an evening meal to reduce nausea.The 28-day pack includes 21 hormone pills (white) and 7 reminder pills (green). Start a new pack the day after finishing the previous one.If you miss a pill, refer to the package insert for instructions. Use backup contraception (e.g., condoms) if needed.Common side effects include nausea, breast tenderness, spotting, and weight changes; these often improve after 2-3 cycles.This medication does not protect against sexually transmitted infections (STIs). Use condoms for STI prevention.Smoking increases risk of serious cardiovascular side effects; women over 35 who smoke should not use this pill.Report signs of blood clots: leg pain/swelling, chest pain, shortness of breath, sudden severe headache, vision changes.