Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 10 11 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 10 11 28.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 10/11-28
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 estrogen-progestin contraceptive; suppresses gonadotropins (FSH, LH) via negative feedback inhibition of hypothalamic-pituitary axis, preventing ovulation; increases cervical mucus viscosity, impeding sperm penetration; alters endometrial development, reducing implantation likelihood.
Prevention of pregnancyAcne vulgaris (for women aged ≥15 who desire contraception)
Prevention of pregnancyTreatment of moderate acne vulgaris (in females ≥15 years who have menarche and desire contraception)Off-label: menstrual cycle regulation, dysmenorrhea, endometriosis-associated pain
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 daily for 28 days, starting on day 1 of menstrual cycle. Each tablet contains 1 mg norethindrone and 10 mcg ethinyl estradiol for first 10 tablets, then 1 mg norethindrone and 35 mcg ethinyl estradiol for next 11 tablets, followed by 7 placebo tablets.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: 5-14 hours; Ethinyl estradiol: 8-20 hours. Steady state reached within 5 days. Clinical significance: missed doses may increase pregnancy risk due to rapid decline.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Ethinyl estradiol: primarily metabolized by CYP3A4; undergoes first-pass metabolism with extensive conjugation (glucuronidation and sulfation). Norethindrone: metabolized via reduction, conjugation (glucuronidation), and hydroxylation; also involves CYP3A4 to a lesser extent.
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, <10% unchanged); fecal (30-40%) with biliary elimination of conjugates.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: 61% bound to albumin and 36% to SHBG; Ethinyl estradiol: 98% bound to albumin.
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: 4 L/kg; Ethinyl estradiol: 4-5 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%; Ethinyl estradiol ~45% (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 specific dose adjustment guidelines for renal impairment. Use with caution in patients with renal impairment, as ethinyl estradiol and norethindrone may accumulate. Monitor 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 patients with severe hepatic disease (Child-Pugh class C) due to potential accumulation and hepatotoxicity. For mild to moderate impairment (Child-Pugh A or B), use with caution; no specific dose adjustment, but monitor liver function tests.
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 for use before menarche. Post-menarche: same dosing as adults (one tablet daily for 28 days). Safety and efficacy in adolescents have not been specifically established; however, use is common off-label.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for use after menopause. No specific geriatric dosing; however, elderly women should not use combination hormonal contraceptives due to increased risk of thromboembolic events and cardiovascular disease. Use alternative contraception if needed.
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 (myocardial infarction, thromboembolism, stroke) from combination hormonal contraceptive use. Risk increases with age and with smoking intensity (especially >15 cigarettes/day). Women >35 years who smoke should not use this medication.
["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."]
["Thromboembolic disorders (DVT, PE, arterial thrombosis, stroke, MI) – increased risk especially in smokers >35 years, obese, or with hypertension","Cerebrovascular disease","Hepatic disease (including hepatic adenoma or impaired liver function)","Gallbladder disease","Hypertension","Glucose intolerance/diabetes mellitus","Headache (including migraine with or without aura)","Uterine bleeding irregularities","Depression","Possible increased risk of cervical cancer with long-term use"]
["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)"]
["Known or suspected pregnancy","Current or past thromboembolic disorders (DVT, PE, stroke, MI)","Cerebrovascular or coronary artery disease","Known or suspected breast cancer","Estrogen-dependent neoplasia","Hepatic adenomas or carcinomas, or active liver disease (e.g., acute hepatitis)","Undiagnosed abnormal uterine bleeding","Heavy smoking (>15 cigarettes/day) in women ≥35 years"]
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 specific food interactions. Grapefruit juice may increase ethinyl estradiol levels, but clinical significance is minimal. Maintain consistent diet. Antacids containing magnesium may reduce absorption if taken within 2 hours. Caution with St. John's Wort, as it may reduce contraceptive efficacy.
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: Increased risk of neural tube defects and cardiovascular malformations; second and third trimesters: Risk of fetal growth restriction, preterm birth, and transient metabolic disturbances. Contraindicated during pregnancy (FDA Category X).
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; M/P ratio approximately 0.4. May reduce milk production and quality. Use alternative contraception during breastfeeding.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
Contraindicated in pregnancy; no dose adjustment applicable. Discontinue if pregnancy occurs.
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 10/11-28 is a biphasic oral contraceptive containing ethinyl estradiol (35 mcg) and norethindrone (0.5 mg/1 mg). The biphasic dosing mimics natural hormonal fluctuations. It is indicated for contraception. Monitor for breakthrough bleeding, especially during the first few cycles. Counsel patients to take at the same time daily and use backup contraception if a dose is missed. Contraindicated in smokers over 35, history of thromboembolism, or 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 tablet daily at the same time, following the scheduled order in the pack.Missing pills increases risk of pregnancy; refer to package insert for missed dose instructions.Use backup non-hormonal contraception for 7 days if you miss a dose or start late.Common side effects: nausea, breast tenderness, breakthrough bleeding, and mood changes.Report severe headache, chest pain, leg swelling/pain, or visual disturbances immediately.Smoking while on this pill increases risk of serious cardiovascular events; avoid smoking.Do not take during pregnancy; stop if pregnancy is suspected.