Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 50 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 50 21.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 1/50 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 oral contraceptive consisting of mestranol (estrogen) and norethindrone (progestin). Mestranol is converted to ethinyl estradiol, which suppresses gonadotropin release (FSH, LH) from the pituitary, inhibiting ovulation. Norethindrone induces changes in cervical mucus (increasing viscosity) and endometrial lining, creating a hostile environment for sperm implantation.
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 orally once daily for 21 days, followed by 7 tablet-free days. Each tablet contains 1 mg norethindrone and 50 mcg mestranol.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: biphasic terminal half-life 7-9 hours for parent compound, 8-11 hours for metabolites; clinical steady-state achieved after 5-7 days.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Mestranol is rapidly demethylated to ethinyl estradiol, primarily by CYP2C9 and CYP3A4. Ethinyl estradiol and norethindrone undergo hepatic metabolism via CYP3A4, with conjugation and excretion in urine and feces.
Renal (∼40% as metabolites, <10% unchanged) and fecal (∼30% as metabolites); conjugated metabolites excreted in bile and undergo enterohepatic circulation.
Renal 50-60% as glucuronide and sulfate conjugates of norethindrone and mestranol/metabolites; fecal 20-30% via biliary elimination.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: 97-98% bound to albumin and sex hormone-binding globulin (SHBG); mestranol: 95-97% bound to albumin.
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: Vd 3-4 L/kg (approx. 210-280 L for 70 kg adult), indicating extensive tissue distribution; mestranol: Vd 1.5-2 L/kg.
Oral: Norelgestromin ~100% (after first-pass conversion from norgestimate); Ethinyl estradiol ~45% (due to first-pass metabolism).
Norethindrone: oral bioavailability 40-60% due to first-pass metabolism; mestranol rapidly converted to ethinyl estradiol with oral bioavailability 40-50%.
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); use with caution.
Contraindicated in Child-Pugh Class B or C (moderate to severe hepatic impairment). Not studied in Child-Pugh Class A; use caution.
Contraindicated in Child-Pugh class B or C (moderate to severe hepatic impairment). For 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.
Not indicated for use before menarche. Post-menarche: same as adult dosing (one tablet daily for 21 days) after evaluating individual risk factors.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for use in postmenopausal women due to increased risk of thrombotic events and lack of benefit.
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 the risk of serious cardiovascular events from combination oral contraceptive use. This risk increases with age, especially in women over 35, and with the 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 (e.g., DVT, PE) and cardiovascular events (MI, stroke).","Elevated blood pressure.","Increased risk of gallbladder disease.","Hepatic adenoma or hepatocellular carcinoma.","Glucose intolerance and adverse effects on lipid metabolism.","Chloasma (melasma) exacerbated by UV exposure.","Retinal thrombosis or other ocular effects.","Menstrual irregularities and amenorrhea.","Cervical cancer risk (HPV-related)."]
["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 history of thrombophlebitis or thromboembolic disorders.","History of DVT or PE.","Cerebrovascular or coronary artery disease.","Known or suspected breast carcinoma or estrogen-dependent neoplasia.","Undiagnosed abnormal genital bleeding.","Cholestatic jaundice of pregnancy or jaundice with prior OC use.","Hepatic adenoma or carcinoma.","Known hypersensitivity to any component."]
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. However, grapefruit juice may increase estrogen levels, but clinically negligible. Avoid excessive alcohol as it may worsen liver metabolism.
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: Mestranol and norethindrone are associated with a slightly increased risk of congenital anomalies, particularly cardiovascular defects and limb reduction defects, although absolute risk is low. Second and third trimesters: Continued exposure may lead to fetal adrenal suppression, liver impairment, and pseudointersexuality in female fetuses due to androgenic effects of norethindrone. Overall, contraceptive use during pregnancy is contraindicated.
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 not established. May reduce milk production and quality, especially with high-dose estrogens. Use during lactation is generally not recommended, particularly in early postpartum. Consider non-hormonal contraception.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
Contraindicated during pregnancy; no dose adjustments apply as it should be discontinued immediately 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 1/50 21 is a combination oral contraceptive containing 1 mg norethindrone and 50 mcg mestranol. It has higher estrogen content than modern pills, increasing thromboembolic risk. Counsel patients to avoid smoking, especially over age 35. Use as directed for 21 days on, 7 days off. Missed pills require backup contraception.
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 consecutive days, then none for 7 days.If you miss a pill, take it as soon as remembered; if more than 24 hours late, use backup contraception for 7 days.Do not smoke while taking this medication, especially if over 35, due to increased risk of blood clots.Common side effects include nausea, breast tenderness, and breakthrough bleeding, especially in the first few months.This pill does not protect against HIV or other sexually transmitted infections.