Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 10 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 10 21.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 10-21
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 release (FSH, LH) from pituitary, inhibiting ovulation; increases viscosity of cervical mucus and alters endometrial lining, reducing sperm penetration and implantation.
Prevention of pregnancyAcne vulgaris (for women aged ≥15 who desire contraception)
Prevention of pregnancyTreatment of menorrhagiaTreatment of dysmenorrheaRegulation of menstrual cyclesEmergency contraception (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 (1 mg norethindrone, 0.035 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 days of no tablets.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone 5-14 hours (mean 8 hours), ethinyl estradiol 7-20 hours (mean 13 hours). Steady-state achieved in 5-10 days.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Hepatic via cytochrome P450 3A4 (CYP3A4) for norethindrone and ethinyl estradiol; first-pass metabolism; enterohepatic recirculation; elimination as glucuronide and sulfate conjugates 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 approximately 50-60% as metabolites, biliary/fecal approximately 30-40% as metabolites and unchanged drug.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: 90-95% bound to albumin and SHBG; ethinyl estradiol: 97-98% 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: 2-4 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 50-80%, ethinyl estradiol 40-60% 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. Not recommended in severe renal impairment (GFR <30 mL/min) due to lack of safety data.
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 hepatic impairment. For Child-Pugh class A, use with caution and monitor liver function; no specific dose adjustment established.
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 in pediatric patients before menarche. Post-menarche: same adult dosing, 1 tablet orally once daily for 21 days, then 7 days off.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for use in postmenopausal women. Not recommended for elderly patients due to lack of efficacy and increased thrombotic risk.
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. Risk increases with age (especially in women >35 years) and with 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, pulmonary embolism), myocardial infarction, stroke; hepatic neoplasia (benign and malignant); gallbladder disease; hypertension; glucose intolerance; elevated triglyceride levels; exacerbation of depression; fluid retention; headache; irregular bleeding; potential for decreased efficacy with concomitant enzyme-inducing drugs; instruct to report visual disturbances or migraine; discontinue if jaundice occurs; monitor for signs of thrombosis.
["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; history of DVT or PE; cerebrovascular or coronary artery disease; known or suspected breast cancer; endometrial cancer or other estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; known or suspected pregnancy; liver tumors (benign or malignant) or active liver disease; hypersensitivity to any component; age >35 years and smoking cigarettes; uncontrolled hypertension; diabetes with vascular involvement; migraine 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.
No significant food interactions. Grapefruit juice may increase estrogen levels but clinical relevance is minimal. Avoid excessive alcohol consumption due to potential liver strain. Maintain consistent dietary habits to reduce gastrointestinal side effects.
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. Second and third trimesters: associated with fetal adrenal suppression, virilization of female fetuses, and potential for long-term neurodevelopmental effects. Use contraindicated in pregnant women.
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 into breast milk in small amounts (M/P ratio approximately 0.5). May reduce milk production and composition. Use during breastfeeding not recommended; alternative contraception advised.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
Contraindicated in pregnancy; no dosing adjustments are applicable. Discontinue 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 10-21 (norethindrone 10 mg with ethinyl estradiol 21 mcg) 21-day regimen: breakthrough bleeding/spotting is common during first 3 cycles; encourage continuation. If a dose is missed, take as soon as remembered and use backup contraception for 7 days. Higher estrogen content increases thromboembolic risk; avoid in smokers >35 years. Monitor blood pressure and liver function at baseline and periodically.
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 for 21 days, then 7 pill-free days.Use backup contraception (e.g., condoms) for the first 7 days of the first pack.If you miss a pill, take it as soon as you remember; if more than 24 hours, take last missed and use backup for 7 days.Common side effects include nausea, breast tenderness, spotting, and mood changes; they often improve within 3 months.Seek medical attention for severe leg pain, chest pain, shortness of breath, or severe headache.Do not smoke while taking this medication, especially if over 35 years old.