Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 2 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 2 21.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 2-21
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 of estrogen (ethinyl estradiol) and progestin (norethindrone) inhibits ovulation via negative feedback on the hypothalamic-pituitary-ovarian axis, suppressing gonadotropin release. Additionally, induces changes in cervical mucus and endometrium.
Prevention of pregnancyAcne vulgaris (for women aged ≥15 who desire contraception)
Prevention of pregnancy in women who elect to use oral contraceptivesTreatment of moderate acne vulgaris in females at least 15 years of age who have no known contraindications and have achieved menarche
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 days off. Each tablet contains norethindrone 2 mg and ethinyl estradiol 0.1 mg.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: terminal half-life 5-12 hours; ethinyl estradiol: terminal half-life 7-20 hours (enterohepatic recirculation may prolong effect). Steady-state achieved after 5-7 days.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Ethinyl estradiol is metabolized primarily via CYP3A4, with contributions from CYP2C9 and CYP2C19. Norethindrone is metabolized via CYP3A4 and reduction pathways.
Renal (∼40% as metabolites, <10% unchanged) and fecal (∼30% as metabolites); conjugated metabolites excreted in bile and undergo enterohepatic circulation.
Renal (approx. 60% as metabolites), fecal (approx. 40% as metabolites). Norethindrone and ethinyl estradiol are extensively metabolized; less than 5% excreted unchanged in urine.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: ~60% bound to albumin, ~1.5% to SHBG; ethinyl estradiol: ~97% bound to albumin (not to SHBG).
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Vd for norethindrone: ~3.1±0.5 L/kg; for ethinyl estradiol: ~3.5–4.5 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% (first-pass metabolism reduces it); ethinyl estradiol ~38-48% (high 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 dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR <30 mL/min) or dialysis, use is not recommended due to potential 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 acute or chronic hepatocellular disease with abnormal liver function, including Child-Pugh class B or C. Adjustment not applicable in mild hepatic impairment (Child-Pugh class A) but use caution and monitor.
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. After menarche, dosing is same as adult (one tablet daily for 21 days, then 7 days off). Weight-based guidelines are not established.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for postmenopausal women. No specific geriatric dosing adjustments have been studied.
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. Risk increases with age (especially in women over 35) and with heavy smoking (≥15 cigarettes/day). Women who use 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."]
["Thrombotic events (venous and arterial)","Cardiovascular risks in smokers over 35","Hepatic neoplasia","Hypertension","Gallbladder disease","Carbohydrate/lipid metabolism effects","Ocular lesions (retinal thrombosis)","Reduced efficacy with hepatic enzyme inducers"]
["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","Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected breast cancer or estrogen-dependent neoplasia","Hepatic adenoma or carcinoma (current or history)","Jaundice or liver disease (acute or chronic)","Hypersensitivity to any component","Smoking in women over 35 (<15 cigarettes/day is relative; >15 is absolute)"]
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 restrictions; grapefruit juice may alter estrogen metabolism but clinical significance is unclear. Maintain consistent diet to avoid GI upset. Avoid excessive alcohol intake.
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.
Category X: Contraindicated in pregnancy. First trimester: Increased risk of cardiovascular and limb reduction defects. Second and third trimesters: Associated with feminization of male fetuses and potential for other teratogenic effects.
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.
Contraindicated during breastfeeding due to potential for reduced milk production and excretion of estrogen/progestin into breast milk. M/P ratio: Not established.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
No dosing adjustments applicable as drug is contraindicated in pregnancy. Pharmacokinetic changes in pregnancy (e.g., increased hepatic metabolism, volume of distribution) are not relevant due to contraindication.
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.
Monitor for thromboembolic events, especially in smokers over 35. Counsel about missed dose protocol: take as soon as remembered, use backup contraception if >12 hours late. Caution with hepatic enzyme inducers (e.g., rifampin, anticonvulsants) reducing efficacy. Check BP at baseline and periodically. Consider VTE risk with obesity or immobilization. Not for use in pregnancy or breastfeeding.
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, even if not sexually active.If you miss a dose, take it as soon as you remember; if more than 12 hours late, use backup contraception for 7 days.Smoking increases risk of serious cardiovascular side effects, especially in women over 35.Notify your doctor if you experience leg pain/swelling, chest pain, shortness of breath, severe headache, or vision changes.This medication does not protect against HIV or other STDs.Inform all healthcare providers that you are taking this drug.