Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 80 28.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 1 80 28.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 1/80 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; primarily inhibits ovulation by suppressing gonadotropin release (FSH and LH). Also increases cervical mucus viscosity and alters endometrial receptivity.
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 at the same time each day for 28 days (21 active tablets containing norethindrone 1 mg and ethinyl estradiol 80 mcg, 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: 7-8 hours; mestranol: 10-13 hours (terminal). Steady-state achieved in 5-7 days.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Ethinyl estradiol is metabolized primarily via CYP3A4 and undergoes glucuronidation; norethindrone is metabolized via reduction and conjugation.
Renal (∼40% as metabolites, <10% unchanged) and fecal (∼30% as metabolites); conjugated metabolites excreted in bile and undergo enterohepatic circulation.
Norethindrone: 50-60% renal, 20-30% fecal; mestranol: 30-40% renal, 60-70% fecal.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: 60-80% bound to albumin and SHBG; mestranol: 90-95% bound to albumin and SHBG.
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: 2-4 L/kg; mestranol: 1-3 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 50-65%, mestranol 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 specific dose adjustment recommended; use with caution in patients with renal impairment due to potential fluid retention. GFR-based modifications not established.
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 Child-Pugh class C cirrhosis. Use with caution in Child-Pugh class A or B; consider alternative contraception due to risk of decreased hormone clearance.
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 premenarchal girls. For postmenarchal adolescents, same dosing as adults: one tablet orally once daily for 28 days.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for use in postmenopausal women. No geriatric dosing established; use not recommended in women over 50 years due to increased risk of thromboembolism and lack of efficacy for contraception.
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 and smoking intensity, especially in women over 35 years of age. Women using 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","Cerebrovascular disease","Myocardial infarction","Breast cancer risk","Hepatic neoplasia","Elevated blood pressure","Gallbladder disease","Glucose intolerance","Ocular lesions","Headache","Menstrual irregularities","Depression","Contact lens intolerance","Fluid retention","Lipid effects"]
["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 thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Known or suspected estrogen-dependent neoplasia","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use","Hepatic adenoma or carcinoma","Known or suspected 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, high-fat meals may delay absorption. Avoid grapefruit juice as it may increase estrogen levels via CYP3A4 inhibition.
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 consistent evidence of major malformations, but oral contraceptives are not recommended due to potential risk. Second/third trimester: No specific fetal risks; exposure is not advised due to hormonal 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.
Excreted in breast milk; may reduce milk production and affect infant. M/P ratio not well established. Avoid use during breastfeeding.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
No dose adjustment applicable; drug is contraindicated in pregnancy. Pharmacokinetic changes in pregnancy may alter efficacy but no standard dose modification exists.
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.
1. If a dose is missed, take it as soon as remembered; if more than 24 hours late, use backup contraception for 7 days. 2. Monitor blood pressure within 3 months of initiation due to potential hypertensive effects. 3. Caution in patients with migraine with aura due to increased stroke risk. 4. The estrogen component (mestranol) is a prodrug of ethinyl estradiol; bioavailability considerations influence dosing. 5. 21 active pills followed by 7 placebo pills; ensure patient understands the tricycle regimen.
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 at the same time daily, preferably after dinner to reduce nausea.If you miss a pill, consult the package insert for instructions; use backup contraception as needed.Report unusual symptoms: leg pain/swelling (DVT), chest pain/shortness of breath (pulmonary embolism), severe headache, vision changes.This does not protect against STIs; use condoms for additional protection.Expect breakthrough bleeding or spotting in the first few months; persistent bleeding requires evaluation.Smoking increases risk of serious cardiovascular side effects, especially in women over 35.