Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 10 11 21.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN LO versus ORTHO NOVUM 10 11 21.
ORTHO TRI-CYCLEN LO vs ORTHO-NOVUM 10/11-21
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 norethindrone (progestin) and ethinyl estradiol (estrogen). Prevents ovulation primarily by suppressing gonadotropin release, including FSH and LH. Also increases cervical mucus viscosity, impeding sperm penetration, and alters endometrial structure, 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 of ageOral contraception with a biphasic hormone regimen providing a low-dose alternative
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 (10 mg norethindrone/0.035 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 placebo days. Start on first Sunday after menstrual period begins or on day 1 of cycle.
None Documented
None Documented
Norelgestromin: 15-20 hours; Ethinyl estradiol: 13-16 hours. Steady-state achieved within 7 days.
Norethindrone: 7-8 hours (terminal); Ethinyl estradiol: 10-20 hours (terminal). Clinically, steady state reached within 5-7 days.
Metabolized primarily via CYP3A4 oxidation; ethinyl estradiol undergoes phase II conjugation (glucuronidation and sulfation).
Norethindrone undergoes extensive first-pass metabolism in the liver via reduction and conjugation, primarily by CYP3A4. Ethinyl estradiol is metabolized by hydroxylation and conjugation, involving CYP3A4 and sulfate conjugation. Both undergo enterohepatic recirculation.
Renal (∼40% as metabolites, <10% unchanged) and fecal (∼30% as metabolites); conjugated metabolites excreted in bile and undergo enterohepatic circulation.
Renal: ~50% (metabolites as glucuronide and sulfate conjugates); Fecal: ~30% (via bile); Urinary unchanged: <1%.
Norelgestromin: 99%, primarily to albumin; Ethinyl estradiol: 97-98%, primarily to albumin and sex hormone-binding globulin (SHBG).
Norethindrone: ~97% bound to albumin and SHBG; Ethinyl estradiol: ~98% bound to albumin (not SHBG).
Norelgestromin: 2.5-3.5 L/kg; Ethinyl estradiol: 2-4 L/kg; extensive tissue distribution.
Norethindrone: ~2-4 L/kg; Ethinyl estradiol: ~2-3 L/kg; indicates extensive tissue distribution and binding.
Oral: Norelgestromin ~100% (after first-pass conversion from norgestimate); Ethinyl estradiol ~45% (due to first-pass metabolism).
Oral: Norethindrone ~60-70% (first-pass metabolism); Ethinyl estradiol ~40-50% (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 severe renal impairment; monitor for fluid retention.
Contraindicated in Child-Pugh Class B or C (moderate to severe hepatic impairment). Not studied in Child-Pugh Class A; use caution.
Contraindicated in severe hepatic disease (Child-Pugh class C). For mild to moderate impairment (Child-Pugh A or B): use only if benefits outweigh risks, as hormonal contraceptives may worsen cholestasis.
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. For postmenarchal adolescents: same dosing as adults (one tablet daily for 21 days, then 7 placebo). Regular menstrual cycles should be established before initiation.
Not indicated for use in postmenopausal women; no geriatric dosing studies conducted.
Not indicated for use after menopause. No specific dosing studies in elderly; estrogen-containing contraceptives are contraindicated in women over 35 who smoke or have cardiovascular risk factors.
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 contraceptives. Risk increases with age and heavy smoking (≥15 cigarettes/day). Women over 35 years old who smoke should not use this product.
["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., venous thrombosis, stroke, MI); discontinue if symptoms occur","Elevated blood pressure; monitor regularly","Hepatic neoplasia risk (benign and malignant); discontinue if jaundice or liver abnormalities","Cholestatic jaundice; caution in patients with history","Risk of retinal thrombosis; discontinue if unexplained vision loss","Altered glucose tolerance; caution in diabetics","Depression; discontinue if severe","Headache (including migraine); discontinue if new pattern or worsening","Breakthrough bleeding and spotting; rule out pregnancy if persistent","Gallbladder disease risk"]
["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","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Estrogen-dependent neoplasia (e.g., endometrial cancer)","Undiagnosed abnormal genital bleeding","Acute liver disease, hepatic adenoma, or impaired liver function","History of cholestatic jaundice with prior OC use","Age >35 years and smoking","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 clinically significant food interactions. However, grapefruit juice may increase ethinyl estradiol levels by inhibiting CYP3A4; avoid large amounts. Take with food if gastrointestinal upset occurs.
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 (OR 1.2-1.4), cardiovascular malformations (OR 1.1-1.3). Second/third trimester: No significant increase in major malformations; possible association with low birth weight, preterm delivery. Postnatal: No known long-term 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.
Excretion into breast milk minimal; estimated relative infant dose <1% of maternal weight-adjusted dose; M/P ratio not reported. American Academy of Pediatrics compatible with breastfeeding; avoid high-dose formulations.
Contraindicated in pregnancy; no dosing adjustments applicable. Discontinue immediately if pregnancy occurs.
No dose adjustment recommended during pregnancy; drug should be discontinued as soon as pregnancy is detected. No pharmacokinetic studies indicating need for change.
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.
For ORTHO-NOVUM 10/11-21 (norethindrone/ethinyl estradiol), a biphasic oral contraceptive, patients must take the 10 white tablets (0.5 mg norethindrone, 35 mcg ethinyl estradiol) for 10 days, followed by 11 peach tablets (1 mg norethindrone, 35 mcg ethinyl estradiol) for 11 days. Missed pills increase breakthrough bleeding and pregnancy risk; if one pill missed, take as soon as remembered, next at regular time. If two consecutive pills missed, take two pills for two days and use backup contraception for 7 days. Advise about increased thromboembolic risk, especially in smokers over 35. Prescribe only after thorough medical history and blood pressure measurement.
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 the pills exactly as directed: white pills for 10 days, then peach pills for 11 days, followed by 7 placebo days.Use backup contraception (e.g., condoms) if you miss any pills, especially during the first week of a new pack.Smoking while on this pill increases risk of serious cardiovascular side effects; avoid smoking, especially if over 35 years old.Contact your doctor immediately if you experience severe leg pain, chest pain, shortness of breath, severe headache, or vision changes.Notify all healthcare providers that you are taking this medication before any surgery or prolonged immobility.This prescription does not protect against HIV or other sexually transmitted infections.