Comparative Pharmacology
Head-to-head clinical analysis: ORTHO CYCLEN 21 versus ORTHO CEPT.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO CYCLEN 21 versus ORTHO CEPT.
ORTHO CYCLEN-21 vs ORTHO-CEPT
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Combination oral contraceptive containing ethinyl estradiol and norgestimate. Suppresses gonadotropin (FSH, LH) release via negative feedback, inhibiting ovulation. Increases cervical mucus viscosity and alters endometrial structure to impair sperm penetration and implantation.
Combination oral contraceptive containing desogestrel and ethinyl estradiol. Inhibits ovulation by suppressing gonadotropin secretion; increases viscosity of cervical mucus, impeding sperm penetration; alters endometrial development.
Prevention of pregnancy (FDA-approved)Treatment of moderate acne vulgaris in females aged ≥15 years who have menarche and desire oral contraception (FDA-approved)Off-label: Irregular menstrual cycles, dysmenorrhea, endometriosis-associated pain, hirsutism
Prevention of pregnancy
One tablet (norgestimate 0.180 mg/ethinyl estradiol 0.035 mg for days 1-7, norgestimate 0.215 mg/ethinyl estradiol 0.035 mg for days 8-14, norgestimate 0.250 mg/ethinyl estradiol 0.035 mg for days 15-21) orally once daily for 21 days, followed by 7 placebo tablets (if included) or 7 drug-free days, then repeat.
One tablet (0.15 mg desogestrel / 0.03 mg ethinyl estradiol) orally once daily at the same time each day for 21 days, followed by 7 placebo tablets (or 7 hormone-free days).
None Documented
None Documented
Terminal elimination half-life: Norgestimate metabolite (norelgestromin) ~28 hours; Ethinyl estradiol ~17 hours (range 13-27 hours). Clinical context: Steady-state achieved within 10-14 days.
Desogestrel: 23 hours (terminal), Etonogestrel active metabolite: 30 hours (terminal); clinical steady state after 7-10 days
Primarily hepatic metabolism via CYP3A4 for ethinyl estradiol and norgestimate undergoes first-pass hydrolysis to norelgestromin and subsequent reduction, conjugation, and further hepatic metabolism. Norelgestromin is further metabolized by CYP3A4.
Ethinyl estradiol: primarily metabolized by CYP3A4; desogestrel: prodrug converted to active metabolite etonogestrel via CYP2C9 and CYP2C19.
Approximately 40% renal (as metabolites), 60% biliary/fecal (as metabolites). Norgestimate metabolites are excreted primarily in urine (40-50%) and feces (50-60%). Ethinyl estradiol metabolites are excreted in urine (40%) and feces (60%).
Renal: 50% (metabolites), Biliary/fecal: 40% (metabolites and unchanged drug), 10% unchanged in urine
Norelgestromin: 97% bound to albumin and sex hormone-binding globulin (SHBG); Ethinyl estradiol: 98% bound to albumin.
Desogestrel: 99% (SHBG), Etonogestrel: ~66% (albumin and SHBG); Ethinyl estradiol: 98% (albumin)
Norelgestromin: Vd ~3.0 L/kg; Ethinyl estradiol: Vd ~2.8 L/kg. Clinical meaning: Extensive distribution into tissues, including breast and reproductive organs.
Desogestrel: 1.5 L/kg, Etonogestrel: 1.7 L/kg; indicates extensive tissue distribution
Oral: Norgestimate ~85% (first-pass metabolism); Ethinyl estradiol ~40-50% (first-pass metabolism and conjugation).
Desogestrel: 76% (oral, as prodrug converted to etonogestrel); Ethinyl estradiol: 45-50% (oral, first-pass metabolism)
No dose adjustment required for mild to moderate renal impairment. Contraindicated in patients with renal disease (e.g., severely impaired renal function).
No dose adjustment required for mild to moderate renal impairment. Limited data in severe renal impairment; use is not recommended due to potential fluid/electrolyte disturbances.
Contraindicated in patients with hepatic adenomas or acute/chronic liver disease. For Child-Pugh A: no adjustment; Child-Pugh B: avoid use; Child-Pugh C: contraindicated.
Contraindicated in Child-Pugh class B or C (severe hepatic impairment) and in acute liver disease. Caution in Child-Pugh class A; monitor liver function; consider alternative method.
Safety and efficacy not established in postmenarchal pediatric patients; use same dosing as adults after menarche. Not indicated in premenarchal females.
Post-menarchal adolescents: Same dosing regimen as adults (1 tablet daily). Not indicated for use before menarche.
Not indicated for use in postmenopausal women; no geriatric-specific dosing studies. In perimenopausal women >35 who smoke, use with caution due to increased cardiovascular risk.
Not indicated for use in postmenopausal women. Contraceptive efficacy not applicable; estrogen-containing combination contraceptives are generally not recommended in women over 35 who smoke or have other cardiovascular risk factors.
Cigarette smoking increases risk of serious cardiovascular events (e.g., myocardial infarction, thromboembolism, stroke) from combined oral contraceptives. Risk increases with age (especially >35 years) and number of cigarettes smoked. Women >35 years who smoke should not use this product.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Women over 35 who smoke should not use this product.
["Thrombotic disorders: Discontinue if thrombophlebitis, thromboembolism, cerebrovascular disorders, or retinal thrombosis occurs.","Hepatic disease: Discontinue if jaundice or liver function abnormalities develop.","Elevated blood pressure: Monitor; discontinue if hypertension occurs.","Gallbladder disease: Increased risk of gallstones.","Carbohydrate/lipid metabolism: Monitor in diabetics; may cause glucose intolerance and lipid changes.","Headache: Discontinue if new-onset or exacerbation of migraine (may signal cerebrovascular event).","Bleeding irregularities: Amenorrhea or spotting may occur; evaluate if persistent.","Ocular effects: Discontinue if unexplained vision loss, proptosis, diplopia, or papilledema (rule out retinal thrombosis).","Depression: Discontinue if severe depression recurs.","Cervical cancer: Increased risk of HPV-related cervical neoplasia.","Breast cancer: Current or past history of breast cancer should not use."]
["Thrombotic disorders (venous thromboembolism, arterial thromboembolism)","Cerebrovascular disease","Cigarette smoking in women >35 years","Hypertension","Gallbladder disease","Hepatic neoplasia","Bleeding irregularities"]
["Hypersensitivity to ethinyl estradiol or norgestimate","Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast cancer","Carcinoma of the endometrium or other 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 pregnancy","Heavy smoking (≥15 cigarettes/day) in women >35 years"]
["High risk of arterial or venous thrombotic events","Current or history of breast cancer or other estrogen-sensitive cancer","Hepatic adenoma or carcinoma","Undiagnosed abnormal uterine bleeding","Pregnancy","Hypersensitivity to any component"]
Data Pending Review
Data Pending Review
No significant food interactions. Grapefruit juice may increase ethinyl estradiol levels; avoid large amounts. Maintain consistent intake of foods rich in folate as oral contraceptives may lower folate levels.
Grapefruit juice may increase ethinyl estradiol levels via CYP3A4 inhibition, but effect is minor; typical dietary intake does not require restriction. High-fat meals may delay absorption but no dose adjustment needed. Maintain consistent dietary patterns for peak concentration predictability.
FDA Pregnancy Category X. Use is contraindicated in pregnancy. First trimester: No increased risk of birth defects from inadvertent exposure, but due to hormonal effects, discontinue if pregnancy occurs. Second and third trimesters: Associated with increased risk of fetal harm, including cardiac defects, limb reduction defects, and possibly other anomalies. Postnatal effects: Potential for long-term developmental issues.
Contraindicated during pregnancy due to risk of fetal harm. First trimester exposure linked to cardiovascular defects and limb reduction defects. Second and third trimester exposure associated with fetal genital abnormalities and potential long-term effects from progestin activity.
Norgestimate and ethinyl estradiol are excreted in breast milk. M/P ratio not specifically determined; low amounts expected. Use may reduce milk production and quality. Generally not recommended during breastfeeding; if used, monitor infant for jaundice, growth, and development. Alternative contraception advised.
Small amounts of desogestrel and ethinyl estradiol excreted in breast milk; M/P ratio not well established. Use not recommended during breastfeeding as it may reduce milk production and quality. Alternative contraception advised.
Contraindicated in pregnancy; no dose adjustment recommended. If pregnancy occurs, discontinue medication immediately. Pharmacokinetic changes in pregnancy not applicable as use is contraindicated.
Not applicable; contraindicated in pregnancy. No dose adjustment recommendations exist as use is not recommended.
Category C
Category C
Ortho Cyclen-21 (norgestimate/ethinyl estradiol) is a monophasic oral contraceptive. Ensure no contraindications like smoking over age 35, hypertension, or history of thromboembolism. Advise taking at same time daily; missed pills require backup contraception. May reduce menstrual cramps and acne.
ORTHO-CEPT (desogestrel/ethinyl estradiol) is a monophasic oral contraceptive. Counsel patients that missed pills increase risk of breakthrough bleeding and pregnancy; refer to package insert for missed dose instructions. Consider reduced efficacy with hepatic enzyme inducers (e.g., rifampin, phenytoin). Caution in patients with migraine with aura due to increased stroke risk. May cause chloasma; advise sun protection.
Take one pill daily at the same time, in the order shown on the pack.If you miss a pill, follow the instructions in the package insert; missed pills increase pregnancy risk.Use a backup contraceptive (e.g., condoms) if you miss pills or start vomiting/diarrhea.Do not smoke; smoking while on this pill increases risk of serious cardiovascular side effects.Call your doctor if you have symptoms of blood clots: sudden chest pain, leg pain/swelling, or trouble breathing.This pill does not protect against HIV or other sexually transmitted infections.
Take one pill daily at the same time each day for 21 days, then 7 placebo pills.If you vomit or have severe diarrhea within 4 hours of taking a pill, use backup contraception for 7 days.Do not smoke while taking this medication due to increased risk of blood clots.Inform your healthcare provider if you develop severe headache, chest pain, shortness of breath, or leg swelling.Use additional contraception if you miss two or more active pills in a row.