Comparative Pharmacology
Head-to-head clinical analysis: ORTHO CYCLEN 28 versus ORTHO CEPT.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO CYCLEN 28 versus ORTHO CEPT.
ORTHO CYCLEN-28 vs ORTHO-CEPT
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Combination oral contraceptive containing ethinyl estradiol and norgestimate. The primary mechanism is inhibition of gonadotropin secretion (FSH and LH) via negative feedback on the hypothalamic-pituitary axis, thereby suppressing ovulation. Additional effects include thickening of cervical mucus (impedes sperm penetration) and alterations in the endometrium (reduces implantation likelihood).
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 pregnancyAcne vulgaris (FDA-approved for females ≥15 years who desire contraception and have no contraindications)
Prevention of pregnancy
One tablet (0.18 mg norgestimate/0.035 mg ethinyl estradiol) orally once daily for 28 days, first tablet on day 1 of menstrual cycle with 7 placebo tablets in last 7 days.
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
Ethinyl estradiol: 13-27 hours; Norelgestromin (active metabolite of norgestimate): 28-52 hours. Terminal half-lives support once-daily dosing.
Desogestrel: 23 hours (terminal), Etonogestrel active metabolite: 30 hours (terminal); clinical steady state after 7-10 days
Ethinyl estradiol is primarily metabolized by CYP3A4, with conjugation (glucuronidation and sulfation) as additional pathways. Norgestimate is rapidly hydrolyzed to norelgestromin (active metabolite) and further to levonorgestrel; norelgestromin is metabolized by CYP3A4 and CYP2C9. Both undergo enterohepatic recirculation.
Ethinyl estradiol: primarily metabolized by CYP3A4; desogestrel: prodrug converted to active metabolite etonogestrel via CYP2C9 and CYP2C19.
Renal (60-70% as metabolites, ~20% unchanged), Fecal (30-40% as metabolites); primarily conjugated metabolites of ethinyl estradiol and norgestimate.
Renal: 50% (metabolites), Biliary/fecal: 40% (metabolites and unchanged drug), 10% unchanged in urine
Ethinyl estradiol: 98% bound to albumin; Norelgestromin: >99% bound to albumin and sex hormone-binding globulin (SHBG).
Desogestrel: 99% (SHBG), Etonogestrel: ~66% (albumin and SHBG); Ethinyl estradiol: 98% (albumin)
Ethinyl estradiol: 2.0-4.0 L/kg; Norelgestromin: 2.0-3.0 L/kg. Indicates extensive distribution into tissues.
Desogestrel: 1.5 L/kg, Etonogestrel: 1.7 L/kg; indicates extensive tissue distribution
Oral: Ethinyl estradiol ~45% (due to first-pass metabolism); Norgestimate gut wall metabolism but active metabolite norelgestromin bioavailability ~60-70%.
Desogestrel: 76% (oral, as prodrug converted to etonogestrel); Ethinyl estradiol: 45-50% (oral, first-pass metabolism)
No dose adjustment recommended for any degree of renal impairment due to minimal renal clearance of contraceptive steroids.
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 acute or chronic hepatic disease (Child-Pugh class B or C) or liver tumors; for mild impairment (Child-Pugh A), use only if benefits outweigh risks; monitor closely.
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.
Not indicated for premenarchal girls; postmenarchal adolescents: same dosing as adults (1 tablet daily for 28-day cycle).
Post-menarchal adolescents: Same dosing regimen as adults (1 tablet daily). Not indicated for use before menarche.
Not indicated for use after menopause due to lack of need for contraception and increased risk of thromboembolic events with age and estrogen exposure.
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 the risk of serious cardiovascular adverse events from combination oral contraceptive use. The risk increases with age (especially in women over 35) and the number of cigarettes smoked. Women who use combination hormonal contraceptives should be strongly advised not to smoke.
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Women over 35 who smoke should not use this product.
["Cardiovascular risks: venous thromboembolism, arterial thromboembolism (e.g., stroke, myocardial infarction), especially in smokers and women over 35","Hypertension: monitor blood pressure; discontinue if hypertension develops","Gallbladder disease: increased risk of cholecystitis and cholelithiasis","Carbohydrate and lipid metabolism: may affect glucose tolerance and lipid levels, monitor in diabetes and hyperlipidemia","Hepatic disease: discontinue if jaundice develops","Ocular lesions: discontinue if unexplained visual loss occurs","Depression: monitor for mood changes","Hereditary angioedema: may precipitate or exacerbate symptoms"]
["Thrombotic disorders (venous thromboembolism, arterial thromboembolism)","Cerebrovascular disease","Cigarette smoking in women >35 years","Hypertension","Gallbladder disease","Hepatic neoplasia","Bleeding irregularities"]
["Hypersensitivity to any component","Thrombophlebitis or thromboembolic disorders (current or history)","Cerebrovascular or coronary artery disease (current or history)","Known or suspected breast cancer or other estrogen- or progestin-sensitive cancer","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior oral contraceptive use","Hepatic adenomas or carcinomas (current or history)","Known or suspected pregnancy","Heavy smoking (≥15 cigarettes/day) in women over 35 years","Uncontrolled hypertension","Diabetes with vascular involvement","Migraine with focal aura (age ≥35)"]
["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 may slightly increase ethinyl estradiol levels, but clinical relevance is minimal. No dietary restrictions required.
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.
Combined hormonal contraceptives (CHCs) are contraindicated in pregnancy. First trimester exposure is not associated with major malformations, but postmarketing data are insufficient to exclude risk. Second and third trimester exposure is associated with increased risk of fetal harm, including cardiovascular and genitourinary anomalies, due to estrogen and progestin effects.
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.
CHCs are generally not recommended during breastfeeding. Estrogen can reduce milk quantity and quality. Small amounts of hormones pass into breast milk; M/P ratio is not well established but is low. Use before breastfeeding is established (first 6 weeks) is contraindicated. Alternative contraception is 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.
Not applicable; CHCs are contraindicated in pregnancy. No dose adjustments are recommended as the drug should be discontinued immediately if pregnancy occurs.
Not applicable; contraindicated in pregnancy. No dose adjustment recommendations exist as use is not recommended.
Category C
Category C
Ortho Cyclen-28 is a monophasic combined oral contraceptive containing norgestimate and ethinyl estradiol. It is indicated for pregnancy prevention and may also treat acne vulgaris. Initiate on first day of menstrual period or first Sunday after onset. Missed pills increase ovulation risk; refer to package instructions for missed dose protocol. Non-contraceptive benefits include reduced dysmenorrhea and menorrhagia. Monitor for thromboembolic events, especially in smokers over 35 or those with migraine with aura. Drug interactions: rifampin, anticonvulsants (e.g., phenytoin), and St. John's wort may reduce efficacy. Consider backup contraception during concurrent antibiotic use (though evidence is mixed).
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, preferably after a meal to reduce nausea.If you miss a pill, refer to the package insert or consult your healthcare provider; use backup contraception if needed.Ortho Cyclen-28 does not protect against sexually transmitted infections (STIs); use condoms for STI prevention.Report leg pain, chest pain, shortness of breath, severe headache, or vision changes immediately.Avoid smoking while taking this medication, especially if you are over 35 years old.Inform your doctor of all medications you are taking, including over-the-counter drugs and herbal supplements.Breast tenderness, nausea, breakthrough bleeding, and mood changes are common side effects that often improve after a few cycles.
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.