Comparative Pharmacology
Head-to-head clinical analysis: ORTHO TRI CYCLEN 28 versus ORTHO CEPT.
Peer-Reviewed Evidence
Head-to-head clinical analysis: ORTHO TRI CYCLEN 28 versus ORTHO CEPT.
ORTHO TRI-CYCLEN 28 vs ORTHO-CEPT
Head-to-head clinical comparison of therapeutic indices and safety profiles.
Combination of ethinyl estradiol and norgestimate primarily suppresses gonadotropin (FSH and LH) secretion via negative feedback on the hypothalamic-pituitary-ovarian axis, inhibiting ovulation. Additionally, it increases cervical mucus viscosity and alters endometrial structure to impede fertilization 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.
FDA-approved: Prevention of pregnancyOff-label: Treatment of moderate acne vulgaris in females ≥15 years of age who have no known contraindications and desire oral contraception
Prevention of pregnancy
One tablet daily for 28 days: 21 active tablets (norgestimate 0.180 mg/ethinyl estradiol 0.035 mg, norgestimate 0.215 mg/ethinyl estradiol 0.035 mg, norgestimate 0.250 mg/ethinyl estradiol 0.035 mg) followed by 7 inert tablets. Route: oral.
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
Norethindrone: ~8 hours; Ethinyl estradiol: ~15 hours (biphasic, terminal: 15-20 hours). Steady-state achieved within 7-14 days.
Desogestrel: 23 hours (terminal), Etonogestrel active metabolite: 30 hours (terminal); clinical steady state after 7-10 days
Ethinyl estradiol undergoes oxidative metabolism primarily via CYP3A4 and undergoes conjugation (glucuronidation and sulfation). Norgestimate is extensively metabolized to its active metabolite norelgestromin via first-pass hepatic (hydrolysis) and further to levonorgestrel; norelgestromin is metabolized by CYP3A4 and CYP2C9.
Ethinyl estradiol: primarily metabolized by CYP3A4; desogestrel: prodrug converted to active metabolite etonogestrel via CYP2C9 and CYP2C19.
Renal: ~60% (metabolites); Fecal: ~40% (metabolites); unchanged drug <1%
Renal: 50% (metabolites), Biliary/fecal: 40% (metabolites and unchanged drug), 10% unchanged in urine
Norethindrone: ~97% (albumin, SHBG); Ethinyl estradiol: ~98% (albumin, SHBG).
Desogestrel: 99% (SHBG), Etonogestrel: ~66% (albumin and SHBG); Ethinyl estradiol: 98% (albumin)
Norethindrone: 3-4 L/kg; Ethinyl estradiol: 2-3 L/kg. Indicates extensive tissue distribution.
Desogestrel: 1.5 L/kg, Etonogestrel: 1.7 L/kg; indicates extensive tissue distribution
Norethindrone: ~65% (first-pass metabolism); Ethinyl estradiol: ~45% (first-pass metabolism).
Desogestrel: 76% (oral, as prodrug converted to etonogestrel); Ethinyl estradiol: 45-50% (oral, first-pass metabolism)
No specific GFR-based dose adjustments established. Use with caution in severe renal impairment (GFR <30 mL/min) due to potential fluid retention and electrolyte disturbances.
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 Child-Pugh class B and C (moderate to severe hepatic impairment). No data for Child-Pugh A; use with caution.
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 use before menarche. For postmenarchal adolescents, same dosing as adults. Safety and efficacy not established in pediatric patients under 18 years for contraception.
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 specific dosing adjustments; risks of thromboembolic events outweigh benefits in women over 35 who smoke or have cardiovascular risk factors.
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 events from combination oral contraceptive use. This risk increases with age (especially in women over 35 years) and with 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.
["Thromboembolic disorders: increased risk of venous thromboembolism and arterial thrombosis","Cigarette smoking increases cardiovascular risk","Hypertension: may cause or worsen hypertension","Gallbladder disease: increased risk of gallbladder disease","Hepatic tumors: risk of hepatic adenomas (rare) and possible hepatocellular carcinoma","Carbohydrate and lipid effects: may affect glucose tolerance and lipid profile","Ocular lesions: retinal thrombosis (discontinue if unexplained vision loss occurs)","Depression: may precipitate or worsen depression","Bleeding irregularities: breakthrough bleeding and spotting common","Hereditary angioedema: may exacerbate symptoms"]
["Thrombotic disorders (venous thromboembolism, arterial thromboembolism)","Cerebrovascular disease","Cigarette smoking in women >35 years","Hypertension","Gallbladder disease","Hepatic neoplasia","Bleeding irregularities"]
["Known or suspected pregnancy","Current or past thrombophlebitis or thromboembolic disorders (e.g., deep vein thrombosis, pulmonary embolism)","Current or past arterial thromboembolic disease (e.g., stroke, myocardial infarction)","Cerebrovascular disease","Known or suspected breast carcinoma or other estrogen- or progestin-sensitive cancer","Undiagnosed abnormal genital bleeding","Cholestatic jaundice of pregnancy or jaundice with prior pill use","Hepatic adenomas or carcinomas","Known liver disease or impaired liver function, including active viral hepatitis","Uncontrolled hypertension (>160/100 mmHg)","Diabetes with vascular involvement","Headaches with focal neurological symptoms (e.g., migraine with aura)","Major surgery with prolonged immobilization","Smoking in women over 35 years","Hypersensitivity to any component of the product"]
["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 slightly increase ethinyl estradiol levels but not clinically relevant. Maintain consistent dietary habits to avoid variability in absorption.
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.
Pregnancy category X. Contraindicated in pregnancy. First trimester: increased risk of neural tube defects, cardiovascular anomalies, and oral clefts. Second and third trimesters: association with fetal genital abnormalities (e.g., hypospadias in males, virilization of female fetuses). No safe use established.
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.
Not recommended during breastfeeding. Combined hormonal contraceptives reduce milk production and nutrient content. Limited ethinyl estradiol and norgestimate transfer into breast milk; M/P ratio not well defined. Use alternative contraception.
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.
No dose adjustment applicable; contraindicated in pregnancy. If exposure occurs, discontinue immediately. No pharmacokinetic data indicate safe use or dose modifications during pregnancy.
Not applicable; contraindicated in pregnancy. No dose adjustment recommendations exist as use is not recommended.
Category C
Category C
Ortho Tri-Cyclen 28 is a triphasic oral contraceptive containing norgestimate and ethinyl estradiol. The triphasic dosing mimics natural hormonal fluctuations and may reduce breakthrough bleeding. It is also FDA-approved for moderate acne vulgaris in women at least 15 years old who desire contraception. Monitor for thromboembolic events, especially in smokers over 35. CYP3A4 inducers (e.g., rifampin, carbamazepine) may reduce efficacy. Advise backup contraception during concurrent antibiotic use.
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.The 28-day pack has 21 active pills and 7 placebo pills; always start a new pack immediately after finishing the previous one.If you miss a pill, check the package insert: take missed pill as soon as remembered and use backup contraception.Common side effects include nausea, breast tenderness, and breakthrough bleeding; these often improve after 3 months.Seek medical attention for severe headache, vision changes, leg pain, or shortness of breath (thrombosis symptoms).Do not smoke while taking this medication, as it increases risk of blood clots and stroke.This pill does not protect against sexually transmitted infections (STIs).
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.