ORTHO CYCLEN-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO CYCLEN-28 (ORTHO CYCLEN-28).
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).
| Metabolism | 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. |
| Excretion | Renal (60-70% as metabolites, ~20% unchanged), Fecal (30-40% as metabolites); primarily conjugated metabolites of ethinyl estradiol and norgestimate. |
| Half-life | Ethinyl estradiol: 13-27 hours; Norelgestromin (active metabolite of norgestimate): 28-52 hours. Terminal half-lives support once-daily dosing. |
| Protein binding | Ethinyl estradiol: 98% bound to albumin; Norelgestromin: >99% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Ethinyl estradiol: 2.0-4.0 L/kg; Norelgestromin: 2.0-3.0 L/kg. Indicates extensive distribution into tissues. |
| Bioavailability | Oral: Ethinyl estradiol ~45% (due to first-pass metabolism); Norgestimate gut wall metabolism but active metabolite norelgestromin bioavailability ~60-70%. |
| Onset of Action | Oral: Contraceptive effect begins after 7 consecutive days of dosing if started on first day of menstruation. |
| Duration of Action | Contraceptive protection lasts 24 hours per dose; anovulatory effect persists throughout cycle if taken consistently. |
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.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment recommended for any degree of renal impairment due to minimal renal clearance of contraceptive steroids. |
| Liver impairment | 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. |
| Pediatric use | Not indicated for premenarchal girls; postmenarchal adolescents: same dosing as adults (1 tablet daily for 28-day cycle). |
| Geriatric use | Not indicated for use after menopause due to lack of need for contraception and increased risk of thromboembolic events with age and estrogen exposure. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO CYCLEN-28 (ORTHO CYCLEN-28).
| Breastfeeding | 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. |
| Teratogenic Risk | 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. |
■ FDA Black Box Warning
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.
| Serious Effects |
["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)"]
| Precautions | ["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"] |
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| Fetal Monitoring | If inadvertently used during pregnancy, monitor for fetal growth and development via ultrasound. No specific fetal monitoring is required beyond routine prenatal care. Discontinue immediately if pregnancy is suspected. |
| Fertility Effects | CHCs suppress ovulation and are used for contraception. After discontinuation, normal ovulation typically resumes within 1-2 cycles, but there may be a transient delay in return to fertility. No permanent effect on fertility. |