ORTHO CYCLEN-21
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORTHO CYCLEN-21 (ORTHO CYCLEN-21).
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.
| Metabolism | 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. |
| Excretion | 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%). |
| Half-life | 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. |
| Protein binding | Norelgestromin: 97% bound to albumin and sex hormone-binding globulin (SHBG); Ethinyl estradiol: 98% bound to albumin. |
| Volume of Distribution | Norelgestromin: Vd ~3.0 L/kg; Ethinyl estradiol: Vd ~2.8 L/kg. Clinical meaning: Extensive distribution into tissues, including breast and reproductive organs. |
| Bioavailability | Oral: Norgestimate ~85% (first-pass metabolism); Ethinyl estradiol ~40-50% (first-pass metabolism and conjugation). |
| Onset of Action | Oral: 7 days of continuous dosing required for contraceptive efficacy; peak plasma concentrations of norelgestromin at 1-2 hours post-dose. |
| Duration of Action | Duration: 24 hours (daily dosing required). Clinical note: Contraceptive protection lasts as long as daily doses are taken; missed doses reduce efficacy. |
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.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Contraindicated in patients with renal disease (e.g., severely impaired renal function). |
| Liver impairment | 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. |
| Pediatric use | Safety and efficacy not established in postmenarchal pediatric patients; use same dosing as adults after menarche. Not indicated in premenarchal females. |
| Geriatric use | 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. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ORTHO CYCLEN-21 (ORTHO CYCLEN-21).
| Breastfeeding | 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. |
| Teratogenic Risk | 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. |
■ FDA Black Box Warning
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.
| Serious Effects |
["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"]
| Precautions | ["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."] |
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| Fetal Monitoring | Monitor for signs of pregnancy before initiating and during therapy. Inadvertent pregnancy: discontinue immediately. No routine fetal monitoring required unless pregnancy occurs; then standard prenatal care including ultrasound and anomaly scan. |
| Fertility Effects | Suppresses ovulation via hormonal feedback. Fertility returns rapidly upon discontinuation; no permanent impairment. Post-pill amenorrhea possible but usually resolves within a few cycles. |