ETHINYL ESTRADIOL AND NORELGESTROMIN
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Combination contraceptive: estrogen (ethinyl estradiol) suppresses gonadotropin release via negative feedback on pituitary; progestin (norelgestromin) thickens cervical mucus and inhibits ovulation.
| Metabolism | Ethinyl estradiol: CYP3A4; norelgestromin: CYP3A4, CYP1A1, and CYP2C9; norelgestromin is metabolized to norgestrel and other metabolites. |
| Excretion | Ethinyl estradiol and norelgestromin are excreted primarily via urine and feces. Ethinyl estradiol undergoes extensive metabolism; about 40% is excreted in urine and 60% in feces as glucuronide and sulfate conjugates. Norelgestromin is metabolized to norgestrel and other metabolites; approximately 45% is excreted in urine and 35% in feces. |
| Half-life | Ethinyl estradiol has a terminal elimination half-life of approximately 13-27 hours (mean ~17 hours). Norelgestromin has a terminal half-life of about 28 hours. These half-lives support once-weekly dosing of the transdermal system, achieving steady-state by the second application. |
| Protein binding | Ethinyl estradiol is approximately 97-98% bound to serum albumin, and induces sex hormone-binding globulin (SHBG). Norelgestromin is about 97% bound, primarily to albumin and SHBG. |
| Volume of Distribution | Ethinyl estradiol: Vd approximately 2.4-2.7 L/kg, indicating extensive tissue distribution. Norelgestromin: Vd approximately 1.6-2.0 L/kg, also indicating distribution into tissues. |
| Bioavailability | Transdermal route: Bioavailability is complete (100%) as the drug is absorbed directly into systemic circulation, avoiding first-pass metabolism. Oral bioavailability of ethinyl estradiol is typically 38-48% due to first-pass effect. |
| Onset of Action | Transdermal route: Onset of contraceptive effect occurs within 24-48 hours of first application. Ovulation suppression is achieved by day 7 of the first cycle if applied on time. |
| Duration of Action | Transdermal system: Each patch is worn for 7 days, maintaining effective hormone levels. After removal, hormone levels decline rapidly, and contraceptive protection is lost; thus, adherence to the 7-day schedule is critical. |
One transdermal patch (releasing 0.035 mg ethinyl estradiol and 0.150 mg norelgestromin per 24 hours) applied once weekly for 3 weeks, followed by 1 week patch-free.
| Dosage form | FILM, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for mild-moderate renal impairment. Insufficient data for severe impairment (CrCl <30 mL/min); contraindicated in patients with acute renal failure or significant renal disease due to potential fluid retention. |
| Liver impairment | Contraindicated in Child-Pugh class B or C (moderate to severe hepatic impairment). Use with caution in class A (mild), with monitoring for signs of hepatic dysfunction. |
| Pediatric use | Approved post-menarche; dosing same as adult (one patch weekly for 3 weeks, then 1 week off). Adjust based on age and Tanner stage per clinical judgment. |
| Geriatric use | Not indicated for use after menopause. If used, consider increased risk of thromboembolism and cardiovascular events; monitor for adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
| FDA category | Positive |
| Breastfeeding | Excreted in breast milk; M/P ratio not established. May reduce milk production and quality. Use only if benefit outweighs risk; consider alternative contraception. |
| Teratogenic Risk | First trimester: Limited data; no increased risk of major birth defects from inadvertent exposure. Second and third trimesters: Associated with feminization of male fetus, urogenital sinus malformations, and potential for cardiovascular and limb defects if used in early pregnancy. Contraindicated during pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events. Women over 35 who smoke should not use this product.
| Common Effects | osteoporosis prevention |
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Known or suspected pregnancy","Undiagnosed abnormal genital bleeding","Known or suspected breast cancer","Liver tumors or active liver disease","Hypersensitivity to any component","Smoking in women over 35"]
| Precautions | ["Thrombotic disorders (smoking, obesity, hypertension, age >35)","Hepatic disease","Gallbladder disease","Hypertension","Carbohydrate and lipid effects","Headache","Bleeding irregularities","Ocular lesions"] |
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| Fetal Monitoring | Monitor blood pressure, signs of thrombotic events, hepatic function, and fetal growth if unintentional exposure during early pregnancy. |
| Fertility Effects | Suppresses ovulation via inhibition of gonadotropins; reversible upon discontinuation. No long-term impact on fertility. |