NORGESTREL AND ETHINYL ESTRADIOL
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Norgestrel is a progestogen that suppresses gonadotropin secretion, primarily LH, inhibiting ovulation and altering cervical mucus to impede sperm penetration. Ethinyl estradiol is an estrogen that stabilizes the endometrium and provides negative feedback on gonadotropin release, contributing to contraceptive efficacy.
| Metabolism | Norgestrel is primarily metabolized via reduction, hydroxylation, and conjugation; CYP3A4 is involved. Ethinyl estradiol is metabolized primarily by CYP3A4, with conjugation to sulfate and glucuronide; undergoes enterohepatic recirculation. |
| Excretion | Norgestrel: 45% renal, 32% fecal as metabolites; Ethinyl estradiol: 40% renal, 60% fecal as glucuronide and sulfate conjugates. |
| Half-life | Norgestrel: terminal half-life ~45 hours (range 24–50 h), supporting once-daily dosing; Ethinyl estradiol: terminal half-life ~17 hours (range 10–24 h). |
| Protein binding | Norgestrel: ~99% bound to SHBG and albumin; Ethinyl estradiol: ~97% bound to albumin. |
| Volume of Distribution | Norgestrel: ~2.5 L/kg, indicating extensive tissue distribution; Ethinyl estradiol: ~4.5 L/kg. |
| Bioavailability | Oral: Norgestrel ~80-100%; Ethinyl estradiol ~55% (first-pass metabolism reduces bioavailability). |
| Onset of Action | Oral: Contraceptive effect requires 7 days of consistent dosing; for emergency contraception, effect within 72 hours of unprotected intercourse. |
| Duration of Action | Contraceptive protection persists for the duration of daily dosing; after discontinuation, fertility returns typically within 1–3 months. |
One tablet (0.3 mg norgestrel/0.03 mg ethinyl estradiol) orally once daily, taken at the same time each day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Use with caution in severe renal impairment (GFR <30 mL/min/1.73 m²) due to potential fluid retention. Contraindicated in acute or chronic hepatic disease with impaired renal function. |
| Liver impairment | Contraindicated in hepatic adenomas, active liver disease, or Child-Pugh B/C cirrhosis. No dose adjustment recommended for Child-Pugh A, but use with caution. |
| Pediatric use | For postmenarchal adolescents, same dosing as adults (one tablet orally once daily). Not indicated for premenarchal use. |
| Geriatric use | Not indicated for use in postmenopausal women. No specific dose recommendations; contraindicated in postmenopausal women due to lack of efficacy and increased risk of adverse events. |
| 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 | Small amounts of ethinyl estradiol and norgestrel are excreted in breast milk. Norgestrel M/P ratio approximately 0.03-0.15. May reduce milk production and quality. The American Academy of Pediatrics considers combination oral contraceptives compatible with breastfeeding but recommends caution and use of progestin-only options if possible. |
| Teratogenic Risk |
■ FDA Black Box Warning
Cigarette smoking increases the risk of serious cardiovascular events (e.g., myocardial infarction, stroke, thromboembolism) from combined oral contraceptive use, particularly in women over 35 years of age and those who smoke 15 or more cigarettes daily.
| Common Effects | osteoporosis prevention |
| Serious Effects |
Known or suspected pregnancy; current or history of thrombophlebitis or thromboembolic disorders; cerebrovascular or coronary artery disease; known or suspected breast cancer; estrogen-dependent neoplasia; undiagnosed abnormal genital bleeding; cholestatic jaundice of pregnancy or jaundice with prior pill use; hepatic adenoma or carcinoma; known hyperlipidemia; hypersensitivity to any component.
| Precautions | Increased risk of thrombotic disorders (e.g., venous thromboembolism, stroke, myocardial infarction); hypertension; hepatic neoplasia; gallbladder disease; carbohydrate and lipid effects; ocular changes including retinal thrombosis; migraine headache; breakthrough bleeding; use in smokers over 35; use in obesity; postpartum Use; lactation. |
Loading safety data…
| Pregnancy category X. Contraindicated in pregnancy. First trimester: increased risk of cardiovascular defects, limb reduction defects, and neural tube defects. Second and third trimesters: reported association with fetal genital tract abnormalities (e.g., hypospadias), low birth weight, and preterm delivery. Use during pregnancy is not recommended. |
| Fetal Monitoring | Monitor for signs of thromboembolism, hypertension, and hepatic dysfunction. If inadvertent use during pregnancy, ultrasound to assess fetal anatomy. Monitor for fetal growth restriction in late pregnancy exposure. |
| Fertility Effects | Reversible suppression of ovulation. Normal fertility typically resumes promptly after discontinuation. No known permanent effects on fertility. |