ETHINYL ESTRADIOL; LEVONORGESTREL
Clinical safety rating: avoid
Inducers of CYP450 enzymes (eg carbamazepine) may decrease estrogen levels Increases risk of thromboembolic disorders and endometrial cancer.
Combination of ethinyl estradiol and levonorgestrel suppresses gonadotropins (FSH and LH) from the anterior pituitary, inhibiting ovulation. Also increases cervical mucus viscosity and induces endometrial changes that reduce implantation likelihood.
| Metabolism | Ethinyl estradiol is primarily metabolized by CYP3A4, undergoes first-pass metabolism with sulfate conjugation in the gut wall. Levonorgestrel is metabolized by CYP3A4 and to a lesser extent by CYP2C9, with conjugation to glucuronide and sulfate metabolites. |
| Excretion | Renal: Ethinyl estradiol ~40% as glucuronide and sulfate conjugates; levonorgestrel ~20% as metabolites. Fecal: Ethinyl estradiol ~60%; levonorgestrel ~80% via biliary excretion. |
| Half-life | Ethinyl estradiol: ~13-27 hours (terminal); Levonorgestrel: ~16-33 hours (terminal). Clinically, steady-state is reached within 5-7 days; elimination half-life supports once-daily dosing with potential accumulation. |
| Protein binding | Ethinyl estradiol: ~95-97% bound to albumin; Levonorgestrel: ~97-99% bound to albumin and SHBG (sex hormone-binding globulin). |
| Volume of Distribution | Ethinyl estradiol: ~2.5-4.5 L/kg; Levonorgestrel: ~1.4-2.1 L/kg. High Vd indicates extensive tissue distribution, including reproductive organs and breast tissue. |
| Bioavailability | Oral: Ethinyl estradiol ~40-55% (first-pass metabolism); Levonorgestrel ~90-100% (minimal first-pass). |
| Onset of Action | Oral: Contraceptive effect begins after 7 days of continuous dosing (if started on day 1-5 of cycle); for emergency contraception, onset within 72 hours of unprotected intercourse. |
| Duration of Action | Contraceptive efficacy persists as long as daily oral dosing continues; after discontinuation, ovulation returns typically within 2-4 weeks. Emergency contraception: single dose effective for that cycle only. |
1 tablet (0.03 mg ethinyl estradiol / 0.15 mg levonorgestrel) orally once daily for 21 consecutive days, followed by 7 days of placebo
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for mild-to-moderate renal impairment. Use caution in severe renal impairment (GFR <30 mL/min) due to potential fluid retention; avoid if dialysis required. |
| Liver impairment | Contraindicated in acute liver disease or decompensated cirrhosis (Child-Pugh class B or C). For compensated cirrhosis (Child-Pugh class A), use only if benefits outweigh risks; no specific dose adjustment established. |
| Pediatric use | Approved for post-menarchal adolescents; same dosing as adults (1 active tablet daily). Weight-based dosing not recommended. |
| Geriatric use | Not indicated for postmenopausal women. No specific studies; use generally not appropriate due to increased thrombotic risk and lack of efficacy in this population. |
| 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 | Contraindicated during breastfeeding; estrogen passes into breast milk with an M/P ratio of ~0.04. Levonorgestrel has M/P ratio ~0.15. May reduce milk production and composition. Small amounts in milk pose risk to infant. |
| Teratogenic Risk | First trimester: Use is contraindicated due to increased risk of cardiovascular defects, neural tube defects, and limb reduction defects; post-conception exposure should be avoided. Second and third trimesters: Exposure associated with fetal adrenal suppression, virilization of female fetuses, and potential hepatotoxicity; not recommended at any stage of pregnancy. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age and smoking intensity (especially in women over 35 years of age). Women who use combination oral contraceptives should be strongly advised not to smoke.
| Common Effects | osteoporosis prevention |
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","Cerebrovascular or coronary artery disease","Known or suspected carcinoma of the breast or endometrium","Undiagnosed abnormal genital bleeding","Pregnancy or suspected pregnancy","Hepatic adenoma or carcinoma","Jaundice or impaired liver function","Severe hypertension","Diabetes with vascular involvement","Headache with focal neurological symptoms (migraine) in women over 35","Hypersensitivity to any component"]
| Precautions | ["Increased risk of thromboembolic disorders including venous thromboembolism and arterial thrombosis","Increased risk of myocardial infarction in smokers over 35","Increased risk of stroke","Possible increased blood pressure","Possible gallbladder disease","Hepatic impairment","Carbohydrate/lipid metabolic effects","Hereditary angioedema exacerbation","Chloasma","Ocular complications (retinal thrombosis, optic neuritis)"] |
Loading safety data…
| Fetal Monitoring | Not applicable as drug is contraindicated in pregnancy. In case of inadvertent exposure, monitor fetal growth, anatomy via ultrasound, and neonatal outcomes. |
| Fertility Effects | Reversible ovulation suppression while on therapy; normal fertility returns after discontinuation. No evidence of permanent impairment. |