LYBREL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYBREL (LYBREL).
Combination of levonorgestrel and ethinyl estradiol: suppression of gonadotropins (FSH and LH) via negative feedback, inhibiting ovulation; thickening of cervical mucus to impede sperm penetration; alteration of endometrium to reduce implantation likelihood.
| Metabolism | Levonorgestrel: primarily metabolized via reduction, hydroxylation, and conjugation; CYP3A4 involvement. Ethinyl estradiol: metabolized by CYP3A4 and undergoes glucuronidation and sulfation. |
| Excretion | Renal: 50-60% as metabolites, ~20% as parent drug; fecal: 30-40%; biliary: 10-20%. |
| Half-life | Terminal elimination half-life: 27 ± 8 hours; requires ~5 days to reach steady-state; clinical significance: missed doses lead to rapid loss of contraceptive efficacy. |
| Protein binding | 99% bound to albumin and sex hormone-binding globulin (SHBG). |
| Volume of Distribution | Vd: 1.7 ± 0.3 L/kg; indicates extensive tissue distribution (e.g., reproductive organs, liver). |
| Bioavailability | Oral: 88% (range 80-95%); first-pass metabolism reduces systemic exposure by ~12%. |
| Onset of Action | Oral: 7 days for full contraceptive effect; initial follicular suppression begins within 24 hours. |
| Duration of Action | Contraceptive effect persists for 28 days with daily dosing; after discontinuation, ovulation may resume within 2-3 weeks. |
One tablet (levonorgestrel 0.1 mg/ethinyl estradiol 0.02 mg) orally once daily for 21 days, followed by 7 placebo tablets for 28-day cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (GFR <30 mL/min); use not recommended. |
| Liver impairment | Contraindicated in Child-Pugh class B and C hepatic impairment. Use with caution in Child-Pugh class A; monitor liver function. |
| Pediatric use | Safety and efficacy not established in postmenarchal pediatric patients for oral contraception. Use same dosing as adults for appropriate indications. |
| Geriatric use | Not indicated for use in postmenopausal women; no age-specific data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYBREL (LYBREL).
| Breastfeeding | Small amounts of ethinyl estradiol and levonorgestrel are excreted in breast milk. The M/P ratio for ethinyl estradiol is approximately 0.05-0.1; for levonorgestrel, it is about 0.1-0.3. Combined hormonal contraceptives may reduce milk production and composition, especially in early postpartum period. Lybrel is not recommended during breastfeeding until weaning, or for at least 6 months postpartum if breastfeeding is established. Progestin-only contraceptives are preferred. |
| Teratogenic Risk | Combined hormonal contraceptives (CHCs) like Lybrel (levonorgestrel/ethinyl estradiol) are contraindicated in pregnancy due to potential fetal harm. First trimester exposure is associated with a slightly increased risk of congenital anomalies, particularly cardiovascular and limb defects, though absolute risk is low. Second and third trimester exposure may lead to adverse outcomes including fetal growth restriction, preterm birth, and neonatal withdrawal symptoms. Data from observational studies suggest no major teratogenic risk at typical contraceptive doses, but use is not recommended once pregnancy is confirmed. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptive use. Risk increases with age (especially in women >35 years) and with number of cigarettes smoked. Women who use oral contraceptives should be strongly advised not to smoke.
| Serious Effects |
["Renal or hepatic impairment","Known or suspected pregnancy","Undiagnosed abnormal uterine bleeding","History of or current thromboembolic disorders (e.g., DVT, PE)","Cerebrovascular or coronary artery disease","Known or suspected breast carcinoma","Estrogen-dependent neoplasia","Active liver disease (e.g., acute viral hepatitis)","Hypersensitivity to any component"]
| Precautions | ["Thrombotic disorders and cardiovascular events (especially in smokers >35 years)","Elevated blood pressure","Gallbladder disease","Hepatic neoplasia","Glucose intolerance","Hereditary angioedema","Chloasma","Ocular changes (e.g., retinal thrombosis) requiring discontinuation"] |
Loading safety data…
| Fetal Monitoring | If unintentional use in pregnancy occurs, monitor fetal growth and anatomy via ultrasound. In late pregnancy exposure, monitor neonate for signs of hormonal withdrawal (e.g., irritability, feeding difficulties). No specific maternal monitoring required beyond routine prenatal care, but assess for thrombotic events (e.g., deep vein thrombosis, pulmonary embolism) if used inadvertently during pregnancy. |
| Fertility Effects | Lybrel suppresses ovulation, providing contraception. After discontinuation, fertility returns promptly (usually within 1-3 months). No evidence of permanent impairment of fertility. Ovarian function returns to baseline after cessation of use. |