LESSINA-28
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LESSINA-28 (LESSINA-28).
Combination of a progestin (levonorgestrel) and an estrogen (ethinyl estradiol). Inhibits ovulation by suppressing gonadotropin release; increases cervical mucus viscosity to impede sperm penetration, and induces endometrial changes that reduce implantation likelihood.
| Metabolism | Levonorgestrel: primarily CYP3A4, with reduction and conjugation to sulfate and glucuronide metabolites. Ethinyl estradiol: primarily CYP3A4, undergoes hydroxylation and conjugation to sulfate and glucuronides. |
| Excretion | Renal: 30% as unchanged drug and metabolites; biliary/fecal: 70% as metabolites. |
| Half-life | Terminal elimination half-life: 18-22 hours; clinically relevant for once-daily dosing. |
| Protein binding | Levonorgestrel: 97-99% bound to albumin and SHBG; ethinyl estradiol: 98% bound to albumin. |
| Volume of Distribution | Levonorgestrel: 1.8 L/kg; ethinyl estradiol: 2.3 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: approximately 90% for levonorgestrel; approximately 45% for ethinyl estradiol (first-pass metabolism). |
| Onset of Action | Oral: 24-48 hours for contraceptive effect; 3-7 days for full suppression of ovulation. |
| Duration of Action | Contraceptive protection persists with daily dosing; if missed dose, window is 12 hours. |
One tablet (0.1 mg levonorgestrel and 0.02 mg ethinyl estradiol) orally once daily for 28 days, starting on the first day of menstrual cycle.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Use caution in severe renal impairment (CrCl <30 mL/min) due to potential for fluid retention; consider alternative contraception. |
| Liver impairment | Contraindicated in acute liver disease or severe cirrhosis (Child-Pugh class B or C). For mild hepatic impairment (Child-Pugh class A), no dose adjustment; use with caution and monitor liver function. |
| Pediatric use | Not indicated for use before menarche. For post-menarcheal adolescents, same dosing as adults (one tablet daily) with monitoring for bone mineral density and thrombotic risk. |
| Geriatric use | Not indicated for use after menopause. In perimenopausal women, same dosing as adults; discontinue at menopause due to increased risk of thrombosis and cardiovascular events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LESSINA-28 (LESSINA-28).
| Breastfeeding | Minimal excretion into breast milk; M/P ratio approx 0.1–0.3. Considered compatible with breastfeeding by AAP; monitor infant for diarrhea or rash. |
| Teratogenic Risk | First trimester: No increased risk of major birth defects based on large cohort studies. Second and third trimesters: Associated with increased risk of intrauterine growth restriction (IUGR), preterm birth, and transient neonatal hepatotoxicity (elevated liver enzymes) with prolonged use. |
| Fetal Monitoring |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives (COCs). Risk increases with age and number of cigarettes smoked (especially in women >35 years). Women who use COCs should be strongly advised not to smoke.
| Serious Effects |
["Thrombophlebitis or thromboembolic disorders","History of deep vein thrombosis or pulmonary embolism","Cerebrovascular or coronary artery disease","Current or history of breast cancer or other estrogen/progestin-sensitive neoplasia","Hepatic adenoma or carcinoma","Undiagnosed abnormal genital bleeding","Known or suspected pregnancy","Active liver disease or impaired liver function","Hypersensitivity to any component","Use with hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir with or without dasabuvir"]
| Precautions | ["Smoking and cardiovascular risk","Increased risk of thromboembolic events (venous and arterial)","Hepatic neoplasia","Gallbladder disease","Hypertension","Carbohydrate and lipid metabolic effects","Headache exacerbation","Bleeding irregularities","Pregnancy and hepatic enzyme induction","Ocular lesions (eg, retinal thrombosis)"] |
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| Maternal: LFTs, serum bile acids, and blood pressure every trimester. Fetal: Serial ultrasound for growth (if used in 2nd/3rd trimester) and postpartum neonatal bilirubin and LFTs. |
| Fertility Effects | No known impairment of fertility in women; may delay return to ovulation if taken cyclically. |