LESSINA-28
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 746.9 |
| Action Class | Combination oral contraceptive (estrogen-progestin) |
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 | Contraindicated due to risk of congenital defects. |
| 2nd trimester | Contraindicated due to risk of fetal harm. |
| 3rd trimester | Contraindicated due to risk of fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for LESSINA-28 (LESSINA-28).
| Placental transfer | Crosses placenta; documented in human studies. |
| Breastfeeding | Excreted in breast milk; may cause adverse effects in nursing infants. Use is not recommended. |
| Lactation Rating | L5 |
| 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 | 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. |
■ 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.
| Common Effects | Nausea, Headache, Breast tenderness, Weight changes, Irregular menstrual bleeding (spotting, breakthrough bleeding), Mood changes (depression, anxiety), Acne (may improve or worsen), Fluid retention |
| Serious Effects | Venous thromboembolism (deep vein thrombosis, pulmonary embolism), Arterial thromboembolism (myocardial infarction, stroke), Hepatic adenoma or hepatocellular carcinoma, Hypertension, Gallbladder disease (cholelithiasis, cholecystitis), Cerebrovascular accident, Retinal thrombosis |
PregnancyBreast cancerLiver tumorsUndiagnosed abnormal genital bleedingKnown or suspected estrogen-dependent neoplasia
| 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) |
| Food/Dietary | No specific dietary restrictions. Grapefruit juice may increase estrogen levels; avoid large quantities. Maintain a consistent intake of caffeine as it can be metabolized more slowly, possibly causing jitteriness. |
| Clinical Pearls | Lessina-28 is a combined oral contraceptive containing ethinyl estradiol and levonorgestrel. Administer at the same time daily to maintain consistent hormone levels and maximize contraceptive efficacy. Use of additional non-hormonal contraception is recommended during the first 7 days of therapy. Missed pills increase breakthrough bleeding and pregnancy risk; consult package insert for missed dose instructions. Drug interactions with rifampin, certain anticonvulsants (e.g., phenytoin, carbamazepine), and St. John's wort may reduce contraceptive effectiveness. |
| Patient Advice | Take one pill daily at the same time; if you miss a pill, follow the instructions in the package insert. · Lessina-28 does not protect against HIV or other sexually transmitted infections; use condoms for STI prevention. · Common side effects include nausea, headache, breast tenderness, and breakthrough bleeding; these often improve after a few cycles. · Report severe headaches, vision changes, leg pain or swelling, chest pain, or jaundice to your healthcare provider immediately. · Do not smoke while using this medication; smoking increases risk of serious cardiovascular events, especially in women over 35. |
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