LESSINA-21
Clinical safety rating
cautionComprehensive clinical and safety monograph for LESSINA-21 (LESSINA-21).
Combination oral contraceptive containing ethinyl estradiol and levonorgestrel. Suppresses gonadotropin release (FSH, LH) from pituitary, inhibiting ovulation. Causes cervical mucus thickening and endometrial alterations, impeding sperm penetration and implantation.
| Metabolism | Ethinyl estradiol: primarily metabolized by CYP3A4, undergoes first-pass metabolism in gut wall and liver. Levonorgestrel: metabolized via reduction and conjugation, partially involving CYP3A4. |
| Excretion | Renal (70% as unchanged drug and metabolites), fecal (30% as metabolites) |
| Half-life | 17-21 hours (terminal elimination half-life; clinical significance: allows once-daily dosing, but missed doses increase risk of ovulation) |
| Protein binding | 98-99% (albumin and sex hormone-binding globulin, SHBG) |
| Volume of Distribution | 2-4 L/kg (extensive distribution into tissues, reflecting lipophilicity and binding to steroid receptors) |
| Bioavailability | Oral: 88% (high bioavailability due to extensive absorption and minimal first-pass metabolism) |
| Onset of Action | Oral: maximal contraceptive effect achieved after 7 days of continuous dosing; inhibition of ovulation begins within 2-3 days |
| Duration of Action | 24 hours (contraceptive efficacy maintained with daily dosing; non-contraceptive benefits persist with continuous use) |
| Molecular Weight | 288.42 |
| Action Class | Oral Contraceptive; Estrogen-Progestin Combination |
One tablet (0.1 mg levonorgestrel, 0.02 mg ethinyl estradiol) orally once daily for 21 days, followed by 7 days placebo or no tablets.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Insufficient data for severe impairment; use with caution. |
| Liver impairment | Contraindicated in acute hepatitis, severe decompensated cirrhosis (Child-Pugh C), or liver tumors. For mild (Child-Pugh A) to moderate (Child-Pugh B) impairment, use only if benefits outweigh risks; monitor liver function. |
| Pediatric use | Use only after menarche. Same dosing as adults (0.1 mg/0.02 mg daily for 21 days) for adolescents aged 12-17 years. Safety and efficacy not established in premenarchal girls. |
| Geriatric use | Not indicated for postmenopausal women. No specific geriatric dosing; consider increased risk of thromboembolic events and cardiovascular disease in women over 35 who smoke. |
| 1st trimester | Contraindicated due to risk of oral clefts and congenital heart defects. |
| 2nd trimester | Contraindicated due to potential virilization of female fetus and other adverse effects. |
| 3rd trimester | Contraindicated due to risk of feminization of male fetus and other hormonal effects. |
Clinical note
Comprehensive clinical and safety monograph for LESSINA-21 (LESSINA-21).
| Placental transfer | Unlikely significant due to oral bioavailability and short half-life; but theoretical risk exists for topical application. |
| Breastfeeding | Small amounts may be excreted in breast milk; not recommended due to potential masculinization of female infants and feminization of male infants. |
| Lactation Rating | Avoid |
| Teratogenic Risk | FDA Pregnancy Category X. First trimester: oral contraceptive use is associated with a slight increase in cardiovascular defects and limb reduction defects, though absolute risk is low. Second and third trimesters: no increased risk of major malformations; however, exposure may increase risk of neonatal jaundice, cholestasis, and transient hormonal effects. Discontinue if pregnancy is suspected. |
| Fetal Monitoring | Monitor for adverse effects: blood pressure every 3-6 months, liver function tests annually, glucose tolerance screening in at-risk patients. If pregnancy occurs, fetal ultrasound may be considered to rule out anomalies. |
| Fertility Effects | Oral contraceptives suppress ovulation, thus preventing fertility. Fertility returns rapidly after discontinuation; no long-term adverse effects on fertility have been demonstrated. |
■ FDA Black Box Warning
Cigarette smoking increases risk of serious cardiovascular events from combination oral contraceptives. Risk increases with age (especially >35 years) and with number of cigarettes smoked. Women who smoke and use OCs should be strongly advised not to smoke.
| Common Effects | Nausea, Headache, Breast tenderness, Weight changes, Irregular uterine bleeding, Mood changes |
| Serious Effects | Venous thromboembolism (VTE), Arterial thromboembolism (e.g., stroke, myocardial infarction), Hypertension, Hepatic adenoma or hepatocellular carcinoma, Gallbladder disease, Hyperkalemia (especially with drospirenone in patients with renal impairment or on potassium-sparing drugs) |
PregnancyBreast cancerActive thromboembolic disordersSevere hepatic diseaseUndiagnosed abnormal genital bleedingHypersensitivity to levonorgestrel or any component
| Precautions | Thrombotic disorders (venous thromboembolism, arterial thromboembolism, stroke, myocardial infarction) - discontinue if signs occur, Increased risk of myocardial infarction and stroke, especially in smokers >35 years, Hepatic neoplasia (benign/malignant) - discontinue if jaundice or hepatic adenoma develops, Hypertension - monitor blood pressure; discontinue if hypertension develops, Gallbladder disease, Carbohydrate/lipid metabolism effects, Headache - evaluate if new/worsening migraine, Bleeding irregularities (breakthrough bleeding, amenorrhea), Ocular lesions (retinal thrombosis) - discontinue if unexplained vision loss, Depression - discontinue if severe, Reduce efficacy with certain drugs (e.g., anticonvulsants, antibiotics) |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase ethinyl estradiol levels. No other significant food interactions. St. John's wort (herbal supplement) reduces contraceptive efficacy. |
| Clinical Pearls | Lessina-21 is a low-dose combination oral contraceptive containing 0.1 mg levonorgestrel and 0.02 mg ethinyl estradiol. Administer on day 1 of menstrual period or first Sunday after onset. Use backup contraception for first 7 days if starting after day 5. Missed pill management: if one pill missed, take as soon as remembered; if two pills missed, take two pills on two consecutive days. CYP34A inducers (e.g., rifampin, St. John's wort) reduce efficacy; consider alternative contraception. Monitor for hypertension, thromboembolism, and migraine with aura. Eating grapefruit may increase ethinyl estradiol levels. Avoid in patients with migraine with aura, history of VTE, or breast cancer. |
| Patient Advice | Take one pill at the same time every day. Do not skip pills. · Start your pack on the first day of your period or the first Sunday after your period starts. · If you miss one pill, take it as soon as you remember. If you miss two pills, take two pills for two days and use a backup method for 7 days. · Lessina-21 does not protect against STIs; use condoms. · Common side effects include nausea, headache, and breast tenderness; these often improve after 3 months. · Smoking increases risk of serious cardiovascular side effects; avoid smoking, especially if over 35 years old. · Call your doctor if you have leg pain, chest pain, shortness of breath, or severe headaches. |
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