LESSINA-21
Clinical safety rating: caution
Comprehensive 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) |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LESSINA-21 (LESSINA-21).
| Breastfeeding | Small amounts of ethinyl estradiol and levonorgestrel are excreted in breast milk (M/P ratio not determined). May reduce milk production and composition. Use is generally not recommended during breastfeeding; alternative contraception should be considered. |
| 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. |
■ 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.
| Serious Effects |
["Known or suspected pregnancy","Current or past history of thromboembolic disorders (e.g., DVT, PE)","Cerebrovascular or coronary artery disease (current or history)","Known thrombophilic conditions (e.g., Factor V Leiden, prothrombin mutation, protein S/C deficiency)","Uncontrolled hypertension (BP ≥160/100 mm Hg)","Diabetes with vascular involvement","Headaches with focal neurological symptoms (e.g., migraine with aura, age >35)","Major surgery with prolonged immobilization","Known or suspected breast carcinoma or other estrogen-sensitive neoplasia","Hepatic adenoma or carcinoma, active liver disease, or impaired liver function","Undiagnosed abnormal uterine bleeding","Cigarette smoking in women >35 years","Hypersensitivity to 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)"] |
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| 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. |