LEVONEST
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEVONEST (LEVONEST).
Levonorgestrel is a synthetic progestin that inhibits ovulation by suppressing luteinizing hormone (LH) surge, alters cervical mucus to impede sperm penetration, and induces endometrial changes that inhibit implantation.
| Metabolism | Primarily hepatic via CYP3A4; undergoes reduction and conjugation; excreted in urine and feces. |
| Excretion | Renal excretion of conjugated metabolites accounts for approximately 60-80% of an administered dose; fecal elimination via bile accounts for 20-40%. |
| Half-life | The terminal elimination half-life is approximately 24-30 hours. This relatively long half-life supports once-daily dosing and allows for stable plasma concentrations within 5-7 days of continuous use. |
| Protein binding | Levonorgestrel is extensively bound to sex hormone-binding globulin (SHBG) and albumin; approximately 97-99% bound, with the free fraction being pharmacologically active. |
| Volume of Distribution | Apparent volume of distribution is about 1.8 L/kg, indicating extensive distribution into tissues beyond plasma water. |
| Bioavailability | Oral bioavailability is approximately 100% due to minimal first-pass metabolism; levonorgestrel is completely absorbed after oral administration. |
| Onset of Action | Oral administration: onset of contraceptive effect occurs within 24 hours if started on the first day of menstrual cycle. Withdrawal bleeding typically begins 2-7 days after completion of active tablets. |
| Duration of Action | Contraceptive efficacy persists for the duration of daily oral administration; after discontinuation, ovulation returns within 4-8 weeks. |
| Molecular Weight | 312.45 |
One tablet (levonorgestrel 1.5 mg) orally as a single dose within 72 hours of unprotected intercourse.
| Dosage form | TABLET |
| Renal impairment | No dosage adjustment required for any degree of renal impairment. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). For mild to moderate impairment, no specific dose adjustment available; use with caution. |
| Pediatric use | Weight ≥ 75 kg: single dose of levonorgestrel 1.5 mg orally. Weight < 75 kg: single dose of 1.5 mg is also used, but efficacy may be reduced; consider alternative methods. |
| Geriatric use | Not indicated for postmenopausal women; no specific dose adjustment established for elderly. |
| 1st trimester | Contraindicated due to risk of congenital defects including cardiac anomalies and neural tube defects. |
| 2nd trimester | Contraindicated due to reports of fetal liver damage, cholestasis, and carcinogenic potential. |
| 3rd trimester | Contraindicated due to risk of fetal cholestatic hepatitis and liver tumors. |
Clinical note
Comprehensive clinical and safety monograph for LEVONEST (LEVONEST).
| Placental transfer | Levonorgestrel readily crosses the placenta; studies demonstrate significant fetal exposure with potential for teratogenicity and fetotoxicity. |
| Breastfeeding | Excreted into breast milk in small amounts; however, due to potential for serious adverse effects (e.g., hepatotoxicity, carcinogenicity) in the nursing infant, breastfeeding is contraindicated. |
| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | LEVONEST (levonorgestrel) is associated with minimal teratogenic risk if inadvertently used during pregnancy. First trimester: No increased risk of major malformations based on epidemiologic data. Second/third trimester: No known adverse fetal effects from occasional use; no evidence of fetotoxicity or teratogenicity from clinical studies. However, as a progestin-only contraceptive, it is not indicated during pregnancy. |
| Fetal Monitoring | No specific monitoring required for routine use. In pregnancy, if inadvertent exposure occurs, standard prenatal care is sufficient. For lactation, observe infant for unusual drowsiness or feeding difficulties. |
| Fertility Effects | Levonorgestrel does not impair future fertility. Fertility returns rapidly after discontinuation. No permanent negative impact on ovarian function or fecundity. |
■ FDA Black Box Warning
None.
| Serious Effects |
PregnancySevere hepatic impairmentHistory of breast cancerUndiagnosed abnormal uterine bleedingHypersensitivity to levonorgestrel or any component
| Precautions | Do not use as regular contraceptive if multiple doses are taken in one cycle, Ectopic pregnancy risk reduced but not eliminated, Menstrual irregularities, Rare cases of hepatic adenoma or thromboembolic events, Use with caution in patients with severe hepatic impairment or malabsorption syndromes |
| Food/Dietary | No clinically significant food interactions. Levonest releases levonorgestrel locally in the uterus, and systemic absorption is minimal. No dietary restrictions required. |
| Clinical Pearls | Levonest (levonorgestrel-releasing intrauterine system) provides effective contraception for up to 5 years. It can be used for emergency contraception if inserted within 5 days of unprotected intercourse. May reduce menstrual bleeding and dysmenorrhea. Expulsion risk is highest in first year, especially right after insertion. Check strings after each period. Contraindicated in acute pelvic inflammatory disease, postpartum endometritis, infected abortion, or untreated cervical infection. |
| Patient Advice | Levonest is a small T-shaped device placed in your uterus that releases a hormone to prevent pregnancy for up to 5 years. · You may have irregular bleeding or spotting for the first 3-6 months, which typically decreases over time. · Check the strings at the end of your period each month to ensure the device is in place. · Do not use Levonest if you think you might be pregnant, have a current pelvic infection, or have certain uterine abnormalities. · Most women can use Levonest safely; serious complications are rare but include perforation, expulsion, and infection. · Seek medical attention if you experience severe abdominal pain, fever, heavy bleeding, or missing strings. |
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