LILETTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LILETTA (LILETTA).
Levonorgestrel, a progestin, suppresses gonadotropin-releasing hormone (GnRH) secretion, inhibits ovulation, thickens cervical mucus, and induces endometrial atrophy, primarily via binding to progesterone receptors in the hypothalamus, pituitary, ovary, and endometrium.
| Metabolism | Hepatic metabolism via CYP3A4 to inactive metabolites; also reduced by CYP3A5, CYP2C8, and CYP2C9. |
| Excretion | Levonorgestrel is excreted primarily as metabolites in urine (45%) and feces (32%), with less than 1% excreted unchanged. Biliary excretion contributes to fecal elimination. |
| Half-life | The terminal elimination half-life of levonorgestrel following LILETTA insertion is approximately 20.0 hours. This supports once-daily assessment of hormone levels and reflects systemic clearance. |
| Protein binding | Levonorgestrel is approximately 97-99% bound to serum proteins, primarily sex hormone-binding globulin (SHBG) and albumin. |
| Volume of Distribution | The apparent volume of distribution for levonorgestrel is estimated to be 1.8 L/kg, indicating extensive distribution into tissues. |
| Bioavailability | Intrauterine administration results in nearly 100% local bioavailability, with low systemic absorption; peak serum concentrations reach ~0.5-1 ng/mL within 2 weeks. |
| Onset of Action | Contraceptive effect begins within 24 hours of intrauterine placement; ovulation suppression may require up to 7 days if inserted after cycle day 7. |
| Duration of Action | LILETTA provides effective contraception for up to 6 years, with sustained local progestin release achieving endometrial suppression throughout the approved duration. |
Intrauterine device (IUD) releasing levonorgestrel 17.5 mcg/day, inserted for up to 5 years.
| Dosage form | SYSTEM |
| Renal impairment | No dosage adjustment required for renal impairment. |
| Liver impairment | Contraindicated in acute liver disease or liver tumors; no dose adjustment defined for Child-Pugh class A or B as safety not established. |
| Pediatric use | Not indicated for use in pediatric patients before menarche; post-menarche adolescents: same as adult dosing (17.5 mcg/day IUD, inserted for up to 5 years). |
| Geriatric use | Not indicated for use in postmenopausal women. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LILETTA (LILETTA).
| Breastfeeding | Limited data; levonorgestrel is excreted in breast milk in small amounts (M/P ratio approximately 0.3-0.6). Considered compatible with breastfeeding; however, caution in patients with postpartum hemorrhage or hepatic impairment. |
| Teratogenic Risk | Pregnancy category X: Contraindicated in pregnancy due to risk of ectopic pregnancy and fetal harm. No first trimester fetal risks data; however, if pregnancy occurs, remove device immediately. Second and third trimester risks unknown but progestin exposure may cause androgenization of female fetus. |
■ FDA Black Box Warning
None
| Serious Effects |
["Pregnancy or suspected pregnancy","Current or recurrent pelvic inflammatory disease (PID)","Postpartum endometritis or infected abortion within past 3 months","Known or suspected uterine or cervical malignancy","Uterine cavity distortion (e.g., fibroids) preventing proper IUD placement","Acute liver disease or liver tumor","Undiagnosed abnormal uterine bleeding","Allergy to any component of LILETTA","Increased susceptibility to infection (e.g., leukemia, AIDS, IV drug use)"]
| Precautions | ["Ectopic pregnancy risk if pregnancy occurs with IUD in place","Pelvic inflammatory disease (PID) risk, especially within first 20 days post-insertion","IUD expulsion or perforation (uterine or cervical)","Breast cancer risk in current users (controversial; consider personal history)","Ovarian cysts (usually benign and self-limiting)","Use with caution in immunocompromised patients (increased PID risk)","Removal indicated if pregnancy occurs, missed period with bleeding, or new onset STD"] |
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| Fetal Monitoring |
| Verify placement by ultrasound or other imaging. Monitor for signs of ectopic pregnancy (unexplained vaginal bleeding, pelvic pain). Assess for uterine perforation. Regular follow-up for device retention and menstrual changes. |
| Fertility Effects | Reversible: Fertility returns rapidly after removal. No long-term impairment of fertility. May reduce endometrial receptivity during use. |