LEVONORGESTREL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LEVONORGESTREL (LEVONORGESTREL).
Synthetic progestin that suppresses gonadotropin release (GnRH, LH, FSH) via negative feedback on the hypothalamic-pituitary-ovarian axis; inhibits ovulation, thickens cervical mucus, and alters endometrial lining.
| Metabolism | Primarily hepatic via CYP3A4; also conjugated with glucuronide and sulfate; metabolites excreted in urine and feces. |
| Excretion | Renal: 45-60% (metabolites), Fecal: 32-45% (unchanged and metabolites). Biliary excretion contributes to fecal elimination. |
| Half-life | Terminal half-life: 24-30 hours (range 11-45 hours). This prolonged half-life supports once-daily or extended-cycle dosing in contraceptive formulations. |
| Protein binding | 97-99% bound, primarily to sex hormone-binding globulin (SHBG) and albumin. Binding affinity to SHBG is approximately 50% that of progesterone. |
| Volume of Distribution | 1.8 L/kg (range 1.4-2.2 L/kg). Indicates extensive tissue distribution, including breast tissue and reproductive organs. |
| Bioavailability | Oral: 89% (mean absolute bioavailability, range 83-96%). Subdermal implant: ~100%. Intrauterine: minimal systemic absorption (local effect). |
| Onset of Action | Oral: 4-6 hours for maximum serum concentration; contraceptive effect requires 2-3 days of consistent dosing. Intrauterine device (IUD): immediate local effect; systemic effects negligible. |
| Duration of Action | Oral: contraceptive protection requires daily administration; progestogenic effects persist for 24 hours following a single dose. IUD: up to 5 years (Mirena). |
For emergency contraception: 1.5 mg orally as a single dose or 0.75 mg orally 12 hours apart. For hormonal contraception: 0.03 mg to 0.05 mg orally once daily in combined oral contraceptives; for progestin-only oral contraceptive (mini-pill): 0.03 mg orally once daily. For intrauterine system (IUD): 52 mg intrauterine device inserted for up to 5 years.
| Dosage form | TABLET |
| Renal impairment | No specific dose adjustment is required for renal impairment. Use with caution in patients with severe renal impairment due to potential for reduced drug clearance. |
| Liver impairment | Contraindicated in severe hepatic impairment (Child-Pugh class C). Use with caution in mild to moderate impairment (Child-Pugh class A or B); no specific dose adjustment guidelines but may require monitoring for adverse effects. |
| Pediatric use | For emergency contraception in adolescents (≥16 years): same as adult dosing (1.5 mg orally as a single dose). For hormonal contraception in adolescents: weight-based dosing not typically used; adult doses apply. For IUD use: 52 mg intrauterine device approved for use in adolescents post-menarche. |
| Geriatric use | No specific dose adjustments for elderly; however, use is not indicated in postmenopausal women. Consider increased risk of thromboembolic events in elderly using combined hormonal contraceptives. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LEVONORGESTREL (LEVONORGESTREL).
| Breastfeeding | Levonorgestrel is excreted into breast milk in small amounts. The milk-to-plasma ratio (M/P ratio) is approximately 0.37. Short-term use for emergency contraception is considered compatible with breastfeeding. For long-term use (e.g., levonorgestrel-releasing intrauterine system), the minimal systemic absorption results in very low levels in milk, and no adverse effects on infant growth or development have been reported. |
| Teratogenic Risk | Levonorgestrel is a progestin used in emergency contraception and hormone-releasing intrauterine devices. The fetal risk from inadvertent use during pregnancy is considered low. There is no evidence of teratogenicity from clinical studies and postmarketing surveillance; however, as with all hormonal contraceptives, exposure during the first trimester is not associated with an increased risk of major congenital anomalies. Use during the second and third trimesters may cause androgenic effects, but clinically significant virilization of female fetuses has not been reported with levonorgestrel alone. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known or suspected pregnancy (except for emergency contraception)","Hypersensitivity to levonorgestrel or components","Undiagnosed abnormal genital bleeding","Severe hepatic disease","Known or suspected breast cancer","Current or history of thromboembolic disorders"]
| Precautions | ["Thrombotic disorders (use caution with history of thromboembolism)","Ectopic pregnancy (possible but rare; consider if severe abdominal pain)","Irregular bleeding (common; rule out pregnancy if persistent)","Liver disease (contraindicated in severe impairment)","Depression (monitor if history)","Glucose intolerance (use caution in diabetics)"] |
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| Fetal Monitoring | For emergency contraception or routine use, no specific maternal or fetal monitoring is required. In the event of pregnancy during long-term use of levonorgestrel-releasing intrauterine devices (e.g., Mirena), rule out ectopic pregnancy; if intrauterine pregnancy continues, monitor for potential adverse effects and consider device removal. No additional fetal surveillance is recommended beyond routine prenatal care. |
| Fertility Effects | Levonorgestrel does not impair long-term fertility. After discontinuation of oral contraceptives or removal of levonorgestrel-releasing intrauterine devices, fertility returns promptly, typically within one menstrual cycle. There is no evidence of permanent reduction in fecundity or ovarian reserve. For emergency contraception, it only delays ovulation if taken prior to ovulation and does not affect subsequent cycles. |