Levonorgestrel [Emergency contraceptive pill]

Approved Indication:

• Emergency contraception for the prevention of pregnancy following unprotected sexual intercourse or contraceptive failure (e.g., condom breakage, missed oral contraceptive pills).
• Most effective when taken within 72 hours after unprotected intercourse.
• May still be taken up to 120 hours (5 days), but effectiveness diminishes over time.

Clinically Accepted Off-label Uses:

• Use as part of the Yuzpe regimen (with ethinylestradiol) when levonorgestrel-only options are unavailable.
• Occasionally used in menstrual regulation in select clinical scenarios.

General Adult and Adolescent Dosage (≥15 years):

• Single-dose regimen (preferred):
• Levonorgestrel 1.5 mg orally as a single dose as soon as possible within 72 hours of unprotected intercourse.
• Two-dose regimen (alternative):
• Levonorgestrel 0.75 mg orally, followed by a second 0.75 mg dose 12 hours later.
• Both doses should be taken within 72 hours of unprotected intercourse.

Special Populations:

• Pediatrics (<15 years): Not routinely recommended; clinical discretion advised for post-pubertal use.
• Obesity (BMI ≥30 kg/m²): Reduced efficacy reported. Consider copper IUD as preferred option if feasible.
• Hepatic impairment: Use with caution; levonorgestrel is metabolized in the liver.
• Renal impairment: No dosage adjustment necessary.

Important Notes:

• If vomiting occurs within 2 hours of taking a dose, the dose should be repeated.
• Not intended for regular contraception.

Levonorgestrel is a synthetic progestogen that primarily works by inhibiting or delaying ovulation. It suppresses the mid-cycle luteinizing hormone (LH) surge necessary for follicular rupture. Additionally, it may alter the endometrial lining, making it less suitable for implantation. However, it does not terminate an existing pregnancy and does not affect fertilized egg implantation if ovulation has already occurred.

• Absorption: Rapidly absorbed orally; peak plasma levels in ~2 hours.
• Bioavailability: ~100%
• Protein Binding: 97.5–99% (primarily to albumin and sex hormone-binding globulin)
• Metabolism: Hepatic metabolism primarily via reduction and conjugation; minor CYP3A4 involvement.
• Half-life: 24–30 hours
• Excretion: Urine (as conjugates and metabolites); minor fecal excretion.

• Pregnancy:
• FDA Pregnancy Category X (not for use during established pregnancy).
• However, no evidence of teratogenicity if inadvertently used during pregnancy.
• Lactation:
• Levonorgestrel is excreted into breast milk in small amounts.
• Breastfeeding may continue, but some guidelines recommend waiting at least 8 hours after ingestion before resuming.

• Primary Class: Emergency contraceptive
• Subclass: Progestin-only hormone (Levonorgestrel-based)

• Known hypersensitivity to levonorgestrel or any component of the product
• Confirmed or suspected pregnancy
• Severe liver disease or hepatic tumors
• Undiagnosed abnormal genital bleeding
• Active or history of breast cancer (hormone-sensitive)

• Not intended as a regular contraceptive method.
• Less effective in individuals with BMI ≥30 kg/m².
• Use with caution in patients with liver impairment.
• Monitor for menstrual irregularities post-dose.
• Does not protect against sexually transmitted infections (STIs).
• If menstruation is delayed by more than 7 days, a pregnancy test should be performed.
• Repeat use within the same cycle is not advised due to increased risk of cycle disruption.

Common (≥1%):

• Gastrointestinal: Nausea, vomiting, abdominal pain
• Neurological: Headache, dizziness, fatigue
• Reproductive: Breast tenderness, spotting, menstrual irregularities (early or delayed periods)

Less Common/Serious:

• Rash, urticaria
• Hypersensitivity reactions
• Ectopic pregnancy (rare, must be considered if severe abdominal pain or delayed menstruation occurs)

Drugs that may reduce efficacy (CYP3A4 inducers):

• Rifampin, phenytoin, carbamazepine, barbiturates
• Efavirenz, nevirapine
• St. John’s Wort

Management:

• Consider doubling the dose (3 mg) in consultation with a clinician
• Copper IUD is the preferred method in cases of known enzyme induction

Other interactions:

• Antiretrovirals: May decrease levonorgestrel exposure
• Cyclosporine: Potential increased plasma levels due to decreased metabolism

• WHO 2023:
  Reaffirmed use of 1.5 mg single-dose levonorgestrel as the preferred oral emergency contraceptive.
• FDA Update:
  Clarified that levonorgestrel does not disrupt an existing pregnancy and is not an abortifacient.
• NICE Guidelines (UK):
  Recommend counseling for emergency contraception with clear explanation of timing, effectiveness, and follow-up.

• Temperature: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C–30°C
• Humidity/Light: Protect from moisture and direct sunlight
• Handling: Store in original packaging. Keep out of reach of children.
• Shelf-life: Follow expiry date printed on packaging. Do not use if damaged.