Levonorgestrel

BRAND NAMES

Plan B One-Step: Plan B One-Step is a single-dose emergency contraceptive containing 1.5 mg levonorgestrel, used within 72 hours of unprotected sex to prevent pregnancy.

Postinor: Postinor is an emergency contraceptive containing 1.5 mg levonorgestrel, taken within 72 hours of unprotected sex to prevent pregnancy by delaying ovulation.

MECHANISM OF ACTION

Levonorgestrel is a synthetic progestin that works primarily by inhibiting or delaying ovulation, which prevents the release of an egg from the ovary. Without ovulation, fertilization cannot occur. Additionally, it causes thickening of cervical mucus, which acts as a barrier to sperm, reducing the likelihood of sperm reaching and fertilizing an egg. Levonorgestrel may also induce endometrial changes that make the uterine lining less receptive to implantation. However, it is important to note that its primary effect is on ovulation, and it is not effective once implantation has occurred. Levonorgestrel does not disrupt an established pregnancy and is not considered an abortifacient.

PHARMACOKINETICS

Absorption

Levonorgestrel is rapidly absorbed after oral administration, with peak plasma concentrations typically reached within 1 to 2 hours.

Distribution

It has a volume of distribution of about 1.8 L/kg and is highly protein-bound, mainly to sex hormone-binding globulin (SHBG) and, to a lesser extent, albumin.

Metabolism

It is extensively metabolized in the liver, primarily by reduction and conjugation, and partially via CYP3A4 enzymes.

Elimination

Levonorgestrel is eliminated through urine and feces, mostly as glucuronide and sulfate conjugate. The terminal half-life is approximately 20–30 hours.

DOSAGE AND ADMINISTRATION

For emergency contraception, levonorgestrel is typically administered as a single oral dose of 1.5 mg as soon as possible within 72 hours after unprotected intercourse or contraceptive failure. Alternatively, in some formulations, it may be taken as two doses of 0.75 mg spaced 12 hours apart.

It can be taken with or without food, and no dose adjustments are needed based on body weight, although effectiveness may be reduced in individuals with higher body mass index (BMI). It is intended for occasional emergency use and not for regular contraception.

DRUG INTERACTIONS

• Rifampin and rifabutin: Strong enzyme inducers; significantly reduce levonorgestrel levels.
• Antiepileptics (e.g., phenytoin, carbamazepine, phenobarbital): Decrease effectiveness by increasing metabolism.
• St. John’s Wort: Herbal enzyme inducer; reduces contraceptive efficacy.
• Efavirenz and some antiretrovirals: May lower levonorgestrel concentration.
• Most antibiotics: Do not interact, except rifampin.
• CYP3A4 inhibitors (e.g., ketoconazole): May increase levonorgestrel levels, but usually not clinically significant.

CONTRAINDICATIONS

• Known or suspected pregnancy - Not intended for use if pregnancy is already established.
• Hypersensitivity to levonorgestrel or any component of the formulation.
• Unexplained vaginal bleeding - Should be evaluated before use.
• Severe liver dysfunction - As the drug is metabolized in the liver.
• Current or past history of thromboembolic disorders (for regular use; less relevant for single-dose emergency use).

SIDE EFFECTS

• Nausea
• Headache
• Dizziness
• Fatigue
• Breast tenderness
• Abdominal pain
• Menstrual changes (early, delayed, or irregular)
• Spotting

TOXICITY

Levonorgestrel is considered to have a high safety margin. Even when taken in doses higher than recommended, it typically causes only mild side effects such as nausea, vomiting, fatigue, and menstrual disturbances. There are no known reports of life-threatening overdose or serious toxic effects.

Long-term or repeated use, however, may lead to hormonal imbalance, irregular cycles, or reduced contraceptive efficacy. It does not cause teratogenicity or harm to an established pregnancy, and no antidote is required in case of overdose only supportive care if symptoms occur.