Levonorgestrel Emergency Contraceptive

Introduction Overview

Generic Name

levonorgestrel emergency contraceptive

Brand Name

Plan B

Dosage Form

tablet (1.5 mg)

Drug Class

Contraceptives

Pharmacokinetics

Absorption:
Levonorgestrel is rapidly absorbed after oral administration, with peak plasma concentrations typically occurring within 1 to 4 hours post-dose. The oral bioavailability is high, as levonorgestrel undergoes minimal first-pass metabolism. The high solubility and permeability of levonorgestrel contribute to its reliable absorption from the gastrointestinal tract. Clinical data indicate that administration soon after unprotected intercourse maximizes efficacy, linked to rapid systemic availability.

Distribution:
Levonorgestrel exhibits moderate plasma protein binding, primarily to sex hormone-binding globulin (SHBG) and albumin, which modulates its free active concentration. The volume of distribution is approximately 1.8 to 2.8 L/kg, indicating extensive distribution into tissues, including reproductive organs. The penetration into the cervical mucus is significant, influencing its mechanism of action by thickening mucus to inhibit sperm migration.

Metabolism:
Levonorgestrel is extensively metabolized in the liver via reduction and conjugation pathways. The primary metabolic route involves conversion by cytochrome P450 enzymes, especially CYP3A4, to inactive metabolites through hydroxylation and reduction. Phase II metabolism includes glucuronidation and sulfation, facilitating excretion. The metabolic clearance is influenced by the activity of hepatic enzymes, and concomitant medications inducing CYP3A4 can reduce levonorgestrel plasma levels.

Elimination:
Levonorgestrel and its metabolites are primarily excreted via the urine (approximately 40-68%) and feces. The elimination half-life ranges from 24 to 32 hours, allowing sufficient systemic presence after a single 1.5 mg dose to delay ovulation effectively. Renal function can moderately influence clearance, though no dosage adjustments are typically necessary. The pharmacokinetic profile supports single-dose administration, with rapid onset and sustained effect within the critical post-coital window.

Dosage Forms

Available Dosage Forms:
Plan B is available as a single-tablet oral dosage form containing 1.5 mg of levonorgestrel. The tablet is designed for over-the-counter use and is provided as a film-coated pill for oral administration.

Dosages for Adults and Adolescents:
The approved dosing regimen for both adults and adolescents is a single oral dose of 1.5 mg levonorgestrel taken as soon as possible, but not later than 72 hours (3 days) after unprotected sexual intercourse. This single-dose regimen replaced an earlier two-dose regimen that consisted of two 0.75 mg tablets taken 12 hours apart, which is now discontinued.

Specific Patient Populations:
Plan B is indicated for emergency contraception in females of reproductive potential. It is approved for use in adolescents without prescription or age restriction. Due to its hormonal nature, women who are breastfeeding should consult healthcare providers, as levonorgestrel may reduce milk production transiently. There are no specific dose adjustments for elderly patients, renal impairment, or hepatic impairment as emergency contraception use in these populations is rare.

Additional Formulation Details:
Plan B tablets contain inactive ingredients such as colloidal silicon dioxide, potato starch, magnesium stearate, talc, corn starch, and lactose monohydrate. The tablet should be stored at controlled room temperature between 20–25°C (68–77°F).

Mechanism Of Action

Plan B’s primary mechanism of action is the delay or inhibition of ovulation, achieved through the administration of levonorgestrel, a synthetic progestin. Levonorgestrel acts by suppressing the mid-cycle surge of luteinizing hormone (LH) from the pituitary gland, a critical hormonal trigger for ovulation. By blocking or postponing this LH surge, Plan B effectively prevents the release of an oocyte from the ovary, thereby reducing the likelihood of fertilization.

In addition to ovulation suppression, levonorgestrel thickens cervical mucus, creating a physical barrier that impedes sperm motility and the sperm's ability to traverse the cervical canal to reach the ovulated egg. This alteration in cervical mucus composition decreases sperm penetration and movement, further preventing fertilization.

There is also evidence suggesting that levonorgestrel induces changes in the endometrium, making it less receptive to implantation, although this is considered a secondary mechanism and is less significant at the doses used in Plan B. The contraceptive effect primarily stems from pre-fertilization actions rather than post-fertilization effects.

Compared to other emergency contraceptive methods, such as ulipristal acetate (ella), which acts as a selective progesterone receptor modulator, levonorgestrel is a progesterone receptor agonist. This distinction influences the timing and mechanism of efficacy, as ulipristal can delay ovulation closer to the LH surge compared to levonorgestrel. Clinical studies reinforce that Plan B should be administered as early as possible within 72 hours post-coitus for maximal effect, given its mechanism relying on prevention of ovulation initiation.

Pharmacological Actions

Acts as a synthetic progestin agonist mimicking natural progesterone.
Delays or inhibits the LH surge responsible for ovulation.
Thickens cervical mucus to reduce sperm motility and penetration.
Alters the endometrial lining to reduce implantation likelihood, though this is a minor effect.
Provides emergency contraception when regular birth control fails or is not used.
Exerts effects predominantly before fertilization of the egg.
Minimal systemic hormonal effects due to single-dose administration.
Rapid onset of action suitable for postcoital use.
Does not terminate established pregnancy.
Effective within 72 hours after unprotected intercourse, with efficacy decreasing over time.
No significant androgenic or estrogenic activity at therapeutic doses.
Does not protect against sexually transmitted infections (STIs).
Can be administered without prescription, enabling quick postcoital access.

Therapeutic Or Clinical Uses

Emergency contraception to prevent unintended pregnancy after unprotected sexual intercourse.
Backup contraception method following contraceptive failure such as condom breakage or missed birth control pills.
Postcoital contraceptive agent for women seeking pregnancy prevention within 72 hours of intercourse.
Use as an accessible over-the-counter option for timely emergency contraception without restrictions on age or gender.
Management of contraceptive emergencies in various clinical and non-clinical settings.
Alternative to more invasive emergency contraception methods like copper intrauterine devices.
Preventive measure in cases of sexual assault or contraceptive failure.
Used worldwide as a first-line emergency contraceptive due to favorable safety and efficacy profiles.
Part of comprehensive reproductive health strategies and family planning services.
Facilitates reduction in unplanned pregnancies and associated social and medical complications.
Considered a temporary measure pending initiation or resumption of regular contraceptive methods.

Side Or Adverse Effects

Common gastrointestinal symptoms including stomach pain, nausea, vomiting, and diarrhea.
Breast pain or tenderness following administration.
Headache and dizziness reported in some users.
Fatigue or general tiredness may occur transiently.
Menstrual disturbances such as early, delayed, heavier, or irregular bleeding.
Rare but serious allergic reactions including hives, swelling of face or throat, difficulty breathing.
Possible increase in the risk of ectopic (tubal) pregnancy, characterized by severe abdominal pain.
No long-term effects on fertility documented with occasional use.
No evidence of teratogenic effects if pregnancy occurs despite use.
Transient hormonal side effects due to single high-dose progestin exposure.
Symptoms typically resolve without intervention within a few days.
Gastrointestinal upset may be worsened by concomitant alcohol consumption.
Does not increase the risk of venous thromboembolism when used for emergency contraception.
Rare reports of mood changes or emotional disturbances.
Hypersensitivity reactions to inactive ingredients may occur but are uncommon.

Precautions

Do not use if allergic to levonorgestrel or any inactive ingredients in the tablet.
Not intended as a regular contraceptive method; only for emergency use.
Consult healthcare provider if breastfeeding, as levonorgestrel may reduce milk production temporarily.
Pregnancy must be excluded before use; Plan B will not terminate an existing pregnancy.
Seek medical evaluation if vomiting occurs within 2 hours of dosing to consider repeat dosing.
Inform physician of any concurrent medications, especially enzyme inducers that may reduce efficacy.
Avoid reliance on Plan B for protection against sexually transmitted infections.
Use caution in patients with a history of ectopic pregnancy.
Not recommended for use in individuals with active thromboembolic disorders without specialist consultation.
No known dose adjustments for renal or hepatic impairment documented, but medical advice is prudent.
Delay in menstrual period of more than one week after expected date warrants pregnancy testing.
Plan B does not protect against subsequent unprotected sexual encounters; use regular contraception thereafter.
Patients should be advised to report severe abdominal pain after use to exclude ectopic pregnancy.
Consider alternative or additional contraception if using medications that induce hepatic enzymes.
Counsel patients on potential side effects and proper timing of administration for optimal effectiveness.

Warnings

Do not use if pregnancy is already established; levonorgestrel does not terminate pregnancy.
Certain medications (e.g., anticonvulsants, rifampin, efavirenz) can reduce levonorgestrel efficacy.
Plan B will not protect against sexually transmitted infections, including HIV/AIDS.
Immediate medical care is necessary if symptoms of ectopic pregnancy occur after use.
Not suitable as a replacement for regular contraceptive methods; increased risk of pregnancy with frequent use.
Use with caution in women with allergies or history of hypersensitivity reactions to hormonal contraceptives.
Avoid use in combination with enzyme-inducing drugs unless alternative contraception is used.
Delayed or irregular menstruation is common and usually temporary, but persistent abnormalities should be evaluated.
Patients should be informed about the limited time window for effective use (within 72 hours).
No clinically significant interactions with alcohol but alcohol may exacerbate side effects.
Consult healthcare providers before administration if underlying health conditions are present.
Emergency contraception should not be relied upon in recurrent unprotected intercourse without additional contraception.
Use immediately after unprotected sex, as efficacy decreases significantly with time.
Plan B is not effective if implantation has occurred; dosing will not affect existing pregnancy.
Watch for signs of serious allergic reactions such as rash, swelling, and respiratory difficulty.

Contraindication

Known or suspected pregnancy at the time of dosing.
Hypersensitivity or allergic reaction to levonorgestrel or any excipient in the tablet.
Use of Plan B as a regular contraception method instead of emergency use.
Use in patients with unexplained vaginal bleeding until etiological diagnosis is established.
Individuals with known or suspected hormone-sensitive tumors without medical supervision.
Use contraindicated in individuals with a history of immediate hypersensitivity reactions to progestin agents.
Patients advised to avoid self-administration if they cannot comply with dosing within the 72-hour efficacy window.
Severe liver disease where metabolism of hormonal agents is impaired may warrant avoidance.
Presence of undiagnosed breast lumps or breast cancer may contraindicate hormonal therapy.
Concomitant use with drugs inducing cytochrome P450 enzymes not contraindicated but requires caution.
Contraindicated when used for pregnancy termination as it is ineffective.
Use contraindicated in patients with known or suspected ectopic pregnancy without medical evaluation.
Not to be used in males; although available over-the-counter, clinical use is limited to women of reproductive potential.
Should not replace medical consultation for routine contraceptive counseling or management.
Contraindicated in cases where menstrual bleeding pattern changes could mask serious disorders without evaluation.

Drug Interactions

Cytochrome P450 3A4 enzyme inducers such as rifampin and rifamycins may decrease levonorgestrel plasma concentrations.
Antiepileptic drugs including carbamazepine, phenobarbital, phenytoin, oxcarbazepine, primidone, and felbamate can reduce effectiveness.
HIV medications such as efavirenz may impair levonorgestrel efficacy due to enhanced metabolism.
Bosentan, used for pulmonary hypertension, can induce hepatic enzymes leading to decreased levonorgestrel levels.
Griseofulvin, an antifungal agent, is a known enzyme inducer that may reduce emergency contraception effectiveness.
Topiramate, another enzyme inducer used for seizure control, can reduce levonorgestrel plasma levels.
Concomitant use with St. John's Wort and other herbal products inducing CYP3A4 should be avoided or closely monitored.
No significant interactions reported with alcohol; alcohol does not affect levonorgestrel pharmacokinetics.
Medications altering gastrointestinal motility might theoretically affect levonorgestrel absorption, though data is limited.
No known antagonistic interactions with typical over-the-counter medications for cold, pain, or allergies.
Interactions with hormonal contraceptives have not been associated with increased risk beyond additive hormonal effects.
Levonorgestrel does not reduce the efficacy of other contraceptive methods when used concurrently.
Some medications requiring dose adjustment in hepatic impairment may overlap with levonorgestrel metabolism pathways.
Enzyme inhibitors such as ketoconazole may increase levonorgestrel levels but clinical significance is minimal in single-dose use.
Patients should inform healthcare providers about all concomitant medications to assess potential interaction risks.

Preparations Of The Drug

Plan B One-Step tablet containing 1.5 mg levonorgestrel as the active ingredient.
Film-coated tablet formulation for oral administration.
Inactive ingredients include colloidal silicon dioxide, potato starch, magnesium stearate, talc, corn starch, and lactose monohydrate.
Single-dose packaging designed for immediate, over-the-counter purchase and use.
Tablet stored at controlled room temperature (20–25°C or 68–77°F) to maintain stability.
Discontinued formulation: earlier Plan B used two 0.75 mg tablets taken 12 hours apart.
Commercially available in blister packs or single unit packages for rapid dispensing.
Non-prescription availability ensures widespread accessibility in retail pharmacies and stores.
Manufactured by Teva Women’s Health, Inc., adhering to regulatory pharmaceutical manufacturing standards.
Packaging includes patient information leaflets outlining dosing instructions and safety precautions.
Designed to be portable for emergency use, facilitating prompt administration post-unprotected intercourse.
No liquid or alternative dosage forms currently available for emergency contraception containing levonorgestrel.
Shelf-life generally ranges from two to three years depending on storage conditions.
Other levonorgestrel-containing contraceptives include IUDs (Mirena, Kyleena) but differ significantly in dosage and use.
Plan B tablets are intended exclusively for emergency contraception and not for routine birth control.