Liletta - Drug Monograph

Introduction

Liletta (levonorgestrel-releasing intrauterine system) is a long-acting reversible contraceptive (LARC) device that provides up to 8 years of pregnancy prevention. This T-shaped intrauterine system continuously releases low doses of the progestin levonorgestrel directly into the uterine cavity, making it one of the most effective contraceptive options available with a typical use failure rate of less than 0.2% per year.

Mechanism of Action

Liletta's primary mechanism of action involves the local release of levonorgestrel, which causes thickening of cervical mucus, inhibiting sperm penetration and migration. Additionally, it suppresses endometrial proliferation and causes endometrial thinning, creating an unfavorable environment for implantation. In some women, it may inhibit ovulation, though this is not its primary mechanism. The local hormonal action minimizes systemic exposure compared to oral contraceptives.

Indications

• Prevention of pregnancy for up to 8 years
• May be used as a transitional method after other hormonal contraceptives
• Not approved for emergency contraception or postcoital contraception

Dosage and Administration

• Single intrauterine system containing 52 mg levonorgestrel
• Initial release rate: approximately 21 mcg/24 hours
• Release rate decreases to approximately 10 mcg/24 hours after 5 years
• Inserted by healthcare provider into uterine cavity
• Replacement: After 8 years of use or when replacement is medically indicated
• Special populations: Not recommended for postmenopausal women. Can be used in nulliparous women. Safety and efficacy established in women of reproductive age.

Pharmacokinetics

• Absorption: Levonorgestrel released directly into uterine cavity with minimal systemic absorption
• Distribution: Serum concentrations range from 150-200 pg/mL initially, declining to 100-125 pg/mL after 12 months
• Metabolism: Hepatic metabolism via cytochrome P450 enzymes (primarily CYP3A4)
• Elimination: Metabolites excreted in urine and feces
• Half-life: Approximately 24 hours for levonorgestrel

Contraindications

• Pregnancy or suspected pregnancy
• Current or history of pelvic inflammatory disease
• Postpartum endometritis or infected abortion within past 3 months
• Known or suspected uterine or cervical malignancy
• Undiagnosed abnormal genital bleeding
• Wilson's disease (copper allergy not applicable as Liletta is hormone-only)
• Hypersensitivity to any component
• Conditions associated with increased susceptibility to pelvic infections
• Acute liver disease or liver tumors

Warnings and Precautions

• Uterine perforation: Risk increased during insertion, especially in lactating women
• Expulsion: Partial or complete expulsion may occur, often unnoticed
• Pelvic inflammatory disease (PID): Usually occurs within first 20 days after insertion
• Embedment: Device may become embedded in myometrium
• Ovarian cysts: Enlarged follicles may occur and usually resolve spontaneously
• Bleeding pattern alterations: Irregular bleeding/spotting common initially, often progressing to amenorrhea
• Ectopic pregnancy: Although rare, if pregnancy occurs with Liletta in place, consider ectopic pregnancy
• MRI safety: Liletta is MR conditional

Drug Interactions

• Enzyme inducers: Drugs that induce CYP3A4 (e.g., rifampin, carbamazepine, St. John's wort) may decrease levonorgestrel efficacy
• Anticoagulants: Theoretical potential for interaction, though limited data
• Corticosteroids: Potential decreased corticosteroid efficacy
• Other hormonal contraceptives: Generally not used concomitantly

Adverse Effects

• Irregular bleeding/spotting
• Amenorrhea
• Vulvovaginitis
• Abdominal/pelvic pain
• Headache

• Ovarian cysts
• Acne/skin disorders
• Breast pain
• Nausea
• Depression/mood changes
• Expulsion
• Dysmenorrhea

• Uterine perforation
• Pelvic inflammatory disease
• Ectopic pregnancy
• Embedment
• Allergic reactions

Monitoring Parameters

• Pre-insertion: Pregnancy test, screening for STIs/PID risk factors, uterine size and position assessment
• Post-insertion: Verify strings 4-6 weeks after insertion, then periodically
• Annual evaluation: Assess for continued desire for contraception, check strings
• Symptom monitoring: Abdominal pain, fever, unusual bleeding patterns, possible expulsion
• Routine gynecologic care: Continue regular cervical cancer screening and STI testing as appropriate

Patient Education

• Liletta provides continuous contraception for up to 8 years
• Expect changes in menstrual pattern (irregular bleeding initially, often leading to lighter periods or amenorrhea)
• Check for presence of strings periodically (after menses)
• Seek immediate care for severe abdominal pain, fever, chills, foul discharge, or possible expulsion
• Does not protect against STIs - additional protection recommended
• Return for string check if unable to feel strings or if pregnancy suspected
• Removal by healthcare provider required for discontinuation
• Fertility typically returns rapidly after removal
• Report persistent pelvic pain, unusual bleeding, or possible pregnancy

References

1. FDA Prescribing Information: Liletta (levonorgestrel-releasing intrauterine system) 2. Curtis KM, Jatlaoui TC, Tepper NK, et al. U.S. Selected Practice Recommendations for Contraceptive Use, 2016. MMWR Recomm Rep. 2016;65(4):1-66 3. Teal S, Edelman A. Contraception Selection, Effectiveness, and Adverse Effects: A Review. JAMA. 2021;326(24):2507-2518 4. American College of Obstetricians and Gynecologists. Long-Acting Reversible Contraception: Implants and Intrauterine Devices. Practice Bulletin No. 186. Obstet Gynecol. 2017;130(5):e251-e269 5. Gemzell-Danielsson K, Mansour D, Fiala C, et al. Management of intrauterine contraceptives in women with adverse events. Contraception. 2021;103(5):285-294 6. Creinin MD, Jansen R, Starr RM, et al. Levonorgestrel release rates over 5 years with the Liletta® 52-mg intrauterine system. Contraception. 2016;94(4):353-356