Kyleena - Drug Monograph

Introduction

Kyleena (levonorgestrel-releasing intrauterine system) is a long-acting reversible contraceptive (LARC) device that provides highly effective pregnancy prevention for up to five years. This T-shaped polyethylene frame contains a reservoir of 19.5 mg levonorgestrel, which is released locally into the uterine cavity at an initial rate of approximately 17.5 mcg/day, decreasing to approximately 7.4 mcg/day after five years.

Mechanism of Action

Kyleena exerts its contraceptive effects through multiple mechanisms. The primary action is thickening of cervical mucus, creating a barrier that impedes sperm penetration and migration. Additionally, it causes endometrial atrophy and suppresses endometrial proliferation, creating an unfavorable environment for implantation. While it may suppress ovulation in some women, this is not its primary mechanism, and many women continue to ovulate regularly while using Kyleena.

Indications

• Contraception for up to 5 years
• Prevention of pregnancy in nulliparous and parous women

Dosage and Administration

• Insertion: Performed by trained healthcare provider during outpatient visit
• Timing: Ideally inserted within 7 days of menstrual cycle onset
• Replacement: Every 5 years for continued contraception
• Postpartum insertion: May be inserted immediately postpartum or after 4 weeks
• Post-abortion insertion: May be inserted immediately following first or second trimester abortion

Pharmacokinetics

• Absorption: Levonorgestrel is released directly into uterine cavity with minimal systemic absorption
• Distribution: Serum concentrations range from 150-200 pg/mL initially, declining to 70-80 pg/mL at 5 years
• Metabolism: Primarily hepatic via cytochrome P450 3A4 system
• Elimination: Metabolites excreted in urine and feces
• Half-life: Approximately 17 hours (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
• Uterine abnormalities that distort cavity
• Acute liver disease or liver tumors
• Hypersensitivity to any component of Kyleena
• Known or suspected breast cancer or other progestin-sensitive cancers

Warnings and Precautions

• Perforation risk: Uterine perforation (1-2 per 1000 insertions) may occur during insertion
• Expulsion: Partial or complete expulsion may occur, especially in nulliparous women
• Pelvic inflammatory disease: Risk highest within first 20 days after insertion
• Ectopic pregnancy: Women with history of ectopic pregnancy should be carefully monitored
• Ovarian cysts: May develop and usually resolve spontaneously
• Embedment: May occur, potentially making removal difficult
• MRI safety: Kyleena is MR conditional (safe in MRI machines up to 3 Tesla)

Drug Interactions

• Enzyme inducers: Drugs that induce CYP3A4 (rifampin, carbamazepine, St. John's wort) may decrease levonorgestrel effectiveness
• Anticoagulants: Theoretical increased risk of bleeding, though clinical significance is unclear
• Corticosteroids: Potential decreased corticosteroid effectiveness
• No significant interactions with most commonly prescribed medications due to local delivery system

Adverse Effects

• Alterations in menstrual bleeding patterns (amenorrhea, oligomenorrhea, spotting)
• Abdominal/pelvic pain
• Ovarian cysts
• Vulvovaginitis

• Headache
• Acne
• Breast tenderness
• Nausea
• Depression
• Alopecia

• Uterine perforation
• Expulsion
• Pelvic inflammatory disease
• Ectopic pregnancy
• Embedment

Monitoring Parameters

• Post-insertion: Follow-up visit 4-12 weeks after insertion to verify placement
• Annual exams: Regular pelvic exams to assess string visibility and device position
• Symptom monitoring: Regular assessment of bleeding patterns, pain, and other symptoms
• String check: Patients should periodically check for presence of strings
• Pregnancy testing: As clinically indicated

Patient Education

• Insertion process: Explain what to expect during and after insertion
• Bleeding patterns: Educate about expected changes in menstrual patterns
• String check: Teach how to verify presence of strings monthly
• Warning signs: Instruct to seek immediate care for severe pain, fever, foul discharge, or possible pregnancy
• Expulsion recognition: Educate about signs of expulsion (length of strings changes, hard plastic felt at cervix)
• Contraceptive efficacy: Inform that Kyleena is effective immediately if inserted during menses
• STI protection: Emphasize that Kyleena does not protect against sexually transmitted infections

References

1. Kyleena [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2022. 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:e251-e269. 5. Gemzell-Danielsson K, Buhling K, Dermout S, et al. A phase III, single-arm study of levonorgestrel 19.5 mg IUD (Kyleena) among parous and nulliparous women: 12-month results. Eur J Contracept Reprod Health Care. 2020;25(2):113-119.