Kyleena Side Effects Center

Last updated on RxList: 1/24/2022
Kyleena Side Effects Center

What Is Kyleena?

Kyleena (levonorgestrel-releasing intrauterine system) is a progestin-containing intrauterine system (IUS) indicated for prevention of pregnancy for up to 5 years.

What Are Side Effects of Kyleena?

Common side effects of Kyleena include:

Dosage for Kyleena

Kyleena is inserted by a trained healthcare provider. The release rate of levonorgestrel (LNG) in Kyleena is 17.5 mcg/day after 24 days and declines to 7.4 mcg/day after 5 years; Kyleena must be removed or replaced after 5 years.

What Drugs, Substances, or Supplements Interact with Kyleena?

Kyleena may interact with other drugs. Tell your doctor all medications and supplements you use.

Kyleena During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant before using Kyleena. Kyleena is not recommended for use during pregnancy. Kyleena should be removed if pregnancy occurs with Kyleena in place. Consult your doctor before breastfeeding.

Additional Information

Our Kyleena (levonorgestrel-releasing intrauterine system) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Choosing Your Birth Control Method See Slideshow
Kyleena Consumer Information

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Get emergency medical help if you have severe pain in your lower stomach or side. This could be a sign of a tubal pregnancy.

The IUD may become embedded into the wall of the uterus, or may perforate (form a hole) in the uterus. If this occurs, the device may no longer prevent pregnancy, or it may move outside the uterus and cause scarring, infection, or damage to other organs. Your doctor may need to surgically remove the device.

Call your doctor at once if you have:

  • severe cramps or pelvic pain, pain during sexual intercourse;
  • extreme dizziness or light-headed feeling;
  • severe migraine headache;
  • heavy or ongoing vaginal bleeding, vaginal sores, vaginal discharge that is watery, foul-smelling discharge, or otherwise unusual;
  • pale skin, weakness, easy bruising or bleeding, fever, chills, or other signs of infection;
  • jaundice (yellowing of the skin or eyes); or
  • sudden numbness or weakness (especially on one side of the body), confusion, problems with vision, sensitivity to light.

Common side effects may include:

  • pelvic pain, painful or irregular menstrual periods, changes in bleeding patterns or flow;
  • vaginal swelling, itching or infection;
  • temporary pain, bleeding, or dizziness during insertion of the IUD;
  • ovarian cysts (pelvic pain that disappears within 3 months);
  • stomach pain, nausea, vomiting, bloating;
  • headache, migraine, depression, mood changes;
  • back pain, breast tenderness or pain;
  • weight gain, acne, oily skin, changes in hair growth, loss of interest in sex; or
  • puffiness in your face, hands, ankles, or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Kyleena (levonorgestrel)

QUESTION

Which of the following are methods for contraception? See Answer
Kyleena Professional Information

SIDE EFFECTS

The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:

  • Ectopic Pregnancy [see WARNINGS AND PRECAUTIONS]
  • Intrauterine Pregnancy [see WARNINGS AND PRECAUTIONS]
  • Group A Streptococcal Sepsis (GAS) [see WARNINGS AND PRECAUTIONS]
  • Pelvic Inflammatory Disease [see WARNINGS AND PRECAUTIONS]
  • Perforation [see WARNINGS AND PRECAUTIONS]
  • Expulsion [see WARNINGS AND PRECAUTIONS]
  • Ovarian Cysts [see WARNINGS AND PRECAUTIONS]
  • Bleeding Pattern Alterations [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The data described below reflect exposure of 1,697 healthy 18 to 41-year-old women (mean age 27.8 ± 5.2 years) to Kyleena. These data come from two multi-center contraceptive trials: A phase 2 study with a 3-year duration was conducted in Europe, enrolling generally healthy, 21 to 41-year old women; 217 subjects were exposed to Kyleena for one year and 174 completed three years. The data in this trial cover approximately 8,000 cycles of exposure. A phase 3 study with a 3-year duration and an optional extension of Kyleena use up to 5 years was conducted in the United States (US), Canada, Europe, and Latin America. The population was generally healthy, 18 to 35-year old women. A total of 1,208 subjects were exposed to Kyleena for at least one year; 707 women entered the optional extension phase after 3 years and 550 completed five years. The data in this trial cover approximately 60,000 cycles.

In total for both studies, 1,425 subjects were exposed for at least 1 year, and 550 subjects completed 5 years of use. Of the total of 1,697 subjects exposed to Kyleena, 563 were from the US and 1,134 were from Europe, Canada and Latin America; 623 (37%) were nulliparous (mean age 24.6 ± 4.5 years) and 1,074 (63%) were parous (mean age 29.7 ± 4.7 years). Most women who received Kyleena were Caucasian (83%) or Black/African American (4.4%); 9.4% of women were of Hispanic ethnicity. The clinical trials had no upper or lower weight or body mass index (BMI) limit. Mean BMI of Kyleena subjects was 25.2 kg/m2 (range 15.2 – 57.6 kg/m2); 16% had a BMI ≥ 30 kg/m2, and 2.0% had a BMI ≥ 40 kg/m2. The frequencies of reported adverse drug reactions represent crude incidences.

The most common adverse reactions (occurring in ≥ 5% users) were vulvovaginitis (24%), ovarian cyst (22%), abdominal pain/pelvic pain (21%), headache/migraine (15%), acne/seborrhea (15%), dysmenorrhea/uterine spasm (10%), breast pain/breast discomfort (10%), and increased bleeding (8%).

In the combined studies, 22% discontinued prematurely due to an adverse reaction. The most common adverse reactions (>1%) leading to discontinuation were increased bleeding (4.5%), abdominal pain/pelvic pain (4.2%), device expulsion (3.1%), acne/seborrhea (2.3%), and dysmenorrhea/uterine spasm (1.3%).

Common adverse reactions (occurring in ≥1% users) are summarized in Table 4 (presented as crude incidences).

Table 4: Adverse reactions that occurred in at least 1% of Kyleena users in clinical trials by System Organ Class (SOC)

System Organ Class Adverse Reaction Incidence (%)
(N=1,697)
Reproductive System and Breast Disorders Vulvovaginitis 24.3
Ovarian cysta 22.2
Dysmenorrhea/uterine spasm 8.0/2.4
Increased bleedingb 7.9
Breast pain/discomfort 7.1/3.5
Genital discharge 4.5
Device expulsion (complete and partial) 3.5
Upper genital tract infection 1.5
Gastrointestinal Disorders Abdominal pain/pelvic pain 13.3/8.2
Nausea 4.7
Skin and Subcutaneous Tissue Disorders Acne/Seborrhea 14.1/1.8
Alopecia 1.0
Nervous System Disorders Headache/Migraine 12.9/3.3
Psychiatric Disorders Depression/Depressed mood 4.4/0.2
a Ovarian cysts were reported as adverse events if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination
b Not all bleeding alterations were captured as adverse reactions [see WARNINGS AND PRECAUTIONS].

In the clinical trials, serious adverse reactions occurring in more than a single subject included: ectopic pregnancy/ruptured ectopic pregnancy (10 subjects); pelvic inflammatory disease (6 subjects); missed abortion/incomplete spontaneous abortion/spontaneous abortion (4 subjects); ovarian cyst (3 subjects); abdominal pain (4 subjects); depression/affective disorder (4 subjects); and uterine perforation/embedded device (myometrial perforation) (3 subjects).

Postmarketing Experience/

Adverse Reactions From Postmarketing Spontaneous Reports

The following adverse reactions have been identified during post-approval use of LNG-releasing IUSs. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

  • Arterial thrombotic and venous thromboembolic events, including cases of pulmonary embolism, deep vein thrombosis and stroke
  • Device breakage
  • Hypersensitivity (including rash, urticaria, and angioedema)
  • Increased blood pressure
Reported Adverse Reactions From Postmarketing Studies

Assessment of Perforation and Expulsion of Intrauterine Devices (APEX IUD) Study

APEX IUD was a large US retrospective cohort study to assess the impact of breastfeeding and timing of postpartum IUD insertion on uterine perforation and IUD expulsion. The analyses included a total of 326,658 insertions, 30% (97,824 insertions) of which were performed in women with a delivery in the previous 12 months. For insertions performed in women who had delivered ≤ 52 weeks before IUD insertion, the majority of postpartum insertions, 57.3% (56,047 insertions) occurred between 6 and 14 weeks postpartum. Breastfeeding data were available in 94,817 insertions performed in women 52 weeks or less after delivery.

The study results indicated that the risk of uterine perforation was highest in women with IUD insertion ≤ 6 weeks postpartum. Immediate postpartum insertion (0–3 days) findings are limited due to the relatively small number of insertions occurring within this time interval. Women who were breastfeeding at the time of insertion were at 33% higher risk of perforation (adjusted hazard ratio [HR]=1.33, 95% confidence interval [CI]: 1.07–1.64) compared to women who were not breastfeeding at the time of insertion. Progressively lower risk of uterine perforation was observed in postpartum time windows beyond 6 weeks, in both breastfeeding and not breastfeeding women. Table 5 presents the uterine perforation rates for LNG IUS stratified by breastfeeding status and postpartum interval.

Table 5: Uterine Perforation1 rates for LNG IUS, by Breastfeeding Status and Postpartum Interval

Breastfeeding at time of insertion Not breastfeeding at time of insertion
Postpartum interval at time of insertion Number of events/ insertions Uterine perforation rate per 1,000 insertions Number of events/ insertions Uterine perforation rate per 1,000 insertions
0 to 3 days 8/1,896 4.22 0/277 0.00
4 days to ≤ 6 weeks 120/10,735 11.18 28/2,377 11.78
> 6 to ≤ 14 weeks 268/29,677 9.03 30/12,011 6.66
> 14 to ≤ 52 weeks 43/6,139 7.00 22/9,089 2.42
> 52 weeks or no delivery no data available 243/184,733 1.32
1 Uterine perforation includes both complete and partial perforation

Risk of expulsion was variable over the postpartum intervals through 52 weeks. Women who were breastfeeding were at 28% lower risk of IUD expulsion (adjusted HR=0.72, 95% CI: 0.64-0.80) compared to women who were not breastfeeding at time of insertion. Table 6 presents the IUD expulsion rates for LNG IUS stratified by breastfeeding status and postpartum interval.

Table 6: Expulsion1 Rates for LNG IUS, by Breastfeeding Status and Postpartum Interval

Breastfeeding at time of insertion Not breastfeeding at time of insertion
Postpartum interval at time of insertion Number of events/ insertions Expulsion rate per 1,000 insertions Number of events/ insertions Expulsion rate per 1,000 insertions
0 to 3 days 187/1,896 98.63 12/277 43.32
4 days to ≤ 6 weeks 185/10,735 17.23 52/2,377 21.88
> 6 to ≤ 14 weeks 421/29,677 14.19 306/12,011 25.48
> 14 to ≤ 52 weeks 120/6,139 19.55 273/9,089 30.04
> 52 weeks or no delivery no data available 5,481/184,733 29.67
1 Expulsion includes both complete and partial expulsion

DRUG INTERACTIONS

No drug-drug interaction studies have been conducted with Kyleena.

Drugs or herbal products that induce or inhibit LNG metabolizing enzymes, including CYP3A4, may decrease or increase, respectively, the serum concentrations of LNG during the use of Kyleena. However, the contraceptive effect of Kyleena is mediated via the direct release of LNG into the uterine cavity and is unlikely to be affected by drug interactions via enzyme induction or inhibition.

Read the entire FDA prescribing information for Kyleena (levonorgestrel)

© Kyleena Patient Information is supplied by Cerner Multum, Inc. and Kyleena Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

Health Solutions From Our Sponsors