Skyla ® is indicated to prevent pregnancy for up to 3 years. Replace the system after 3 years if continued use is desired. Skyla is a progestin-containing intrauterine system (IUS) indicated for prevention of pregnancy for up to 3 years. ( 1 )
Contraindications
The use of Skyla is contraindicated when one or more of the following conditions exist:
Pregnancy or suspicion of pregnancy [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.1 )]
For use as post-coital contraception (emergency contraception)
Congenital or acquired uterine anomaly including fibroids, that distorts the uterine cavity
Acute pelvic inflammatory disease (PID) or a history of PID unless there has been a subsequent intrauterine pregnancy [see Warnings and Precautions ( 5.4 )]
Postpartum endometritis or infected abortion in the past 3 months
Known or suspected uterine or cervical malignancy
Known or suspected breast cancer or other progestin-sensitive cancer, now or in the past
Uterine bleeding of unknown etiology
Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infections until infection is controlled
Acute liver disease or liver tumor (benign or malignant)
Conditions associated with increased susceptibility to pelvic infections [see Warnings and Precautions ( 5.4 )]
A previously inserted intrauterine device (IUD) that has not been removed
Hypersensitivity to any component of this product [see Adverse Reactions ( 6.2 ) and Description ( 11.1 )]
Pregnancy or suspicion of pregnancy. Cannot be used for post-coital contraception (emergency contraception) ( 4 )
Congenital or acquired uterine anomaly if it distorts the uterine cavity ( 4 )
Acute pelvic inflammatory disease (PID) or a history of PID unless there has been a subsequent intrauterine pregnancy ( 4 )
Postpartum endometritis or infected abortion in the past 3 months ( 4 )
Known or suspected uterine or cervical malignancy ( 4 )
Known or suspected breast cancer or other progestin-sensitive cancer ( 4 )
Untreated acute cervicitis or vaginitis or other lower genital tract infections ( 4 )
Acute liver disease or liver tumor (benign or malignant) ( 4 )
Increased susceptibility to pelvic infection ( 4 )
A previous intrauterine device (IUD) that has not been removed ( 4 )
Hypersensitivity to any component of Skyla ( 4 )
Warnings and precautions
Remove Skyla if pregnancy occurs with Skyla in place. If a pregnancy occurs, there is increased risk of ectopic pregnancy including loss of fertility, pregnancy loss, septic abortion (including septicemia, shock and death), and premature labor and delivery. ( 5.1 , 5.2 )
Group A streptococcal infection has been reported following insertion of LNG IUS; strict aseptic technique is essential during insertion. ( 5.3 )
Before using Skyla, consider the risks of PID. ( 5.4 )
Uterine perforation may occur and may reduce contraceptive effectiveness or require surgery. Risk is increased if inserted in lactating women and may be increased if inserted in women with fixed retroverted uteri and postpartum. ( 5.5 )
Partial or complete expulsion may occur, which can be unnoticed, leading to loss of contraceptive efficacy. ( 5.6 )
Bleeding patterns become altered, may remain irregular and amenorrhea may ensue. ( 5.8 )
Skyla can be safely scanned with MRI only under certain conditions ( 5.11 )
5.1Risk of Ectopic Pregnancy
Evaluate women for ectopic pregnancy if they become pregnant with Skyla in place because the likelihood of a pregnancy being ectopic is increased with Skyla. Approximately one-half of pregnancies that occur with Skyla in place are likely to be ectopic. Also consider the possibility of ectopic pregnancy in the case of lower abdominal pain, especially in association with missed menses or if an amenorrheic woman starts bleeding.
The incidence of ectopic pregnancy in clinical trials with Skyla, which excluded women with a history of ectopic pregnancy, was approximately 0.1% per year. The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use Skyla is unknown. Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy. Ectopic pregnancy may result in loss of fertility.
5.2Risks with Intrauterine Pregnancy
If pregnancy occurs while using Skyla, remove Skyla because leaving it in place may increase the risk of spontaneous abortion and preterm labor. Removal of Skyla or probing of the uterus may also result in spontaneous abortion. In the event of an intrauterine pregnancy with Skyla, consider the following: Septic abortion In patients becoming pregnant with an IUS in place, septic abortion—with septicemia, septic shock, and death—may occur.
Continuation of pregnancy If a woman becomes pregnant with Skyla in place and if Skyla cannot be removed or the woman chooses not to have it removed, warn her that failure to remove Skyla increases the risk of miscarriage, sepsis, premature labor and premature delivery. Advise her of isolated reports of virilization of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place [see Use in Specific Populations ( 8.1 )].
Follow her pregnancy closely and advise her to report immediately any symptom that suggests complications of the pregnancy.
5.3Sepsis
Severe infection or sepsis, including Group A streptococcal sepsis (GAS), have been reported following insertion of a LNG-releasing IUS. In some cases, severe pain occurred within hours of insertion followed by sepsis within days. Because death from GAS is more likely if treatment is delayed, it is important to be aware of these rare but serious infections. Aseptic technique during insertion of Skyla is essential in order to minimize serious infections such as GAS.
Skyla is contraindicated in the presence of known or suspected PID or in women with a history of PID unless there has been a subsequent intrauterine pregnancy [see Contraindications ( 4 )] . IUDs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion. In clinical trials, PID was observed in 0.4% of women overall and occurred more frequently within the first year and most often within the first month after insertion of Skyla.
Promptly examine users with complaints of lower abdominal or pelvic pain, odorous discharge, unexplained bleeding , fever, genital lesions or sores. Remove Skyla in cases of recurrent endometritis or pelvic inflammatory disease, or if an acute pelvic infection is severe or does not respond to treatment. Women at increased risk for PID PID is often associated with a sexually transmitted infection (STI), and Skyla does not protect against STI.
The risk of PID is greater for women who have multiple sexual partners, and also for women whose sexual partner(s) have multiple sexual partners. Women who have had PID are at increased risk for a recurrence or re-infection. In particular, ascertain whether the woman is at increased risk of infection (for example, leukemia, acquired immune deficiency syndrome [AIDS], intravenous drug abuse). Subclinical PID PID may be asymptomatic but still result in tubal damage and its sequelae.
Treatment of PID Following a diagnosis of PID, or suspected PID, bacteriologic specimens should be obtained, and antibiotic therapy should be initiated promptly. Removal of Skyla after initiation of antibiotic therapy is usually appropriate. Actinomycosis Actinomycosis has been associated with IUDs. Remove Skyla from symptomatic women and treat with antibiotics. The significance of actinomyces-like organisms on Pap smear in an asymptomatic IUD user is unknown, and so this finding alone does not always require Skyla removal and treatment.
When possible, confirm a Pap smear diagnosis with cultures.
5.5Perforation Perforation (total
or partial, including penetration/embedment of Skyla in the uterine wall or cervix) may occur most often during insertion, although the perforation may not be detected until sometime later. The incidence of perforation during clinical trials was < 0.1%. The risk of uterine perforation is increased in women who have recently given birth, and in women who are breastfeeding at the time of insertion. In a large postmarketing safety study conducted in the US, the risk of uterine perforation was highest when insertion occurred within ≤ 6 weeks postpartum, and also higher with breastfeeding at the time of insertion [see Adverse Reactions ( 6.2 )].
The risk of perforation may be increased if Skyla is inserted when the uterus is fixed, retroverted or not completely involuted. If perforation occurs, locate and remove Skyla. Surgery may be required. Delayed detection or removal of Skyla in case of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses and erosion of adjacent viscera.
In addition, perforation may reduce contraceptive efficacy and result in pregnancy.
5.6Expulsion Partial
or complete expulsion of Skyla may occur resulting in the loss of efficacy. Expulsion may be associated with symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed. Skyla typically decreases menstrual bleeding over time; therefore, an increase of menstrual bleeding may be indicative of an expulsion. Consider further diagnostic imaging, such as x-ray, if expulsion is suspected based on ultrasound [see Warnings and Precautions ( 5.10 )].
In clinical trials, a 3-year expulsion rate of 3.2% (54 out of 1,665 subjects) was reported. The risk of expulsion is increased with insertions immediately after delivery and appears to be increased with insertion after second-trimester abortion based on limited data. In a large postmarketing safety study conducted in the US, the risk of expulsion was lower with breastfeeding status [see Adverse Reactions ( 6.2 )]. Remove a partially expelled Skyla.
If expulsion has occurred, a new Skyla can be inserted any time the provider can be reasonably certain the woman is not pregnant.
5.7Ovarian Cysts Because
the contraceptive effect of Skyla is mainly due to its local effect
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
No drug-drug interaction studies have been conducted with Skyla. 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 Skyla. However, the contraceptive effect of Skyla 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.
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
The use of Skyla is contraindicated in pregnancy or with a suspected pregnancy and Skyla may cause adverse pregnancy outcomes [see Contraindications ( 4 ), Warnings and Precautions ( 5.1 , 5.2 )]. If a woman becomes pregnant with Skyla in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery . Remove Skyla, if possible, if pregnancy occurs in a woman using Skyla.
If Skyla cannot be removed, follow the pregnancy closely [see Warnings and Precautions ( 5.1 , 5.2 )]. There have been isolated cases of virilization of the external genitalia of the female fetus following local exposure to LNG during pregnancy with an LNG IUS in place. Animal reproduction studies have not been conducted with Skyla.
Adverse reactions
The following serious or otherwise important adverse reactions are discussed elsewhere in the labeling:
Ectopic Pregnancy [see Warnings and Precautions ( 5.1 )]
Intrauterine Pregnancy [see Warnings and Precautions ( 5.2 )]
Group A Streptococcal Sepsis (GAS) [see Warnings and Precautions ( 5.3 )]
Pelvic Inflammatory Disease [see Warnings and Precautions ( 5.4 )]
Perforation [see Warnings and Precautions ( 5.5 )]
Expulsion [see Warnings and Precautions ( 5.6 )]
Ovarian Cysts [see Warnings and Precautions ( 5.7 )]
Bleeding Pattern Alterations [see Warnings and Precautions ( 5.8 )] The most common adverse reactions reported (>10% users) are bleeding pattern alterations, vulvovaginitis, abdominal/pelvic pain, acne/seborrhea, headache/migraine, ovarian cyst and dysmenorrhea/uterine spasm. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Bayer HealthCare Pharmaceuticals Inc. at 1-888-842-2937 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical 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 to Skyla in 1,672 patients in two contraception studies, including 1,383 exposed for one year and 993 who completed the three year studies.
The population was generally healthy, 18 to 40-year old females requesting contraception and predominately Caucasian (82.6%). The data cover more than 40,000 cycles of exposure. The frequencies of reported adverse drug reactions represent crude incidences. Most common adverse reactions (occurring in ≥ 5% users) were increased bleeding (7.8%), vulvovaginitis (20.2%), abdominal/pelvic pain (18.9%), acne/seborrhea (15.0%), ovarian cyst (13.2%), headache (12.4%), dysmenorrhea (8.6%), breast pain/discomfort (8.6%) and nausea (5.5%).
In the contraception studies, 18% discontinued prematurely due to an adverse reaction. The most common adverse reactions leading to discontinuation (in >1% of users) were uterine bleeding complaints (4.6%), device expulsion (3.2%), acne/seborrhea (2.9%), abdominal pain (2.5%) dysmenorrhea/uterine spasms (2.0%) and pelvic pain (1.8%). Other common adverse reactions (occurring in ≥ 1% users) by System Organ Class (SOC): The frequencies of adverse reactions observed in clinical trials are summarized in Table 4 by SOC (presented as crude incidences).
Table 4: Adverse reactions that occurred in at least 1% of Skyla users in clinical trials by SOC System Organ Class Adverse Reaction Incidence (%) (N=1,672) Reproductive System and Breast Disorders Vulvovaginitis
20.2 Ovarian cyst Ovarian cysts were reported as adverse events if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination
13.2 Dysmenorrhea
8.6 Increased bleeding Not all bleeding alterations were captured as adverse reactions [see Warnings and Precautions (5.8)].
7.8 Breast pain/discomfort 5.3/3.3 Genital discharge
4.2 Device expulsion (complete and partial)
3.2 Upper genital tract infection
1.4Gastrointestinal Disorders
Abdominal pain/pelvic pain 12.7/6.2 Nausea
5.5 Skin and Subcutaneous Tissue Disorders Acne/Seborrhea 13.6/1.4 Alopecia
1.2 Nervous System Disorders Headache
12.4 Migraine
2.3Psychiatric Disorders
Depression/Depressed mood 3.8/0.5
6.2Postmarketing 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 80/12,011 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
Composition
Active ingredients
LEVONORGESTREL 13.5MG
Official product information
Drugs@FDA lists the approved labels, letters and reviews for application NDA203159.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
At a glance
Brand name
Skyla
Active substance
levonorgestrel
Pharmacologic class
Progestin, Progestin-containing Intrauterine System
