Included as part of the "PRECAUTIONS" Section
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 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 periods 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.
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:
In patients becoming pregnant with an IUD 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. Follow her pregnancy closely and advise her to report immediately any symptom that suggests complications of the pregnancy.
Long-Term Effects And Congenital Anomalies
When pregnancy continues with Skyla in place, long-term effects on the offspring are unknown. With a LNG-releasing IUS, congenital anomalies in live births have occurred infrequently. No clear trend towards specific anomalies has been observed. Because of the local exposure of the fetus to LNG, the possibility of teratogenicity following exposure to Skyla cannot be completely excluded. Some observational data support a small increased risk of masculinization of the external genitalia of the female fetus following exposure to progestins at doses greater than those currently used for oral contraception. Whether these data apply to Skyla is unknown.
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.
Pelvic Inflammatory Disease (PID)
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]. IUDs have been associated with an increased risk of PID, most likely due to organisms being introduced into the uterus during insertion.1 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, and Skyla does not protect against sexually transmitted infection. 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], IV drug abuse).
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. Guidelines for PID treatment are available from the Centers for Disease Control (CDC), Atlanta, Georgia.
Actinomycosis has been associated with IUDs. Symptomatic women should have Skyla removed and should receive 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.
Bleeding Pattern Alterations
Skyla can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first 3–6 months of Skyla use, the number of bleeding and spotting days may be higher and bleeding patterns may be irregular. Thereafter, the number of bleeding and spotting days usually decreases but bleeding may remain irregular. Amenorrhea develops by the end of the first year of use in approximately 6% of Skyla users. In Skyla clinical trials, a total of 77 subjects out of 1,672 (4.6%) discontinued due to uterine bleeding complaints. Table 1 shows the bleeding patterns as documented in the Skyla clinical trials based on 90-day reference periods. Table 2 shows the number of bleeding and spotting days based on 28-day cycle equivalents.
Table 1: Bleeding Patterns Reported with Skyla in Contraception Studies (by 90-day reference periods)
||First 90 days
|Second 90 days
|End of year 1
|End of year 3
|1Defined as subjects with no bleeding/spotting throughout the 90-day reference period
2Defined as subjects with 1 or 2 bleeding/spotting episodes in the 90-day reference period
3Defined as subjects with more than 5 bleeding/spotting episodes in the 90-day reference period
4Defined as subjects with bleeding/spotting episodes lasting more than 14 days in the 90-day reference period. Subjects with prolonged bleeding may also be included in one of the other categories (excluding amenorrhea)
5Defined as subjects with 3 to 5 bleeding/spotting episodes and less than 3 bleeding/spotting-free intervals of 14 or more days
6Subjects with irregular and prolonged bleeding may also be included in one of the other categories (excluding amenorrhea)
Table 2: Mean number of Bleeding and Spotting Days per 28-day Cycle Equivalent
|28-day Cycle Equivalent
|Days on treatment
|Number of bleeding days
|Number of spotting days
Because irregular bleeding/spotting is common during the first months of Skyla use, exclude endometrial pathology (polyps or cancer) prior to the insertion of Skyla in women with persistent or uncharacteristic bleeding. If a significant change in bleeding develops during prolonged use, take appropriate diagnostic measures to rule out endometrial pathology. The possibility of pregnancy should be considered if menstruation does not occur within six weeks of the onset of a previous menstruation. Once pregnancy has been excluded, repeated pregnancy tests are generally not necessary in amenorrheic women unless indicated, for example, by other signs of pregnancy or by pelvic pain.
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. Perforation may reduce contraceptive efficacy and result in pregnancy. The incidence of perforation during clinical trials was < 0.1%.
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.
The risk of perforation may be increased if Skyla is inserted when the uterus is fixed retroverted or not completely involuted. Delay Skyla insertion a minimum of six weeks or until involution is complete following a delivery or a second trimester abortion.
Clinical trials with Skyla excluded breast-feeding women. A large postmarketing safety study conducted in Europe over a 1-year observational period reported that lactation at the time of insertion of an IUD/IUS was associated with an increased risk of perforation. For users of another LNG-releasing IUS, the incidence of uterine perforation was reported as 6.3 per 1,000 insertions for lactating women, compared to 1.0 per 1,000 insertions for non-lactating women.
Partial or complete expulsion of Skyla may occur resulting in the loss of contraceptive protection. 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. The risk of expulsion may be increased when the uterus is not completely involuted. In clinical trials, a 3-year expulsion rate of 3.2% (54 out of 1665 subjects) was reported.
Delay Skyla insertion a minimum of six weeks or until uterine involution is complete following a delivery or a second trimester abortion. Remove a partially expelled Skyla. If expulsion has occurred, Skyla may be replaced within 7 days after the onset of a menstrual period, after pregnancy has been ruled out.
Because the contraceptive effect of Skyla is mainly due to its local effects within the uterus, ovulatory cycles with follicular rupture usually occur in women of fertile age using Skyla. During clinical trials, ovarian cysts (reported as adverse reactions if they were abnormal, non-functional cysts and/or had a diameter >3 cm on ultrasound examination) were reported in 13.2% of women using Skyla. Most of these cysts are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases the ovarian cysts disappear spontaneously during two to three months observation. Evaluate persistent ovarian cysts. Surgical intervention is not usually required.
Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception because some breast cancers are hormone-sensitive [see CONTRAINDICATIONS].
Spontaneous reports of breast cancer have been received during postmarketing experience with a LNG-releasing IUS. Observational studies of the risk of breast cancer with use of a LNG-releasing IUS do not provide conclusive evidence of increased risk.
Clinical Considerations For Use And Removal
- Use Skyla with caution after careful assessment if any of the following conditions exist, and consider removal of the system if any of them arise during use:
- Coagulopathy or use of anticoagulants
- Migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia
- Exceptionally severe headache
- Marked increase of blood pressure
- Severe arterial disease such as stroke or myocardial infarction
In addition, consider removing Skyla if any of the following conditions arise during use [see CONTRAINDICATIONS]:
- Uterine or cervical malignancy
- If the threads are not visible or are significantly shortened they may have broken or retracted into the cervical canal or uterus. Consider the possibility that the system may have been displaced, (for example, expelled or perforated the uterus) [see Perforation, Expulsion ]. Exclude pregnancy and verify the location of Skyla, for example, by sonography, X-ray, or by gentle exploration of the cervical canal with a suitable instrument. If Skyla is displaced, remove it. A new Skyla may be inserted at that time or during the next menses if it is certain that conception has not occurred. If Skyla is in place with no evidence of perforation, no intervention is indicated.
Magnetic Resonance Imaging (MRI) Information
Non-clinical testing has demonstrated that Skyla is MR Conditional. Skyla can be safely scanned only under specific conditions:
- Static magnetic field of 3 Tesla or less
- Spatial gradient field of 36,000 Gauss/cm (T/m) or less
- Maximum whole body averaged specific absorption rate (SAR) of 4W/kg in the First Level Controlled mode for 15 minutes of continuous scanning
In non-clinical testing, the Skyla produced a temperature rise of less than 1.8°C at a maximum whole body averaged specific absorption rate (SAR) of 2.9 W/kg, for 15 minutes of MR scanning at 3T using a transit/receive body coil.
MR Image quality may be compromised (that is, a small amount of artifact may occur) if the area of interest is in the exact same area or relatively close to the position of Skyla. Image artifact extended up to 5 mm from Skyla in a Gradient Echo pulse sequence.
Patient Counseling Information
Advise the patient to read the FDA-approved patient labeling (PATIENT INFORMATION)
- Sexually Transmitted Infections: Counsel the patient that this product does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).
- Risk of Ectopic Pregnancy: Inform the patient about the risks of ectopic pregnancy, including the loss of fertility. Teach her to recognize and report to her healthcare provider promptly any symptoms of ectopic pregnancy. [See WARNINGS AND PRECAUTIONS]
- Pregnancy or Suspected Pregnancy: Counsel the patient to inform her healthcare provider if she determines or suspects she is pregnant with Skyla in place.
- Pelvic Infection: Inform the patient about the possibility of pelvic inflammatory disease (PID) and that PID can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death. Teach the patient to recognize and report to her healthcare provider promptly any symptoms of PID. These symptoms include development of menstrual disorders (prolonged or heavy bleeding), unusual vaginal discharge, abdominal or pelvic pain or tenderness, dyspareunia, chills, and fever. [See WARNINGS AND PRECAUTIONS]
- Bleeding Pattern Alterations: Counsel the patient that irregular or prolonged bleeding and spotting, and/or cramps may occur during the first few weeks after insertion. If her symptoms continue or are severe she should report them to her healthcare provider. [See WARNINGS AND PRECAUTIONS]
- Perforation and Expulsion: Counsel the patient that the IUS may be expelled from or perforate the uterus and instruct her on how she can check that the threads still protrude from the cervix. Caution her not to pull on the threads and displace Skyla. Inform her that there is no contraceptive protection if Skyla is displaced or expelled. [See WARNINGS AND PRECAUTIONS]
- Clinical Considerations for Use and Removal: Instruct the patient to contact her healthcare provider if she experiences any of the following:
- A stroke or heart attack
- Very severe or migraine headaches
- Unexplained fever
- Yellowing of the skin or whites of the eyes, as these may be signs of serious liver problems
- Pregnancy or suspected pregnancy
- Pelvic pain or pain during sex
- HIV positive seroconversion in herself or her partner
- Possible exposure to sexually transmitted infections (STIs)
- Unusual vaginal discharge or genital sores
- Severe vaginal bleeding or bleeding that lasts a long time, or if she misses a menstrual period
- Inability to feel Skyla's threads
- Magnetic Resonance Imaging (MRI) Information: Inform the patient that Skyla can be safely scanned with MRI only under specific conditions [see WARNINGS AND PRECAUTIONS]. Instruct patients who will have an MRI to tell their doctor that they have Skyla. This information is included on the Follow-Up Reminder Card.
Complete the Follow-up Reminder Card and give to the patient.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
[See WARNINGS AND PRECAUTIONS.]
Use In Specific Populations
The use of Skyla during an existing or suspected pregnancy is contraindicated. Many studies have found no harmful effects on fetal development associated with long-term use of contraceptive doses of oral progestins. The few studies of infant growth and development that have been conducted with progestin-only pills have not demonstrated significant adverse effects. [See CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS.]
In general, no adverse effects of progestin-only contraceptives have been found on breastfeeding performance or on the health, growth, or development of the infant. Isolated postmarketing cases of decreased milk production have been reported. Small amounts of progestins were observed to pass into the breast milk of nursing mothers who used a LNG-releasing IUS, resulting in detectable steroid levels in infant serum. [See WARNINGS AND PRECAUTIONS.]
Safety and efficacy of Skyla have been established in women of reproductive age. Efficacy is expected to be the same for postpubertal females under the age of 18 as for users 18 years and older. Use of this product before menarche is not indicated.
Skyla has not been studied in women over age 65 and is not approved for use in this population.
No studies were conducted to evaluate the effect of hepatic disease on the disposition of LNG released from Skyla [see CONTRAINDICATIONS].
No studies were conducted to evaluate the effect of renal disease on the disposition of LNG released from Skyla.