Approved Drug Label (PDF)
5
Warnings and Precautions
… The incidence of
perforation during clinical trials was < 0.1%.
Additions and/or
revisions underlined:
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 less
than or equal to 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.
5.6 Expulsion
Additions and/or
revisions underlined:
Partial or complete
expulsion of Skyla may occur resulting in the loss of efficacy … 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)].
6
Adverse Reactions
6.2 Postmarketing Experience
6.2
Postmarketing Experience
Additions and/or
revisions underlined:
Adverse Reactions from Postmarketing
Spontaneous Reports
The following adverse
reactions have been identified during post approval use of LNG-releasing IUSs …
Newly added information:
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 less than or equal to 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 greater
than or equal to 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 (Newly added table;
please refer to labeling for complete information).
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
(Newly added table;
please refer to labeling for complete information).
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT INFORMATION
Additions and/or revisions underlined:
How is SKYLA placed?
SKYLA is placed by your
healthcare provider during an in-office visit or immediately after giving
birth.
What are the possible side effects of SKYLA?
SKYLA can cause serious side effects
including:
- Perforation.
The risk of perforation is increased if SKYLA
is inserted while you are breastfeeding, or if you have recently given
birth.
- Expulsion. If you think that SKYLA has come out, avoid intercourse or use a
non-hormonal back-up birth control (such as condoms or spermicide) and
call your healthcare provider. The risk of expulsion is increased with
insertion right after delivery or second-trimester abortion.
Approved Drug Label (PDF)
5
Warnings and Precautions
5.2 Risks with Intrauterine Pregnancy
Additions
underlined
…
![]()
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.
5.6 Expulsion
Additions
underlined
…
Consider
further diagnostic imaging, such as x-ray, if expulsion is suspected based on
ultrasound [see Warnings and Precautions
(5.10)]. 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 1,665 subjects) was
reported.
…
8
Use in Specific Populations
8.1 Pregnancy
Additions underlined
…
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.
8.3 Females and Males of Reproductive Potential
New subsection added
Return to Fertility After Discontinuing Skyla
About 77% of women who desired pregnancy after study discontinuation and
provided follow-up information, conceived within 12 months after removal of
Skyla.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions
underlined
…
Risks of
Intrauterine Pregnancy: Advise the patient to contact her healthcare provider
if she thinks she might be pregnant. Inform the patient about the risks of
intrauterine pregnancy while using Skyla, including the risks of leaving Skyla
in place and the risks of removing Skyla or probing of the uterus. If Skyla
cannot be removed in a pregnant patient, advise her to report immediately any
symptom that suggests complications of the pregnancy. 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 Warnings and Precautions (5.2) and Use in
Special Populations (8.1).]
…
Perforation and Expulsion: Advise 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. Inform
her that excessive pain or vaginal bleeding during Skyla placement, worsening
pain or bleeding after placement, or the inability to feel Skyla strings may
occur with Skyla perforation and expulsion. 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. Instruct the patient to
contact her healthcare provider if she cannot feel the threads and to avoid
intercourse or use a non-hormonal back-up birth control (such as condoms or
spermicide) until the location of Skyla has been confirmed. Advise her that if
perforation occurs, Skyla will have to be located and removed; surgery may be
required. [See Warnings and Precautions (5.5,
5.6, 5.10).]
…
PATIENT INFORMATION
Additions underlined
…
How
well does Skyla work for contraception?
…
Skyla, an intrauterine device (IUD), also known
as an intrauterine system (IUS), is in the box at the top of the chart.
…
Before having
Skyla placed, tell your healthcare provider about all of your medical
conditions including if you:
…
have AIDS, HIV, or any other
sexually transmitted infection
Tell your healthcare provider about all of the
medicines you take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
…
Can I use tampons
or menstrual cups with Skyla?
Yes,
tampons or menstrual cups may be used with Skyla. Change tampons or
menstrual cups with care to avoid pulling the threads of Skyla. If you think
you may have pulled Skyla out of place, avoid intercourse or use a non-hormonal
back-up birth control (such as condoms or spermicide), and contact your healthcare
provider.
What if I become
pregnant while using Skyla?
…
There
are also risks if you get pregnant while using Skyla and the pregnancy is in
the uterus. Severe infection, miscarriage, premature delivery, and even death
can occur with pregnancies that continue with an intrauterine device (IUD).
Because of this, your healthcare provider may try to remove Skyla, even though
removing it may cause a miscarriage. If Skyla cannot be removed, talk with your
healthcare provider about the benefits and risks of continuing the pregnancy and
possible effects of the hormone on your unborn baby.
…
What are the
possible side effects of Skyla?
Skyla can cause
serious side effects, including:
…
Perforation. Skyla may go into
the wall of the uterus (become embedded) or go through the wall of the uterus.
This is called perforation. If this occurs, Skyla may no longer prevent
pregnancy. If perforation occurs, Skyla may move outside the uterus and can
cause internal scarring, infection, or damage to other organs, and you may need
surgery to have Skyla removed. Excessive pain or vaginal bleeding during
placement of Skyla, pain or bleeding that gets worse after placement, or not
being able to feel the threads may happen with perforation. The risk of
perforation is increased if Skyla is inserted while you are breastfeeding.
Expulsion. Skyla may come out by itself. This is called expulsion. Expulsion occurs
in about 3 out of 100 women. Excessive pain or vaginal bleeding during
placement of Skyla, pain or bleeding that gets worse after placement, or not
being able to feel the threads may happen with expulsion. You may become
pregnant if Skyla comes out. If you think that Skyla has come out, avoid
intercourse or use a non-hormonal backup birth control (such as
condoms or spermicide) and call your healthcare provider.
…
Other
common side effects include:
abdominal or pelvic pain
acne or greasy skin
headache or migraine
inflammation or infection of the outer part of your
vagina (vulvovaginitis)
painful periods
…
What are the
ingredients in Skyla?
Active ingredient:
levonorgestrel
Inactive
ingredients: silicone,
polyethylene, silver, silica, barium sulfate, iron oxide
…
Approved Drug Label (PDF)
4
Contraindications
Additions and/or
revisions underlined:
The
use of Skyla is contraindicated when one or more of the following conditions
exist:
5
Warnings and Precautions
Additions and/or
revisions underlined:
5.1 Risk of Ectopic Pregnancy
Menses
replaces periods in this subsection.
5.2 Risks with
Intrauterine Pregnancy
IUS
replaces IUD in this subsection.
5.4 Pelvic
Infection
Additions and/or
revisions are underlined:
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. 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 …
5.6 Expulsion
…
If expulsion has occurred, a new Skyla can be inserted any time the provider
can be reasonably certain the woman is not pregnant.
5.7 Ovarian Cysts
…
Ovarian cysts (reported as adverse reactions if they were abnormal,
non-functional cysts and/or had a diameter greater than 3 cm on ultrasound
examination) were reported at least once over the course of clinical trials in
13.2% of women using Skyla, and 0.3% of subjects discontinued because of an
ovarian cyst. Most ovarian cysts are asymptomatic …
5.8 Bleeding
Pattern Alterations
Thereafter,
the number of bleeding and spotting days usually decreases but bleeding may
remain irregular.
In
Skyla clinical trials, amenorrhea developed by the end of the first year of use
in approximately 6% of Skyla users. A total of 77 subjects out of 1,672
(4.6%) discontinued due to uterine bleeding complaints. Table 2 shows the
bleeding patterns as documented in the Skyla clinical trials based on 90-day
reference periods. Table 3 shows the number of bleeding and spotting days based
on 28-day cycle equivalents.
Table
2: Bleeding Patterns Reported with Skyla in Contraception Studies (by 90-day
reference periods) Table inserted here; please refer to label for complete information.
Table 3: Mean number of Bleeding and Spotting Days
per 28-day Cycle Equivalent Table
inserted here; please refer to label for complete information.
… If a significant change in bleeding develops
during prolonged use, take appropriate diagnostic measures to rule out
endometrial pathology. Consider
the possibility of pregnancy if menstruation does not occur within six weeks of
the onset of a previous menstruation. Once pregnancy has been excluded,
repeated pregnancy tests …
5.11
Magnetic Resonance Imaging (MRI) Safety Information
Non-clinical
testing has demonstrated that Skyla is MR Conditional. A patient with
Skyla can be safely scanned in an MR system meeting the following
conditions:
Static magnetic
field of 3.0 T or less
Maximum spatial
field
gradient of 36,000 gauss/cm (360 T/m)
Maximum MR
system reported, whole body averaged specific absorption rate (SAR) of
4W/kg (First Level Controlled Operating Mode)
Under
the scan conditions defined above, the Skyla IUS is expected to produce a
maximum temperature rise of less than 2°C after 15 minutes of
continuous scanning.
In
non-clinical testing, the image artifact caused by the IUS
extended up to 5 mm from the IUS when imaged with a gradient echo pulse
sequence and a 3.0 T MRI system.
6
Adverse Reactions
6.2 Postmarketing Experience
Additions and/or
revisions underlined:
…
it is not always possible to reliably estimate their frequency or establish a
causal relationship to drug exposure.
7
Drug Interactions
Additions and/or
revisions underlined:
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.
8
Use in Specific Populations
8.1 Pregnancy
Additions and/or
revisions underlined:
Risk Summary
The
use of Skyla is contraindicated in pregnancy or with a suspected
pregnancy because there is no need for pregnancy prevention in a
woman who is already pregnant and Skyla may cause adverse pregnancy outcomes. 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.
Studies
report no adverse
effects on fetal and infant development associated with long-term use of
contraceptive doses of oral progestins in a pregnant woman. However, there
have been reported cases of masculinization of the external genitalia of the
female fetus following exposure to progestins at doses greater than those
currently used for oral contraception. Animal reproduction studies have not
been conducted with Skyla.
8.2 Lactation
Additions and/or
revisions underlined:
Risk Summary
Published
studies report the presence of LNG in human milk. Small amounts of progestins
(approximately 0.1% of the total maternal doses) were detected in the breast
milk of nursing mothers who used other LNG-releasing IUSs, resulting in
exposure of LNG to the breastfed infants. There are no reports of adverse effects in
breastfed infants with maternal use of progestin-only contraceptives. Isolated
cases of decreased milk production have been reported with a LNG-releasing IUS.
The developmental and health benefits of breastfeeding should be considered
along with the mother’s clinical need for Skyla and any potential adverse
effects on the breastfed child from Skyla or from the underlying maternal
condition.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION
Additions and/or revisions
underlined:
Risks of
Intrauterine Pregnancy: Instruct the patient to contact her
healthcare provider if she thinks she might be pregnant. Inform the patient
about the risks of intrauterine pregnancy while using Skyla, including the
risks of leaving Skyla in place and the risks of removing Skyla or probing of the
uterus. If Skyla cannot be removed in a pregnant patient, advise her to report
immediately any symptom that suggests complications of the pregnancy.
Sepsis: Counsel the
patient that severe infection or sepsis, including Group A streptococcal sepsis
(GAS), can occur within the first few days after Skyla is inserted. Instruct
her to contact a healthcare provider immediately if she develops severe pain or
fever shortly after Skyla is inserted.
Pelvic Infection: Inform the patient
about the possibility of pelvic infections including PID and that these
infections can cause tubal damage leading to ectopic pregnancy or
infertility, or infrequently can necessitate hysterectomy, or cause death. Teach
patients to recognize and report to their healthcare provider
promptly any symptoms of pelvic infection.
Perforation and
Expulsion: … caution
her not to pull on the threads and displace Skyla. Inform her that there is
no contraceptive protection if Skyla is displaced (for example, expelled or
perforated the uterus). If perforation occurs, Skyla will have to be located
and removed; surgery may be required. Instruct the patient to contact her
healthcare provider if she cannot feel the threads.
Ovarian Cysts: Counsel the
patient regarding the risk of ovarian cysts and that cysts can cause clinical
symptoms including pelvic pain, abdominal pain or dyspareunia. Advise the
patient to contact her healthcare provider if she experiences these symptoms.
Bleeding Pattern
Alterations: … cramps may occur
during the first few weeks after insertion. Inform the patient that, 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. If her symptoms continue …
Clinical
Consideration for Use and Removal:
Magnetic Resonance Imaging (MRI) Safety Information
PATIENT INFORMATION
Additions and/or
revisions underlined:
What
if I want to stop using Skyla?
Skyla
is intended for use up to 3 years but you can stop using Skyla at any
time by asking your healthcare provider to remove it. You could become pregnant
as soon as Skyla is removed, so you should use another method of birth control
if you do not want to become pregnant. Talk to your healthcare provider
about the best birth control methods for you, because your new method may need
to be started 7 days before Skyla is removed to prevent pregnancy.
What
if I become pregnant while using Skyla?
Call
your healthcare provider right away if you think you may be pregnant. If
possible, also do a urine pregnancy test. If you get pregnant …
This
is not a complete list of possible side effects with Skyla. For more
information, ask your healthcare provider. Tell your healthcare provider if
you have any side effect that bothers you or does not go away.
Call
your healthcare provider for medical advice about side effects.
After Skyla has been placed, when should I call my healthcare provider?
If
Skyla is accidentally removed and you had vaginal intercourse within the
preceding week, you may be at risk of pregnancy, and you should talk to a
healthcare provider.
Call
your healthcare provider if you have any concerns about Skyla. Be sure to call
if you:
Have pelvic pain,
abdominal pain, or pain during sex
Are concerned that
Skyla may have been expelled (came out)
Become HIV
positive
or your partner becomes HIV positive
Have severe
vaginal bleeding or bleeding that concerns you
General
advice about the safe and effective use of Skyla
Approved Drug Label (PDF)
5
Warnings and Precautions
5.6 Perforation
(Additions and/or revisions are underlined)
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.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
17 PATIENT COUNSELING INFORMATION
(Additions and/or revisions are underlined)
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…
- 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)…
- Bleeding
Pattern Alterations: Counsel the patient that irregular or
prolonged bleeding…
- 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…
- Clinical
Considerations for Use and Removal: Instruct the patient to
contact her healthcare provider if she experiences any of the following…
- Magnetic
Resonance Imaging (MRI) Information: Inform the patient that Skyla
can be safely scanned…
Patient Information
(Additions and/or revisions
are underlined)
Is it safe to breastfeed while using Skyla?
…The risk of Skyla becoming attached to (embedded) or going through
the wall of the uterus is increased if Skyla is inserted while you are
breastfeeding.
Skyla can cause serious side effects, including:
- Perforation.
…The risk of perforation is increased if Skyla is inserted while
you are breastfeeding.
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