Included as part of the PRECAUTIONS section.
Evaluate women for ectopic pregnancy if they become
pregnant with LILETTA in place because the likelihood of a pregnancy being
ectopic is increased with LILETTA. Approximately half of pregnancies that occur
with LILETTA 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. If
an ectopic pregnancy is confirmed, LILETTA should be removed.
The incidence of ectopic pregnancy in the clinical trial
with LILETTA, which excluded women with a history of ectopic pregnancy who did
not have a subsequent intrauterine pregnancy, was approximately 0.12 per 100
women-years. The risk of ectopic pregnancy in women who have a history of
ectopic pregnancy and use LILETTA is unknown. Women with a previous history of
ectopic pregnancy, tubal surgery or pelvic infection have a higher risk of
ectopic pregnancy. Ectopic pregnancy may require surgery and may result in loss
Tell women who choose LILETTA about the risks of ectopic
pregnancy, including the loss of fertility. Teach them to recognize and report
to their healthcare provider promptly any signs of ectopic pregnancy.
If pregnancy occurs while using LILETTA, determine if
LILETTA is in the uterus. If LILETTA is in the uterus, attempt to remove
LILETTA because leaving it in place may increase the risk of spontaneous
abortion and preterm labor. Removal of LILETTA or probing of the uterus may
also result in spontaneous abortion. In the event of an intrauterine pregnancy
with LILETTA, consider the following:
In patients becoming pregnant with an IUS in place,
septic abortion – with septicemia, septic shock, and death – may occur. Septic
abortion typically requires hospitalization and treatment with intravenous
antibiotics. Septic abortion may result in spontaneous abortion or a medical
indication for pregnancy termination. Should severe infection of the uterus
occur, hysterectomy may be required, which will result in permanent
Continuation of pregnancy
If a woman becomes pregnant with LILETTA in place and if
LILETTA cannot be removed or the woman chooses not to have it removed, warn her
that failure to remove LILETTA increases the risk of miscarriage, sepsis,
premature labor, and premature delivery. Prenatal care should include
counseling about these risks and that she should report immediately any
flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge
or leakage of fluid, or any other symptom that suggests complications of the
Severe infection or sepsis, including Group A
streptococcal sepsis (GAS), have been reported following insertion of other
LNG-releasing IUSs. 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 LILETTA is essential in order
to minimize serious infections such as GAS.
Pelvic Inflammatory Disease Or Endometritis
Insertion of LILETTA is contraindicated in the presence
of known or suspected PID or endometritis or a history of PID unless there has
been a subsequent intrauterine pregnancy [see CONTRAINDICATIONS]. IUSs
have been associated with an increased risk of PID, most likely due to
organisms being introduced into the uterus during insertion.
In the clinical trial with LILETTA, pelvic infection was
diagnosed in 0.6% of women. The infection was diagnosed as PID in 0.4% of women
and as endometritis in 0.2% of women. About 1/3 of women diagnosed with PID
developed the infection within a week of LILETTA insertion, while the remainder
were diagnosed more than six months after insertion. The cases of endometritis
had onset less than 40 days after LILETTA insertion.
Counsel women who receive LILETTA to notify a healthcare
provider if they have complaints of lower abdominal or pelvic pain, odorous
discharge, unexplained bleeding, fever, or genital lesions or sores. In such
circumstances, perform a pelvic examination promptly to evaluate for possible
pelvic infection. Remove LILETTA in cases of recurrent PID or endometritis, or
if an acute pelvic infection is severe or does not respond to treatment.
Women at increased risk for PID or endometritis
PID and endometritis are often associated with a sexually
transmitted infection (STI), and LILETTA does not protect against STIs. The
risk of PID or endometritis 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 or endometritis 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).
Asymptomatic PID or endometritis
PID or endometritis may be asymptomatic but still result
in tubal damage and its sequelae.
Treatment of PID or endometritis
Following a diagnosis of PID or endometritis, or
suspected PID or endometritis, perform appropriate testing for sexually
transmitted infection and initiate antibiotic therapy promptly. LILETTA does
not need to be removed immediately if the woman needs ongoing contraception
(1). In the LILETTA clinical trial, 7 of the 10 women who developed PID or
endometritis were successfully treated without removal of LILETTA.
Reassess the woman in 48-72 hours. If no clinical
improvement occurs, continue antibiotics and consider removal of LILETTA. If
the woman wants to discontinue use, remove LILETTA after antibiotics have been
started to avoid the potential risk for bacterial spread resulting from the
removal procedure. Guidelines for PID or endometritis treatment are available
from the Centers for Disease Control (CDC), Atlanta, Georgia (1).
Actinomycosis has been associated with IUS use.
Symptomatic women with known actinomycosis infection should have LILETTA
removed and receive antibiotics. Actinomycetes can be found in the genital tract
cultures in healthy women without IUSs. The significance of actinomyces-like
organisms on Pap test in an asymptomatic IUS user is unknown, and so this
finding alone does not always require LILETTA removal and treatment. When
possible, confirm a Pap test diagnosis with cultures.
Perforation (total or partial, including
penetration/embedment of LILETTA 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 or following LILETTA insertion
in the clinical trial, which excluded breastfeeding women, was 0.1%.
If perforation occurs, locate and remove LILETTA. Surgery
may be required. Delayed detection or removal of LILETTA in case of perforation
may result in migration outside the uterine cavity, adhesions, peritonitis,
intestinal perforations, intestinal obstruction, abscesses, and erosion of
A large post-marketing safety study with other IUSs
demonstrated an increased risk of perforation in lactating women. The risk of
perforation may be increased if LILETTA is inserted when the uterus is fixed
retroverted or not completely involuted during the postpartum period. Delay
LILETTA insertion a minimum of six weeks or until involution is complete
following a delivery or a second trimester abortion.
Partial or complete expulsion of LILETTA may occur,
resulting in the loss of contraceptive protection. In the clinical trial with
LILETTA, an overall expulsion rate of 3.5% was reported, with a rate of 2.0% in
nulliparous women and 5.6% in parous women. Expulsion may be associated with
symptoms of bleeding or pain, or it may be asymptomatic and go unnoticed.
LILETTA typically decreases menstrual bleeding over time; therefore, an
increase in menstrual bleeding may be indicative of an expulsion.
The risk of expulsion may be increased when the uterus is
not completely involuted at the time of insertion. Delay LILETTA insertion a
minimum of 6 weeks or until uterine involution is complete following a delivery
or a second trimester abortion.
Remove a partially expelled LILETTA. If expulsion has
occurred, a new LILETTA may be inserted within 7 days after the onset of a
menstrual period after pregnancy has been ruled out.
Because the contraceptive effect of LILETTA is mainly due
to its local effects within the uterus, ovulatory cycles with follicular
rupture usually occur in women of fertile age using LILETTA. Sometimes atresia
of the follicle is delayed and the follicle may continue to grow. Most ovarian
cysts that occur during use of LNG-releasing IUSs are asymptomatic and disappear
spontaneously during two to three months of observation. Cysts that cause
clinical symptoms can result in pelvic or abdominal pain or dyspareunia.
Symptomatic ovarian cysts occurred in 3.4% of subjects using LILETTA, and 0.3%
of subjects discontinued use of LILETTA because of an ovarian cyst.
Evaluate persistent ovarian cysts. Surgical intervention
is not usually required, but may be necessary in some cases. Discuss this risk
with patients who choose to use LILETTA.
Bleeding Pattern Alterations
LILETTA can alter the bleeding pattern and result in
spotting, irregular bleeding, heavy bleeding, oligomenorrhea, and amenorrhea.
During the first three to six months of LILETTA use, the number of bleeding and
spotting days may be increased and bleeding patterns may be irregular.
Thereafter, the number of bleeding and spotting days usually decreases but
bleeding may remain irregular.
In the LILETTA clinical trial, amenorrhea developed in
approximately 19% of LILETTA users by the end of the first year of use, in 26%
by the end of the second year of use, and in approximately 38% of users by the
end of year 3. In the trial, 1.5% of LILETTA subjects discontinued due to
bleeding complaints). Table 2 shows the bleeding and spotting days based on
28-day cycle equivalents.
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
|Note: Includes all LILETTA
In the LILETTA clinical trial,
248 of 255 (97.3%) of women evaluated experienced menses within 3 months after
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 are
generally not necessary in amenorrheic women unless indicated, for example, by
other signs of pregnancy or by pelvic pain.
Women who currently have or
have had breast cancer, or have a suspicion of breast cancer, should not use
hormonal contraception, including LILETTA, because some breast cancers are
hormone-sensitive [see CONTRAINDICATIONS].
Spontaneous reports of breast
cancer have been received during postmarketing experience with another
LNG-releasing IUS. Observational studies have not provided consistent evidence
of an increased risk of breast cancer with use of a LNG-releasing IUS.
Clinical Considerations For Use and Removal
Obtain a complete medical and social history, including
partner status, to determine conditions that might influence the selection of
an IUS for contraception.
Because irregular bleeding/spotting is common during the
first months of LILETTA use, exclude endometrial pathology (polyps or cancer)
prior to the insertion of LILETTA in women with persistent or uncharacteristic
Special attention must be given to ascertaining whether
the woman is at increased risk of infection (for example, leukemia, acquired
immune deficiency syndrome [AIDS], IV drug abuse), or has a history of PID
unless there has been a subsequent intrauterine pregnancy. LILETTA does not protect
against HIV/STI transmission. [See Pelvic Inflammatory Disease or Endometritis]
Use LILETTA with caution after careful assessment if any
of the following conditions exist, and consider removal of the IUS 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
In addition, consider removing LILETTA 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 IUS may have been displaced, (for example,
expelled or perforated the uterus) [see Perforation and Expulsion above].
Exclude pregnancy and verify the location of LILETTA, for example, by
sonography, by X-ray, or by gentle exploration of the cervical canal with a
suitable instrument [see DOSAGE AND ADMINISTRATION]. If LILETTA is
displaced, remove it. A new LILETTA may be inserted at that time or during the
next menses if it is certain that conception has not occurred. If LILETTA is in
place with no evidence of perforation, no intervention is indicated.
Magnetic Resonance Imaging (MRI) Information
LILETTA is MR Safe.
Patient Counseling Information
Information For Patients
Advise the patient to read the
FDA-approved patient labeling (Patient Information).
- Advise the patient that this
product does not protect against HIV infection (AIDS) and other sexually
transmitted infections (STIs).
- 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]
- Counsel the patient that if pregnancy occurs while using
- LILETTA will likely need to be removed because leaving it
in place may increase the risk of spontaneous abortion and preterm labor;
however, removal of LILETTA or probing of the uterus may also result in
spontaneous abortion. [See WARNINGS AND PRECAUTIONS]
- Septic abortion may occur. Warn her that if LILETTA
cannot be removed or she chooses not to have it removed, there may be an
increased risk of miscarriage, sepsis, premature labor, and premature delivery.
[See WARNINGS AND PRECAUTIONS]
- Counsel the patient that severe infection or sepsis,
including Group A streptococcal sepsis (GAS), can occur within the first few
days after LILETTA is inserted. Instruct her to contact a healthcare provider
immediately if she develops severe pain or fever shortly after LILETTA is
inserted. [See WARNINGS AND PRECAUTIONS]
- Inform the patient about the possibility of PID or
endometritis and that these infections 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, including development of menstrual
disorders (prolonged or heavy bleeding), unusual vaginal discharge, abdominal
or pelvic pain or tenderness, dyspareunia, chills, and fever. [See WARNINGS
- Inform the patient that perforation may occur, most often
during insertion, although the perforation may not be detected until sometime
later. Counsel her that if perforation occurs, LILETTA will have to be located
and removed. Surgery may be required. Inform her that delayed detection or
removal of LILETTA in case of perforation may result in migration of the IUS
outside the uterine cavity, adhesions, peritonitis, intestinal perforations,
intestinal obstruction, abscesses, and erosion of adjacent viscera. [See WARNINGS
- Review the signs and symptoms of LILETTA expulsion with
the patient. Counsel the patient on how she can check that the threads still
protrude from her cervix, and not to pull on them. Inform her that there is no
contraceptive protection if LILETTA is displaced or expelled. [See WARNINGS
- Counsel the patient regarding the risk of ovarian cysts
and that cysts can cause clinical symptoms including pelvic pain, abdominal
pain or dyspareunia and infrequently will need surgery. [See WARNINGS AND
- Counsel the patient that irregular or prolonged bleeding
and spotting, and/or cramps may occur during the first three to six months
after insertion. If her symptoms continue or are severe, she should report them
to her healthcare provider. [See WARNINGS AND PRECAUTIONS]
- Inform the patient that LILETTA is MR Safe and that it is
safe for her to have an MRI with LILETTA in place. [See WARNINGS AND
- 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
- She or her partner becomes HIV positive
- Possible exposure to sexually transmitted infections
- 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 LILETTA's threads
Complete the Follow-up Reminder Card and give it to the
Carcinogenesis, Mutagenesis, Impairment Of Fertility
[See WARNINGS AND PRECAUTIONS]
Use In Specific Populations
LILETTA is contraindicated for use in pregnant women
because there is no need for pregnancy prevention in a woman who is already
pregnant and LILETTA may cause adverse pregnancy outcomes. If a woman becomes
pregnant with LILETTA in place, there is an increased risk of miscarriage,
sepsis, premature labor, and premature delivery. Published studies report no
harmful effects on fetal development associated with long-term use of
contraceptive doses of oral progestins in a pregnant woman. The background risk
in the U.S. general population of major birth defects is 2-4% and of
miscarriage is 15-20% of clinically recognized pregnancies. Advise a woman of
the potential risks if pregnancy occurs with LILETTA in place.
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. 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 another LNG-releasing IUS.
The developmental and health benefits of breastfeeding should be considered
along with the mother's clinical need for LILETTA and any potential adverse
effects on the breastfed child from LILETTA or from the underlying maternal
Safety and efficacy of LILETTA have been established in
females of reproductive age. Efficacy is expected to be the same for
postpubertal females under the age of 16 as for users 16 years and older. Use
of this product before menarche is not indicated [see CLINICAL PHARMACOLOGY].
LILETTA has not been studied in women over age 65 and is
not indicated for postmenopausal women.
No studies were conducted to evaluate the effect of
hepatic disease on the disposition of LNG released from LILETTA [see CONTRAINDICATIONS].
No studies were conducted to evaluate the effect of renal
disease on the disposition of LNG released from LILETTA.
The safety and efficacy of LILETTA have been evaluated in
overweight, obese, and morbidly obese patients. There was no apparent effect of
BMI or body weight on contraceptive efficacy [see CLINICAL PHARMACOLOGY].