Included as part of the PRECAUTIONS section.
Evaluate women for ectopic pregnancy if they become
pregnant with Mirena in place because the likelihood of a pregnancy being
ectopic is increased with Mirena. Up to half of pregnancies that occur with
Mirena 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 Mirena, 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 Mirena 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 Mirena, remove Mirena
because leaving it in place may increase the risk of spontaneous abortion and
preterm labor. Removal of Mirena or probing of the uterus may also result in
spontaneous abortion. In the event of an intrauterine pregnancy with Mirena,
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 Mirena in place and if
Mirena cannot be removed or the woman chooses not to have it removed, warn her
that failure to remove Mirena 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
Long-term Effects And Congenital Anomalies
When pregnancy continues with Mirena in place, long-term
effects on the offspring are unknown. 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 Mirena 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 Mirena is unknown.
Severe infection or sepsis, including Group A
streptococcal sepsis (GAS), have been reported following insertion of Mirena.
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 Mirena is essential in order to minimize
serious infections such as GAS.
Pelvic Inflammatory Disease (PID)
Mirena 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. In clinical trials, total
combined upper genital infections were reported in 3.5% of Mirena users. More
specifically, endometritis was reported in 2.1%, PID in 0.6%, and all other
upper genital infections in ≤ 0.5% of women overall. These infections
occurred more frequently within the first year. In a clinical trial with other
IUDs1 and a clinical trial with an IUD similar to Mirena, the
highest rate occurred within the first month after insertion.
Promptly examine users with complaints of lower abdominal
or pelvic pain, odorous discharge, unexplained bleeding, fever, genital lesions
or sores. Remove Mirena in cases of recurrent endometritis or PID, 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 Mirena 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 Mirena 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 Mirena 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 Mirena
removal and treatment. When possible, confirm a Pap smear diagnosis with
Irregular Bleeding And Amenorrhea
Mirena can alter the bleeding pattern and result in
spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea.
During the first three to six months of Mirena 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. If bleeding irregularities develop during
prolonged treatment, appropriate diagnostic measures should be taken to rule
out endometrial pathology.
Amenorrhea develops in approximately 20% of Mirena users
by one year. The possibility of pregnancy should be considered if menstruation
does not occur within six weeks of the onset of 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 [see Clinical Studies].
In most women with heavy menstrual bleeding, the number
of bleeding and spotting days may also increase during the initial months of
therapy but usually decrease with continued use; the volume of blood loss per
cycle progressively becomes reduced [see Clinical Studies].
Perforation (total or partial, including
penetration/embedment of Mirena 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, which excluded
breast-feeding women, was < 0.1%.
If perforation occurs, locate and remove Mirena. Surgery
may be required. Delayed detection or removal of Mirena in case of perforation
may result in migration outside the uterine cavity, adhesions, peritonitis,
intestinal perforations, intestinal obstruction, abscesses and erosion of
The risk of perforation may be increased if Mirena is
inserted when the uterus is fixed retroverted or not completely involuted.
Delay Mirena insertion a minimum of six weeks or until involution is complete
following a delivery or a second trimester abortion.
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 Mirena users, 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
Partial or complete expulsion of Mirena 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.
Mirena 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 4.5% expulsion rate was reported over the 5-year study duration.
Delay Mirena insertion a minimum of six weeks or until
uterine involution is complete following a delivery or a second trimester
abortion. Remove a partially expelled Mirena. If expulsion has occurred, Mirena
may be replaced within 7 days after the onset of a menstrual period, after
pregnancy has been ruled out.
Because the contraceptive effect of Mirena is mainly due
to its local effects within the uterus, ovulatory cycles with follicular
rupture usually occur in women of fertile age using Mirena. Sometime atresia of
the follicle is delayed and the follicle may continue to grow. Ovarian cysts
have been reported in approximately 8% of women using Mirena. Most of these cysts
are asymptomatic, although some may be accompanied by pelvic pain or
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 Mirena. 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 Mirena 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
In addition, consider removing Mirena 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 WARNINGS AND PRECAUTIONS]. Exclude
pregnancy and verify the location of Mirena, for example, by sonography, X-ray,
or by gentle exploration of the cervical canal with a suitable instrument. If
Mirena is displaced, remove it. A new Mirena may be inserted at that time or
during the next menses if it is certain that conception has not occurred. If
Mirena is in place with no evidence of perforation, no intervention is
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 Mirena 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]
- Irregular Bleeding and Amenorrhea: 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
- 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 Mirena. Inform her that there is no
contraceptive protection if Mirena is displaced or expelled. [See WARNINGS
- 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
- 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 Mirena's threads
Complete the Follow-up Reminder Card and give to the
Carcinogenesis, Mutagenesis, Impairment Of Fertility
[See WARNINGS AND PRECAUTIONS]
Use In Specific Populations
The use of Mirena 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 Mirena, resulting in
detectable steroid levels in infant serum. [See WARNINGS AND PRECAUTIONS]
Safety and efficacy of Mirena 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.
Mirena 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 Mirena [see
No studies were conducted to evaluate the effect of renal
disease on the disposition of LNG released from Mirena.
1Farley T M M, Rosenberg M J, Rowe P J, Chen
J, Meirik O. Intrauterine devices and pelvic inflammatory disease: an
international perspective. Lancet 1992; 339:785-788.