Drug Safety-related Labeling Changes (SrLC)

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MIRENA (NDA-021225)

(LEVONORGESTREL)

Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)

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08/12/2022 (SUPPL-43)

Approved Drug Label (PDF)

6 Adverse Reactions

6.2 Clinical Trials Experience

Additions and/or revisions underlined:

…

A separate study with 362 women who have used Mirena for more than 5 years showed a consistent adverse reaction profile in Years 6 through 8 as shown in Table 2. By the end of Year 8 of use, amenorrhea and infrequent bleeding are experienced by 34% and 26% of users, respectively; irregular bleeding occurs in 10%, frequent bleeding in 3%, and prolonged bleeding in 3% of users. In this study, 9% of women reported the adverse event of weight gain; it is unknown if the weight gain was caused by Mirena.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

Additions and/or revisions underlined:

…

What is MIRENA?

• MIRENA is a hormone-releasing system placed in your uterus by your healthcare provider to prevent pregnancy for up to 8 years.

• MIRENA can also be used to decrease menstrual blood loss for up to 5 years in women who have heavy menstrual flow and who also want to use a birth control method that is placed in the uterus to prevent pregnancy.

• MIRENA can be removed by your healthcare provider at any time.

• MIRENA can be used whether or not you have given birth to a child.

…

What if I need birth control for more than 8 years?

MIRENA must be removed after 8 years. Your healthcare provider can place a new MIRENA during the same office visit if you choose to continue using MIRENA.

…

What if I change my mind about birth control and want to become pregnant in less than 8 years?

Your healthcare provider can remove MIRENA at any time. You may become pregnant as soon as MIRENA is removed. About 8 out of 10 women who want to become pregnant will become pregnant sometime in the first year after MIRENA is removed.

…

Who might use MIRENA?

You might choose MIRENA if you:

• want long-term birth control that provides a low chance of getting pregnant (less than 1 in 100)

• want birth control that works continuously for up to 8 years

• want birth control that is reversible

• want a birth control method that you do not need to take daily

• want treatment for heavy periods up to 5 years and are willing to use a birth control method that is placed in the uterus

• want birth control that does not contain estrogen

…

08/11/2021 (SUPPL-42)

Approved Drug Label (PDF)

6 Adverse Reactions

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

…

A separate study with 362 women who have used Mirena for more than 5 years showed a consistent adverse reaction profile in Years 6 and 7 as shown in Table 2. By the end of Year 7 of use, amenorrhea and infrequent bleeding are experienced by 28% and 26% of users, respectively; irregular bleeding occurs in 12%, frequent bleeding in 8%, and prolonged bleeding in 2% of users. In this study, 6% of women reported the adverse event of weight gain; it is unknown if the weight gain was caused by Mirena.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT INFORMATION

(Additions and/or revisions underlined)

…

What is MIRENA?

• MIRENA is a hormone-releasing system placed in your uterus by your healthcare provider to prevent pregnancy for up to 7 years.

• MIRENA can also be used to decrease menstrual blood loss for up to 5 years in women who have heavy menstrual flow and who also want to use a birth control method that is placed in the uterus to prevent pregnancy.

• MIRENA can be removed by your healthcare provider at any time.

• MIRENA can be used whether or not you have given birth to a child.

…

What if I need birth control for more than 7 years?

MIRENA must be removed after 7 years. Your healthcare provider can place a new MIRENA during the same office visit if you choose to continue using MIRENA.

…

What if I want to stop using MIRENA?

MIRENA is intended for use up to 7 years, but you can stop using MIRENA at any time by asking your healthcare provider to remove it. You could become pregnant as soon as MIRENA 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 MIRENA is removed to prevent pregnancy.

What if I change my mind about birth control and want to become pregnant in less than 7 years?

Your healthcare provider can remove MIRENA at any time. You may become pregnant as soon as MIRENA is removed. About 8 out of 10 women who want to become pregnant will become pregnant sometime in the first year after MIRENA is removed.

…

Who might use MIRENA?

You might choose MIRENA if you:

• want long-term birth control that provides a low chance of getting pregnant (less than 1 in 100)

• want birth control that works continuously for up to 7 years

• want birth control that is reversible

• want a birth control method that you do not need to take daily

• want treatment for heavy periods up to 5 years and are willing to use a birth control method that is placed in the uterus

• want birth control that does not contain estrogen

…

06/08/2021 (SUPPL-36)

Approved Drug Label (PDF)

4 Contraindications

(Additions and/or revisions underlined)

The use of Mirena 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)]

5 Warnings and Precautions

5.1 Risk of Ectopic Pregnancy

(Subsection title revised; Additions and/or revisions underlined)

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. Approximately one-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 menses 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.

5.2 Risks with Intrauterine Pregnancy

(Subsection title revised; Additions and/or revisions underlined)

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:

Septic abortion

In patients becoming pregnant with an IUS in place, septic abortion - with septicemia, septic shock, and death - may occur.

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. 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.

5.4 Pelvic Infection

(Additions and/or revisions underlined)

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.

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 (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, 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 less than or equal to 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.

Women at increased risk for PID

PID is often associated with a sexually transmitted infection (STI), and Mirena 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 Mirena after initiation of antibiotic therapy is usually appropriate.1

Actinomycosis

Actinomycosis has been associated with IUDs. Remove Mirena 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 Mirena removal and treatment. When possible, confirm a Pap smear diagnosis with cultures.

5.5 Perforation

(Additions and/or revisions underlined)

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. The incidence of perforation during clinical trials, which excluded breast-feeding women, 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 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 Mirena is inserted when the uterus is fixed, retroverted or not completely involuted.

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 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 Mirena 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. Mirena 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 4.5% expulsion rate was reported over the 5-year study duration.

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 Mirena. If expulsion has occurred, a new Mirena can be inserted any time the provider can be reasonably certain the woman is not pregnant.

5.8 Bleeding Pattern Alterations

(Subsection title revised; Additions and/or revisions underlined)

Mirena can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first 3–6 months of Mirena 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. 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.

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 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 (14.1)].

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 (14.2)].

5.9 Breast Cancer

(Additions and/or revisions underlined)

Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception, including Mirena, because some breast cancers are hormone-sensitive [see Contraindications (4)].

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.

6 Adverse Reactions

(Additions and/or revisions underlined)

The following serious or otherwise important adverse reactions are discussed in 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)]

6.1 Clinical Trials Experience

(Additions and/or revisions underlined)

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.

…

6.2 Postmarketing Experience

(Extensive changes; please refer to label)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions underlined)

Risk Summary

The use of Mirena is contraindicated in pregnancy or with a suspected pregnancy and Mirena may cause adverse pregnancy outcomes [see Contraindications (4), Warnings and Precautions (5.1, 5.2)]. If a woman becomes pregnant with Mirena in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery. Remove Mirena, if possible, if pregnancy occurs in a woman using Mirena. If Mirena 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.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

(Additions and/or revisions underlined)

Advise the patient to read the FDA-approved patient labeling (Patient Information)

• Sexually Transmitted Infections: Advise the patient that this product does not protect against HIV infection (AIDS) and other sexually transmitted infections (STIs).

• Risk of Ectopic Pregnancy: Advise 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 (5.1).]

• 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 Mirena, including the risks of leaving Mirena in place and the risks of removing Mirena or probing of the uterus. If Mirena 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).]

• Sepsis: Counsel the patient that severe infection or sepsis, including Group A streptococcal sepsis (GAS), can occur within the first few days after Mirena is inserted. Instruct her to contact a healthcare provider immediately if she develops severe pain or fever shortly after Mirena is inserted. [See Warnings and Precautions (5.3).]

• Pelvic Infection: Advise 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. 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 (5.4).]

• 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 Mirena placement, worsening pain or bleeding after placement, or the inability to feel Mirena strings may occur with Mirena perforation and expulsion. 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. 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 Mirena has been confirmed. Advise her that if perforation occurs, Mirena will have to be located and removed; surgery may be required. [See Warnings and Precautions (5.5, 5.6, 5.10).]

• Ovarian Cysts: Advise 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. [See Warnings and Precautions (5.7).]

• Bleeding Pattern Alterations: Advise the patient that irregular or prolonged bleeding and spotting, and/or cramps may occur during the first few weeks after insertion. Inform the patient that, during the first 3–6 months of Mirena use, the number of bleeding and spotting days may be higher and bleeding patterns may be irregular. If her symptoms continue or are severe, she should report them to her healthcare provider. [See Warnings and Precautions (5.8).]

• Clinical Considerations for Use and Removal: Advise 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, abdominal pain, or pain during sex

• HIV positive seroconversion in herself or her partner

• Possible exposure to 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 Mirena's threads

PATIENT INFORMATION

(Extensive changes; please refer to label)

08/20/2020 (SUPPL-40)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.7 Expulsion

Additions and/or revisions underlined:

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. 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 …

6 Adverse Reactions

6.1 Clinical Trials Experience

Additions and/or revisions underlined:

The data provided in Table 2 reflect the experience with the use of Mirena in the adequate and well-controlled studies as well as in the supportive and uncontrolled studies for contraception and heavy menstrual bleeding (n=5,091). The data cover more than 12,101 women-years of exposure up to 5 years of use, mainly in the contraception studies (11,761 women-years). The frequencies of reported adverse drug reactions represent crude incidences.

Table 2 Adverse Reactions greater than or equal to 5% Reported in Clinical Trials with Mirena

Other adverse reactions occurring in <5% of subjects include alopecia, (partial and complete) device expulsion, hirsutism, nausea, and PID/endometriosis.

A separate study with 362 women who have used Mirena for more than 5 years showed a consistent adverse reaction profile in Year 6. By the end of Year 6 of use, amenorrhea and infrequent bleeding are experienced by 24% and 31% of users, respectively; irregular bleeding occurs in 15%, and prolonged bleeding in 2% of users.

7 Drug Interactions

Additions and/or revisions underlined:

No drug-drug interaction studies have been conducted with Mirena.

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 Mirena. However, the contraceptive effect of Mirena 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

Newly added subsection

8.3 Females and Males of Reproductive Potential

Return to Fertility After Discontinuing Mirena

In two studies, return to fertility was investigated in a total of 229 women who desired pregnancy after study discontinuation and provided follow-up information. The probability to conceive within 12 months after removal of Mirena was approximately 80%.

17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)

PATIENT COUNSELING INFORMATION

Additions and/or revisions underlined:

• 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 Mirena placement, worsening pain or bleeding after placement, or the inability to feel Mirena strings may occur with Mirena perforation and expulsion. 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 and Precautions (5.6,  5.7).]

PATIENT INFORMATION

Additions and/or revisions underlined:

MIRENA is a hormone-releasing system placed in your uterus by your healthcare provider to

prevent pregnancy for up to 6 years.

What if I need birth control for more than 6 years?

MIRENA must be removed after 6 years. Your healthcare provider can place a new MIRENA during

the same office visit if you choose to continue using MIRENA.

What if I want to stop using MIRENA?

MIRENA is intended for use up to 6 years, but you can stop using MIRENA at any time by asking your

healthcare provider to remove it …

What if I change my mind about birth control and want to become pregnant in less than 6 years? …

Who might use MIRENA?

• want birth control that works continuously for up to 6 years

06/08/2017 (SUPPL-38)

Approved Drug Label (PDF)

8 Use in Specific Populations

8.1 Pregnancy

(Additions and/or revisions are underlined)

Risk Summary

The use of Mirena 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 Mirena may cause adverse pregnancy outcomes. If a woman becomes pregnant with Mirena in place, the likelihood of ectopic pregnancy is increased and there is an increased risk of miscarriage, sepsis, premature labor, and premature delivery. Remove Mirena, if possible, if pregnancy occurs in a woman using Mirena. If Mirena 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.

8.2 Lactation

(Newly added subsection)

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 Mirena, 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 Mirena. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Mirena and any potential adverse effects on the breastfed child from Mirena or from the underlying maternal condition.

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)

• Pregnancy or Suspected Pregnancy: Counsel the patient to inform her healthcare provider if she determines or suspects she is pregnant with Mirena in place. Advise women of the potential risks if pregnancy occurs with Mirena in place. If Mirena cannot be removed in a pregnant patient, advise her to report immediately any symptom that suggests complications of the pregnancy.

FDA-Approved Patient Labeling Patient Information Mirena® (mur-a-nah) (levonorgestrel-releasing intrauterine system)

(Additions and/or revisions are underlined)

What is Mirena?

• Mirena can be used whether or not you have had a child.

05/25/2017 (SUPPL-39)

Approved Drug Label (PDF)

5 Warnings and Precautions

5.7 Expulsion

Additions and/or revisions underlined:

… If expulsion has occurred, a new Mirena can be  inserted any time the  provider can be reasonably certain the woman is not pregnant.

12/21/2016 (SUPPL-37)

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)…
• Irregular Bleeding and Amenorrhea: 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…

Patient Information

(Additions and/or revisions are underlined)

Is it safe to breastfeed while using Mirena?

…The risk of Mirena becoming attached to (embedded) or going through the wall of the uterus is increased if Mirena is inserted while you are breastfeeding.

Mirena can cause serious side effects including:

• Perforation. … The risk of perforation is increased if Mirena is inserted while you are breastfeeding.