Mirena

Patient Information Leaflet: Information for the User

Mirena 20 micrograms/24 hours intrauterine system

levonorgestrel
Please read this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

1. What Mirena is and what it is used for
2. What you need to know before using Mirena
3. How to use Mirena
4. Possible side effects
5. How to store Mirena
6. Contents of the pack and other information

1. What Mirena is and what it is used for

Mirena is a T-shaped intrauterine system (IUS) that, after insertion, releases the hormone
levonorgestrel into the uterus. The T-shaped body is designed to conform to the shape of the uterus.
The vertical stem carries a medicinal reservoir containing levonorgestrel. Attached to the loop at the
lower end of the vertical stem are two removal threads.
Mirena is used for the prevention of pregnancy (contraception), for excessive bleeding during
menstruation (idiopathic menorrhagia), and for protection against excessive growth of the
uterine lining (endometrial hyperplasia) during estrogen-only hormone replacement therapy.
Children and adolescents
Mirena should not be used if the first menstrual period (menarche) has not yet occurred.

2. What you should know before using Mirena

General notes
Before you start using Mirena, your doctor will ask you some questions about your personal health history and that of your family.
This patient information leaflet describes various situations in which Mirena must be removed or its effectiveness may decrease. In such cases, you must abstain from sexual intercourse or use additional non-hormonal contraceptive measures, such as a condom or another barrier method.
Do not use the rhythm method or the basal body temperature method. These methods may be inadequate because Mirena alters the monthly variations in body temperature and cervical mucus.
Like all other hormonal contraceptives, Mirena does not protect against HIV (AIDS) infection or other sexually transmitted diseases.

Do not use Mirena in any of the following conditions:

• if you are allergic to levonorgestrel or to any of the other ingredients of this medicine (listed in section 6);
• if you are pregnant or think you might be;
• if you have tumours whose growth is sensitive to progestogenic hormones (e.g. breast cancer);
• if you currently have or have recurrent pelvic inflammatory disease (infection of the female reproductive organs);
• if you have a cervical infection (infection of the cervix);
• if you have an infection of the lower genital tract;
• if you have a uterine infection after childbirth;
• if you had a uterine infection after an abortion within the previous three months;
• if you have conditions associated with increased susceptibility to infections;
• if you have abnormal cells in the cervix;
• if you have confirmed or suspected cancer of the uterus or cervix;
• if you have unexplained abnormal vaginal bleeding;
• if you have abnormalities of the cervix or uterus, including fibroids that distort the uterine cavity;
• if you have acute liver disease or liver tumour.

Warnings and precautions
Talk to your doctor or pharmacist before using Mirena.
Use of Mirena together with oestrogen for hormone replacement therapy
If Mirena is used together with oestrogen for hormone replacement therapy, the safety information relating to the oestrogen also applies and must be followed.
Consult a specialist who will decide whether to continue using Mirena or to remove the device, if any of the following conditions are present or appear for the first time during use of Mirena:

• migraine, asymmetric vision loss, or other symptoms that could indicate transient ischaemic attack (temporary interruption of blood supply to the brain);
• severe headache;
• jaundice (yellowing of the skin, eyes, and/or nails);
• marked increase in blood pressure;
• severe arterial diseases such as stroke or myocardial infarction;
• acute venous thromboembolism (formation of blood clots inside blood vessels).

Use Mirena with caution if you suffer from congenital heart disease or heart valve disorders at risk of bacterial endocarditis (inflammation of the transparent membrane lining the heart chambers, caused by bacteria in the bloodstream).
If you have diabetes, you should monitor your blood glucose levels. However, it is generally not necessary to adjust your antidiabetic treatment during use of Mirena.
Irregular bleeding may mask symptoms and signs of endometrial polyps or cancer (the mucosa lining the uterine cavity), and in such cases appropriate diagnostic measures should be considered.
Mirena is not the first-choice method for young women who have never given birth or for postmenopausal women (the period after the final cessation of menstruation) with advanced uterine atrophy.

Medical examination/consultation
The examination before insertion may include a pelvic exam, Pap test, breast examination, and other tests, for example for infections, including sexually transmitted infections, and pregnancy test if necessary.
A gynaecological examination must be performed to determine the position and size of the uterus.
Mirena is not suitable for use as an emergency contraceptive (post-coital contraception).

Infections
The insertion tube helps protect Mirena from microbial contamination during the insertion procedure, and the inserter has been designed to minimise the risk of infections. Nevertheless, there is an increased risk of pelvic infection immediately and during the first month after insertion of copper intrauterine devices. Pelvic infections in women using intrauterine devices (IUDs) are often associated with sexually transmitted infections. The risk of infection is increased if you or your partner have unprotected sexual intercourse. Pelvic infections must be treated promptly. Pelvic infections may impair fertility and increase the risk of ectopic pregnancy (pregnancy outside the uterus).
In extremely rare cases, severe infections or sepsis (a severe systemic infection) may occur shortly after insertion of an intrauterine device (severe infections can be fatal).
The device must be removed in case of recurrent episodes of pelvic infection or endometritis (inflammation of the uterine lining) or in case of a severe acute infection that does not respond to treatment within a few days.
Contact your doctor immediately if you have persistent lower abdominal pain, fever, pain during sexual intercourse, or abnormal bleeding.

Breast cancer
Women who take oral contraceptives have a slightly increased risk of breast cancer. This returns to the age-appropriate baseline risk within 10 years after stopping the pill.
Some scientific studies have suggested a slight increase in the risk of breast cancer with the use of levonorgestrel-releasing intrauterine systems such as Mirena, while other studies have not indicated an increased risk. For any concerns, contact your doctor.
The risk of breast cancer is increased in postmenopausal women using systemic hormone replacement therapy (HRT) (e.g. oral or transdermal). This risk is higher with combined oestrogen-progestin HRT than with oestrogen-only HRT. Refer to the product information for the oestrogen-containing product for further details. For any concerns, contact your doctor.

Expulsion
Uterine muscle contractions during menstruation may sometimes displace the device or cause its expulsion. This is more likely to occur if you are overweight at the time of insertion or if you have a history of heavy periods. If the intrauterine system is misplaced, it may not function properly, and the risk of pregnancy increases. If the intrauterine system is expelled, pregnancy protection is lost.
Possible symptoms of expulsion include pain and abnormal bleeding, but Mirena may also be expelled without your awareness. Since Mirena reduces menstrual flow, an increase in flow may indicate expulsion.
It is recommended to check the threads with your fingers, for example when showering. See also section 3 “How to use Mirena – How can you feel that Mirena is correctly positioned?”. If you notice signs of expulsion or can no longer feel the threads, use another contraceptive method (e.g. condom) and consult your healthcare provider.

Uterine perforation
Perforation or penetration of the uterine wall may occur, most often during insertion, although it may not be detected until some time later. In such cases, Mirena is not effective in preventing pregnancy and should be removed as soon as possible. Surgical intervention may be required to remove Mirena. The risk of uterine perforation increases during breastfeeding and in women who have given birth within 36 weeks before insertion, and may increase in women with a fixed retroverted uterus (tilted backwards). If you suspect perforation, seek immediate medical advice and inform the doctor that you have Mirena inserted, especially if it is not the person who inserted it.
Possible signs and symptoms of uterine perforation may include:

• severe pain (similar to menstrual cramps) or more pain than expected;
• very heavy bleeding (after insertion);
• pain and bleeding that persist for more than a few weeks;
• sudden change in menstrual cycle;
• pain during sexual intercourse;
• you can no longer feel the Mirena threads (see section 3 “How to use Mirena – How can you feel that Mirena is correctly positioned?”).

Ectopic pregnancy (pregnancy outside the uterus)
While using Mirena, pregnancy is very rare.
In users of Mirena, the risk of ectopic pregnancy, although low in absolute terms, is relatively increased.
The absolute risk of ectopic pregnancy in Mirena users is low due to the overall reduced likelihood of pregnancy in Mirena users compared to women not using any contraceptive.
The absolute rate of ectopic pregnancies with Mirena is approximately 0.1% per year, compared to 0.3–0.5% per year in women not using any contraceptive. However, if pregnancy occurs in a woman using Mirena, the relative probability that it is an ectopic pregnancy is increased.
A woman who has previously had an ectopic pregnancy, tubal surgery, or pelvic infection has a higher risk. Ectopic pregnancy is a serious condition requiring immediate medical attention. The following symptoms may indicate an ectopic pregnancy; contact your doctor immediately:

• if your menstrual cycles have stopped and you experience persistent bleeding or pain;
• if you have lower abdominal pain;
• if you have normal signs of pregnancy but also experience bleeding and dizziness.

Weakness
Some women may feel dizzy after insertion of Mirena. This is a normal physical response. Your doctor will advise you to rest for a while.

Enlarged ovarian follicles (cells surrounding a maturing egg in the ovary)
Since the contraceptive action of Mirena is mainly local, ovulatory cycles with follicular rupture generally occur in women of reproductive age. Occasionally, follicular degeneration may be delayed and follicular development may continue. Most of these follicles are asymptomatic, although some may be associated with pelvic pain or pain during intercourse. These follicular enlargements may require medical attention but usually resolve spontaneously.

Psychiatric disorders
Some women using hormonal contraceptives, including Mirena, have reported depression or depressed mood. Depression can be severe and may sometimes lead to suicidal thoughts. If you experience mood changes or depressive symptoms, consult your doctor as soon as possible for further medical advice.

Other medicines and Mirena
The mechanism of action of Mirena is primarily local, and it is believed that taking other medicines does not increase the risk of pregnancy during use of Mirena. However, inform your doctor if you are taking, or have recently taken, any other medicines, including over-the-counter medicines.
Medicines that increase the metabolism of levonorgestrel, for example:
The metabolism of levonorgestrel may be increased by concomitant use of other medicines, such as drugs for epilepsy (e.g., topiramate, felbamate, barbiturates, phenytoin, carbamazepine, oxcarbazepine, etc.) and certain antibiotics (e.g. rifampicin, rifabutin, etc.), griseofulvin, and products containing the herbal remedy St. John's wort.
Medicines that have variable effects on the metabolism of levonorgestrel, for example:
When co-administered with sex hormones, many HIV/HCV protease inhibitors and non-nucleoside reverse transcriptase inhibitors may increase or decrease plasma concentrations of the progestogen.
Medicines that reduce the metabolism of levonorgestrel, for example:
Strong and moderate inhibitors of CYP3A4 such as azole antifungals (e.g. fluconazole, itraconazole, ketoconazole, voriconazole), verapamil, macrolides (e.g. clarithromycin, erythromycin), diltiazem, and grapefruit juice may increase plasma concentrations of the progestogen.

Pregnancy, breastfeeding and fertility
If you are pregnant, suspect or are planning a pregnancy, or are breastfeeding, consult your doctor or pharmacist before using this medicine.
Pregnancy
Do not use Mirena if you are or suspect you are pregnant.
It is very rare for a woman to become pregnant if Mirena is correctly positioned. However, if Mirena is expelled, you are no longer protected and must use another contraceptive method until you consult your doctor.
Some women may not have periods while using Mirena. The absence of menstruation is not necessarily a sign of pregnancy. If you do not have your period and have other signs of pregnancy (e.g. nausea, fatigue, breast tenderness), contact your doctor for an examination and a pregnancy test.
If you become pregnant with Mirena in place, contact your doctor immediately for removal of the device. Removal may cause miscarriage. However, if Mirena remains in place during pregnancy, not only is the risk of miscarriage higher, but also the risk of preterm delivery. If Mirena cannot be removed, discuss with your doctor the benefits and risks of continuing the pregnancy. If you decide to continue the pregnancy, you will be closely monitored, and you must contact your doctor immediately if you experience cramp-like abdominal pain, stomach pain, or fever.
Mirena contains a hormone called levonorgestrel, and isolated cases of effects on the external genitalia of female fetuses have been observed following exposure to levonorgestrel intrauterine devices during intrauterine life.

Breastfeeding
Mirena can be used during breastfeeding.
Levonorgestrel has been found in small amounts in the breast milk of nursing women (0.1% of the dose is transferred to the infant). There appear to be no harmful effects on the growth and development of the child when Mirena is used after 6 weeks postpartum.
Progestogen-only methods do not seem to affect the quantity or quality of breast milk.

Fertility
After removal of Mirena, a woman returns to her normal fertility condition.

Driving and use of machines
No studies on the effects on the ability to drive vehicles and use machines have been conducted.

Mirena contains barium sulphate
The T-shaped body of Mirena contains barium sulphate, which makes it visible on X-rays.

3. How to use Mirena

Use this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

How effective is Mirena?
In contraception, Mirena is as effective as the most effective copper-containing device currently available. Clinical studies have shown that in the first year, approximately two pregnancies occurred per 1,000 women using Mirena. This rate may increase in case of expulsion or perforation (see section “Medical examination/consultation”).

In the treatment of idiopathic menorrhagia (excessive blood loss during menstruation), Mirena causes a marked reduction in menstrual bleeding as early as after three months. Some users may stop having menstrual periods altogether.

When should Mirena be inserted?

Starting to use Mirena

• Before Mirena is inserted, it must be confirmed that you are not pregnant.
• Mirena should be inserted within 7 days from the start of menstruation. If Mirena is inserted during this time, it works immediately and will prevent pregnancy.
• If it is not possible to insert Mirena within 7 days from the start of menstruation, or if your menstrual cycle is irregular, Mirena may be inserted on any other day. In this case, you must not have had unprotected sexual intercourse since your last menstrual period and must have a negative pregnancy test before insertion. Furthermore, Mirena may not reliably prevent pregnancy immediately. Therefore, you must use a barrier contraceptive method (such as condoms) or abstain from vaginal intercourse during the first 7 days after Mirena insertion.
• Mirena is not intended for use as emergency contraception (post-coital contraception).

Starting to use Mirena after childbirth

• Mirena may be inserted after childbirth only once the uterus has returned to its normal size, but not earlier than 6 weeks after delivery (see section 2 “What you need to know before using Mirena – Uterine perforations”).
• See also “Starting to use Mirena” for information on timing of insertion.

Starting to use Mirena after an abortion
Mirena may be inserted immediately after an abortion if the pregnancy lasted less than 3 months, provided there are no genital infections. Mirena will work immediately.

Replacing Mirena
Mirena may be replaced with a new Mirena at any time during the menstrual cycle. The new Mirena will work immediately.

Switching from another contraceptive method (such as combined hormonal contraceptives, implants)

• Mirena may be inserted immediately if it is reasonably certain that you are not pregnant.
• If more than 7 days have passed since the start of your menstrual cycle, you must abstain from vaginal intercourse or use additional contraceptive protection for the following 7 days.

How is Mirena inserted?
Mirena must be inserted by a healthcare provider experienced in Mirena insertion.
After a gynecological examination, a device called a speculum is inserted into the vagina, and the cervix is cleaned with an antiseptic solution. The device is then inserted into the uterus using a thin, flexible plastic tube (the inserter). If deemed appropriate, local anaesthesia may be administered to the cervix prior to insertion.
Some women may experience pain and dizziness after insertion. If these symptoms do not resolve within 30 minutes of resting, the device may not be correctly positioned. An examination must be performed and, if necessary, the device must be removed.
After Mirena placement, your doctor will give you a patient reminder card for follow-up visits. Bring this card with you to every scheduled appointment.

When should you contact your doctor?
You should have the device checked 4–12 weeks after insertion and subsequently at regular intervals, at least once a year. Your doctor will determine the frequency and type of check-ups needed in your particular case. Bring your patient reminder card, which you received from your doctor, to every scheduled appointment. In addition, contact your doctor if any of the following occur:

• You cannot feel the threads in the vagina;
• You feel the end of the device;
• You think you might be pregnant;
• You have persistent abdominal pain, fever, or unusual vaginal discharge;
• You or your partner feel pain or discomfort during sexual intercourse;
• You experience sudden changes in your menstrual cycles (for example, if you previously had light or absent periods and now experience persistent bleeding or pain, or start having heavy bleeding);
• You develop other medical problems such as migraine or severe and recurrent headaches, sudden vision problems, jaundice, or high blood pressure;
• You are diagnosed with any of the conditions listed in the section “What you need to know before using Mirena”.

Remember to inform your doctor that you have Mirena inserted, especially if it is not the same doctor who inserted it.

How long can you use Mirena?
Mirena is effective for 8 years when used for pregnancy prevention (contraception). Are you using Mirena for this reason? If so, Mirena must be removed or replaced no later than after 8 years.

Mirena is effective for 5 years for excessive menstrual blood loss (idiopathic menorrhagia). Are you using Mirena for this reason? If so, Mirena must be removed or replaced if excessive menstrual bleeding recurs or no later than after 8 years.

Mirena is effective for 5 years in protecting against excessive growth of the uterine lining (endometrial hyperplasia) during estrogen-only hormone replacement therapy. Are you using Mirena for this reason? If so, Mirena must be removed after 5 years.

What should you do if you wish to become pregnant or wish to have Mirena removed for another reason?
The device can be easily removed by a doctor at any time, after which pregnancy is possible. Usually, removal is a painless procedure. After removal of Mirena, fertility returns to normal.

Continuation of contraception after removal
If you do not wish to become pregnant, Mirena should not be removed after the 7th day of the menstrual cycle (monthly cycle), unless contraception is ensured by another method (e.g., condom) for at least 7 days before removal. If you have irregular menstrual cycles or no periods, you must use a barrier contraceptive method in the 7 days before removal until menstruation resumes. A new Mirena may also be inserted immediately after removal, in which case no additional protection is needed. If you do not wish to continue with the same method, consult your doctor about other reliable contraceptive methods.

Can you become pregnant after stopping Mirena?
Yes. After removal, Mirena does not interfere with your normal fertility. You may become pregnant during the first menstrual cycle following Mirena removal.

Can Mirena affect your menstrual cycle?
Mirena affects the menstrual cycle: you may experience spotting (light bleeding), shorter or longer cycles, lighter or heavier periods, or no periods at all.
Many women experience frequent spotting or light bleeding in addition to their menstrual periods during the first 3–6 months after Mirena insertion. Some women may have heavy or prolonged bleeding during this time. Inform your doctor, especially if these symptoms persist.
In general, the number of bleeding days and the amount of blood lost each month are likely to gradually decrease. In some women, menstruation stops completely. Because menstrual blood loss is usually reduced with Mirena, most women experience an increase in haemoglobin levels in the blood.
The menstrual cycle returns to normal once the device is removed.

Is it abnormal not to have menstrual periods?
No, not when using Mirena. The hormone’s effect on the uterine lining may cause periods to stop. The monthly thickening of the lining does not occur, and therefore there is nothing to shed during menstruation. This does not necessarily mean you are in menopause or pregnant. Your hormone levels remain normal.
In fact, not having menstrual periods can be a significant health benefit for women.

How can you tell if you are pregnant?
Pregnancy is unlikely in women using Mirena, even if they do not have periods.
If you have missed your period for six weeks and are concerned, you should consider taking a pregnancy test. If the test is negative, no further testing is needed unless you develop other signs of pregnancy, such as nausea and morning vomiting, fatigue, or breast tenderness.

Can Mirena cause pain or discomfort?
Some women experience pain (similar to menstrual cramps) in the first few weeks after insertion. If you have severe pain or if the pain persists for more than three weeks after Mirena insertion, you should return to your doctor.

Does Mirena interfere with sexual intercourse?
Neither you nor your partner should feel the device during intercourse. If you do, avoid sexual intercourse until your doctor has checked that the device is still correctly positioned.

How long should you wait before having sexual intercourse after insertion?
It is best to wait approximately 24 hours after Mirena insertion to allow your body to rest before having sexual intercourse. Depending on when in the menstrual cycle Mirena is inserted, you may need to use a barrier contraceptive (such as condoms) or abstain from sexual intercourse for the first 7 days after insertion (see section 3 “How to use Mirena – When should Mirena be inserted?”).

Can you use internal sanitary pads (tampons) or menstrual cups?
External sanitary pads are recommended. If you use internal sanitary pads or menstrual cups, you must change them very carefully to avoid pulling on the Mirena threads. If you think Mirena may have moved from its position (see “When should you contact your doctor?” for possible signs), avoid sexual intercourse or use a barrier contraceptive method (such as a condom) and contact your doctor.

What happens if Mirena comes out on its own?
It is rare but possible that Mirena is expelled during menstrual flow without you noticing. An unusually heavy flow during menstruation may indicate that Mirena has been expelled from the uterus. It is also possible that part of Mirena has been partially expelled from the uterus (you or your partner may notice this during sexual intercourse). If Mirena is completely or partially expelled, you are no longer protected against pregnancy.

How can you check that Mirena is correctly positioned?
You can check yourself whether the threads are in place. Gently insert a finger into the vagina and feel for the threads at the end of the vagina near the opening of the uterus (cervix).
Do not pull on the threads, as you might accidentally dislodge Mirena. If you cannot feel the threads, this may mean that expulsion or perforation has occurred. In this case, use a barrier contraceptive method (e.g., a condom) and contact your doctor.

If you have any questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Below are the side effects that may occur when Mirena is used for contraception (prevention of pregnancy) and idiopathic menorrhagia (excessive blood loss during menstruation).
The possible side effects associated with the use of Mirena for protection against endometrial hyperplasia (excessive growth of the uterine lining) during hormone replacement therapy have been observed at a similar frequency, except where specified with a note.

Very common side effects (may affect more than 1 in 10 patients):

• Headache
• Abdominal/pelvic pain
• Changes in bleeding patterns, including increased or decreased menstrual bleeding, spotting, oligomenorrhea (infrequent menstruation), and amenorrhea (absence of menstruation)
• Vulvovaginitis* (inflammation of the external genitalia or vagina)
• Genital discharge*

Common side effects (may affect up to 1 in 10 patients):

• Depressed mood / depression
• Migraine
• Dizziness
• Nausea
• Acne
• Hirsutism (excessive hair growth)
• Back pain§
• Infection of the upper genital tract
• Ovarian cysts
• Dysmenorrhea (painful menstruation)
• Breast pain§
• Expulsion of the intrauterine contraceptive device (complete or partial)
• Decreased libido
• Weight gain

Uncommon side effects (may affect up to 1 in 100 patients):

• Alopecia (hair loss)
• Chloasma / skin pigmentation
• Uterine perforation

Frequency not known (frequency cannot be estimated from the available data):

• Hypersensitivity (allergic reaction), including skin rash, urticaria, and angioedema (characterized by sudden swelling, for example of the eyes, mouth, or throat)
• Increased blood pressure

* Studies in endometrial hyperplasia protection: "common"
Studies in endometrial hyperplasia protection: "very common"

Description of specific adverse reactions:
The removal threads may be felt by the partner during sexual intercourse.
When a woman becomes pregnant while using Mirena, the relative risk of ectopic pregnancy is increased.
The risk of breast cancer when Mirena is used for the indication of prevention of endometrial hyperplasia (excessive growth of the uterine mucosa) during estrogen-containing hormone replacement therapy is unknown.
Cases of breast cancer have been reported (frequency not known, see section “Warnings and precautions”).

The following possible side effects have been reported in association with the insertion or removal of Mirena:
Procedural pain, procedural bleeding, vasovagal reaction with dizziness or syncope (fainting). The procedure may trigger a seizure in epileptic patients.
Cases of sepsis (a severe systemic infection that may be fatal) have been reported following the insertion of intrauterine devices.
The risk of breast cancer when Mirena is used for the indication of protection against endometrial hyperplasia (excessive growth of the uterine mucosa) during hormone replacement therapy is unknown.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Mirena

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp". The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Mirena contains

• The active substance is levonorgestrel. One intrauterine system contains 52 mg of levonorgestrel.
• The other components are: elastomeric polydimethylsiloxane, anhydrous colloidal silica, polyethylene, barium sulfate, iron oxide.

Description of the appearance of Mirena and contents of the pack

• 1x1 sterile intrauterine system for intrauterine use.
• 5x1 sterile intrauterine system for intrauterine use. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Bayer AG
Leverkusen - Germany
Italian Representative: Bayer S.p.A. - Viale Certosa, 130 - 20156 Milan, Italy.
Manufacturer:
Bayer Oy
Pansiontie, Turku - Finland

Other sources of information
Detailed and up-to-date information on this medicinal product is available by scanning the QR code on the package leaflet, the outer carton, and the reminder card using a smartphone. The same information is also available at the following URL: www.pi.bayer.com/mirena/it and on the AIFA website (https://www.aifa.gov.it/home)
[QR code on the package leaflet to be inserted at national level]

The following information is intended exclusively for physicians or healthcare professionals

INSERTION INSTRUCTIONS

• Medical examination / consultation Prior to insertion, the woman must be informed about the efficacy, risks—including signs and symptoms of these risks as described in the Package Leaflet—and adverse effects of Mirena. A complete gynecological examination, including a pelvic examination and breast examination, must be performed. A cervical smear should be carried out if necessary, according to the gynecologist's assessment. Pregnancy and sexually transmitted infections must be ruled out, and any genital tract infections should be adequately treated before insertion. The position of the uterus and the size of the uterine cavity must be determined. Correct placement of Mirena at the fundus of the uterus is particularly important to ensure uniform endometrial exposure to the progestin, prevent expulsion of the device, and optimize its efficacy. Therefore, the insertion instructions must be followed carefully. Since the insertion technique differs from other intrauterine systems, proper training in the correct insertion technique is essential. Insertion and removal of the device may cause some pain and bleeding. Vasovagal reactions leading to fainting or, in epileptic patients, seizures may occur. Because irregular bleeding or spotting is common during the first few months after Mirena insertion, any endometrial pathology must be excluded before insertion. In women using Mirena for contraception who wish to continue its use and who develop vaginal bleeding after starting estrogen replacement therapy, endometrial pathology must be ruled out. Similarly, careful diagnostic evaluation is necessary if irregular bleeding occurs during prolonged treatment.

• Infrequent bleeding/amenorrhea Infrequent bleeding and/or amenorrhea gradually develop in approximately 20% of fertile women using Mirena. By the end of the eighth year of Mirena use, 26% and 34% of Mirena users experience infrequent bleeding and amenorrhea, respectively. Pregnancy should be considered if menstruation does not occur within 6 weeks of the previous period. Repeating a pregnancy test is not necessary in amenorrheic women unless other signs of pregnancy are present. When Mirena is used in combination with continuous estrogen replacement therapy, amenorrhea typically develops gradually in most women during the first year after insertion.

• Expulsion Partial expulsion may reduce the efficacy of Mirena. If partial expulsion occurs, Mirena must be removed. A new system may be inserted at the time of removal provided that pregnancy has been excluded.

• Missing threads If the removal threads are not visible at the cervix during follow-up examinations, an ongoing pregnancy must be ruled out. The threads may have been drawn into the uterine cavity or cervical canal and may reappear during the next menstrual period. If pregnancy has been excluded, the threads can usually be located by gently sounding with an appropriate instrument. If the threads cannot be located, expulsion or uterine perforation should be considered. Ultrasound may be used to verify correct positioning of the device. If ultrasound is not available or unsuccessful, an abdominal X-ray may be used to locate Mirena.

• Enlarged follicles Since the contraceptive action of Mirena is primarily local, ovulatory cycles with follicular rupture generally occur in women of reproductive age. Occasionally, follicular atresia is delayed and follicular growth continues. These enlarged follicles cannot be clinically distinguished from ovarian cysts. Ovarian cysts have been reported as an adverse reaction in approximately 7% of women using Mirena. In most cases, these follicles are asymptomatic, although in some cases they may be associated with pelvic pain or dyspareunia. In most cases, ovarian cysts resolve spontaneously within 2–3 months. If resolution does not occur, ultrasound monitoring and other appropriate diagnostic and therapeutic measures are recommended. Surgical intervention is rarely required.

• Insertion and removal/replacement
  Insertion It is strongly recommended that Mirena be inserted only by healthcare providers experienced in Mirena insertion and/or adequately trained in the proper insertion technique. Prior to insertion, the patient must be carefully evaluated for any contraindications to IUS use. Pregnancy must be excluded before insertion. Consider the possibility of ovulation and conception prior to using this product. Mirena is not intended for use as a post-coital contraceptive (see section 4.3 and section 4.4 Medical examination/consultation).

Table 1: When to insert Mirena in women of reproductive age

In case of difficult and/or particularly painful insertion or bleeding during or after insertion,
the possibility of uterine perforation should be considered and appropriate measures taken, such as
gynecological examination and ultrasound.
After insertion, the woman should be re-examined 4–12 weeks later to check the threads
and confirm that the device is in the correct position.
Gynecological examination alone (including thread check) may not be sufficient to exclude
partial perforation.

Removal/replacement
See the Summary of Product Characteristics for removal/replacement.

Contraception: The system must be removed or replaced no later than after 8 years.

Continuation of contraception after removal

• If the woman wishes to continue using the same method, a new system may be inserted at the time of removal.
• If the woman does not wish to continue with the same method but does not desire pregnancy, the device must be removed within 7 days of the onset of menstruation in women of reproductive age, provided the woman has regular menstrual cycles. If the device is removed at other times during the cycle, or if the woman does not have regular menstrual cycles and has had sexual intercourse during the week prior to removal, pregnancy may occur. To ensure continuous contraceptive protection, a barrier contraceptive method (such as condoms) must be used starting at least 7 days before removal. After removal, the new contraceptive method must be started immediately (follow the instructions for use of the new contraceptive method).

Replacement idiopathic menorrhagia: The system should be removed or replaced if symptoms of replacement idiopathic menorrhagia recur. If symptoms have not recurred after 5 years of use, continued use of the system may be considered. Remove or replace no later than after 8 years.

Prevention of endometrial hyperplasia during estrogen replacement therapy: The system must be removed after 5 years.

Mirena is removed by gently pulling on the threads with a dressing forceps. The use of excessive force or sharp instruments during removal may cause the system to break.
After removal of Mirena, the system should be examined to confirm its integrity and complete removal. During difficult removals, in isolated cases it has been reported that the hormone-containing cylinder has slipped over the horizontal arms, concealing them within. Once device integrity is confirmed, this situation does not require further intervention. The protrusions on the horizontal arms usually prevent complete detachment of the cylinder from the T-shaped body. If the threads are not visible, the position of the system should be established by ultrasound or other methods. If the device is located within the uterine cavity, it may be removed using a thin forceps. Dilation of the cervical canal or other surgical procedure may be necessary.

• Pregnancy If pregnancy occurs in a woman with Mirena in situ, the system should be removed as soon as possible, since an intrauterine contraceptive left in place may increase the risk of spontaneous abortion or preterm delivery. Removal of Mirena, as well as uterine exploration, may provoke spontaneous abortion. An ectopic pregnancy must be excluded. In women who wish to continue the pregnancy and in whom the system cannot be removed, the woman must be informed of the risks and possible consequences of preterm delivery on the fetus. In such cases, the pregnancy must be closely monitored. The woman must be warned to report immediately any symptoms indicating pregnancy complications, such as cramp-like abdominal pain with fever.