Mirena - instructions for use, doses, side effects, contraindications

The intrauterine system is placed in the conductor tube. The system consists of a white or almost white hormonal-elastomeric core placed on a T-shaped body and covered with an opaque membrane regulating the release of levonorgestrel. The T-shaped body is provided with a loop at one end and two shoulders on the other. Loops are attached to the loop to remove the system. The system and the conductor are free of visible impurities.

Pharmacotherapeutic group:Gestagen

ATX: & nbsp

Levonorgestrel

Pharmacodynamics:

Preparation Mirena^® - intrauterine therapy system (IUD) releasing levonorgestrel, has mainly a local gestagenic effect.Gestagen (levonorgestrel) is released directly into the uterine cavity, which makes it possible to use it at an extremely low daily dose. High concentrations of levonorgestrel in the endometrium contribute to a decrease in the sensitivity of its estrogen and progesterone receptors, making the endometrium immune to estradiol and exerting a strong antiproliferative effect. When using Mirena^® morphological changes in the endometrium and a weak local reaction to the presence of a foreign body in the uterus. Increasing the viscosity of the secretion of the cervix prevents the penetration of sperm into the uterus. Preparation Mirena^® prevents fertilization, due to inhibition of mobility and function of spermatozoa in the uterus and fallopian tubes. Some women experience oppression of ovulation.

Previous use of Mirena^® does not affect the childbearing function. About 80% of women who wish to have a child become pregnant within 12 months after removal of the IUD.

In the first months of application of Mirena^®, due to the process of oppression of endometrial proliferation, initial increase of spotting spotting from the vagina can be observed.Following this, a marked suppression of endometrial proliferation leads to a decrease in the duration and volume of menstrual bleeding in women using Mirena^®. Scant bleeding is often transformed into oligo- or amenorrhea. In this case, the function of the ovaries and the concentration of estradiol in the blood plasma remain normal.

Preparation Mirena^® can be used to treat idiopathic menorrhagia, i.e. menorrhagia in the absence of hyperplastic processes in the endometrium (endometrial cancer, metastatic uterine lesions, submucous or large interstitial myomatous node leading to uterine cavity deformations, adenomyosis), endometritis, extragenital diseases and conditions accompanied by severe hypocoagulation (eg, von Willebrand disease, severe thrombocytopenia) , the symptoms of which are menorrhagia. After 3 months of application of Mirena^®, menstrual blood loss in women with menorrhagia is reduced by 62-94% and 71-95% after 6 months of use. When using Mirena^® for 2 years the effectiveness of the drug (reduction of menstrual blood loss) is comparable with surgical methods of treatment (ablation or resection of the endometrium).A less favorable response to treatment is possible with menorrhagia caused by submucous myoma of the uterus. Reducing menstrual blood loss reduces the risk of iron deficiency anemia. Preparation Mirena^® reduces the severity of symptoms of dysmenorrhea.

Effectiveness of Mirena^® in the prevention of endometrial hyperplasia during constant estrogen therapy was equally high in both oral and percutaneous estrogen applications.

Pharmacokinetics:Absorption

After the administration of Mirena^® levonorgestrel begins to be immediately released into the uterine cavity, as evidenced by the data of measurements of its concentration in the blood plasma. High local exposure of the drug in the uterine cavity, necessary for the local effect of Mirena^® on the endometrium, provides a high concentration gradient in the direction from the endometrium to the myometrium (the concentration of levonorgestrel in the endometrium exceeds its concentration in the myometrium by more than 100 times) and low concentrations of levonorgestrel in the blood plasma (the concentration of levonorgestrel in the endometrium exceeds its concentration in the blood plasma more than 1000 times).The release rate of levonorgestrel in the uterus in vivo initially is approximately 20 μg per day, and after 5 years it is reduced to 10 μg per day.

Distribution

Levonorgestrel binds non-specifically to plasma albumin and specifically to sex hormone binding globulin (SHBG). About 1-2% of circulating levonorgestrel is present as a free steroid, whereas 42-62% is specifically associated with SHBG. During the application of Mirena^® the concentration of SHBG decreases. Accordingly, the fraction associated with SHBG, during the period of application of the Mirena preparation^® The free fraction increases. The average apparent volume of levonorgestrel distribution is about 106 liters.

After the administration of Mirena^® levonorgestrel is detected in the blood plasma after an hour. The maximum concentration is achieved 2 weeks after the administration of Mirena^®. In accordance with the decreasing release rate, the median concentration of levonorgestrel in plasma in women of reproductive age with a body weight above 55 kg decreases from 206 pg / ml (25th-75th percentile: 151-264 pg / ml), determined 6 months later, to 194 pg / ml (146-266 pg / ml) after 12 months and to 131 pg / ml (113-161 pg / ml) after 60 months.

It was shown that body weight and concentration of SHBG in blood plasma influence the systemic concentration of levonorgestrel, i.e. with a low body weight and / or high concentration of SHBG, the concentration of levonorgestrel is higher. In women of reproductive age with a low body weight (37-55 kg), the median concentration of levonorgestrel in the blood plasma is approximately 1.5 times higher.

In postmenopausal women who use Mirena^® simultaneously with the use of estrogen intravaginally or transdermally, the median concentration of levonorgestrel in the blood plasma decreases from 257 pg / ml (25th-75th percentile: 186-326 pg / ml), determined after 12 months, to 149 pg / ml (122-180 pg / ml) after 60 months. When using Mirena^® Simultaneously with oral administration of estrogens, the concentration of levonorgestrel in blood plasma, determined after 12 months, increases to about 478 pg / ml (25th-75th percentile: 341-655 pg / ml), which is due to the induction of HSA synthesis.

Biotransformation

Levonorgestrel is largely metabolized. The main metabolites in the blood plasma are unconjugated and conjugated forms 3α-, 5β-tetrahydrollevorgestrel.Based on research results in vitro and in vivo, the main isoenzyme involved in the metabolism of levonorgestrel is CYP3A4. The isoenzymes CYP2E1, CYP2C19 and CYP2C9 can also participate in the metabolism of levonorgestrel, but to a lesser extent.

Elimination

The total clearance of levonorgestrel from plasma is approximately 1.0 ml / min / kg. Unchanged levonorgestrel is only deduced in trace amounts. Metabolites are excreted through the intestine and kidneys with an excretion coefficient of about 1.77. The half-life in the terminal phase, represented mainly by metabolites, is about one day.

Linearity / nonlinearity

The pharmacokinetics of levonorgestrel depends on the concentration of SHBG, which, in turn, is influenced by estrogens and androgens. When using Mirena^® A decrease in the average concentration of SHBG by approximately 30% was observed, which was accompanied by a decrease in the concentration of levonorgestrel in the blood plasma. This indicates a nonlinear pharmacokinetics of levonorgestrel over time. Taking into account the predominantly local effect of Mirena^®, the effect of changes in systemic levonorgestrel concentrations on the efficacy of Mirena^® unlikely.

Indications:

- Contraception.

- Idiopathic menorrhagia.

- Prophylaxis of endometrial hyperplasia during estrogen replacement therapy.

Contraindications:

- Pregnancy or suspicion of it.

- Existing or recurrent inflammatory diseases of the pelvic organs.

- Infections of the lower parts of the urinary and genital tract.

- Postpartum endometritis.

- Septic abortion within the last three months.

- Cervicitis.

- Diseases accompanied by increased susceptibility to infections.

- Cervical dysplasia.

- Malignant neoplasms of the uterus or cervix.

- Progestogen-dependent tumors, including breast cancer.

- Pathological uterine bleeding of unclear etiology.

- Congenital or acquired abnormalities of the uterus, including fibroids, leading to deformation of the uterine cavity.

- Acute diseases or liver tumors.

- Hypersensitivity to the components of the drug.

- Preparation Mirena^®was not studied in women older than 65 years, so the use of the drug Mirena^® It is not recommended for this category of patients.

Carefully:

In the conditions listed below, Mirena® should be used with caution, after consultation with a specialist. We should discuss the expediency of removing the system in the presence or the first occurrence of any of the following conditions:

- migraine, focal migraine with asymmetric loss of vision or other symptoms indicative of transient ischemia of the brain;

- unusually severe headache;

- jaundice;

- severe arterial hypertension;

- severe circulatory disorders, including stroke and myocardial infarction;

- congenital heart disease or heart valve disease (due to the risk of developing septic endocarditis);

- diabetes.

Pregnancy and lactation:

- Pregnancy

Application of Mirena^® contraindicated in pregnancy or suspected of it.

Pregnancy in women who have the drug Mirena^®, the phenomenon is extremely rare. But if there was a loss of the IUD from the uterine cavity, the woman is no longer protected from pregnancy and should use other methods of contraception before consulting a doctor.

During the application of Mirena^® some women do not have menstrual bleeding. Absence of menses is not necessarily a sign of pregnancy. If a woman does not have menstruation, and at the same time there are other signs of pregnancy (nausea, fatigue, tenderness of the mammary glands), then you need to see a doctor for examination and a pregnancy test. If pregnancy occurs in a woman during the application of the drug Mirena^®, it is recommended to remove the IUD, since any intrauterine contraceptive left in situ, increases the risk of spontaneous abortion, infection, or premature birth. Removal of Mirena^® or probing the uterus can lead to spontaneous abortion. If it is not possible to remove the intrauterine contraceptive gently, the advisability of medical abortion should be discussed. If a woman wants to stay pregnant and the IUD can not be removed, the patient should be informed of the risks, in particular the possible risk of septic abortion in the second trimester of pregnancy, postpartum purulent-septic diseases that can be complicated by sepsis, septic shock and death, and possible consequences premature birth for a child.

In such cases, the course of pregnancy should be carefully monitored. It is necessary to exclude ectopic pregnancy. A woman should be told that she should tell the doctor about all the symptoms that allow her to assume complications of pregnancy, in particular about the appearance of spasticity pain in the lower abdomen, bleeding or spotting from the vagina, and a rise in body temperature. The hormone contained in the preparation of Mirena^®, is released into the uterine cavity. This means that the fetus is exposed to a relatively high local concentration of the hormone, although the blood and the placenta enter the hormone in small amounts. Because of intrauterine application and local action of the hormone, it is necessary to take into account the possibility of a virilizing effect on the fetus. Due to the high contraceptive effectiveness of Mirena^® Clinical experience related to pregnancy outcomes in its use is limited. However, the woman should be informed that at the time of the testimony of the inherent effects caused by the use of the drug Mirena^® in cases of continuation of pregnancy before delivery without removal of the IUD, there are no.

- Breastfeeding period

Breastfeeding of a child when using Mirena^® not contraindicated. About 0.1% of the dose of levonorgestrel can enter the baby's body during breastfeeding. However, it is unlikely that he would pose a risk to the baby at doses released into the uterus after the installation of Mirena's drug^®.

It is believed that the use of Mirena^® six weeks after birth does not have a harmful effect on the growth and development of the child. Monotherapy with gestagens does not affect the quantity and quality of breast milk. There were reports of rare cases of uterine bleeding in women using Mirena^®, during the lactation period.

- Fertility

After the removal of Mirena's drug^® women are recovering fertility.

Dosing and Administration:

The preparation Mirena® is introduced into the uterine cavity and remains effective for 5 years.

The release rate of levonorgestrel in vivo is initially about 20 μg per day and decreases after 5 years to approximately 10 μg per day.The average release rate of levonorgestrel is approximately 14 μg per day for up to five years. Mirena® can be used in women receiving hormone replacement therapy, in combination with oral or transdermal estrogen preparations that do not contain progestins.

With the correct installation of MIRENA®, carried out in accordance with the instructions for medical use, the Pearl index (the indicator reflecting the number of pregnancies in 100 women who use the contraceptive during the year) is approximately 0.2% for 1 year. The cumulative index, reflecting the number of pregnancies in 100 women who use the contraceptive for 5 years, is 0.7%.

Instructions on the use and handling of the IUD

MIRENA® is supplied in a sterile package, which is opened only just before the installation of the intrauterine system. It is necessary to follow the rules of asepsis when handling an opened system. If the sterility of the package appears to be impaired, the IUD should be destroyed as medical waste. You should also handle the removed from the uterus of the IUD, because it contains the remains of a hormone.

Installation, removal and replacement of the intrauterine system

It is recommended that the Mirena® preparation should be installed only by a doctor who has experience with this IUD or is well trained in performing this procedure.

Before installing Mirena®, a woman should be informed about the effectiveness, risks and side effects of this IUD. It is necessary to conduct a general and gynecological examination, including examination of the pelvic organs and mammary glands, as well as a study of a smear from the cervix. It is necessary to exclude pregnancy and sexually transmitted diseases, and inflammatory diseases of the genital organs should be completely cured. Determine the position of the uterus and the size of its cavity. If it is necessary to visualize the uterus before the introduction of the Mirena® IUD, ultrasound examination (ultrasound) of the pelvic organs should be performed. After a gynecological examination, a special instrument is inserted into the vagina, the so-called vaginal mirror, and the cervix is treated with an antiseptic solution. Then, the Mirena® preparation is injected through a thin, flexible plastic tube into the uterus. Especially important is the correct location of Mirena® in the womb,which provides a uniform effect of the gestagene on the endometrium, prevents the expulsion of the IUS and creates conditions for its maximum effectiveness. Therefore, the instructions for the installation of Mirena® should be carefully followed. Since the technique of installation in the uterus of different IUDs is different, special attention should be paid to working out the correct technique for installing a particular system. A woman can feel the introduction of the system, but it should not cause her much pain. Before the introduction, if necessary, you can apply local anesthesia of the cervix.

In some cases, patients may have stenosis of the cervical canal. Do not use excessive force when injecting MIRENA® to such patients.

Sometimes after the introduction of the IUD, pain, dizziness, sweating and pallor of the skin are observed. Women are encouraged to rest for some time after the administration of Mirena®. If after a half-hour stay in a calm position these phenomena do not pass, it is possible that the intrauterine system is incorrectly located. A gynecological examination should be performed; if necessary, the system is removed.In some women, the use of Mirena® causes skin allergic reactions.

The woman needs to be re-examined 4-12 weeks after the installation, and then 1 time a year or more often if there are clinical indications.

In women of childbearing age, Mirena® should be placed in the uterine cavity within 7 days of the onset of menstruation. The Mirena® preparation can be replaced by a new IUD on any day of the menstrual cycle. The IUD can also be installed immediately after the abortion in the first trimester of pregnancy, provided there are no inflammatory diseases of the genitals.

Postpartum IUD placement should be carried out when the uterus involution occurs, but not earlier than 6 weeks after the birth. With prolonged subinvolution, postpartum endometritis should be eliminated and the decision to administer Mirren® before the completion of the involution should be postponed. In case of difficulty in setting the IUD and / or very severe pain or bleeding during or after the procedure, physical examination and ultrasound should be performed immediately to exclude perforation.

To protect the endometrium during estrogen replacement therapy in women with amenorrheaMIRENA® can be installed at any time; in women with persistent menstruation, the setting is performed in the last days of menstrual bleeding or bleeding "cancellation".

Remove the Mirena® preparation by gently pulling on the threads gripped with forceps. If the filaments are not visible, and the system is in the uterine cavity, it can be removed using a traction hook for extracting the IUD. This may require an expansion of the cervical canal.

The system should be removed five years after installation. If a woman wants to continue using the same method, the new system can be installed right after removing the previous one.

If further contraception is necessary in women of childbearing age, the removal of the IUD should be performed during menstruation, provided that the menstrual cycle is maintained. If the system is removed in the middle of the cycle, and a woman has had sexual intercourse during the previous week, she is at risk of becoming pregnant, except when the new system was installed immediately after removing the old one.

The installation and removal of the IUD can be accompanied by certain pain and bleeding.The procedure can cause syncope due to vasovagal reaction, bradycardia or seizure in epileptic patients, especially in patients with a predisposition to these conditions or in patients with cervical stenosis.

After removing Mirena®, you should check the system for integrity. With difficulties with the removal of the IUD, there were isolated cases of slipping of the hormone-elastomeric core on the horizontal shoulders of the T-shaped body, as a result of which they were hidden inside the core. Once the integrity of the IUD is confirmed, this situation does not require additional intervention. Limiters on horizontal arms usually prevent complete separation of the core from the T-shaped body.

Additional information for some groups of patients

Children and teens

MIRENA® is indicated only after the onset of menarche (setting the menstrual cycle).

Older patients

MIRENA® has not been studied in women older than 65 years, so the use of MIRENA® is not recommended for this category of patients.

MIRENA® does not apply to first-choice drugs for postmenopausal women up to 65 years old with severe uterine atrophy.

Patients with hepatic impairment

The drug Mirena® is contraindicated in women with acute diseases or liver tumors (see also the section "Contraindications").

Patients with impaired renal function

The drug Mirena® has not been studied in patients with impaired renal function.

Annex INSTRUCTION ON INTRODUCTION

It is only installed by a doctor using sterile instruments. MIRENA® is delivered with a conductor in a sterile package, which can not be opened before installation.

Do not re-sterilize. Only for single use. Do not use MIRENA® if inner packaging is damaged or open. Do not install MIRENA® after the expiration of the month and year indicated on the package.

Before installation, please read the information on the use of Mirena®.

PREPARATION FOR INTRODUCTION

- Conduct a gynecological examination to establish the size and position of the uterus and to exclude any signs of acute inflammatorydiseases of the genitals, pregnancy or other gynecological contraindications for the installation of Mirena®.

- Visualize the cervix with the help of mirrors and completely process the cervix and vagina with antiseptic solution.

- Use the help of an assistant if necessary.

- Grasp the front lip of the cervix with forceps. With cautious traction forceps straighten the cervical canal. The forceps should be in this position during the entire period of administration of the Mirena® preparation to ensure cautious traction of the cervix in front of the inserted instrument.

- Carefully pushing the uterine probe through the cavity to the bottom of the uterus, determine the direction of the cervical canal and the depth of the uterine cavity (the distance from the outer throat to the bottom of the uterus), exclude septa in the uterine cavity, synechia and submucosal fibroids. In case the cervical canal is too narrow, an extension of the canal is recommended and an anesthetic / paracervical blockade can be used.

INTRODUCTION

1. Open the sterile package (Figure 1). After this, all manipulations should be carried out using sterile instruments and in sterile gloves.

Picture 1

2.Move the slider forward in the direction of the arrow to the farthest position to draw the IUD into the conductor (Figure 2).

Figure 2

IMPORTANT INFORMATION!

Do not move the slider in a downward direction, as this may lead to premature release of Mirren®. If this happens, the system will not be able to be placed again inside the conductor.

3. While holding the slider in the furthest position, set the upper edge of the index ring according to the measured probe distance from the outer throat to the bottom of the uterus (Figure 3).

Figure 3

4. While continuing to hold the slider in the farthest position, push the conductor gently through the cervical canal into the uterus until the index ring is about 1.5-2 cm from the cervix (Figure 4).

Figure 4

IMPORTANT INFORMATION!

Do not force the conductor. If necessary, the cervical canal should be widened.

5. Hold the conductor motionless, slide the slider to the mark to open the horizontal shoulders of the Mirena® preparation (Figure 5). Wait 5-10 seconds until the horizontal hangers fully open.

Figure 5

6.Gently push the conductor inward until the index ring contacts the cervix. The Mirena® preparation should now be in the foundation position (Figure 6).

Figure 6

7. While holding the conductor in the same position, release the MIRENA® preparation by moving the slider as far down as possible (Figure 7). While holding the slider in the same position, carefully remove the conductor by pulling it. Cut the threads so that their length is 2-3 cm from the outer throat of the uterus.

Figure 7

IMPORTANT INFORMATION!

If you have any doubts that the system is installed correctly, check the position of the Mirena® preparation, for example, with ultrasound or, if necessary, remove the system and enter a new, sterile system. Remove the system if it is not completely in the uterine cavity. The remote system should not be reused.

SYSTEM ERASE / REPLACEMENT

Before removing / replacing MIRENA®, please read the instructions for using Mirena®.

The Mirena® preparation is removed by careful pulling by the threads caught by the forceps (Figure 8).

Figure 8

You can install the IUD immediately after deleting the old one.

Side effects:

In most women after the installation of Mirena^® there is a change in the nature of cyclic bleeding. During the first 90 days of using Mirena^® an increase in the duration of bleeding is noted by 22% of women, and irregular bleeding is observed in 67% of women, the incidence of these phenomena decreases, respectively, to 3% and 19% by the end of the first year of its use. Simultaneously, amenorrhea develops in 0%, and rare bleeding - in 11% of patients during the first 90 days of use. By the end of the first year of application, the frequency of these phenomena increases to 16% and 57%, respectively.

When using Mirena^® in combination with prolonged estrogen replacement therapy, in most women during the first year of use, cyclic bleeding gradually ceases.

The table gives data on the incidence of undesirable drug reactions that were reported with Mirena^®. On the frequency of occurrence, unwanted reactions (HP) are divided into very frequent (≥ 1/10), frequent (from ≥ 1/100 to <1/10), infrequent (from ≥ 1/1000 to <1/100), rare ≥ 1/10 000 to <1/1000) and with an unknown frequency. In the table, HP is represented by the classes of the organ system according to MedDRA.The frequency data reflect the approximate incidence of HP, recorded during clinical trials of Mirena^® on indications "contraception" and "idiopathic menorrhagia" with the participation of 5,091 women.

HP, reported in the course of clinical studies of Mirena^® according to the indication "prophylaxis of endometrial hyperplasia in carrying out estrogen replacement therapy" (involving 514 women), were observed with the same frequency, except for the cases indicated by footnotes (*, **).

System-Organ Class	Often	Often	Infrequently	Rarely	Frequency unknown
Immune system disorders					Hypersensitivity to the drug or component of the drug, including rash, hives and angioedema
Mental disorders		Depressed mood, depression
Disturbances from the nervous system	Headache	Migraine
Gastrointestinal disorders	Abdominal pain / pelvic pain	Nausea
Disturbances from the skin and subcutaneous tissues		Acne Hirsutism	Alopecia Itching Eczema
Disturbances from the musculoskeletal system and connective tissue		Backache**
Disorders from the reproductive system and mammary glands	The change in the volume of blood loss, including an increase and decrease in the intensity of bleeding, spotting spotting, oligomenorrhea and amenorrhea Vulvovaginitis * Discharge from the genital tract *	Infections of the pelvic organs Ovarian cysts Dysmenorrhea Pain in the mammary glands ** Breast engorgement The expiration of the IUD (full or partial)		Perforation of the uterus (including penetration)
Survey results					High blood pressure

* "Often" according to the indication "prophylaxis of endometrial hyperplasia during estrogen replacement therapy".

** "Very often" according to the indication "prophylaxis of endometrial hyperplasia during estrogen replacement therapy".

To describe specific reactions, their synonyms and associated states, in most cases the terminology corresponding to MedDRA is used.

Additional Information

If a woman with a medication Mirena^® there comes pregnancy, the relative risk of ectopic pregnancy rises.

A partner can feel the threads during intercourse.

The risk of breast cancer when using the drug Mirena^® according to the indication "prophylaxis of endometrial hyperplasia during estrogen replacement therapy" is unknown. Reported cases of breast cancer (the frequency is unknown, see the section "With caution" and "Special instructions").

Women in the period of breastfeeding were not included in the clinical studies of Mirena^®. At the same time, in large-scale post-marketing safety studies of Mirena^® an increased risk of perforation of the uterus during breastfeeding.

The following HP has been reported in connection with the procedure for setting or removing the drug

Mirena^®: pain during the procedure, bleeding during the procedure, vasovagal reaction associated with the installation, accompanied by dizziness or fainting. The procedure can provoke an epileptic seizure in patients suffering from epilepsy. Infection

After the IUD installation, cases of sepsis (including streptococcal group A sepsis) have been reported (see section "Special instructions").

Overdose:

Not applicable.

Interaction:

The metabolism of gestagens can be enhanced by the simultaneous use of substances that are inducers of enzymes, especially cytochrome P450 isoenzymes involved in the metabolism of medications, such as anticonvulsants (for example, phenobarbital, phenytoin, carbamazepine) and agents for the treatment of infections (eg, rifampicin, rifabutin, nevirapine, efavirenz). The effect of these drugs on the effectiveness of Mirren ® is not known, but it is believed that it is not essential, since the Mirena® preparation has mainly a local action.

Special instructions:

Before installation MIRENA® should exclude pathological processes in the endometrium, because in the first months of its use, irregular bleeding / spotting bleeding is often noted. Also, it is necessary to exclude pathological processes in the endometrium in the event of bleeding after the initiation of estrogen replacement therapy in a woman who continues to use Mirena®, previously prescribed for contraception. Appropriate diagnostic measures must also be taken when irregular bleeding develops during prolonged treatment.

Mirena® is not used for postcoital contraception.

Preparation Mirena^® should be used with caution in women with congenital or acquired valvular heart disease, referring to the risk of septic endocarditis. When installing or removing the IUD, these patients should be prescribed antibiotics for the purpose of prevention.

Levonorgestrel in low doses can affect glucose tolerance, and therefore its concentration in the blood plasma should be monitored regularly in women with diabetes, using the drug Mirena^®. As a rule, correction of the dose of hypoglycemic drugs is not required.

Some manifestations of polyposis or endometrial cancer can be masked by irregular bleeding. In such cases, an additional examination is needed to clarify the diagnosis.

Preparation Mirena^® does not apply to drugs of the first choice, either for young, never pregnant women, or for women in the postmenopausal period with severe atrophy of the uterus.

The available data indicate that the use of Mirena^® does not increase the risk of developing breast cancer in postmenopausal women under the age of 50 years. Due to limited data obtained during the study of Mirena^® by the indication "prophylaxis of endometrial hyperplasia in the conduct of estrogen replacement therapy," the risk of breast cancer when using Mirena^® on this indication can not be confirmed or refuted.

- Oligo- and amenorrhea

Oligo- and amenorrhea in women of fertile age develops gradually, approximately in 57% and 16% of cases by the end of the first year of application of the drug Mirena^® respectively.

If menses are absent within 6 weeks after the start of the last menses, pregnancy should be excluded. Repeated pregnancy tests for amenorrhea are not necessary if there are no other signs of pregnancy.

When the preparation Mirena^® used in combination with estrogen replacement therapy in a continuous regime, most women gradually develop amenorrhea within the first year.

- Inflammatory diseases of the pelvic organs (PID)

The tube-conductor helps to protect the preparation Mirena^® from infection during the installation, and the device for the administration of Mirena^® It is specially designed to minimize the risk of infection.PID in patients using the IUD, often refer to diseases transmitted sexually. It has been established that the presence of multiple sexual partners is a risk factor for PID. PID can have serious consequences: they are able to disrupt the reproductive function and increase the risk of ectopic pregnancy.

As with other gynecological or surgical procedures, severe infection or sepsis (including group A streptococcal sepsis) can develop after the IUD insertion, although this is extremely rare.

With recurrent endometritis or PID, as well as with severe or acute infections resistant to treatment for several days, Mirena^® must be deleted. If a woman has constant pain in the lower abdomen, chills, fever, pain associated with sexual intercourse (dyspareunia), prolonged or profuse bleeding / bleeding from the vagina, changing the nature of vaginal discharge, you should immediately consult a doctor. Severe pain or fever, which occurs soon after the IUD insertion, may indicate a severe infection that must be treated immediately.Even in cases where only individual symptoms indicate the possibility of infection, bacteriological research and monitoring are indicated.

- Expansion

Possible signs of partial or complete expulsion of any IUD - bleeding and pain. Contractions of the uterus during menstruation sometimes lead to a displacement of the IUD or even to expulsion from the uterus, which leads to an end to the contraceptive effect. Partial expulsion may decrease the effectiveness of Mirena's drug^®. Since the preparation Mirena^® reduces menstrual blood loss, its increase can indicate the expulsion of the IUD. A woman is recommended to check the threads with her fingers, for example, during showering. If a woman has detected signs of displacement or prolapse of the IUD or has not groped for threads, sexual intercourse or other methods of contraception should be avoided, and a doctor should be consulted as soon as possible.

If the position is incorrect, the IUD should be removed. At the same time, a new system can be installed.

It is necessary to explain to a woman how to check the threads of Mirena's drug^®.

- Perforation and penetration

Perforation or penetration of the body or cervix of the IUD is rare,mainly during the installation, and may reduce the effectiveness of Mirena's drug^®. In these cases, the system should be removed. If the diagnosis of perforation and migration of the IUD is delayed, complications such as adhesions, peritonitis, intestinal obstruction, intestinal perforation, abscesses or erosion of adjacent internal organs can occur. The risk of uterine perforation is elevated in women with breastfeeding. It is possible to increase the risk of perforation during IUD insertion after delivery and in women with fixed uterine bend.

- Ectopic pregnancy

Women with an ectopic (ectopic) pregnancy in history, who underwent operations on the fallopian tubes or infection of the pelvic organs are at a higher risk of ectopic pregnancy. The possibility of an ectopic pregnancy should be considered in case of abdominal pain, especially if it is combined with the cessation of menstruation, or when a woman with amenorrhea starts bleeding. The frequency of ectopic pregnancy with Mirena^® is approximately 0.1% per year. Absolute risk of ectopic pregnancy in women using Mirena^®, is low.However, if a woman with Mirena^® there is a pregnancy, the relative probability of an ectopic pregnancy is higher.

- Loss of threads

If gynecological examination of the strand for removal of the IUD can not be detected in the cervical region, pregnancy should be excluded. Threads can be drawn into the uterine cavity or cervical canal and become visible again after another menstrual period. If pregnancy is excluded, the location of the strands can usually be determined by careful probing with the appropriate instrument. If it is not possible to detect the filaments, it is possible that the IUS has expelled from the uterine cavity. To determine the correct location of the system, you can use ultrasound (ultrasound). If it is unavailable or unsuccessful to determine the location of Mirena's drug^® use X-ray examination.

- Ovarian Cysts

Because the contraceptive effect of Mirena^® is mainly due to its local effect, in women of fertile age, ovulatory cycles with rupture of follicles are usually observed.Sometimes atresia of the follicles is delayed, and their development can continue. Such enlarged follicles are clinically impossible to distinguish from ovarian cysts. About cysts of the ovaries as an adverse reaction was reported in approximately 7% of women who used the drug Mirena^®. In most cases these follicles do not cause any symptoms, although sometimes they are accompanied by pain in the lower abdomen or pain during sexual intercourse.

As a rule, the ovarian cysts disappear on their own for two to three months of observation. If this does not happen, it is recommended to continue monitoring with ultrasound, as well as the provision of medical and diagnostic measures. In rare cases, it is necessary to resort to surgical intervention.

- Application of Mirena^® in combination with estrogen replacement therapy

When using Mirena^® in combination with estrogen it is necessary to additionally take into account the information specified in the instruction manual for the corresponding estrogen.

The excipients contained in Mirena^®

T-shaped base of Mirena^® contains barium sulfate, which becomes visible during X-ray examination.

It should be borne in mind that the MIRENA® preparation does not protect against HIV infection and other sexually transmitted diseases!

Additional information for patients

Regular inspections

The doctor should examine you in 4-12 weeks after the installation of the IUD, in the future, regular medical examinations are required at least once a year.

Consult your doctor as soon as possible if:

- You have ceased to feel the threads in the vagina.

- You can find the bottom end of the system.

- You assume that you are pregnant.

- You feel constant pain in the abdomen, fever, or notice a change in the usual nature of vaginal discharge.

- You or your partner feel pain during intercourse.

- You noted sudden changes in the menstrual cycle (for example, if you had menstruation poor or absent, and then there was constant bleeding or pain, or menstruation became excessively plentiful).

- You have other medical problems, such as migraine headache or severe recurring headache, sudden visual impairment, jaundice, increased blood pressure, or any other diseases and conditions listed under "Contraindications" and "Use with caution."

What to do if you want to get pregnant or remove Mirena^® for other reasons

Your doctor can easily remove the IUD at any time, after which the pregnancy becomes possible. Usually the removal is painless. After the removal of Mirena's drug^® the childbearing function is restored.

When pregnancy is undesirable, the drug Mirena^® must be removed no later than the seventh day of the menstrual cycle. If the drug Mirena^® will be deleted later than the seventh day of the cycle, barrier methods of contraception (for example, a condom) should be used for at least seven days before it is removed. If using Mirena^® there are no menstruation, seven days before the removal of the IUD, it is necessary to start using barrier contraceptive methods and continue using them until menstruation resumes. You can also install a new Navy immediately after you delete the previous one; in this case, no additional measures of protection from pregnancy is required.

How long can I use Mirena^®

Preparation Mirena^® provides protection from pregnancy for five years, after which it should be removed.At your desire it is possible to install a new IUD after removing the old one.

Restoration of the ability to conceive (can I get pregnant after stopping the use of Mirena^®)

Yes, you can. After the preparation Mirena^® will be removed, it ceases to affect your normal reproductive function. Pregnancy can occur during the first menstrual cycle after the removal of Mirena's drug^®.

Influence on the menstrual cycle (can the drug Mirena^® affect your menstrual cycle)

Preparation Mirena^® affects the menstrual cycle. Under its influence, menstruation can change and acquire the character of smearing excreta, become longer or shorter, leak with more abundant or leaner bleeding than usual, or even stop altogether.

In the first 3-6 months after the installation of Mirena^® in many women, in addition to their usual menstruation, frequent bloody spotting or meager bleeding. In some cases during this period there are very abundant or prolonged bleeding. If you have found these symptoms, especially if they do not disappear, tell your doctor.

Most likely, when using Mirena^® with each month the number of days of bleeding and the amount of blood lost will gradually decrease. Some women eventually find that they have completely stopped menstruating. Since the amount of blood lost with menstruation when using Mirena^®, usually decreases, in most women there is an increase in hemoglobin in the blood.

After system removal the menstrual cycle is normalized. Absence of menstruation (is it normal not to have menstruation)

Yes, if you apply Mirena^®. If after the installation of Mirena^® You noted the disappearance of menstruation, this is due to the influence of the hormone on the mucous membrane of the uterus. Monthly thickening of the mucosa does not occur, therefore, there is no rejection of it during menstruation. This does not necessarily mean that you have reached menopause or that you are pregnant. The concentration in the blood plasma of your own hormones remains normal.

In fact, the absence of menstruation can be a great advantage for a woman's comfort.

How can you find out if you are pregnant?

Pregnancy in women using the drug Mirena^®, even if they are not menstruating, is unlikely.

If you do not have menstruation for six weeks and you are concerned about it, take a pregnancy test. In case of a negative result, additional tests are not necessary if you have no other signs of pregnancy, such as nausea, fatigue or tenderness of the mammary glands.

Can the preparation Mirena^® cause pain or discomfort

Some women experience pain (resembling menstrual pain) in the first two to three weeks after the installation of the IUD. If you feel severe pain or if the pain continues for more than three weeks after the system is installed, contact your doctor or the hospital where you have been placed with Mirena®.

Does the drug Mirena^® on intercourse

Neither you nor your partner should feel the IUD during intercourse. Otherwise, sexual acts should be avoided until your doctor is satisfied that the system is in the right position.

What time should pass between the installation of Mirena^® and sexual intercourse

It is best to give your body a break, to refrain from having sexual intercourse within 24 hours after the introduction of Mirena in the uterus^®. However, the contraceptive effect of Mirena^® has since the installation.

Can I use tampons

It is recommended to use sanitary napkins. If you use tampons, they should be changed very carefully, so as not to pull the threads of Mirena's drug^®.

What happens if the drug Mirena^® spontaneously out of the uterus

Very rarely during menstruation, an IUS expulsion from the uterine cavity may occur. An unusual increase in blood loss in menstrual bleeding may mean that the drug Mirena^® fell through the vagina. Partial expulsion of the IUD from the uterine cavity to the vagina is also possible (you and your partner may notice this during intercourse). With a complete or partial exit of Mirena^® from the uterus, its contraceptive effect ceases immediately.

By what signs can be judged that the drug Mirena^® is in place

You can check for yourself if the filaments of Mirena^®, after you have run out of menstruation.After the end of menstruation carefully enter your finger into the vagina and grope the threads at the end, near the entrance to the uterus (cervix).

Do not pull thread, since you can accidentally pull out the drug Mirena^® from the uterus. If you are unable to grope for a thread, consult a doctor.

Effect on the ability to drive transp. cf. and fur:

Not observed.

Form release / dosage:

The intrauterine therapy system is 20 μg / 24 hours.

Packaging:1 intrauterine therapeutic system levonorgestrel 20 mcg / 24 hours is placed in a sterile blister of TYVEK material and polyester (PETG or APET). Blister together with instructions for use are placed in a cardboard box.

Storage conditions:

In the dark place at a temperature of no higher than 30 ° C. Keep out of the reach of children.

Shelf life:

3 years.

To enter not later than the expiry date stated on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014834 / 01

Date of registration:03.03.2009 / 10.04.2012

The owner of the registration certificate:Bayer OyBayer Oy Finland

Manufacturer: & nbsp

BAYER, OY Finland

Representation: & nbspBAYER, AOBAYER, AO