Mire

Active material: Levonorgestrel
When ATH: G02BA03
CCF: Vnutrymatochnыy contraceptive
ICD-10 codes (testimony): N92, Z30.1
When CSF: 15.11.03
Manufacturer: BAYER SCHERING PHARMA OY (Finland)

PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING

Intrauterine therapy system (VMTS) with the release rate of the active substance 20 ug / 24 hr consists of a white or almost white hormonally elastomeric core, placed on the T-shaped body and covered with an opaque membrane, regulating the release of levonorgestrel. T-shaped body is provided with a loop at one end and two shoulders at the other; attached to a loop of thread to remove. VMTS placed in a tube conductor. The system and the conductor free from visible impurities.

Excipients: polydimethylsiloxane elastomer.

1 PC. – sterile blisters (1) – packs cardboard.

Pharmacological action

Vnutrymatochnыy contraceptive. VMTS, releasing levonorgestrel, It has mainly local progestational. Progestogen (levonorgestrel) discharged directly into the uterus, it can be used in a very low daily dose. High concentrations of levonorgestrel in the endometrium help to reduce the sensitivity of its estrogen and progesterone receptors, making the endometrium insensitive to estradiol, and providing a strong antiproliferative effect. When using Mirena^® observed morphological changes of the endometrium and a weak local reaction to the presence of a foreign body in the uterus. Thickening of the cervical mucous membrane prevents the penetration of sperm into the uterus, Mirena^® prevents fertilization, due to inhibition of the mobility and function of sperm in the uterus and fallopian tubes. In some women, ovulation occurs and depression.

Research contraceptive efficacy of Mirena^® It produced mainly by comparing it with the effectiveness of various copper-containing VMTS. To date these studies covered 13 000 person-years of use Mirena^®; the overall pregnancy rate was 0.16 on 100 women per year.

The previous use of Mirena^® no effect on fertility. Approximately 80% Women, wishing to have a child, pregnancy occurs during 12 months after removal VMTS.

In the first months of Mirena use^®, as a result of the oppression of endometrial proliferation, there may be a strengthening of the original spotting. Thereupon marked suppression leads to a reduction of the endometrium and duration of menstrual bleeding in women, use MIRENA^®. Scarce bleeding is often transformed into an oligo- or amenorrhea. The function of the ovaries and blood estradiol levels remain normal.

Mirena^® It can be successfully used for the treatment of idiopathic menorrhagia, ie. menorrhagia in the absence of genital diseases (eg, such as cancer of the endometrium, metastatic lesions of the uterus, or a large submucosal interstitial node uterine fibroids, resulting in deformation of the uterus, adenomyosis, endometrial hyperplasia, endometritis), extragenital diseases and conditions, accompanied by severe anticoagulation (eg, von Willebrand disease, tyazhelaya thrombocytopenia), symptom is menorrhagia.

By the end of the third month since the installation of Mirena^® female, suffering from menorrhagia, the volume of menstrual bleeding was decreased by 88%. When menorrragii, caused by submucosal fibroid, treatment effect is less pronounced. Reducing menstrual blood loss reduces the risk of iron deficiency anemia. Mirena^® also reduces the severity of dysmenorrhea.

The efficacy of Mirena^® in the prevention of endometrial hyperplasia during continuous estrogen therapy was equally high as in the oral, and in transdermal estrogen. Ionotherapy observed at the incidence of estrogen endometrial hyperplasia reached 20%. In a clinical study MIRENA^® used in 201 perimenopausal women and 259 postmenopausal women; during follow-up 5 age group of women, were in postmenopausal, no cases of endometrial hyperplasia.

Pharmacokinetics

The initial release of levonorgestrel into the uterus after installation Mirena^® is 20 mg / day. This provides a stable concentration of levonorgestrel in plasma, component within a few weeks after installation 0.4-0.6 nmoli / (150-200 pg / ml) women of childbearing age and around 1 nmoli / (300 pg / ml) female, receiving estrogen replacement therapy. After a long (12, 24 and 60 months) Spent Mirena^® in the uterus in young women in the plasma concentration of levonorgestrel were 180 ± 66 pg / ml, 192 + 140 pg / ml 159 ± 60 pg / ml, respectively. Women, using MIRENA and being postmenopausal, levonorgestrel concentrations were 276 ± 119 pg / ml 196 ± 87 pg / ml 152 ± 43 pg / ml, respectively. Due to the low level of levonorgestrel plasma its systemic effect is minimal.

Levonorgestrel binds serum albumin and globulin, binding sex steroids (GTN). Relative distribution (free, bound to albumin, associated with SHBG) It depends on the concentration of SHBG serum. Only about 2.5% levonorgestrel serum is in the form of, whereas 47.5% and 50% associated with SHBG and albumin, respectively. Average V_d levonorgestrel is about 137 l. Rate of metabolic clearance of serum - about 5.7 l /.

Testimony

- Contraception;

- Idiopathic menorrhagia;

- Prevention of endometrial hyperplasia during estrogen replacement therapy.

Dosage regimen

Miren^® is introduced into the uterine cavity, VMTS effectiveness persists for 5 years. The release rate of levonorgestrel in vivo at the beginning is about 20 mg / day and reduced by 5 years approximately 11 mg / day. The average release rate of levonorgestrel – about 14 mg / day for up to five years. Miren^® It can be used in women, receiving hormone replacement therapy, in combination with oral or transdermal estrogen preparations, not containing progestogens.

When properly installed, Mirena^®, carried out in accordance with instructions for use, Pearl Index (index, reflecting the number of pregnancies 100 Women, applying a contraceptive for a year) approximately 0.1% in year. If the expulsion or perforation Pearl Index may rise.

For contraception women of childbearing age Miren^® It should be set into the uterine cavity during 7 days from the beginning of menstruation. Mirena^® It may be replaced by a new VMTS any day of the menstrual cycle. VMTS can also be installed immediately after abortion in the I trimester of pregnancy.

After childbirth VMTS installation should be deferred until the involution of the uterus does not happen, but not less than 6 weeks after giving birth. When the involution significantly delayed the procedure may be postponed until the end of involution. If you have trouble installing VMTS and / or very severe pain or bleeding during or after the procedure, should immediately undertake physical examination and ultrasound to rule out perforation.

In order to prevent endometrial hyperplasia in estrogen replacement therapy amenorrhea in women with Mirena^® It can be set at any time; in women with preserved menstrual installation is made in the last days of menstruation or withdrawal bleeding.

Terms of Use VMTS

Mirena^® It is supplied in sterile packaging, which opened only immediately prior to installation VMTS. Observe aseptic techniques for handling with opening system. If the sterile packaging seems impaired, VMTS should be destroyed as medical waste. It should also be handled and removed from the uterus with VMTS, because it contains residues hormone.

Recommended, to MIRENA^® Install only the doctor, I have experience with this, or a well-trained VMTS completing this procedure.

Before using Mirena^® you must hold a general and gynecological examination, including a pelvic exam and breast, and a study of cervical smear. There should be no pregnancy and disease, sexually transmitted, Genital infection should be completely cured. It should exclude pathological processes in the endometrium, because in the first months of application of this VMTS often observed irregular bleeding / spotting.

You should also exclude the pathological processes in the endometrium in case of bleeding after the initiation of estrogen therapy in women, which continues to use MIRENA^®, previously set for contraception. Appropriate diagnostic measures should be taken as, when irregular bleeding occur during long-term treatment.

Miren^® does not apply to post-coital contraception.

Before installation Mirena^® women should be informed about the effectiveness of, risks and side effects of this VMTS. Determine the position of the uterus and the size of its cavity. Especially important to the correct location of Mirena^® in the bottom of the uterus, which provides uniform exposure to the progestogen on the endometrium, warns expulsion VMTS and create conditions for its maximum efficiency. Therefore, you should carefully to comply with the installation instructions Mirena^®. Since the installation of equipment in the uterus various different VMTS, special attention should be paid to the testing of proper installation techniques specific system.

After installation VMTS woman should be reevaluated through 4-12 weeks, and then 1 once a year or more frequently if clinically indicated.

When you delete VMTS removed by carefully pulling the strings, captured tongs. If the thread is not visible, and the system is in the uterine cavity, you can use the traction hook to retrieve VMTS. This may require an extension of the cervical canal.

The system should be removed through 5 years after installation. If a woman wants to continue using the same method, new system can be installed immediately after the removal of the previous.

If pregnancy is not desired, women of childbearing age should perform the removal VMTS during menstruation provided, that the menstrual cycle, saved. If the system is removed in the middle of the cycle, and the woman in the previous week had sexual intercourse, She is at risk of becoming pregnant, except, when the new system was installed immediately after removing the old.

Installing and removing VMTS may be accompanied by certain pain and bleeding. The procedure can cause fainting due to a vasovagal reaction or seizure in patients with epilepsy.

Side effect

From the digestive system: rarely – nausea.

CNS: rarely – headache.

On the part of the reproductive system: rarely – breast engorgement, menstrual dysfunction (incl. spotting, shortening or lengthening of the cycle, irregular bleeding, oligo- and amenorrhea, dysmenorrhoea).

Dermatological reactions: rarely – acne.

Side effects, usually, not require additional treatment and disappear within a few months.

Perhaps the development of the expulsion of the intrauterine system, uterine perforation, ectopic pregnancy, described the application of other intrauterine.

Side effects are more likely to develop in the first months after the introduction of Mirena^® the uterus; with prolonged use VMTS they fade.

Often (more 10%): uterine / vaginal bleeding, spotting, oligo- and amenorrhea, benign ovarian cysts. The average number of days, When is spotting, women of childbearing age gradually decreases 9 to 4 days per month during the first 6 months after installation VMTS. The number of women with prolonged (more 8 days) bleeding decreases with 20% to 3% first 3 months of Mirena use^®. In clinical studies it has been found, that in the first year of Mirena^® in 17% women had amenorrhea lasting, at least, 3 of the month. When MIRENA^® used in combination with estrogen replacement therapy, in the first months of treatment in the majority of women in the peri- and post-menopausal observed spotting and irregular bleeding. In the future, their frequency decreases, and approximately 40% Women treated with this therapy in the past 3 month of the first year of treatment, bleeding generally disappear. Changes in bleeding pattern often found in perimenopausal period, than postmenopauzny. The frequency of benign ovarian cysts depends on the diagnostic method used. According to clinical trials, enlarged follicles have been diagnosed in 12% Women, used the MIRENA^®. In most cases, an increase of follicles asymptomatic and disappear within a 3 months.

The table below shows adverse effects, the frequency of which corresponds to clinical studies.

If a woman with an installed Mirren^® become pregnant, the relative risk of ectopic pregnancy increases.

Reported cases of breast cancer (Frequency unknown).

Contraindications

- Pregnancy or suspected it;

- Inflammatory diseases of the pelvic organs (incl. recurrent);

- Infections of the lower parts of the urinary tract;

- Malignant neoplasms of the uterus or cervix;

- Postpartum endometritis;

- Septic abortion during the last three months;

- Cervicitis;

- Cervical dysplasia;

- Abnormal uterine bleeding of unknown etiology;

- Progestin-dependent tumors, incl. mammary cancer;

- Diseases, accompanied by increased susceptibility to infections;

- Congenital and acquired abnormalities of the uterus, incl. fibroids, leading to deformation of the uterus;

- Acute liver disease, liver tumors;

- Hypersensitivity to the drug.

Pregnancy and lactation

Mirena^® contraindicated during pregnancy or suspected her.

If pregnancy occurs in a woman while using Mirena^®, It recommended to remove VMTS, tk. Any intrauterine, оставленный in situ, It increases the risk of miscarriage and premature birth. Removal of Mirena^® or probing the uterus can lead to spontaneous abortion. If carefully remove intrauterine impossible, should discuss the feasibility of abortion. If a woman wants to keep the pregnancy and can not be deleted VMTS, should inform the patient about the risks and possible consequences of premature birth to the child. In such cases of pregnancy should be carefully monitored. It is necessary to exclude ectopic pregnancy.

Women should be explained, she should report any symptoms, to suggest pregnancy complications, in particular colicky abdominal pain, febrile.

Because of the use of intrauterine and local action of the hormone can not completely exclude its teratogenic (especially virilization). Due to the high contraceptive efficacy of Mirena^® clinical experience, related to pregnancy outcomes in its application, limited. However, women should be informed, that today the evidence of birth defects, caused by the use of Mirena^® In case of continued pregnancy to childbirth without removing VMTS, no.

Levonorgestrel is excreted in breast milk, but it is unlikely, that it represents a risk to the child at doses, released Mirren^®, located in the uterus.

It is believed, that the use of any method of contraception with only progestogen through 6 weeks after the birth does not adversely affect the growth and development of the child. Contraception with progestogen only does not influence the quantity and quality of breast milk. It was reported about rare cases of uterine bleeding in women, use MIRENA^®, during lactation.

Cautions

It should discuss the feasibility of removing VMTS with or first appearance of any of the following diseases or conditions: migraine, focal migraine with asymmetrical visual loss or other symptoms, indicating a transient cerebral ischemia; unusually severe headache; jaundice; severe hypertension; severe circulatory disorders, incl. stroke, and myocardial infarction.

Some studies have recently shown, that women, taking contraceptives, contain only progestogen, perhaps a slight increase in the risk of venous thrombosis; however, these results are not definite. Nonetheless, When symptoms of deep vein thrombosis, should immediately take appropriate diagnostic and therapeutic measures.

To date, no established, Is there a connection between the varicose veins or superficial thrombophlebitis of the phenomenon of venous thromboembolism. Miren^® should be used with caution in women with congenital or acquired valvular heart disease, bearing in mind the risk of bacterial endocarditis. When installing or removing VMTS these patients should be given antibiotics to prevent.

Levonorgestrel in low doses can affect glucose tolerance, in this connection should regularly monitor the level of glucose in the blood of women with diabetes mellitus, use MIRENA^®. But, usually, there is no need to adjust the therapy of diabetes mellitus during use Mirena^®.

Some manifestations of polyposis or endometrial cancer may be masked by irregular bleeding. In such cases, additional tests to confirm the diagnosis.

Mirena^® It does not refer to the methods of the first audio selection for young women, who have never become pregnant, nor for postmenopausal women with uterine atrophy.

Oligo- and amenorrhea

Oligo- and amenorrhea in women of childbearing age develops gradually, about 20% Mirena use cases^®. If no menses within 6 weeks after the last menstrual period, pregnancy should be ruled. Repeated pregnancy tests with amenorrhea are not binding, unless there are no other signs of pregnancy.

When MIRENA^® is used in combination with constant replacement estrogenic therapy, most women amenorrhea develops gradually in the first year.

Pelvic infection

The tube-conductor helps protect MIRENA^® from microbial contamination during installation, a device for introducing Mirena^® specially designed so, to minimize the risk of infection. When using copper-containing VMTS maximum risk of pelvic infection occurs in the first month after installation; further risk is reduced. A number of studies have shown, that the frequency of pelvic infection in women in the application of Mirena^® below. than when using copper-containing VMTS. Established, that the presence of multiple sexual partners is a risk factor for pelvic infection. Pelvic infection can have serious consequences: impaired fertility and increased risk of ectopic pregnancy.

In cases of recurrent endometritis or pelvic infections, as well as severe or acute infections, resistant to treatment for a few days, MIRENA must be removed.

Even in cases, when only a few symptoms prick the possibility of infection, show bacteriological research and monitoring.

Expulsion

Possible signs of partial or complete expulsion of any VMTS – bleeding and pain. However, the system can be expelled from the uterine cavity unnoticed by women. Partial expulsion may decrease the effectiveness of Mirena^®. As Mirena^® It reduces menstrual blood loss, its increase may indicate expulsion VMTS.

When the wrong position Mirena^® It should be removed. At the same time can be a new system.

It is necessary to explain to the woman, how to check the threads of Mirena^®.

Perforation

Perforation or penetration of the body or the cervix is ​​rare intrauterine, mainly during installation. In these cases, the system should be removed. Possible increased risk of perforation during installation VMTS after childbirth, lactation in women with a fixed bend uterus.

Ectopic pregnancy

Women with ectopic pregnancy history, had undergone surgery on the fallopian tubes or pelvic infection are at higher risk of ectopic pregnancy. The possibility of ectopic pregnancy should be considered in the case of lower abdominal pain, especially if they are combined with the cessation of menstruation, or when a woman starts bleeding with amenorrhea. The frequency of ectopic pregnancy in women, used the MIRENA^®, was 0.06 on 100 women per year. This is lower, than in women, did not use contraception (0.3-0.5 on 100 women per year). The absolute risk of ectopic pregnancy in women, use MIRENA^®, It is low. However, if a woman has installed Mirren^® become pregnant, the relative likelihood of ectopic pregnancy above.

Loss threads

If Gynecology thread to remove VMTS is not detectable in the area of ​​the cervix, Pregnancy must be excluded. The filaments may be pulled into the uterus or cervical canal and become visible again after the next menstruation. If pregnancy is excluded, Location yarns are usually able to determine with the help of careful probing an appropriate tool. If you can not find the thread, perhaps, that there was expulsion from the uterus VMTS. To determine the correct position of the system, You can use ultrasound (US). In the event of downtime or the failure to determine the localization of Mirena^® using X-ray examination.

Delayed follicular atresia

Since the contraceptive effect of Mirena^® mainly due to its local action, women of childbearing age are usually observed ovulatory cycles with follicular rupture. Sometimes atresia of the follicle is delayed, and their development can continue. These enlarged follicles can not be distinguished clinically from ovarian cysts. Enlarged follicles have been found in 12% Women, used the MIRENA^®. In most cases, these follicles causes no symptoms, although they are sometimes accompanied by pain in the lower abdomen or pain during sexual intercourse. In most cases the enlarged follicles disappear spontaneously during two to three months of observation. If this does not happen, it is recommended to continue monitoring using ultrasound, and conducting medical and diagnostic measures. In rare cases it is necessary to resort to surgery.

Effects on ability to drive vehicles and management mechanisms

There was no effect of the drug on the ability to drive vehicles and other activities, require high concentration and speed of psychomotor reactions.

Overdose

With this method of application can not overdose.

Drug Interactions

Perhaps increased metabolism of progestogens while the application substances, are enzyme inducers, especially cytochrome P450 isoenzymes, involved in the metabolism of drugs, such as anticonvulsants (eg, phenobarbital, phenytoin, Carbamazepine) and for the treatment of infections (eg, rifampicin, rifabutin, Nevirapine, efavirenz). The impact of these drugs on the efficacy of Mirena^® unknown, but it is assumed, it is immaterial, because Mirena^® It has mainly local effect.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children, dry, dark place at a temperature no higher than 30 ° C. Shelf life – 3 year.