Pharmacokinetics Mirena
Diffusion of levonorgestrel from the vertical rod T-shaped device is continuously at 20 mg / day. A few weeks after installation of the device in plasma concentrations are 0.4-0.6 nmol / L (150-200 pg / ml) in women of childbearing age, and about 1 nmol / L (300 pg / ml) in women receiving substitution estrogen therapy. After a long (12, 24 and 60 months), the presence of the device in the uterus of levonorgestrel concentration in the plasma of young women was (180 ± 66), (192 ± 140) (159 ± 60) pg / ml, respectively, in postmenopausal women – (276 ± 119) (196 ± 87) and (152 ± 43) pg / ml. These concentrations are low and because of this systemic effect is minimal progestin.
When administered levonorgestrel is rapidly and completely absorbed, absolute bioavailability approaches 90%. Levonorgestrel binds serum albumin and globulin, sex hormone binding (SHBG). The relative distribution (free, bound to albumin, associated with SHBG) depends on the concentration of SHBG in serum. Only about 2.5% of levonorgestrel in serum in free form, whereas 47.5 and 50% are associated with SHBG and albumin, respectively. The average volume of distribution of levonorgestrel is about 137 liters, the rate of metabolic clearance from serum – about 5.7 l / h. Terminal T1 / 2 of levonorgestrel in serum after a single dose is within 14-20 hours Levonorgestrel in the form of metabolites released at about the same ratio in the urine and feces. Metabolites have low pharmacological activity or do not have it all. The main metabolite in urine – tetragidronorgestrel, which accounts for 10% of the radioactivity detected in urine after administration of levonorgestrel with a radioactive metkoy.Okolo 0.1% received doses of levonorgestrel, a mother can pass the milk to the baby.
Pharmacodynamics Mirena
Mirena IUD – intrauterine system (IUS), releasing levonorgestrel, has mainly local progestogenic effects. Progestin (levonorgestrel) is released directly into the uterus, it can be used in extremely low daily dose. High concentrations of levonorgestrel in the endometrium contribute to reduced sensitivity to estrogen and progesterone receptors, making the endometrium unreceptive to estradiol and exerting a strong antiproliferative effect. When using MIRENA IUD observed morphological changes in the endometrium and a weak local reaction to the presence in the uterus of a foreign body. Thickening of the mucosa of cervical canal prevents the penetration of sperm into the uterus. Mirena IUD prevents fertilization by inhibition of the mobility and function of sperm into the uterus and fallopian tubes. Some women experience depression and ovulation.
Clinical Pharmacology Mirena
Studies of contraceptive efficacy MIRENA IUD conducted mainly by comparing it with the efficiency of various copper IUDs. To date, these studies covered 13 000 person-years of MIRENA IUD ; the overall incidence of pregnancy was 0.16 per 100 women per year.
Prior use MIRENA IUD has no effect on future fertility: fertility is restored after removal of the IUD after 12 months in 80% of women.
In the first months of due process MIRENA IUD oppression endometrial proliferation may be a strengthening of the initial spotting. After this marked suppression of the endometrium leads to a decrease in the duration and volume of menstrual bleeding in women using MIRENA IUD . Scanty bleeding is often transformed into an oligo-or amenorrhea. The function and ovarian estradiol levels in the blood remain normal.
Mirena IUD can be used for the treatment of idiopathic menorrhagia. By the end of the third month since the installation of MIRENA IUD in women with menorrhagia, the amount of menstrual bleeding decreased by 88%. When menorrragii caused by submucosal fibroids, the effect of treatment is less pronounced. Reduced menstrual blood loss reduces the risk of iron deficiency anemia. Mirena IUD also facilitates the severity of dysmenorrhea.
The effectiveness of MIRENA IUD in the prevention of endometrial hyperplasia during continuous estrogen therapy was equally high as with oral or transdermal application of estrogen for. Observed with estrogen monotherapy the incidence of endometrial hyperplasia was 20%. In a clinical study MIRENA IUD was used in 201 women in the perimenopausal and 259 postmenopausal women, during the observation period of 5 years in a cohort of women who were postmenopausal, no cases of endometrial hyperplasia.
Statement Mirena
Contraception, idiopathic menorrhagia, protection from endometrial hyperplasia during estrogen replacement therapy.
Contraindications Mirena
Hypersensitivity to the drug, pregnancy or suspicion of it, and inflammatory diseases of the pelvic organs, infections of the lower genital tract, postpartum endometritis, septic miscarriage within the last 3 months, cervicitis disease, accompanied by an increased susceptibility to infections, cervical dysplasia with atypia ; malignant processes of the uterus or cervix, abnormal uterine bleeding of unknown etiology, congenital or acquired abnormalities of the uterus, including fibroids, leading to deformation of the uterine cavity, acute disease or liver tumors.
Dosage and administration Mirena
Intrauterine. The initial release rate of levonorgestrel in vivo is approximately 20 mg / day, it gradually decreases, and after 5 years is approximately 11 mg / day. The average rate of release of levonorgestrel – about 14 mg / day for up to 5 years.
Mirena IUD can be used in women receiving hormone replacement therapy, in combination with oral or transdermal estrogen preparations containing no progestogen.
Instructions for using the Navy and handling
Mirena IUD is supplied in sterile packaging, which reveal just before IUD. With the opening of the system must be handled with aseptic precautions. If the sterile package appears damaged, the Navy should be destroyed as medical waste. The same should apply to and removed from the uterus Navy, because it contains the remains of the hormone. With a conductor used to be treated as hospital waste, and with its outer carton and inner packaging blister – as household waste. Special instructions for installing the Navy are in the package.
Since the installation of various equipment the Navy in the uterus is different, special attention should be paid to perfect the proper technique install a particular system.
Installation and removal or replacement of the Navy
Before installing MIRENA IUD women should be informed about the effectiveness, risks and side effects of the IUD. Necessary to carry out general medical and gynecological examination, including examination of the pelvic organs and mammary glands, as well as the smear of the cervix. It is necessary to exclude pregnancy and disease, sexually transmitted diseases, and pelvic infection should be completely healed. Determine the position of the uterus and the size of its cavity. It is especially important right location at the bottom of MIRENA IUD uterus, which provides uniform exposure progestogen on the endometrium, prevents the expulsion of the IUD and creates the conditions for its maximum effectiveness. Therefore, you should carefully comply with instructions for installing MIRENA IUD . The woman must be re-examined 4-12 weeks after installation, and then once a year or more frequently if clinically indicated.
Mirena IUD in women of childbearing age should be established in the uterus within 7 days of onset of menstruation. Mirena IUD can be replaced by a new Navy any day of the menstrual cycle. CPA can also be installed immediately after the abortion I trimester of pregnancy. Postpartum installation should be delayed for 6 weeks. Do not use MIRENA IUD for postcoital contraception. In women without menstrual periods, to protect the endometrium during the replacement of estrogen therapy, Mirena IUD can be installed at any time, in women with retained menstruation installation is carried out in the last days of menstruation or withdrawal bleeding.
Prior to the installation MIRENA IUD should be excluded pathological processes in the endometrium, as in the first months of its use have been frequently reported irregular bleeding and spotting. You should also avoid the pathological processes in the endometrium in case of bleeding after the replacement of estrogen therapy in women who continued to use MIRENA IUD , previously established for contraception. Appropriate diagnostic measures should be taken as well as irregular bleeding occur during prolonged treatment.
MIRENA IUD was removed by gently pulling the strings captured with forceps. If the threads are not visible, and the system is in the uterus, it can be removed with a narrow vaginal mirror. You may need to expand the cervical canal.
System must be removed within 5 years after installation. At the same time, if a woman wants to continue using the same method can be installed a new IUD.
If pregnancy is desired, women of childbearing age should carry out removal of IUD during menstruation, provided that the menstrual cycle is saved. If the system is removed at mid-cycle, and the woman in the previous week had sexual intercourse, she is at risk of pregnancy, except when the new system was installed immediately after removing the old one.
Installation and removal of IUDs may be associated with certain pain and bleeding. The procedure can cause fainting due vazovagusnoy reaction or convulsive seizures in epilepsy patients.
Pregnancy and breastfeeding Mirena
MIRENA IUD can not be used during pregnancy or suspicion of it. If pregnancy occurs in women during use MIRENA, recommended to remove the IUD because any contraceptive left in situ, increasing the risk of miscarriage and premature birth. Removing MIRENA IUD or sounding of the uterus may also lead to miscarriage. If you carefully remove the intrauterine device is impossible, you need to consider the feasibility of abortion. If a woman wants to continue the pregnancy, it should be informed about the risk and possible consequences of premature birth to a child. In such cases, for during pregnancy should be carefully monitored. Necessary to exclude an ectopic pregnancy. She should explain that she should report any symptoms suggestive of pregnancy complications, in particular about the type of colic pain in the abdomen, accompanied by fever.
Despite the use of intrauterine and local action of the hormone can not completely exclude its teratogenic effects (especially virilization). Due to the high contraceptive effectiveness of MIRENA IUD clinical experience related to the outcome of pregnancy in its application is limited. However, the woman should be informed that at present the certificate of birth defects caused by the use of MIRENA IUD in cases of continuing pregnancy until delivery without removal of IUD, no.
Levonorgestrel has been detected in breast milk, but it is unlikely that it has added risk to the child at doses released Mirren IUD , located in the uterine cavity.
It is assumed that the use of any method of contraception progestogen only 6 weeks after giving birth does not have a major impact on child growth and development. Progestin only methods do not affect the quantity and quality of breast milk. Reported on rare occasions, uterine bleeding in women using MIRENA IUD , during lactation.
Interaction Mirena
The effectiveness of hormonal contraceptives may be reduced when taking medications that alter liver enzymes work, in particular primidona, barbiturates, phenytoin, carbamazepine, rifampicin, oxcarbazepine; suggest that griseofulvin acts the same way. The effect of these drugs on the contraceptive activity MIRENA IUD is not known, it is probably not significant because Mirena IUD has mainly local effects.
Precautionary measures Mirena
Recent epidemiological studies show that women who receive a mini-pill containing only progestogen, there may be some increased risk of venous thromboembolism, but these findings were not statistically significant. Nevertheless, the detection of symptoms of thrombosis, you should immediately take the appropriate diagnostic and therapeutic measures.
Women should consult a doctor if symptoms develop venous or arterial thrombosis, which can include: unilateral leg pain and / or swelling, sudden severe chest pain, with or without irradiation in the left arm, sudden shortness of breath, sudden onset of coughing; any unusual, severe, prolonged headache; sudden partial or complete loss of vision, diplopia, slurred speech or aphasia, dizziness, loss of consciousness and / or without convulsive seizure, weakness or very marked numbness suddenly affecting one side or one part of the body, engine violations, “acute abdomen”.
Symptoms indicating a thrombosis of the retina, are unexplained partial or complete loss of vision, the appearance of ptosis or diplopia century, swelling of the optic nerve papilla or vascular lesions of the retina.
There is no consensus about the possible role of varicose veins and thrombophlebitis of superficial veins in the occurrence of venous thromboembolism is missing.
MIRENA IUD should be used with caution in women with congenital or acquired valvular heart disease, keeping in mind the risk of septic endocarditis. When installing or removing the IUD in these patients, antibiotic prophylaxis should be performed.
Low-dose levonorgestrel may affect glucose tolerance, and therefore its concentration in the blood should be checked regularly for women with diabetes and using MIRENA IUD .
Some manifestations of polyposis, or endometrial cancer may be masked by irregular bleeding. With long and persistent intermenstrual bleeding requiring additional investigation to clarify the diagnosis.
Mirena IUD does not refer to the methods of choice for young or who had never been pregnant women or women in postmenopauzny from severe atrophy of the uterus.
Oligo-and amenorrhea
Oligo-and amenorrhea in women of childbearing age is usually gradual, approximately 20% of cases of MIRENA IUD . If no menses for 6 weeks after the last menstrual period, pregnancy should be excluded. Repeated tests for pregnancy in amenorrhea not required unless there are no other signs of pregnancy.
When MIRENA IUD is used in combination with the constant replacement of estrogen therapy in most women within 5 years, gradually developed amenorrhea.
Pelvic infection
Tube Explorer helps protect against contamination MIRENA IUD micro-organisms during the installation and conductor MIRENA IUD is specifically designed so as to minimize the risk of infection. It is established that multiple sexual partners is a risk factor for pelvic infection. Pelvic infections can have serious consequences: they can disturb the function of fertility and increased risk of ectopic pregnancy.
In recurrent endometritis or pelvic infection, and in severe or resistant to treatment within a few days of acute infection Mirena IUD should be removed.
Even in cases where only some of the symptoms indicate the possibility of infection, showed bacteriological research and monitoring.
Expulsion
Possible signs of expulsion of any IUD – bleeding and pain. However, the system can be expelled from the uterus unnoticed by women. Partial expulsion may decrease the effectiveness of MIRENA IUD. Since Mirena IUD reduces menstrual blood loss, increasing it may indicate expulsion of the IUD.
If the wrong position IUD should be removed. Immediately after removal can be installed a new system.
Women should explain how to check the thread MIRENA IUD.
Perforation
Perforation or penetration of the body or cervix IUD is rare, mainly during the installation. In these cases, the system must be removed.
Ectopic pregnancy
Women with a history of ectopic pregnancy who had undergone surgery on the fallopian tubes or pelvic infection are at high risk of ectopic pregnancy. The possibility of ectopic pregnancy should be considered in case of abdominal pain, especially if it is combined with the cessation of menstruation, or when the patient starts bleeding from amenorrhea. The frequency of ectopic pregnancies in women using MIRENA IUD, was 0.06 per 100 women per year. This is lower than that of women who did not use contraceptives (0.3-0.5 per 100 women per year).
The loss of filaments
If the filaments to remove the IUD in the study during the long observation can not be found in the cervix, it is necessary to exclude pregnancy. The filaments may be drawn into the uterus or cervix and become visible again after the next menstruation. If pregnancy is ruled out, the thread is usually possible to localize by careful probing. If you can not find the thread, it is possible that the Navy had been ejected from the uterus. To determine the correct location of the system, you can use an ultrasonic diagnosis. In the case of its unavailability or failure of containment for MIRENA IUD uses X-rays.
Delayed follicular atresia
Since the contraceptive effect of MIRENA ® due mainly its local effect in 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 were detected in 12% of women using MIRENA IUD. In most cases, these follicles do not cause any symptoms, although they are sometimes accompanied by pain in the abdomen or pain during sexual intercourse.
In most cases the enlarged follicles disappear on their own for 2-3 months of observation. If not, continue ultrasound monitoring, and conducting therapeutic and diagnostic measures and the implementation of relevant recommendations. In rare cases, one has to resort to surgery.
Under the following conditions MIRENA IUD should be used with caution, after consultation with a specialist. Should discuss the advisability of removing the system in the presence or the first occurrence of any of the following conditions:
- Headache, focal migraine with asymmetrical visual loss or other symptoms suggestive of ischemia of the brain;
- An unusually severe headache;
- Jaundice;
- Severe hypertension;
- Confirmed or presumptive diagnosis of hormone-dependent tumors, including breast cancer;
- Severe disease of the cardiovascular system, including stroke and myocardial infarction.
Side effects Mirena
Side effects often develop in the months following the introduction of MIRENA ® in the uterus, with prolonged use they will gradually disappear. The following undesirable effects have been reported in women using MIRENA IUD, but their relationship to the use of the drug was not confirmed in all cases.
To the usual side effects (occurring in more than 10% of women using MIRENA ®) include the changing nature of uterine bleeding and benign ovarian cysts.
Changes in the nature of different types of bleeding (frequent, prolonged or heavy bleeding, spotting, oligo-and amenorrhea) are observed in all women using MIRENA IUD. The average number of days and months, when recorded spotting in women of childbearing age is gradually reduced from 9 to 4 days during the first 6 months after IUD insertion. The proportion of women with prolonged (more than 8 days) bleeding is reduced from 20 to 3% in the first 3 months of use MIRENA IUD. In clinical studies it was found that in the first year MIRENA IUD in 17% of women had amenorrhea lasting at least 3 months.
When MIRENA IUD used in combination with estrogen replacement therapy in the first months of treatment for most women in the peri-and postmenopauznom period observed spotting and irregular bleeding. In the future, their frequency is reduced, and about 40% receiving this treatment of women in the last 3 months the first year of treatment of bleeding in general vanish. Violations of bleeding are more common in the perimenopausal period than in postmenopauzny.
The incidence of benign ovarian cysts depends on the applied diagnostic method. In clinical trials, larger follicles have been diagnosed in 12% of women using MIRENA. In most cases, an increase in the follicles are asymptomatic and disappeared within 3 months.
