Pharmacological properties MIRENA IUD:
levonorgestrel – progestogen used in gynecology as progestagenovy component in oral contraceptives and hormone replacement therapy or oral contraceptives at itself, containing only progestogen and subcutaneous implants. Levonorgestrel may also be introduced into the uterus with an intrauterine system. This allows to use very low doses, because the hormone released directly into the body.
Mirena is characterized by mainly local effect of progestogen into the womb. High concentrations of levonorgestrel in the endometrium reduces the function of receptors of endometrial estrogen and progesterone, making the endometrium becomes insensitive to the circulating estradiol, as well as mark a pronounced antiproliferative effect. During the application MIRENA marked morphological changes in the endometrium and a weak local reaction to an alien object. Thickening cervical mucus to prevent the passage of sperm cervical canal. The local environment of the uterus and tubes suppresses ovarian function and mobility of sperm, preventing fertilization. Some patients suppressed ovulation.
The study of contraceptive efficacy MIRENA IUD conducted mainly by comparing it with various copper intrauterine devices. At the moment, they cover 13 000 women / year of MIRENA IUD to the overall pregnancy 0.16 per 100 women / year.
Using MIRENA not alter fertility in the future. Approximately 80% of women who wish to become pregnant, pregnant for 12 months after removal of the system.
The nature of menstruation is the result of direct action of levonorgestrel on the endometrium and does not display the ovulation cycle. Clear differences in the development of follicles, ovulation, or in the production of estradiol and progesterone in women with different character of menstruation does not. In the process of inactivation of endometrial proliferation in the initial phase of the first few months may be increased spotting. Over time, a strong inhibition of endometrial proliferation leads to a reduction in the duration and volume of menstrual bleeding while using MIRENA IUD. Neobilnye menstruation often move in oligomenorrhea or amenorrhea. Even with amenorrhea patients who use MIRENA IUD normally functioning ovaries and maintained levels of estradiol.
MIRENA IUD can be successfully used in the treatment of idiopathic menorrhagia. In women with menorrhagia the amount of menstrual bleeding decreased by 88% after the third month of the system. Menorrhagia caused by submucosal fibroids, may produce a less pronounced positive reaction. Reduction of menstruation leads to increased levels of hemoglobin in the blood. Mirena also facilitates dysmenorrhea.
Effectiveness in preventing MIRENA IUD endometrial hyperplasia during prolonged treatment with estrogens was equally high when administered orally and transdermally estrogen. The incidence of hyperplasia during estrogen therapy, only 20%. In clinical studies involving 201 MIRENA IUD women in perimenopausal period and 259 women postmenopausal within five years of follow up was not a single case of endometrial hyperplasia in the group of patients in postmenopaualnom period.
After the introduction of the initial allocation MIRENA IUD levonorgestrel into the uterine cavity is 20 mg / day. This provides a constant level of concentration of levonorgestrel in plasma, which for the first few weeks after the administration set at 0.4-0.6 nmol / L (150-200 pg / ml) in women of childbearing age, and approximately 1 nmol / l (300 pg / ml) in women receiving estrogen replacement therapy. After prolonged use for 12, 24 and 60 months in young women in the concentrations of plasma levonorgestrel 180 ± 66 pg / ml, 192 ± 140 pg / ml and 159 ± 60 pg / ml. We use MIRENA in postmenopausal concentrations of levonorgestrel in plasma were 276 ± 119 pg / ml, 196 ± 87 pg / ml and 152 ± 43 pg / ml, respectively. Due to the low level of levonorgestrel in plasma systemic effects of progestogen has been minimal.
Levonorgestrel when taken orally is rapidly and completely absorbed, its absolute bioavailability of approximately 90%. Levonorgestrel is bound to plasma albumin and globulin, sex hormone binding (SHBG). The relative distribution (free, albuminsvyazanny and SHBG-bound) depends on the concentration of SHBG in the blood plasma. In the form of free steroid is only about 2.5% of the total drug in plasma, but 47.5 and 50% are associated with SHBG and albumin, respectively. For the average volume of distribution of levonorgestrel is about 137 liters, the level of excretion of metabolites from blood plasma – about 5.7 l / h. The half-life of levonorgestrel – 14-20 h after a single dose. Levonorgestrel is excreted as metabolites in approximately equal proportions with urine and feces. Little or metabolites are inactive pharmacologically. The primary metabolite are excreted in the urine is tetragidronorgestrel, which accounts for about 10% of the total volume of all radioactive elements, which are excreted in the urine after administration of radiolabeled levonorgestrel.
About 0.1% of the dose of levonorgestrel, which is received by the mother, can be transmitted through breast milk to baby during breastfeeding.
INDICATIONS MIRENA IUD:
Contraception.
Idiopathic menorrhagia.
Prevention of endometrial hyperplasia during estrogen replacement therapy.
APPLICATION MIRENA IUD:
Mirena is introduced into the uterus and be valid for 5 years.
The initial rate of dissolution in vivo is 20 mg / day and after 5 years is reduced to 11 mg / day. The average five-year period the dissolution rate of levonorgestrel is 14 mg / day.
Mirena is packaged in a sterile package, which should not be disclosed to the establishment of the system. When contacting with the tool without the need to adhere to aseptic packaging of preventive measures. If the protective layer of packaging is torn, an intrauterine system should discard as medical waste. On the remote system also comes as medical waste, because it may contain residues of the hormone.
Special instructions for administration are in the package.
Since the technique of introducing this system differs from the technique of introducing other IUDs, it is necessary to pay special attention to the mastery of skills (technique) correct installation of the system.
Contraindications: pregnancy (including estimated); pelvic inflammatory disease (or recurrence), infections of the lower genital tract, postpartum endometritis, infected abortion in the past 3 months; cervicitis cervical dysplasia, cancers of the cervix or uterus, abnormal vaginal undiagnosed bleeding, congenital or acquired pathology of the cervix or uterus, including fibroids distorting the uterine cavity, the conditions associated with increased susceptibility to infections, acute liver disease or liver tumors, hypersensitivity to the drug.
SIDE EFFECTS MIRENA IUD:
more likely to occur in the first months after the introduction of the system and their severity decreased with time. In addition to the side effects listed in PRECAUTIONS, women using MIRENA IUD, reported the following adverse events (although a causal relationship with Mirren can not always be confirmed):
- Changes in the nature of menstruation and benign ovarian cysts (more than 10% of patients);
- Changes in the nature of bleeding (frequent, prolonged or heavy bleeding, spotting, oligomenorrhea, amenorrhea). Patients of childbearing age average number of days with spotting per month decreased gradually from 9 to 4 days during the first 6 months of use. Percentage of women with prolonged bleeding (more than 8 days) decreased from 20 to 3% in the first 3 months of use. In clinical studies during the first year of 17% of women developed amenorrhea lasting at least 3 months;
- The application of MIRENA in combination with estrogen replacement therapy, most patients in the peri-and postmenopausal women reported spotting and irregular bleeding during the first months of treatment. Over time, bleeding and spotting decreased and almost 40% over the past 3 months the first year of bleeding disappeared. Patients in the perimenopausal period violations menstrual bleeding occurred more frequently in patients than in postmenopausal women.
The frequency of occurrence of benign cysts depends on the method used diagnosis. In clinical trials, increased in size follicles was diagnosed in 12% of patients who use MIRENA. Most cases are increasing the size of the follicles were asymptomatic and disappeared within 3 months.
Common side effects> 1 / 100,
Edema (peripheral or abdominal);
Weight gain;
Depression, irritability, emotional lability;
Headache;
Abdominal pain and / or pelvis, nausea;
acne;
Back pain;
Dysmenorrhea, vaginal discharge, cervicitis, a sense of tension in the chest, mastalgia;
Expulsion system;
Rare side effects> 1 / 1000,
Genital infections;
Hirsutism, hair loss, itchy skin;
Very rare side effects> 1 / 10 000,
Decreased libido;
migraine;
Bloating;
Rash, hives, eczema;
Uterine perforation;
SPECIAL INSTRUCTIONS MIRENA IUD:
the possibility of using Mirena system should be analyzed carefully, if the patient identified any of the following conditions or if these symptoms occurred for the first time while using MIRENA IUD (in these cases, your doctor may raise the question about removing the system): migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia, a severe headache, jaundice, increased blood pressure, or suspected hormone-dependent tumors, including breast cancer, disease of the arteries (stroke or myocardial infarction).
Patients who use oral contraceptives containing only progestin, according to recent epidemiological studies, the risk of venous thromboembolism, but the results of these studies are not statistically significant.
Necessary to make a diagnosis and treatment if symptoms of thrombosis. Symptoms of venous or arterial thrombosis can include: unilateral pain and / or swelling of the legs, sudden severe chest pain, radiating or not radiating to left arm, sudden shortness of breath, sudden cough, intense, prolonged headache; sudden partial or complete loss of vision, double vision in the eyes, promiscuity or speech aphasia, vertigo, collapse (with focal epileptic seizures with or without), weakness, numbness of one side of the body; dysmotility and severe abdominal pain. Symptoms suggestive of thrombosis of retinal vessels: unexplained partial or complete loss of vision, proptosis or the beginning of swelling of the optic nerve, double vision, loss of retinal vessels.
There is no consensus regarding the likely role of varicose veins and thrombophlebitis of superficial veins in venous thromboembolism.
MIRENA IUD used with caution in patients with congenital heart disease, valvular heart when there is a risk for endocarditis. Therefore patients should be prescribed prophylactic antibiotics before the introduction or removal of an intrauterine system.
Low-dose levonorgestrel may affect glucose tolerance, so patients with diabetes who use MIRENA IUD, it is necessary to control the concentration of glucose in the blood.
Irregular bleeding may mask symptoms and signs of polyps or cancer of the endometrium in these cases should consider the diagnostics.
Mirena is not the method of choice for young patients who had no pregnancies, or for patients in postmenopausal women with severe atrophy of the uterus.
Introduction and removal / replacement
Before the introduction of an intrauterine system should inform the patient about the effectiveness, risks and side effects of MIRENA IUD. Should conduct a physical inspection of the patient, including pelvic examination, breast and cervical smear taking. Need to exclude pregnancy and sexually transmitted diseases through, to treat infectious diseases of the pelvis.
Necessary to determine the location of the uterus and the size of the uterus. It is particularly important place in MIRENA IUD uterus to provide the same effect of progestogen on the entire surface of the endometrium. This prevents the expulsion and to achieve maximum efficiency.
The patient must see a doctor in 4-12 weeks after injection system and after a year (or more often if there are medical reasons).
Patients of childbearing age MIRENA injected into the uterine cavity for 7 days from the onset of menstruation. Replace the system to a new Mirena at any time of the menstrual cycle. The system can also be administered immediately after the abortion, if it is held in the I trimester of pregnancy. Postpartum administration – 6 weeks after birth. MIRENA IUD can not be used as a postcoital contraceptive.
When using MIRENA IUD to protect the endometrium during estrogen replacement therapy it can be administered to patients with amenorrhea at any time or in the last days of menstruation.
In the first months of therapy often report irregular bleeding / spotting, so before the introduction of MIRENA recommended to exclude endometrial pathology. If the patient continues to use the system Mirena, which was introduced earlier for contraception, it is necessary to exclude endometrial pathology in cases of abnormal bleeding after the appointment of estrogen replacement therapy. If irregular bleeding appeared during the long use of the system, it is necessary to the proper diagnosis.
MIRENA IUD removed by gently pulling the threads of surgical tweezers. If the thread is invisible, and the system in the uterus, it can be removed with a narrow acute surgical clamp. It may be necessary to hold the cervical canal expansion.
The system must be removed after 5 years. If a patient wishes to continue to use this method, you can immediately introduce a new system.
If pregnancy is desired, women of childbearing age should be carried out removal system during menstruation (menstrual cycle if any). If the system is removed in the middle of the menstrual cycle and the patient during the previous week had sexual relations, it is possible the chance of pregnancy when removing the old system is not replaced by new ones.
Introduction and removal of the system can cause pain and bleeding, dizziness as vazovaginalnuyu reaction; attack in patients with epilepsy.
Oligoamenoreya
Among patients of childbearing age who used Mirren, 20% gradually developed oligomenorrhea and / or amenorrhea. If a woman 6 weeks after the last menstrual period does not come new, you need to test for pregnancy. Conduct a second test for pregnancy in women with amenorrhea should not be, unless noted other signs of pregnancy.
When applied in combination with MIRENA IUD continuous estrogen replacement therapy in most women during the first year there was a gradual disappearance of menstruation.
Infectious diseases of the pelvis
Tube for introducing system prevents contamination of the microorganisms in the process of introducing and minimizes the risk of infection. Patients who use copper intrauterine systems, very high levels of infectious diseases of the pelvis reported in the first month after introduction, over time, decreasing the level of disease. Several studies indicate that the level of infectious diseases of the pelvic organs are lower in patients using MIRENA IUD than using copper intrauterine device. It is proved that a risk factor for pelvic inflammatory disease is the presence of women had multiple sexual partners. Infectious diseases of the pelvis can affect future fertility and increase the risk of ectopic pregnancy.
If relapse endometritis or severe acute inflammation, acute infection, no treatment for several days, MIRENA IUD must be removed. Necessary to carry out bacteriological tests and monitor the patient even if only some of the symptoms of infection.
Expulsion
The symptoms of partial or complete expulsion of intrauterine devices of any: pain and abnormal bleeding. However, the system can get out of the uterus, and invisible to women. Partial MIRENA IUD falling out of the uterus reduces its effectiveness. Since Mirena reduces the amount of menstrual flow, their gain can be a sign of expulsion. If Mirena moved, it should be removed. At the same time we can introduce a new system. The patient must be advise how to check the presence of filaments MIRENA IUD.
Perforation
In very rare cases (usually during the introduction), intrauterine device can penetrate or pierce the wall of the uterus or cervix. Such a system must be removed.
Ectopic pregnancy
Patients with ectopic pregnancy, a history of surgery on the tubes or infectious diseases of genital organs are at increased risk of ectopic pregnancy. The possibility of ectopic pregnancy should be excluded in case of abdominal pain, especially in the absence of menstrual bleeding, or if there are in women with amenorrhea. The frequency of ectopic pregnancies using MIRENA IUD is 0.06 per 100 women / year. This level is below the level of 0.3-0.5 per 100 women / year, calculated for patients who do not use contraception at all.
There are no threads
If during the next inspection to remove the thread visually absent from the cervix, it is necessary to exclude pregnancy. The filaments may be included in the uterus or cervix and may reappear during the next menstrual period. If pregnancy is ruled out, we can determine the location of filaments careful probing of a suitable tool. If you find a thread fails, the system may have left. To verify the correct location of the system, you can use an ultrasonic diagnosis. If the opportunity to spend an ultrasound or not it has not provided the desired results, to determine the placement of MIRENA IUD can spend X-ray examination.
Delayed follicular atresia
Since the contraceptive effect is associated with MIRENA IUD local effect, cycle of ovulation with follicle rupture usually occurs in patients of childbearing age. Sometimes atresia of the follicle is delayed and development of the follicle may continue. These enlarged follicles can not be distinguished clinically from ovarian cysts. Enlarged follicles were diagnosed in 12% of patients using MIRENA IUD. Most of these follicles are asymptomatic, although some may be accompanied by abdominal pain or dyspareunia.
In most cases the enlarged follicles disappear spontaneously over 2-3 months of observation. If this does not happen, we recommend regular ultrasound examinations or other diagnostic / therapeutic procedures. In rare cases, require surgery.
Pregnancy
MIRENA IUD not used during pregnancy or suspected it. If the pregnancy is in the installed system Mirena is recommended to remove the system, since any intrauterine device, which will remain in the uterus during pregnancy increases the risk of miscarriage and premature birth. Delete or palpation of the uterus MIRENA IUD can lead to spontaneous abortion. If you gently pull the system failed to resolve the issue of abortion. If the client wishes to keep the pregnancy and not being able to remove the system, it must be informed about the risk of preterm birth and the consequences of premature birth to a child. Over the course of a pregnancy must be constantly monitored. Necessary to exclude an ectopic pregnancy. The physician should advise the woman to inform him of any symptoms that might be associated with complications of pregnancy, such as paroxysmal abdominal pain accompanied by fever.
Because of the intrauterine administration and the local action of the hormone can not completely exclude teratogenicity (especially virilization). The drug has a high contraceptive efficacy, so the results of clinical experience in pregnancy with Mirena system is limited (but be poinformirovat patient that is not currently observed in congenital defects in children of mothers with MIRENA IUD in cases where the pregnancy develops in the installed system Mirena) .
Lactation
Levonorgestrel passes into breast milk, but the risk of impact on the child’s dose of the drug, released from MIRENA IUD is unlikely.
Undue influence on child growth and development have been identified in the application of a progestogen only 6 weeks after birth. Methods of using progestogen only showed no effect on the quantity or quality of breast milk. Cases of uterine bleeding during lactation – are rare.
Effects on ability to avtotranosportnymi means or mechanism is not known.
INTERACTION MIRENA IUD:
effectiveness of hormonal contraceptives may decrease the drugs that induce liver enzymes, especially cytochrome P450-dependent system – primidone, barbiturates, fenotoin, carbamazepine, rifampicin, oksarbazepin, (possibly) griseofulvin. The effect of these drugs on the contraceptive action MIRENA IUD not been studied, but it is believed that it was insignificant because the drug has a local effect.
OVERDOSE MIRENA IUD:
not mentioned.
