Mirena Intrauterine Therapy system

COMPOSITION:
1 IUD
levonorgestrel (micronized) 52 mg
Excipients: core made of polydimethylsiloxane elastomer; a membrane of polydimethylsiloxane elastomer containing silicon dioxide colloidal anhydrous 30-40% of the mass.
Other components: Polyethylene T-body containing barium sulfate 20-24% wt., fine brown polyethylene thread dyed with iron oxide black ≤1% wt.
Delivery device: conductor - 1 pc.
The composition is given on 1 Navy with a conductor.
The intrauterine therapeutic system (IUD) is a T-shaped levonorgestrel-releasing construction placed in a conductor tube (conductor components: insertion tube, plunger, index ring, handle and slider). The IUD consists of a white or almost white hormonal elastomeric core placed on a T-shaped body and covered with an opaque membrane that regulates the release of levonorgestrel (20 µg/24 h). The T-body is provided with a loop at one end and two arms at the other; brown threads are attached to the loop to remove the system. The T-shaped design contains barium sulfate, which makes it visible on x-rays. The IUD is free from visible impurities.
Clinico-pharmacological group:
Gestagen.
Pharmachological effect:
IUD Mirena®, which releases levonorgestrel, has a mainly local progestogenic effect. The progestogen (levonorgestrel) is released directly into the uterine cavity, which allows it to be used 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 the Mirena IUD, morphological changes in the endometrium and a weak local reaction to the presence of a foreign body in the uterus are observed. An increase in the viscosity of the secretion of the cervix prevents the penetration of sperm into the uterine cavity, due to a decrease in sperm motility and changes in the endometrium, the likelihood of fertilization of the egg decreases. Some women experience inhibition of ovulation.
Previous use of the Mirena IUD does not affect reproductive function. Approximately 80% of women who want to have a baby become pregnant within 12 months after the IUD is removed.
In the first months of using the Mirena IUD, due to the process of inhibition of endometrial proliferation, there may be an initial increase in "spotting" bloody discharge from the vagina. Following this, a pronounced suppression of endometrial proliferation leads to a decrease in the duration and volume of menstrual bleeding in women using the Mirena IUD. Scanty bleeding often transforms into oligo- or amenorrhea. At the same time, ovarian function and the concentration of estradiol in the blood plasma remain normal.
The Mirena IUD can be used to treat idiopathic menorrhagia, i.e. menorrhagia in the absence of hyperplastic processes in the endometrium (endometrial cancer, metastatic lesions of the uterus, submucosal or large interstitial myomatous node, leading to deformation of the uterine cavity, adenomyosis), endometritis, extragenital diseases and conditions accompanied by severe hypocoagulation (for example, von Willebrand disease, severe thrombocytopenia) symptoms of which is menorrhagia. After 3 months of using the Mirena IUD, menstrual blood loss in women with menorrhagia is reduced by 62-94% and by 71-95% after 6 months of use. When using the IUD Mirena for 2 years, the effectiveness of the drug (reducing menstrual blood loss) is comparable to surgical methods of treatment (ablation or resection of the endometrium). A less favorable response to treatment is possible with menorrhagia due to submucosal uterine myoma. Reducing menstrual blood loss reduces the risk of iron deficiency anemia. IUD Mirena reduces the severity of symptoms of dysmenorrhea.
The effectiveness of the Mirena IUD in preventing endometrial hyperplasia during chronic estrogen therapy was equally high with both oral and transdermal estrogen.
Pharmacokinetics:
The active substance of the Mirena IUD, levonorgestrel, is released directly into the uterine cavity. The calculated in vivo release rate at various time points is shown in Table 1.
Table 1:
Calculated in vivo release rate for Mirena® IUD:
Time Calculated release rate in vivo (mcg/24 h)
Initial stage 20
1 year after the introduction of 18
5 years after the introduction of 10
Average over 5 years 15.
Suction:
After the introduction of the Mirena IUD, levonorgestrel begins to be immediately released into the uterine cavity, as evidenced by the measurement data of its concentration in the blood plasma. The systemic bioavailability of released levonorgestrel is over 90%.
After the introduction of the IUD, Mirena levonorgestrel is detected in the blood plasma after 1 hour. Cmax is 414 pg / ml and is achieved within 2 weeks after administration. In accordance with the decreasing release rate, the median plasma concentration of levonorgestrel in women of reproductive age with a body weight above 55 kg decreases from 206 pg / ml (25-75th percentile: 151 pg / ml - 264 pg / ml), determined through 6 months, up to 194 pg/ml (146 pg/ml-266 pg/ml) at 12 months and up to 131 pg/ml (113 pg/ml-161 pg/ml) at 60 months.
The high local exposure of the drug in the uterine cavity, which is necessary for the local effect of the Mirena® IUD 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 plasma concentrations of levonorgestrel blood (the concentration of levonorgestrel in the endometrium exceeds its concentration in blood plasma by more than 1000 times).
In postmenopausal women using the Mirena IUD simultaneously with the use of estrogen, the median plasma concentration of levonorgestrel decreases from 257 pg / ml (25-75th percentile: 186 pg / ml - 326 pg / ml), determined after 12 months, to 149 pg/ml (122 pg/ml-180 pg/ml) at 60 months. When Mirena® IUD is used simultaneously with oral estrogen, the concentration of levonorgestrel in blood plasma, determined after 12 months, increases to approximately 478 pg / ml (25-75th percentile: 341 pg / ml - 655 pg / ml), which is due to induction synthesis of SHPG.
Distribution:
Levonorgestrel binds nonspecifically to plasma albumin and specifically to sex hormone-binding globulin (SHBG). Less than 2% of circulating levonorgestrel is present as the free steroid.
Levonorgestrel binds to SHBG with high affinity. In this regard, a change in the concentration of SHBG in the blood plasma entails an increase (at a higher concentration of SHBG) or a decrease (at a lower concentration of SHBG) in the total concentration of levonorgestrel in the blood plasma. The concentration of SHBG decreases on average by approximately 20-30% within 1 month after the introduction of the Mirena® IUD, remains at this level during the first year of use and slightly increases thereafter. The average apparent Vd of levonorgestrel is about 106 liters.
It has been shown that body weight and plasma SHBG concentration affect the systemic concentration of levonorgestrel, i.e. with low body weight and / or high concentration of SHBG, the concentration of levonorgestrel is higher. In women of reproductive age with low body weight (37-55 kg), the median plasma concentration of levonorgestrel is approximately 1.5 times higher.
Metabolism:
Levonorgestrel is largely metabolized. The most important metabolic pathways are reduction of the Δ4-3-oxo group and hydroxylation at positions 2α, 1β and 16β followed by conjugation. CYP3A4 is the main enzyme involved in the oxidative metabolism of levonorgestrel. Available in vitro data suggest little significance for CYP-mediated biotransformation reactions for levonorgestrel compared to reduction and conjugation.
Clearance:
The total clearance of levonorgestrel from blood plasma is approximately 1 ml / min / kg. In unchanged form, levonorgestrel is excreted only in trace amounts. Metabolites are excreted through the intestines and kidneys with an excretion rate of approximately 1.77. T1 / 2 in the terminal phase, represented mainly by metabolites, is about a day.
Linearity/Nonlinearity:
The pharmacokinetics of levonorgestrel depends on the concentration of SHBG, which, in turn, is influenced by the concentration of estrogens and androgens. A decrease in the concentration of SHBG leads to a decrease in the total concentration of levonorgestrel in the blood plasma, which indicates the non-linearity of the pharmacokinetics of levonorgestrel depending on time. Given the predominantly local action of the Mirena IUD, the effect of changes in systemic concentrations of levonorgestrel on the effectiveness of the Mirena IUD is unlikely.
INDICATIONS FOR MIRENA:
Contraception
Idiopathic menorrhagia;
Prevention of endometrial hyperplasia during hormone replacement therapy (HRT) with estrogens.
DOSING MODE:
Mirena is inserted into the uterine cavity. Efficiency is maintained for 5 years.
The release rate of levonorgestrel in vivo at the beginning of use is approximately 20 μg/day and decreases to approximately 18 μg/day after one year and to approximately 10 μg/day after 5 years. The average release rate of levonorgestrel is approximately 15 µg/day for up to 5 years.
The Mirena IUD can be used in women receiving oral or transdermal estrogen-only hormone replacement therapy (HRT).
With the correct installation of the Mirena IUD, carried out in accordance with the instructions for medical use, the Pearl index (an indicator reflecting the number of pregnancies in 100 women using a contraceptive during the year) is approximately 0.2%. The cumulative rate, reflecting the number of pregnancies in 100 women using a contraceptive for 5 years, is 0.7%.
INSTRUCTIONS FOR USE OF MIRENA IUD:
IUD Mirena is supplied in a sterile package, which is opened only immediately before the installation of the IUD. Asepsis must be observed when handling an opened system. If the sterility of the packaging appears to be compromised, the IUD should be disposed of as medical waste. The same should be done with the IUD removed from the uterus, since it contains hormone residues.
Insertion, removal and replacement of the IUD:
It is recommended that the Mirena IUD be inserted only by a doctor who is experienced with this IUD or well trained in the procedure.
Before installing the Mirena IUD, a woman should be informed about the effectiveness, risks and side effects of the IUD. A general and gynecological examination should be performed, including examination of the pelvic organs and mammary glands. If necessary, according to the decision of the doctor, a smear from the cervix should be examined. Pregnancy and sexually transmitted diseases should be excluded, and pelvic inflammatory disease 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, an ultrasound of the pelvic organs should be performed. After a gynecological examination, a vaginal speculum is inserted into the vagina and the cervix is treated with an antiseptic solution. Mirena is then inserted into the uterus through a thin, flexible plastic tube. The correct location of the Mirena IUD in the fundus of the uterus is especially important, which ensures a uniform effect of the progestogen on the endometrium, prevents the expulsion of the IUD and creates conditions for its maximum effectiveness. Therefore, you should carefully follow the instructions for installing the Mirena Navy. Since the technique of insertion in the uterus of different IUDs is different, special attention should be paid to working out the correct technique for inserting a particular system. The woman may feel the insertion of the system, but it should not cause her much pain. Before the introduction, if necessary, you can apply a paracervical blockade and / or analgesics.
In some cases, patients may have cervical stenosis. Do not use excessive force when inserting the Mirena IUD in such patients.
Sometimes after the introduction of the IUD, pain, dizziness, sweating and pallor of the skin are noted. Women are advised to rest for some time after the insertion of the Mirena IUD. If these phenomena do not go away after a half-hour stay in a calm position, it is possible that the IUD is not positioned correctly. A gynecological examination should be performed; if necessary, the system is removed. In some women, the use of the Mirena IUD causes allergic skin reactions.
The woman should be re-examined 4-12 weeks after insertion, and then once a year or more often if clinically indicated.
In women of reproductive age, the Mirena IUD should be inserted into the uterine cavity within 7 days from the onset of menstruation.
Mirena can be replaced with a new IUD on any day of the menstrual cycle. The IUD can also be installed immediately after an abortion in the first trimester of pregnancy, provided there are no inflammatory diseases of the genital organs.
The use of an IUD is recommended for women with a history of at least one birth. The installation of the Mirena IUD in the postpartum period should be carried out only after the complete involution of the uterus, but not earlier than 6 weeks after childbirth. With prolonged subinvolution, it is necessary to exclude postpartum endometritis and postpone the decision to insert the Mirena IUD until the involution is completed. In the event of difficulty inserting an IUD and/or severe pain or bleeding during or after the procedure, the possibility of perforation should be considered and appropriate measures taken, such as physical examination and ultrasound.
For the prevention of endometrial hyperplasia during HRT with estrogen-only drugs, in women with amenorrhea, the Mirena IUD can be installed at any time; in women with preserved menstruation, the installation is performed in the last days of menstrual bleeding or bleeding of "cancellation".
Remove the Mirena IUD by gently pulling on the threads captured by the forceps. If the threads are not visible and the system is in the uterine cavity, it can be removed using a traction hook to remove the IUD. This may require the expansion of the cervical canal.
The system should be removed 5 years after installation. If a woman wants to continue using the same method, a new system can be installed immediately after the previous one is removed.
If further contraception is needed in women of reproductive age, the removal of the IUD should be performed within 7 days after the onset of menstruation, provided that the woman has regular periods. If the system is removed at a different time in the cycle, or if the woman has irregular periods and had intercourse during the previous week, the woman is at risk of becoming pregnant. To ensure continuous contraception, a new IUD must be inserted immediately after removal of the previous IUD, or an alternative method of contraception must be initiated.
The insertion and removal of an IUD can be accompanied by some pain and bleeding. The procedure may cause vasovagal syncope, bradycardia or seizures in patients with epilepsy, especially if there is a predisposition to these conditions or in the case of cervical stenosis.
After removing the Mirena IUD, the system should be checked for integrity. In case of difficulties with the removal of the IUD, isolated cases of slipping of the hormonal-elastomer core on the horizontal arms of the T-shaped body were noted, 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 the horizontal arms usually prevent the core from completely separating from the T-body.
Additional information for some groups of patients:
Children and adolescents under 18 years of age: The Mirena IUD is indicated only after the onset of menarche (the establishment of the menstrual cycle).
Elderly patients: The Mirena IUD has not been studied in women over the age of 65, therefore the use of the Mirena IUD is not recommended for this category of patients. IUD Mirena is not a first-choice drug for postmenopausal women up to 65 years of age with severe uterine atrophy.
Patients with impaired liver function: The Mirena IUD is contraindicated in women with acute liver disease or tumors.
Patients with impaired renal function: The Mirena IUD has not been studied in patients with impaired renal function.
INSTRUCTIONS FOR IUD INSERTION:
It is installed only by a doctor using sterile instruments.
IUD Mirena is supplied with a guidewire in a sterile package that must not be opened prior to installation.
Do not re-sterilize. For single use only. Do not use the Mirena IUD if the inner packaging is damaged or opened. Do not install the Mirena IUD after the expiry date stated on the package.
Before installation, you should read the information on the use of the Mirena IUD.
Preparation for the introduction:
Conduct a gynecological examination to determine the size and position of the uterus and to exclude any signs of acute inflammatory diseases of the genital organs, pregnancy or other gynecological contraindications for the installation of the Mirena IUD.
The cervix should be visualized using speculums and the cervix and vagina should be completely cleaned with an antiseptic solution.
If necessary, use the help of an assistant.
Grab the anterior lip of the cervix with forceps. Straighten the cervical canal by gentle traction with forceps. The forceps must be in this position during the entire time of insertion of the Mirena IUD to ensure gentle traction of the cervix towards the inserted instrument.
Carefully moving the uterine probe through the cavity to the bottom of the uterus, you should determine the direction of the cervical canal and the depth of the uterine cavity (the distance from the external os to the bottom of the uterus), exclude septa in the uterine cavity, synechia and submucosal fibroma. If the cervical canal is too narrow, widening of the canal is recommended and pain medication/paracervical block may be used.
Introduction:
Open the sterile package. After that, all manipulations should be carried out using sterile instruments and sterile gloves.
Move the slider forward to its farthest position in order to draw the IUD into the guide tube. You should not move the slider in a downward direction, because. this may lead to premature release of the Mirena IUD. If this happens, the system will not be able to be placed inside the conductor again.
Holding the slider in the farthest position, set the upper edge of the index ring in accordance with the measured probe distance from the external os to the fundus of the uterus.
While continuing to hold the slider in the farthest position, the guidewire should be advanced carefully through the cervical canal and into the uterus until the index ring is about 1.5-2 cm from the cervix. Do not push the conductor with force. If necessary, expand the cervical canal.
Keeping the conductor motionless, move the slider to the mark to open the Mirena horizontal hangers. You should wait 5-10 seconds until the horizontal hangers are fully opened.
Gently push the guidewire inward until the index ring is in contact with the cervix. IUD Mirena should be in the fundus of the uterus.
Holding the conductor in the same position, release the Mirena IUD by moving the slider as far down as possible. While holding the slider in the same position, carefully remove the conductor by pulling on it. Cut the threads so that their length is 2-3 cm from the external os of the uterus.
If the doctor has doubts that the system is installed correctly, the position of the Mirena IUD should be checked, for example, using ultrasound or, if necessary, remove the system and insert a new, sterile system. The system should be removed if it is not completely in the uterine cavity. The remote system must not be reused.
Removal / replacement of the Mirena IUD:
Before removing / replacing the Mirena IUD, you should read the instructions for use of the Mirena IUD.
The Mirena IUD is removed by gently pulling on the threads grasped by the forceps.
A new IUD Mirena can be installed immediately after the removal of the previous one.
SIDE EFFECTS:
In most women, after the installation of the Mirena IUD, a change in the nature of cyclic bleeding occurs. During the first 90 days of using the Mirena IUD, an increase in the duration of bleeding is noted by 22% of women, and irregular bleeding occurs in 67% of women, the frequency of these phenomena decreases to 3% and 19%, respectively, by the end of the first year of its use. At the same time, 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 use, the frequency of these phenomena increases to 16% and 57%, respectively.
When Mirena is used in combination with long-term estrogen HRT in most women during the first year of use, cyclic bleeding gradually stops.
The following are data on the incidence of adverse drug reactions that have been reported with the use of the Mirena IUD. Determining the frequency of adverse reactions: very often (≥1/10), often (from ≥1/100 to <1/10), infrequently (from ≥1/1000 to <1/100), rarely (from ≥1/10000 to <1/1000) and with an unknown frequency. Adverse reactions (ARs) are presented by organ system class according to MedDRA. The frequency data reflect the approximate incidence of adverse reactions reported during clinical trials of the Mirena IUD for the indications "contraception" and "idiopathic menorrhagia" involving 5091 women.
Undesirable reactions:
Immune system: Allergic reactions including rash, urticaria, and angioedema
Mental disorders: Depressed mood, depression
Nervous system: Headache, migraine
Digestive system: Abdominal/pelvic pain, nausea
Skin and subcutaneous tissues: Acne, hirsutism, alopecia, pruritus, eczema, skin hyperpigmentation
Musculoskeletal system: Backache
Reproductive system: Changes in the volume of blood loss, including 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, IUD expulsion (complete or partial), Perforation of the uterus.
ADDITIONAL INFORMATION:
If a woman with a Mirena IUD inserted becomes pregnant, the relative risk of ectopic pregnancy increases.
The partner can feel the threads during intercourse.
The risk of breast cancer when using the Mirena IUD for the indication "prevention of endometrial hyperplasia during HRT with estrogens" is unknown. Cases of breast cancer have been reported (frequency unknown).
The following adverse events have been reported in connection with the insertion or removal of the Mirena IUD: pain during the procedure, bleeding during the procedure, insertion-related vasovagal reaction accompanied by dizziness or fainting. The procedure can provoke a seizure in patients with epilepsy.
Infection:
Cases of sepsis (including group A streptococcal sepsis) have been reported following IUD insertion.
CONTRAINDICATIONS FOR USE:
Pregnancy or suspicion of pregnancy.
Congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity.
Acute pelvic inflammatory disease or a history of pelvic inflammatory disease unless there has been a subsequent intrauterine pregnancy.
Postpartum endometritis or infected abortion in the past 3 months.
Known or suspected uterine or cervical neoplasia or unresolved, abnormal Pap smear.
Genital bleeding of unknown etiology.
Untreated acute cervicitis or vaginitis, including bacterial vaginosis or other lower genital tract infections until infection is controlled.
Acute liver disease or liver tumor (benign or malignant).
Conditions associated with increased susceptibility to pelvic infections.
A previously inserted IUD that has not been removed.
Hypersensitivity to any component of this product.
Known or suspected carcinoma of the breast.
Carefully:
In the following diseases / conditions / risk factors, the Mirena IUD should be used with caution after consultation with a specialist:
Ectopic Pregnancy:
Evaluate women who become pregnant while using Mirena for ectopic pregnancy. Up to half of pregnancies that occur with Mirena in place are ectopic. The incidence of ectopic pregnancy in clinical trials that excluded women with risk factors for ectopic pregnancy was about 1 ectopic pregnancy per 1000 users per year. Tell women who choose Mirena about the risks of ectopic pregnancy, including the loss of fertility. Teach them to recognize and report to their physician promptly any symptoms of ectopic pregnancy. Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy. The risk of ectopic pregnancy in women who have a history of ectopic pregnancy and use Mirena is unknown. Clinical trials of Mirena excluded women with a history of ectopic pregnancy.
Intrauterine Pregnancy:
If pregnancy should occur with Mirena in place, Mirena should be removed. Removal or manipulation of Mirena may result in pregnancy loss. In the event of an intrauterine pregnancy with Mirena, consider the following:
a. Septic abortion
In patients becoming pregnant with an IUD in place, septic abortion—with septicemia, septic shock, and death—may occur.
b. Continuation of pregnancy
If a woman becomes pregnant with Mirena in place and if Mirena cannot be removed or the woman chooses not to have it removed, she should be warned that failure to remove Mirena increases the risk of miscarriage, sepsis, premature labor and premature delivery. She should be followed closely and advised to report immediately any flu-like symptoms, fever, chills, cramping, pain, bleeding, vaginal discharge or leakage of fluid.
c. Long-term effects and congenital anomalies
When pregnancy continues with Mirena in place, long-term effects on the offspring are unknown. As of September 2006, 390 live births out of an estimated 9.9 million Mirena users had been reported. Congenital anomalies in live births have occurred infrequently. No clear trend towards specific anomalies has been observed. Because of the intrauterine administration of levonorgestrel and local exposure of the fetus to the hormone, the possibility of teratogenicity following exposure to Mirena cannot be completely excluded. Some observational data support a small increased risk of masculinization of the external genitalia of the female fetus following exposure to progestins at doses greater than those currently used for oral contraception. Whether these data apply to Mirena is unknown.
Sepsis:
As of September 2006, 9 cases of Group A streptococcal sepsis (GAS) out of an estimated 9.9 million Mirena users had been reported. In some cases, severe pain occurred within hours of insertion followed by sepsis within days. Because death from GAS is more likely if treatment is delayed, it is important to be aware of these rare but serious infections. Aseptic technique during insertion of Mirena is essential. GAS sepsis may also occur postpartum, after surgery, and from wounds.
Pelvic Inflammatory Disease (PID):
Mirena is contraindicated in the presence of known or suspected PID or in women with a history of PID unless there has been a subsequent intrauterine pregnancy. Use of IUDs has been associated with an increased risk of PID. The highest risk of PID occurs shortly after insertion (usually within the first 20 days thereafter). A decision to use Mirena must include consideration of the risks of PID.
a. Women at increased risk for PID
PID is often associated with a sexually transmitted disease, and Mirena does not protect against sexually transmitted disease. The risk of PID is greater for women who have multiple sexual partners, and also for women whose sexual partner(s) have multiple sexual partners. Women who have had PID are at increased risk for a recurrence or re-infection.
b. PID warning to Mirena users
All women who choose Mirena must be informed prior to insertion about the possibility of PID and that PID can cause tubal damage leading to ectopic pregnancy or infertility, or infrequently can necessitate hysterectomy, or cause death. Patients must be taught to recognize and report to their physician promptly any symptoms of pelvic inflammatory disease. These symptoms include development of menstrual disorders (prolonged or heavy bleeding), unusual vaginal discharge, abdominal or pelvic pain or tenderness, dyspareunia, chills, and fever.
c. Asymptomatic PID
PID may be asymptomatic but still result in tubal damage and its sequelae.
d. Treatment of PID
Following a diagnosis of PID, or suspected PID, bacteriologic specimens should be obtained and antibiotic therapy should be initiated promptly. Removal of Mirena after initiation of antibiotic therapy is usually appropriate. Guidelines for PID treatment are available from the Centers for Disease Control (CDC), Atlanta, Georgia.
Actinomycosis has been associated with IUDs. Symptomatic women with IUDs should have the IUD removed and should receive antibiotics. However, the management of the asymptomatic carrier is controversial because actinomycetes can be found normally in the genital tract cultures in healthy women without IUDs. False positive findings of actinomycosis on Pap smears can be a problem. When possible, confirm the Pap smear diagnosis with cultures.
Irregular Bleeding and Amenorrhea:
Mirena can alter the bleeding pattern and result in spotting, irregular bleeding, heavy bleeding, oligomenorrhea and amenorrhea. During the first three to six months of Mirena use, the number of bleeding and spotting days may be increased and bleeding patterns may be irregular. Thereafter the number of bleeding and spotting days usually decreases but bleeding may remain irregular. If bleeding irregularities develop during prolonged treatment, appropriate diagnostic measures should be taken to rule out endometrial pathology.
Amenorrhea develops in approximately 20% of Mirena users by one year. The possibility of pregnancy should be considered if menstruation does not occur within six weeks of the onset of previous menstruation. Once pregnancy has been excluded, repeated pregnancy tests are generally not necessary in amenorrheic women unless indicated, for example, by other signs of pregnancy or by pelvic pain.
Embedment:
Embedment of Mirena in the myometrium may occur. Embedment may decrease contraceptive effectiveness and result in pregnancy. An embedded Mirena should be removed. Embedment can result in difficult removal and, in some cases surgical removal may be necessary.
Perforation:
Perforation or penetration of the uterine wall or cervix may occur during insertion although the perforation may not be detected until some time later. If perforation occurs, pregnancy may result. Mirena must be located and removed; surgery may be required. Delayed detection of perforation may result in migration outside the uterine cavity, adhesions, peritonitis, intestinal perforations, intestinal obstruction, abscesses and erosion of adjacent viscera.
The risk of perforation may be increased in lactating women, in women with fixed retroverted uterus, and during the postpartum period. To decrease the risk of perforation postpartum, Mirena insertion should be delayed a minimum of 6 weeks after delivery or until uterine involution is complete. If involution is substantially delayed, consider waiting until 12 weeks postpartum. Inserting Mirena immediately after first trimester abortion is not known to increase the risk of perforation, but insertion after second trimester abortion should be delayed until uterine involution is complete.
Expulsion:
Partial or complete expulsion of Mirena may occur. Symptoms of the partial or complete expulsion of any IUD may include bleeding or pain. However, the system can be expelled from the uterine cavity without the woman noticing it. Partial expulsion may decrease the effectiveness of Mirena. As menstrual flow typically decreases after the first 3 to 6 months of Mirena use, an increase of menstrual flow may be indicative of an expulsion. If expulsion has occurred, Mirena may be replaced within 7 days of a menstrual period after pregnancy has been ruled out.
Ovarian Cysts:
Since the contraceptive effect of Mirena is mainly due to its local effect, ovulatory cycles with follicular rupture usually occur in women of fertile age using Mirena. Sometimes atresia of the follicle is delayed and the follicle may continue to grow. Enlarged follicles have been diagnosed in about 12% of the subjects using Mirena. Most of these follicles are asymptomatic, although some may be accompanied by pelvic pain or dyspareunia. In most cases the enlarged follicles disappear spontaneously during two to three months observation. Persistent enlarged follicles should be evaluated. Surgical intervention is not usually required.
Breast Cancer:
Women who currently have or have had breast cancer, or have a suspicion of breast cancer, should not use hormonal contraception because breast cancer is a hormone-sensitive tumor.
Spontaneous reports of breast cancer have been received during postmarketing experience with Mirena. Because spontaneous reports are voluntary and from a population of uncertain size, it is not possible to use post-marketing data to reliably estimate the frequency or establish causal relationship to drug exposure. Two observational studies have not provided evidence of an increased risk of breast cancer during the use of Mirena.
Risks of Mortality:
The available data from a variety of sources have been analyzed to estimate the risk of death associated with various methods of contraception. These estimates include the combined risk of the contraceptive method plus the risk of pregnancy or abortion in the event of method failure.
SPECIAL INSTRUCTIONS:
Prior to the installation of the Mirena IUD, pathological processes in the endometrium should be excluded, since irregular bleeding / "spotting" spotting is often noted in the first months of its use. Pathological processes in the endometrium should also be excluded if bleeding occurs after the start of HRT with estrogens in a woman who continues to use the Mirena IUD, previously established for contraception. Appropriate diagnostic measures should also be taken when irregular.
How long can I use the Mirena IUD:
The Mirena IUD provides protection against pregnancy for 5 years, after which it should be removed. A new IUD Mirena can be installed immediately after the removal of the previous one.
Restoring the ability to conceive (Is it possible to get pregnant after stopping the use of the Mirena IUD):
Yes, you can. Once the Mirena IUD is removed, it will no longer interfere with your normal reproductive function. Pregnancy can occur during the first menstrual cycle after removal of the Mirena IUD.
Effect on the menstrual cycle (Can the Mirena IUD affect your menstrual cycle):
The Mirena IUD affects the menstrual cycle. Under its influence, menstruation can change and acquire the character of "smearing" discharge, become longer or shorter, flow with more abundant or less than usual bleeding, or even stop altogether.
In the first 3–6 months after the installation of the Mirena IUD, many women experience, in addition to their normal menstruation, frequent spotting or light bleeding. In some cases, very heavy or prolonged bleeding is noted during this period. If you experience any of these symptoms, especially if they persist, tell your doctor.
It is most likely that with the use of the Mirena IUD, the number of days of bleeding and the amount of blood lost will gradually decrease every month. Some women eventually find that their periods have completely stopped. Since the amount of blood lost during menstruation usually decreases with the use of the Mirena IUD, most women experience an increase in hemoglobin in the blood.
After removing the system, the menstrual cycle is normalized.
Absence of periods (Is it normal not to have periods):
Yes, if you are using the Mirena IUD. If, after installing the Mirena IUD, you noted the disappearance of menstruation, this is due to the effect of the hormone on the uterine mucosa. There is no monthly thickening of the mucous membrane, therefore, it is not rejected during menstruation. This does not necessarily mean that you have reached menopause or that you are pregnant. The plasma concentration of your own hormones remains normal.
In fact, the absence of menstruation can be a big advantage for a woman's comfort.
How can you find out if you are pregnant:
Pregnancy in women using the Mirena IUD, even if they do not have menstruation, is unlikely.
If you haven't had a period in 6 weeks and you're concerned about it, take a pregnancy test. If the result is negative, no further tests are needed unless you have other signs of pregnancy such as nausea, fatigue, or breast tenderness.
Can the Mirena IUD cause pain or discomfort:
Some women experience pain (similar to menstrual cramps) for the first 2–3 weeks after IUD insertion. If you experience severe pain or if the pain continues for more than 3 weeks after the insertion of the system, contact your doctor or the hospital where you had the Mirena inserted.
Does the Mirena IUD affect sexual intercourse:
Neither you nor your partner should feel an IUD during intercourse. Otherwise, sexual intercourse should be avoided until your doctor is satisfied that the system is in the correct position.
How much time should elapse between the installation of the Mirena IUD and sexual intercourse:
The best way to give your body a rest is to refrain from sexual intercourse for 24 hours after Mirena is inserted into the uterus. However, the Mirena IUD has a contraceptive effect from the moment of installation.
Tampons can be used:
The use of sanitary pads is recommended. If you use tampons, you should change them very carefully so as not to pull out the threads of the Mirena IUD.
What happens if the Mirena IUD spontaneously comes out of the uterine cavity:
Very rarely, during menstruation, IUD expulsion from the uterine cavity can occur. An unusual increase in blood loss during menstrual bleeding may mean that the Mirena IUD has fallen out through the vagina. Partial expulsion of the IUD from the uterine cavity into the vagina is also possible (you and your partner may notice this during intercourse). With the complete or partial exit of the Mirena® IUD from the uterus, its contraceptive effect immediately stops.
By what signs can one judge that the Mirena IUD is in place:
You can check for yourself if the Mirena IUD threads are in place after your period has ended. After the end of menstruation, carefully insert your finger into the vagina and feel for the threads at the end of it, near the entrance to the uterus (cervix).
Do not pull the threads, because you may accidentally pull the Mirena out of your uterus. If you can't feel the threads, see your doctor.
Overdose:
Not applicable.
Drug interaction:
The effect of other drugs on the Mirena IUD:
Interaction with drugs that induce or inhibit microsomal liver enzymes is possible, as a result of which the clearance of sex hormones may increase or decrease.
Substances that increase the clearance of levonorgestrel, for example: phenytoin, barbiturates, primidone, carbamazepine, rifampicin, and possibly also oxcarbazepine, topiramate, felbamate, griseofulvin, as well as preparations containing St. John's wort. The effect of these substances on the contraceptive effectiveness of the Mirena IUD is unknown, but it is assumed that it is not important due to the local mechanism of action.
Substances with different effects on the clearance of levonorgestrel: when used together with sex hormones, many HIV or hepatitis C protease inhibitors and non-nucleoside reverse transcriptase inhibitors can either increase or decrease the concentration of progestogen in plasma.
Substances that reduce the clearance of levonorgestrel (enzyme inhibitors), e.g.: strong and moderate inhibitors of CYP3A4, such as azole antifungals (e.g., fluconazole, itraconazole, ketoconazole, voriconazole), verapamil, macrolide antibiotics (e.g., clarithromycin, erythromycin), diltiazem and grapefruit juice may increase plasma concentrations of progestogen.
Mirena storage conditions:
The drug should be stored out of the reach of children at a temperature not exceeding 30 °C.
Mirena shelf life:
Shelf life (before administration) – 3 years. Enter no later than the expiration date indicated on the package.
Package:
IUD (1), sterile blisters (1), carton box.