FE | Risk Minimisation Patient
Essential information
Mirena® product description: Mirena® is a levonorgestrel-releasing intrauterine system (IUS) containing a total of 52 mg of levonorgestrel.
Indication: Contraception for up to 5 (6) years. Idiopathic menorrhagia. Protection from endometrial hyperplasia during estrogen replacement therapy for up to 5 years.
Contraindications: Known or suspected pregnancy; progestogen-dependent tumors, e.g. breast cancer; current or recurrent pelvic inflammatory disease; cervicitis; Lower genital tract infection; Postpartum endometritis; infected abortion during the past three months; conditions associated with increased susceptibility to infections; cervical dysplasia; uterine or cervical malignancy; undiagnosed abnormal uterine bleeding; congenital or acquired uterine anomaly including fibroids if they distort the uterine cavity; acute liver disease or liver tumor; hypersensitivity to the active substance or to any of the excipients.
Ectopic pregnancy: Women with a previous history of ectopic pregnancy, tubal surgery or pelvic infection carry a higher risk of ectopic pregnancy. The possibility of ectopic pregnancy should be considered in the case of lower abdominal pain - especially in connection with missed periods or if an amenorrheic woman starts bleeding. The absolute risk of ectopic pregnancy with Mirena® users is low due to the overall reduced likelihood of pregnancy in Mirena® users compared to non-users of any contraception. In a large prospective comparative non-interventional cohort study with an observation period of 1 year, the ectopic pregnancy rate with Mirena® was 0.02%. In clinical trials, the absolute rate of ectopic pregnancies with Mirena® was approximately 0.1% per year, compared to 0.3-0.5 % per year in women not using any contraception. However, if a woman becomes pregnant with Mirena® in situ, the relative likelihood of this pregnancy being ectopic is increased.
Enlarged follicles: 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. Sometimes atresia of the follicle is delayed and folliculogenesis may continue. These enlarged follicles cannot be distinguished clinically from ovarian cysts. 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.
Perforation: Perforation or penetration of the uterine corpus or cervix by an intrauterine contraceptive may occur, most often during insertion, although it may not be detected until sometime later, and may decrease the effectiveness of Mirena®. Such a system must be removed; surgery may be required. In a large prospective comparative non-interventional cohort study in IUD users (N = 61,448 women) with a 1-year observational period, the incidence of perforation was 1.3 (95% CI: 1.1–1.6) per 1,000 insertions in the entire study cohort; 1.4 (95% CI: 1.1–1.8) per 1,000 insertions in the Mirena® cohort and 1.1 (95% CI: 0.7–1.6) per 1,000 insertions in the copper IUD cohort. The study showed that both breastfeeding at the time of insertion and insertion up to 36 weeks after giving birth were associated with an increased risk of perforation. Both risk factors were independent of the type of IUD inserted.
Table 1: Incidence of perforation per 1,000 insertions for the entire study cohort observed over 1 year, stratified by breastfeeding and time since delivery at insertion (parous women)
|
|
BREASTFEEDING AT TIME |
NOT BREASTFEEDING AT TIME |
|---|---|---|
|
Insertion ≤ 36 weeks after delivery |
5.6 |
1.7 |
|
Insertion > 36 weeks after delivery |
1.6 |
0.7 |
Extending the observational period to 5 years in a subgroup of this study (N=39,009 women inserted with Mirena® or copper IUD, 73% of these women had information available over the complete 5 years of follow-up), the incidence of perforation detected at any time during the entire 5-year period was 2.0 (95% CI: 1.6–2.5) per 1,000 insertions. Breastfeeding at the time of insertion and insertion up to 36 weeks after giving birth were confirmed as risk factors, also in the subgroup that were followed up for 5 years.The risk of perforation may be increased in women with fixed retroverted uterus.
Re-examination after insertion should follow the guidance given under the heading "Medical examination/consultation" of the Mirena® SmPC, which may be adapted as clinically indicated in women with risk factors for perforation.
Expulsion: 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, leading to loss of contraceptive protection. Partial expulsion may decrease the effectiveness of Mirena®. As Mirena® decreases menstrual flow, increase of menstrual flow may be indicative of an expulsion.
Psychiatric disorders: Depressed mood and depression are well-known undesirable effects of hormonal contraceptive use. Depression can be serious and is a well-known risk factor for suicidal behavior and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.
Pelvic infection: As with other gynecological or surgical procedures, severe infection or sepsis (including group A streptococcal sepsis) can occur following IUD insertion, although this is extremely rare. If the woman experiences recurrent endometritis or pelvic infections or if an acute infection is severe or does not respond to treatment within a few days, Mirena® must be removed.
Warnings and precautions for use: Migraine, focal migraine with asymmetrical visual loss or other symptoms indicating transient cerebral ischemia; exceptionally severe headache; jaundice; marked increase in blood pressure; severe arterial disease such as stroke or myocardial infarction; acute venous thromboembolism. For full product information see package insert. For further information please contact Bayer
Undesirable effects: Undesirable effects are more common during the first months after the insertion and subside during prolonged use. Very Common undesirable effects (occurring in more than 10% of users) include uterine/vaginal bleeding including spotting, oligomenorrhea, amenorrhea and benign ovarian cysts.
In fertile women, the average number of spotting days/months decreases gradually from nine to four days during the first six months of use. The percentage of women with prolonged bleeding (more than eight days) decreases from 20% to 3% during the first three months of use. In clinical studies during the first year of use, 17% of women experienced amenorrhea of at least three months duration. By the end of Year 6 of Mirena® use, prolonged bleeding and irregular bleeding are experienced by 2% and 15% of Mirena® users, respectively; amenorrhea occurs in 24% and infrequent bleeding in 31% of Mirena® users.
The frequency of benign ovarian cysts depends on the diagnostic method used and, in clinical trials, enlarged follicles have been diagnosed in 12% of the subjects using Mirena®. Most of the follicles are asymptomatic and disappear within three months.
Adverse reaction by MedDRA system organ classes
|
SYSTEM ORGAN CLASS |
VERY COMMON |
COMMON |
UNCOMMON |
RARE |
|---|---|---|---|---|
|
Psychiatric disorders |
|
Depressed |
|
|
|
Nervous system disorders |
|
Headache |
Migraine |
|
|
Vascular disorders |
|
Dizziness |
|
|
|
Gastrointestinal disorders |
|
Abdominal pain |
Abdominal distension |
|
|
Skin and subcutaneous |
|
Acne |
Alopecia |
Rash |
|
Musculoskeletal, connective |
|
Back pain |
|
|
|
Reproductive system and |
Benign ovarian cysts |
Pelvic pain |
Uterine perforation* |
|
|
General disorders and |
|
|
Edema |
|
|
Investigations |
|
Weight increase |
|
|
The most appropriate MedDRA term is used to describe a certain reaction and its synonyms and related conditions.
- This frequency is based on a large prospective comparative non-interventional cohort study in IUD users which showed that breastfeeding at the time of insertion and insertion up to 36 weeks after giving birth are independent risk factors for perforation. In clinical trials with Mirena® that excluded breastfeeding women, the frequency of perforation was "rare". Return to content
Bayer AG, 13342 Berlin, Germany. www.Bayer.com
CI – confidence interval; IUD – intrauterine device; IUS – intrauterine system; SmPC – Summary of Product Characteristics
- Mirena® Summary of Product Characteristics. Return to content
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