Mirena (52mg levonorgestrel)

A total of 647 patients (LNG-IUS [n=437], CMTs [n=135]) diagnosed with HMB were recruited to this non-interventional study from the eight participating countries in Asia. Patient satisfaction was recorded at the last visit (at 12 months or premature discontinuation). At each visit (at 3, 6, and 12 months), patients completed the menorrhagia multi-attribute scale to assess health related quality of life.
 

^{Adapted from: Xu L, et al. International Journal of Women’s Health. 2014;6:547–554.}

Women who had used the LNG-IUS for six months or more completed a standardised questionnaire on reasons for use, user satisfaction and other aspects. A total of 8680 questionnaires were completed by survey participants in 18 countries across Europe and the Near East. The average woman using the LNG-IUS was 38 years old, was married or lived with her partner, and had two children. Overall, 95% of patients were satisfied with the LNG-IUS; the percentage rose to 99% among those using their second LNG-IUS. Reasons mentioned for using the LNG-IUS included the need for contraception (68%), its high efficacy (59%) and the shorter/lighter menstrual bleeding (55%). Of the women with prior bleeding problems, 93% reported an improvement in their symptoms with the LNG-IUS. Participants also rated the reliability, tolerability and convenience of the method highly.
 

^{Adapted from: Romer T and Linsberger D. The European Journal of Contraception and Reproductive Health Care. 2009;14(6):391–398.}

Very common undesirable effects (occurring in more than 10% of users) include uterine/vaginal bleeding including spotting, oligomenorrhoea (infrequent periods) and amenorrhoea (an absence of periods).^[4]

Undesirable effects are more common during the first months after the insertion of Mirena^® (52mg intrauterine delivery system levonorgestrel) and subside during prolonged use.

In less than 1 in 10 women, common side effects of Mirena^® include:^[4]

• ovarian cysts
• painful periods
• weight gain
• depression, nervousness
• headache
• migraine
• abdominal, pelvic or back pain
• nausea
• acne
• increased growth of hair on the face and body
• reduced sex drive
• increased vaginal discharge
• tender, painful breasts
• Mirena^® expulsion

IMPORTANT SAFETY INFORMATION 

Perforation: Most commonly occurs during insertion but can be detected later. If difficult insertion and/or exceptional pain or bleeding, exclude perforation. If perforation is suspected the system should be removed as soon as possible; surgery may be required. Incidence of perforation with Mirena was 1.4 per 1000 insertions in 1-year observational trial. Both breastfeeding and insertion up to 36 weeks post-partum were associated with increased risk of perforation.  

Ectopic pregnancy: The absolute risk of ectopic pregnancy in Mirena users is low. However, when a woman becomes pregnant with Mirena in situ, the relative likelihood of ectopic pregnancy is increased. The possibility of ectopic pregnancy should be considered in the case of lower abdominal pain - especially in connection with missed periods or if an amenorrhoeic woman starts bleeding. 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 pregnancy in users of Mirena was approximately 0.1% per year. This rate is lower than the rate of 0.3-0.5 % per year estimated for women not using any contraception. Women with a previous history of ectopic pregnancy carry a higher risk of a further ectopic pregnancy.  

Pelvic infection: Severe infection or sepsis (including group A streptococcal sepsis) can occur following IUS insertion, although this is extremely rare. Pelvic infection may impair fertility and increase risk of ectopic pregnancy. If symptoms and signs suggest pelvic infection, antibiotics should be started. There is no need to remove Mirena unless the symptoms fail to resolve following 72 hours or unless the woman wishes Mirena to be removed. Mirena must be removed if recurrent endometritis or pelvic infection occurs, or if an acute infection is severe.   

Expulsion: In clinical trials with Mirena in the indication contraception, incidence of expulsion was low (<4% of insertions) and in the same range as that reported for other IUDs and IUSs. Symptoms of the partial or complete expulsion of Mirena may include bleeding or pain.  

For a full list of potential side effects, refer to the Summary of Product Characteristics.

If the patient does experience side effects, they should speak to a doctor, pharmacist or nurse. This includes any possible side effects not listed in the contraception package leaflet.

Reporting adverse events and quality complaints

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Bayer plc.

If you want to report an adverse event or quality complaint, reports can be directed to: Tel: 01182063500 or email: pvuk@bayer.com

Further information is available on the “contact” tab at www.bayer.co.uk.

Women who suffer from idiopathic menorrhagia or require endometrial protection during oestrogen replacement therapy may benefit from Mirena^® (52mg intrauterine delivery system levonorgestrel), which is indicated as a contraceptive option that prevents pregnancy and as a treatment option for both conditions.^[4]

Mirena^® is a long-acting reversible contraceptive device that may be particularly useful in women with idiopathic menorrhagia (also known as heavy menstrual bleeding) who also require (reversible) contraception.^[4]

Mirena® (levonorgestrel-releasing intrauterine system) is a hormone-releasing IUS that helps prevent pregnancy for up to 8 years. Mirena also treats heavy periods for up to 5 years in women. If symptoms do not return after 5 years of use, Mirena can be considered for continued use for up to eight years. Mirena provides endometrial protection for up to 4 years.^[4]

A recent study of more than 6,000 women showed that 73% across all age ranges (18–49) would consider long-acting reversible contraception (LARC) if provided with substantial information from their healthcare professional (HCP) on this method (compared with 38% estimated by HCPs).^[19]

In general, fewer patients are uncomfortable with the idea of having a foreign device inside their bodies if they were previously aware of an LNG-IUS such as Mirena^® (52mg intrauterine delivery system levonorgestrel) vs those who were not aware. This highlights the importance of effective counselling to increase awareness and knowledge.^[20]

A patient may feel reticent to have a Mirena^® (52mg intrauterine delivery system levonorgestrel) inserted, this could be due to the following myths and misperceptions:

• 'Fitting and removal will be painful'.
  • Some patients may feel pain or have some bleeding during insertion or removal^[4]
     
• 'The IUS will perforate and end up somewhere other than my uterus without me knowing'.
  • Perforation occurs in ≥ 1/1000 to < 1/100 women and can be detected by severe pelvic pain and continued heavy bleeding for more than a few weeks after insertion^[21]
     
• 'I will suffer years of irregular bleeding'.
  • Irregular bleeding may happen during the first 3-6 months after insertion, the frequency may decrease with continued use^[4]

Women have other perceptions of IUS which it is important to counsel them around:

• 11% of women consider the hormone level to be very high^[22]
• 30% of women are opposed to having something like a hormonal coil inserted in their body^[22]
• 37% of women feel they don’t know enough about hormonal coils^[22]

However, a study by Whitaker et al showed that adolescents and young women report a positive attitude towards intrauterine contraceptives before and after a 3-minute educational intervention counselling tool, which included information about IUS effectiveness, insertion and removal process, risks, benefits, costs, effect on fertility, menstrual effects, length of use, similarities and differences between types of IUSs available. Attitudes before and after the education intervention were assessed by questionnaire.^[23]

Bayer-led survey of 506 women (105 LARC users) in the UK who were either using and/or considering birth control to understand consumer insights.

Graph adapted from Whitaker AK et al. Contraception. 2008.

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*women who had heard of IUD previously, n=57
**all women, n=144

The intrauterine device Mirena^® contains levonorgestrel 52mg. Levonorgestrel is a well-established progestogen with antioestrogenic activity.^[4]

The effect of hormonal contraceptives such as Mirena^® may be reduced by medicines that increase the amounts of enzymes made by the liver. These include:^[4]

• Medicines used to treat epilepsy
• Antifungal medicines (e.g. griseofulvin, fluconazole, itraconazole, ketoconazole, voriconazole)
• Certain antibiotics (rifampicin & macrolides [e.g. clarithromycin, erythromycin])
• Medicines used to treat HIV and Hepatitis C virus infections (so-called protease inhibitors and non-nucleoside reverse transcriptase inhibitors)
• Certain sedatives (called barbiturates)
• Medicines used to treat chest pain (angina) and/or high blood pressure
• Products containing St John’s Wort (a herbal remedy)

For a full list of medicinal interactions with Mirena^® and contraindications, refer to the Summary of Product Characteristics.

Weight gain has been reported as common (can occur in 1 in 100 or more but less than 1 in 10 women) in women fitted with Mirena^® (52mg intrauterine delivery system levonorgestrel).^[4]

Depression has been reported in 1 in 100 or more but less than 1 in 10 women fitted with Mirena^® (52mg intrauterine delivery system levonorgestrel).^[4]

There is no clear data to establish whether there is an increased risk of suicidal thoughts and behaviour associated with the use of hormonal contraceptives. 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 behaviour and suicide. Women should be advised to contact their physician in case of mood changes and depressive symptoms, including shortly after initiating the treatment.^[24]

Mirena^® (52mg intrauterine delivery system levonorgestrel) will affect the patient’s menstrual cycle.^[4]

Patients fitted with the Mirena^® coil may experience lighter bleeding or some spotting (light bleeding in between periods) and irregular bleeding during the first 3–6 months after it is fitted.^[4]

Some patients may have prolonged or heavy bleeding or an increase in the frequency of bleeding, usually in the first 2–3 months, before a reduction in blood loss is achieved.^[4]

However, overall patients are likely to have fewer days bleeding in each month and might eventually have no periods at all. This is due to the effect of the hormone (levonorgestrel) on the lining of the womb.^[4]

For women with menorrhagia (n=25), Mirena resulted in lighter periods and decreased blood loss by 90% (AR-110 mL) at 3 cycles and 96% (AR 117 mlL) at 6 cycles.^[25]

Study: Randomised, open-label phase 3 trial involving 51 women with objective menorrhagia to compare the efficacy and tolerability of Mirena with oral mefenamic acid.

Fertility is restored immediately and conception can occur from the first cycle following removal of the system.^[26]

Studies have suggested that in women who discontinue Mirena^® (52mg intrauterine delivery system levonorgestrel) for planned pregnancy the pregnancy rate at one year is similar to those who do not use contraception.^[4]

If a patient becomes pregnant while Mirena^® (52mg intrauterine delivery system levonorgestrel) is in place, ectopic pregnancy should be excluded, the system must be removed and termination of the pregnancy should be considered.^[4]

Removal of the intrauterine device (IUD) Mirena^® or probing of the uterus may result in spontaneous miscarriage. If the patient wishes to continue the pregnancy and the system cannot be withdrawn, she should be informed about the increased risks and the possible consequences of premature birth to the infant. Such pregnancies should be closely monitored. The patient should be instructed to report all symptoms that suggest complications of the pregnancy, like cramping abdominal pain with fever.^[4]

For more information and a complete list of contraindications, refer to the Mirena^® Summary of Product Characteristics.

In women of fertile age, Mirena^® (52mg intrauterine delivery system levonorgestrel) is inserted into the uterine cavity within 7 days of the onset of menstruation. It can be replaced by a new system at any time of the cycle.

Mirena^® should be inserted during the patient’s menstrual cycle or within 7 days from the beginning of the period.^[4]

Some patients may find the fitting of a Mirena^® coil uncomfortable.^[4] Managing your patient’s expectations with regards to pain is important and many healthcare professionals have found that talking to the patient throughout the fitting helps to reduce anxiety and make them more comfortable. However, it is important to check with your patient if this would be helpful.

The National Institute for Health and Care Excellence (NICE) guidelines for long-acting reversible contraceptives (LARC) recommends: 'insertion of an intrauterine device/intrauterine system may cause pain and discomfort for a few hours and light bleeding for a few days, and they should be informed about appropriate pain relief'.^[27]

Some patients may feel pain or have some bleeding during insertion or removal of Mirena^®.^[4]

Clinical guidance from the Faculty of Sexual and Reproductive Healthcare states that there is no evidence from current trials to support the use of topical lidocaine, misoprostol or non-steroidal inflammatory drugs (NSAIDs) for improving ease of insertion or reducing pain during insertion of intrauterine devices.^[28]