Mirena 52mg Intrauterine Delivery System *

Pharmacy Only: Prescription

Re-added document

BP22001, REC20852+REC30572+REC30681

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4.2 Posology and method of administration

Method of administration

Mirena is inserted into the uterine cavity. It and is effective for 86 years in the indication contraception and 5 years in the indications idiopathic menorrhagia and protection from endometrial hyperplasia during oestrogen replacement therapy. For timing regarding removal/replacement see section “Removal/Replacement”.

Insertion

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Insertion and removal/replacement

It is strongly recommended that Mirena should only be inserted by physicians/health care professionals who are experienced in Mirena insertions and/or have undergone sufficient training for Mirena insertion. Mirena must be inserted using aseptic technique.

Removal/Replacement

Mirena is removed by gently pulling on the threads with a forceps. If the threads are not visible and the system is in the uterine cavity, it may be removed using a narrow tenaculum. This may require dilatation of the cervical canal or other surgical intervention.

Contraception: The system should be removed or replaced after 86 years in the indication contraception and after 5 years in the indication idiopathic menorrhagia and protection from endometrial hyperplasia during oestrogen replacement therapy. If the user wishes to continue using the same method, a new system can be inserted at the same time.

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Idiopathic menorrhagia: The system should be removed or replaced in case symptoms of idiopathic menorrhagia return. If symptoms have not returned after 5 years of use, continued use of the system may be considered. Remove or replace after 8 years at the latest. 

Protection from endometrial hyperplasia during oestrogen replacement therapy: The system should be removed or replaced after 5 years.

Mirena is removed by gently pulling on the threads with forceps. The use of excessive force/sharp instruments during removal may cause breakage of the device. After removal of Mirena, the device should therefore be examined to ensure that it is removed entirely. During difficult removals, single cases have been reported of the hormone cylinder sliding over the horizontal arms and hiding them together inside the cylinder. This situation does not require further intervention once completeness of the IUS has been ascertained. The knobs of the horizontal arms usually prevent complete detachment of the cylinder from the T-body. If the threads are not visible and the system is in the uterine cavity, it may be removed using a narrow tenaculum. This may require dilatation of the cervical canal or other surgical intervention.

If the user wishes to continue using the same method, a new system can be inserted at the time of removal.

After removal of Mirena, the system should be checked to be intact. During difficult removals, single cases have been reported of the hormone cylinder sliding over the horizontal arms and hiding them together inside the cylinder. This situation does not require further intervention once completeness of the intrauterine system (IUS) has been ascertained. The knobs of the horizontal arms usually prevent complete detachment of the cylinder from the T-body.

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4.4 Special warnings and precautions for use

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Infrequent bleedingOligo/amenorrhoea

Women of fertile age

Infrequent bleeding Oligomenorrhoea and/or amenorrhoea develops gradually in 57 % and 16 % of women during the first year of use respectively. By the end of Year 86 of Mirena use, infrequent bleeding oligomenorrhoea and amenorrhea are experienced by 2631 % and 3424 % of Mirena users, respectively.

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Precautions at time of removal

The use of excessive force/sharp instruments during removal may cause breakage of the device (see section 4.2). After removal of Mirena, the device should therefore be examined to ensure that it is removed entirely.

4.8 Undesirable Effects

Summary of the safety profile

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By the end of Year 86 of Mirena use, prolonged bleeding and irregular bleeding are experienced by 32 % and 1015 % of Mirena users, respectively; amenorrhea occurs in 3424 %, and infrequent bleeding in 2631 % of Mirena users.

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Table 2: adverse drug reactions

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A separate study with 362 women who have used Mirena for more than 5 years showed a consistent adverse reaction profile in Years 6 through 8.

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5.1 Pharmacodynamic Properties

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The contraceptive efficacy of Mirena has been studied in 5 major clinical studies with 3330 women using Mirena. The Pearl Index was approximately 0.2 at 1 year and the cumulative failure rate was approximately 0.7 % at 5 years. The contraceptive efficacy of Mirena beyond 5 years has been studied in a clinical study with 362 women in a clinical trial using Mirena, with 221 women completing year 8 of the study. During years 6 to 8 of Mirena use, the Pearl Index was 0.28 [95% CI (0.03; 1.00)]. The contraceptive efficacy of Mirena is summarised in table 3. During year 6 of Mirena use, the Pearl Index was 0.35 [95 % CI (0.01; 1.95)].

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*Kaplan Meier method

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5.2 Pharmacokinetic Properties

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Table 4: Estimated in vivo release rates for Mirena:

Absorption

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After insertion of Mirena, levonorgestrel is detectable in serum/plasma after 1 hour. The maximum concentration is reached within 2 weeks after insertion and amounts to about 180 ng/L (CV 38.3%). In correspondence with the declining release rate, the geometric mean median serum/plasma concentration of levonorgestrel declines continuously, as shown in table 5. from 206 pg/ml (25^th to 75^th percentiles: 151 pg/ml to 264 pg/ml) at 6 months to 194 pg/ml (146 pg/ml to 266 pg/ml) at 12 months, and to 131 pg/ml (113 pg/ml to 161 pg/ml) at 60 months in women of reproductive age weighing above 55 kg. After 72 months (6 years) median levonorgestrel concentration amounted to 113 pg/ml (87.3 pg/ml to 155 pg/ml).

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Distribution

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The concentration of SHBG declined on average by about 20 30% during the first two months after insertion of Mirena and remained stable thereafter during the first year and increased increasing only slightly until the end of the 8 years of use thereafter. During Year 6 of use SHBG concentration remained stable.

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10 Date of revision of the text

September November 2022

BP22001, REC20852+REC30572+REC30681

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1. What Mirena is and what it is used for

Mirena is an intrauterine delivery system (IUS) placed inside the womb (uterus) where it slowly releases the hormone levonorgestrel. It can be used in the following three ways:

1. As an effective long-term and reversible method of contraception.

It is can be used for contraception (prevention of pregnancy) (contraception) for a maximum of  6 8 years, unless it is removed earlier.

2. For reducing menstrual blood flow, so it can be used if you suffer from heavy periods (heavy menstrual bleeding). This is called menorrhagia.

It is can be used for heavy menstrual bleeding (idiopathic menorrhagia) (excessive menstrual bleeding) for up to a maximum of 5 years,unless it is removed earlier.

3. If you are going through the menopause, a gradual process which usually takes place between the ages of about 45 and 55.

It is can be used for protection from endometrial hyperplasia ( excessive growth of the lining of the womb (endometrial hyperplasia)) during oestrogen replacement therapy for a maximum of 5 years, unless it is removed earlier.

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3. How to use Mirena

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The initial release of levonorgestrel is about 2019 micrograms per day 1 year after insertion, reducing to about 1110 micrograms per day after 5 years and 79 micrograms per day after 86 years. Therefore you receive an average of 15 micrograms per day levonorgestrel for 5  years and an average of 135 micrograms per day levonorgestrel for 86 years.

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6. Contents of the pack and other information

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This leaflet was last revised in September October 2022.

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The following information is intended for healthcare professionals only:

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Removal/ replacement

For removal/replacement, please consult the Mirena prescribing information.

Mirena is removed by gently pulling on the threads with a forceps (Figure 8).

You may insert a new Mirena immediately following removal.

After removal of Mirena, the device should be examined to ensure that it is removed entirely. See Summary of Product Characteristics for further information.

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DATE OF REVISION OF THE TEXT: December 2021 October 2022

BP22036, REC30610

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Bayer Ltd.,

The Atrium, Blackthorn Road, Sandyford, Dublin 18, The Grange Offices, Stillorgan, Co. Dublin, A94 H2K7, Ireland

BP22036, REC30610

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7. Marketing Authorisation holder

Bayer Limited

1st Floor

The Grange Offices

The Grange

Brewery Road

Stillorgan

Co. Dublin

A94 H2K7

The Atrium

Blackthorn road

Dublin 18

Ireland

10. Date of revision of text

December 2021 September 2022

BP22036, REC30610

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6. Contents of the pack and other information

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Marketing Authorisation Holder

Bayer Limited

1st Floor

The Grange Offices

The Grange

Brewery Road

Stillorgan

Co. Dublin

A94 H2K7

The Atrium

Blackthorn road

Dublin 18

Ireland

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This leaflet was last revised in May September 2022.

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BEC20783+BEC18310

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[…]

Mirena

52 mg Iintrauterine Ddelivery Ssystem

Llevonorgestrel

[…]

(REC30360, BP22014)

The Mirena Patient information leaflet was updated to implement the additional wording requested by PRAC, following the outcome of the finished PSUSA procedure of all levonorgestrel-containing products (PSUSA/00010828/202105).

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2. What you need to know before you use Mirena

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Pregnancy, breast-feeding and fertility

Pregnancy

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If you do become pregnant with Mirena in place, contact your healthcare professional immediately so that ectopic pregnancy can be excluded and to have Mirena removed. The removal may cause a miscarriage. However, if Mirena is left in place during pregnancy, not only is the risk of having a miscarriage higher, but also the risk of preterm labour. If Mirena cannot be removed, talk with your healthcare professional about the benefits and risks of continuing the pregnancy, and possible effects of the hormone on the developing baby. If the pregnancy is continued, you will be closely monitored during your pregnancy and you should contact your doctor right away if you experience stomach cramps, pain in your stomach or fever.

Mirena contains a hormone, called levonorgestrel, and there have been isolated reports of effects on the genitalia of female babies if exposed to levonorgestrel intra-uterine devices while in the womb.

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6. Contents of the pack and other information

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This leaflet was last revised in March May 2022.

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REC30414

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3. How to use Mirena

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How quickly does Mirena work?

Contraception:

You are protected from pregnancy as soon as Mirena is fitted. The possibility of becoming pregnant is approximately 0.2 % (2 in 1000) in the first year. The failure rate may increase in case of expulsion (see section 2 “Expulsion”) or perforation (see section 2 “Perforation”).

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6. Contents of the pack and other information

What Mirena contains

- The active substance is levonorgestrel 52 mg.

- The other ingredients are: polydimethylsiloxane elastomer and tubing, polyethylene, barium sulfate, iron oxide (E 172).

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This leaflet was last revised in December 2021March 2022.

BEC20783+BEC18310

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1. NAME OF THE MEDICINAL PRODUCT

Mirena 52 mg iIntrauterine dDelivery sSystem

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance:

 lLevonorgestrel 52 mg.

For the full list of excipients, see sSection 6.1.

For details on release rates, see section 5.2.

4.2 Posology and method of administration

4.2.1 Method of administration

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4.2.1.1 Contraception and idiopathic menorrhagia

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4.2.1.2 Protection from endometrial hyperplasia during oestrogen replacement therapy

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4.2.1.3 Insertion and removal/replacement

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Instructions for use and handling

Mirena is supplied in a sterile pack which should not be opened until required for insertion. The exposed product should be handled with aseptic precautions. If the seam of the sterile package is broken, the product should be discarded.

Do not insert after the date which is stated on the outer carton and foil package after “To be inserted before”. The “To be inserted before” date refers to the last day of that month.

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4.2.2 Additional information on special populations

4.2.2.1 Paediatric population

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Elderly patients 4.2.2.2 Geriatric patients

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4.2.2.3Patients with hepatic impairment

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4.2.2.4Patients with renal impairment

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4.3 Contraindications

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• Hypersensitivity to the active substance levonorgestrel or to any of the excipients listed in section 6.1

4.4 Special warnings and precautions for use

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Medical examination/consultation

Before insertion, the woman must be informed of the efficacy, risks including signs and symptoms of these risks as described in the pPackage leaflet booklet and side effects of Mirena.

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4.5 Interaction with other medicinal products and other forms of interaction

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4.5.1 Effects of other medicinal products on Mirena

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4.6 Fertility, pregnancy and lactation

4.6.1 Pregnancy

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 4.6.2 Lactation Breast-feeding

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4.6.3 Fertility

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4.8 Undesirable effects

4.8.1 Summary of the safety profile

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4.8.2 Tabulated list of adverse reactions

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4.8.3 Description of selected adverse reactions

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6. PHARMACEUTICAL PARTICULARS

6.1 List of eExcipients

Polydimethylsiloxane elastomer

Polydimethylsiloxane tubing

Polyethylene

Barium sulphate

Iron oxide (E 172)

6.6 Special precautions for disposal Instruction for Use and other hHandling

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For further information see also sSection 4.2, Posology and Method Administration “Insertion and removal/replacement”.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

10. DATE OF REVISION OF THE TEXT

DecemberSeptember 2021

BEC20783+BEC18310

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Package leafletbooklet: Iinformation for the user

Mirena 52 mg iIntrauterine dDelivery sSystem

lLevonorgestrel

Read all of this leafletbooklet carefully before you start using this medicine decide to have Mirena fitted because it contains important information for you.

• Keep this leafletbooklet. You may need to read it again.

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• This medicine has been prescribed for you only. Do not pass it on to others.

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What is in this leafletbooklet:

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2. What you need to know before you have Mirena fitteduse Mirena

3. How to useand when Mirena is used

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1. What Mirena is and what it is used for

Mirena is an intrauterine delivery system (IUS) placed inside the womb (uterus) where it slowly releases the hormone lLevonorgestrel.

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Children and adolescents

Mirena is not indicated for use before the first menstural bleeding (menarehe)

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2. What you need to know before you have Mirena fitteduse Mirena

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Do not use Mirena and please tell your doctor if you:

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• are allergic to sensitive to the hormone levonorgestrel or to any of the other ingredients in Mirenaof this medicine (listed in seesection 6), “What Mirena contains”.

Warnings and precautions

Mirena may not be suitable for all women.

Talk to your doctor before using Mirena is fitted if you:

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Expulsion

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See also section 3 “How to use and when Mirena is used – How can I tell whether Mirena is in place?”.

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Perforation

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• you can no longer feel the Mirena threads (see section 3 “How and when Mirena is usedto use Mirena - How can I tell whether Mirena is in place?”).

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Children and adolescents

Mirena is not indicated for use before the first menstrual bleeding (menarche).

Other medicines and Mirena

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Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Including medicines obtained without prescription.

Pregnancy, and breast-feeding and fertility

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Fertility

If you wish Mirena to be removed so that you can get pregnant, your usual level of fertility will return very quickly after it is removed.

Driving and using machines

No studies on the effects on the ability to drive or use machines have been performed.

3. How to and when Mirena is used Mirena

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If you have any concerns over its usage, you should discuss it with your doctor (see section 2 “What you need to know before you usehave Mirena fitted – Perforation”).

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How will Mirena affect my periods?

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There is a calendar on the last page of this patient information leafletbooket.

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4. Possible side effects

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Very cCommon: (may affect more than 1 in 10 people women)

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Common: (may affect up to 1 in 10 people women)

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Uncommon: (may affect up to 1 in a 100 peoplewomen)

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Not Unknown: frequency cannot be estimated from the available data

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5. How to store Mirena

Keep this medicine out of the sight and reach of children.

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Mirena should not be insertedused after the date which is stated printed on the outer carton and foil package afteras indicated by  “To be inserted before”. The “To be inserted before” expiry date refers to the last day of that month.

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Do not dispose via household waste, your doctor or nurse will dispose Mirena for you. These measures will help protect the environment.

6. Contents of the pack and other information

What Mirena contains

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iron oxide (E 172).

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What Mirena looks like and contents of the pack

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Pack size:

1x1 intrauterine delivery system

Product Marketing Authorisation Holder

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Manufacturer Mirena is manufactured by:

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This leafletbooklet was last revised in SeptemberDecember 2021.

BEC18534

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4.4 Special Warnings and Precautions for Use

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Expulsion

In clinical trials with Mirena in the indication contraception, the 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 any IUDMirena 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 explusion may decrease the effectiveness of Mirena. As Mirena decreases menstrual flow, increase of menstrual flow may be indicative of an expulsion.

Risk of expulsion is increased in

• Women with history of heavy menstrual bleeding (including women who use Mirena for treatment of heavy menstrual bleeding)
• Women with greater than normal BMI at the time of insertion; this risk increases gradually with increasing BMI

The woman should be counselled on possible signs of expulsion and how to check the threads of Mirena and advised to contact a healthcare professional if the threads cannot be felt. A barrier contraceptive (such as a condom) should be used until the location of Mirena has been confirmed.

After expulsion, Mirena may be replaced within 7 days from the onset of the next menstruation.

Partial expulsion may decrease the effectiveness of Mirena.

A displaced partially expelled Mirena should be removed. A new system can be inserted at thatthe time of removal, provided pregnancy has been excluded.

The woman should be advised how to check the threads of Mirena.

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10 Date of revision of the text

July 2021September 2021

BEC18534

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2. What you need to know before you have Mirena fitted

Warnings and precautions

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Expulsion

The muscular contractions of the womb during your period may sometimes push Mirena out of place or expel it. This is more likely to occur if you are overweight at the time of Mirena insertion or have a history of heavy periods. If Mirena is out of place, it may not work as intended and therefore, the risk of pregnancy is increased. If Mirena is expelled, you are not protected against pregnancy anymore.

Possible symptoms of an expulsion are pain and abnormal bleeding but Mirena may also come without you noticing. If it is expelled, you are not protected against pregnancy anymore. It is recommended that you check for the threads with your finger, for example while having a shower. If you have signs indicative of an expulsion or you cannot feel the threads, you should avoid intercourse or use another contraceptive, and consult your doctor. As Mirena makes periods lighter, heavier periods than usual may mean that Mirena is no longer in place. 

It is recommended that you check for the threads with your finger for example while having a shower. See also section 3 “How and when Mirena is used – How can I tell whether Mirena is in place?”. If you have signs indicative of an expulsion or you cannot feel the threads, you should avoid intercourse or use another contraceptive (such as condoms), and consult your healthcare professional doctor.

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3. How and when Mirena is used

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How can I tell whether Mirena is in place?

You can check yourself if the threads are in place. Gently put a finger into your vagina and feel for the threads at the end of your vagina near the opening of your womb (cervix).

Do not pull the threads because you may accidentally pull it out. If you cannot feel the threads, this may mean that it is no longer in place or has pierced the wall of the womb. In this case you should either not have intercourse or avoid sex or use a barrier contraceptive (such as condoms), and contact your doctor.

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6. Contents of the pack and other information

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This booklet was revised: July 2021September 2021

(BP20061_BEC17811+BEC14962)

Patient Information Leaflet

2. What you need to know before you have Mirena fitted

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Can tampons or menstrual cups be used?