BP22036, REC30610

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

6. Contents of the pack and other information

[….]

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

[….]

This leaflet was last revised in June September 2022.

BP22036, REC30610

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

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

July September 2022

Section 10 for the SmPC was updated from June 2022 to July 2022.

(REC30360+30040, BP22031)

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

4.4 Special warnings and precautions for use

[….]

Expulsion

In clinical trials with Jaydess, the incidence of expulsion was low (<4% of insertions) and in the same range as that reported for other IUDs and IUSs. Symptoms ofthe partial or complete expulsion of Jaydess may include bleeding or pain. However, the system can be expelled from the uterine cavity partial or complete expulsion can occurwithout the woman noticing it, leading todecrease or loss of contraceptive protection. As Jaydesstypically decreases menstrual bleedingflow, over time anincrease of menstrual flowbleeding may be indicative of an expulsion.

[….]

Partial expulsion may decrease the effectiveness of Jaydess.

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

[….]

4.6 Fertility, pregnancy and lactation

[….]

Pregnancy

The insertion of Jaydess in pregnant women is contraindicated (see section 4.3).

The use of Jaydess during an existing or suspected pregnancy is contraindicated, see section 4.3 Contraindications. If the a woman becomes pregnant while using Jaydessectopic pregnancy should be excluded and the system should be removed as soon as possible, since any intrauterine contraceptive left in situ may increase the risk of abortion and preterm labour. Removal of Jaydess or probing of the uterus may also result in spontaneous abortion. Ectopic pregnancy should be excluded.

[….]

There have been isolated cases of masculiniszation of the external genitalia of the female foetus following local exposure to levonorgestrel during pregnancy with an LNG-IUS in place.

[….]

10. DATE OF REVISION OF THE TEXT

September 2021 June 2022

(REC30360+30040, BP22031)

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

2. What you need to know before you use Jaydess

[….]

Pregnancy, breast-feeding and fertility

Pregnancy

[….]

If you become pregnant with Jaydess in place, you should see your healthcare professional immediately to have Jaydess removed. The removal may cause a miscarriage. However, if Jaydess is left in place during pregnancy, not only is the risk of having a miscarriage higher, but also the risk of havingpreterm labour. If Jaydess cannot be removed, talk with your healthcare professional about the benefits and risks of continuing the pregnancyand 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 healthcare professional right away if you experience stomach cramps, pain in your stomach or fever.

Jaydess 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.

If you want to become pregnant you should contact your healthcare professional to have Jaydess removed.

[….]

4. Possible side effects

[….]

Expulsion

[….]

Possible symptoms of an expulsion are pain and abnormal bleeding but Jaydess may also come out without you noticing. As Jaydesstypically decreases menstrual flowovertime, increase of menstrual flow may be indicative of an expulsiona sign that Jaydess has been expelled.

It is recommended that you check for the threads with your finger, for example while having a shower. See also section 2 “Warnings and precautions” for how to check if Jaydess is in placeand what to do if you suspect that Jaydess is no longer in place. If you have signs indicative of an expulsion or you cannot feel the threads, you should use another contraceptive (such as condoms), and consult your healthcare professional.

[….]

6. Contents of the pack and other information

[….]

This medicineal product is authorised in the Member States of the European Economic Area under the following names:

·        Austria, Belgium, Bulgaria, Czech Republic, Denmark, Finland, France, Germany, Hungary, Iceland, Ireland, Italy, Luxembourg, Malta, Norway,Poland, Portugal, Romania,Slovak Republic, Slovenia, Spain, Sweden, United Kingdom: Jaydess

·        Estonia, Latvia, Lithuania: Fleree

This leaflet was last revised in September 2021June 2022.

[….]

"Ireland" has been added to the Marketing Authorisation Holder address.

BEC 18536

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

4.4 Special warnings and precautions for use

[…]

Expulsion

In clinical trials with Jaydess, 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 Jaydess may include bleeding or pain. However, partial or complete expulsion can occur without the woman noticing it, leading to decrease or loss of contraceptive protection. As Jaydess typically decreases menstrual bleeding over time, an increase of menstrual bleeding may be indicative of an expulsion.

Risk of expulsion is increased in

- Women with history of heavy menstrual bleeding

- Women with greater than normal BMI at the time of insertion; this risk increases gradually with increasing BMI

Women should be counselled on possible signs of expulsion and how to check the threads of Jaydess 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 Jaydess has been confirmed.

A partially expelled Jaydess should be removed. A new system can be inserted at that time the time of removal, provided pregnancy has been excluded.

A woman should be advised how to check the threads of Jaydess and to contact her healthcare provider if the threads cannot be felt.

10. Date of revision of the text

July 2021September 2021

BEC 18536

Note:

Text in blue = added text

Text in red with strikethrough = deleted text

2. What you need to know before you use Jaydess

[.…]

Warnings and precautions

[.…]

Contact your healthcare professional promptly if any of the following occur (see also section 4) and remind them that you have a Jaydess device, especially if they were not the person who inserted it:

[.…]

• you no longer feel the threads in your vagina. This may be a sign of expulsion or perforation. You can check by gently putting a finger into your vagina and feeling 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 out Jaydess. Avoid intercourse or u Use a barrier contraceptive (such as condoms) until your healthcare professional has checked that the IUS is still in position.

[.…]

4. Possible side effects

[.…]

Expulsion

The muscular contractions of the womb during menstruation may sometimes push the IUS out of place or expel it. This is more likely to occur if you are overweight at the time of IUS insertion or have a history of heavy periods. If the IUS is out of place, it may not work as intended and therefore, the risk of pregnancy is increased. If the IUS is expelled, you are not protected against pregnancy anymore. It is rare but possible for Jaydess to come out during your menstural period without you noticing.

It is also possible for your Jaydess to partially expel from your womb, meaning that it is displaced but not completely expelled ( you and your partner may notice this during sexual intercourse).If Jaydess is completely or partially expelled , you will not be protected from pregnancy.

Possible symptoms of an expulsion are pain and abnormal bleeding but Jaydess may also come out without you noticing. As Jaydess typically decreases menstrual flow over time, increase of menstrual flow may be a sign that Jaydess has been expelled. See section 2 “Warnings and precautions” for how to check if Jaydess is in place and what to do if you suspect that Jaydess is no longer in place.

[.…]

6 Contents of the pack and other information

[.…]

This leaflet was last revised in July 2021September 2021.

[.…]

(BP20061_BEC17810+BEC14963)

2. What you need to know before you use Jaydess

[…]

Warnings and precautions

[…]

If you think you may have pulled Jaydess out of place (see list above for possible signs), avoid intercourse or use a barrier contraceptive (such as condoms), and contact your healthcare professional.

[…]

Pregnancy, breast-feeding and fertility

Pregnancy

[…]

There is a risk of spontaneous miscarriage if Jaydess is removed during pregnancy. The removal may cause a miscarriage. However, if Jaydess is left in place during pregnancy, not only is the risk of having a miscarriage higher, but also the risk of having preterm labour. If Jaydess 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 you leave Jaydess in place during pregnancy, the risk of having a miscarriage, infection or preterm labour will be increased. Talk with your healthcare professional about the risks of continuing the pregnancy.

[…]

3. How to use Jaydess

Placement of Jaydess

[…]

After placement of Jaydess you should receive a patient reminder card from your doctor for follow-up examinations. Bring this with you to every scheduled appointment.

[…]

Bring the patient reminder card you have received from your doctor to every scheduled appointment.

[…]

6. Contents of the pack and other information

Marketing Authorisation Holder

Bayer Limited,

The Atrium,

Blackthorn Road,

Dublin 18

Ireland..

[…]

This leaflet was last revised in July 2021September 2020.

[…]

INSERTION INSTRUCTIONS

[…]

Jaydess is supplied with a patient reminder card in the outer carton. Complete the patient reminder card and give it to the patient, after insertion.

[…]

(BP20061_BEC17810+BEC14963)

4.2 Posology and method of administration

[…]

Method of administration

[…]

Jaydess is supplied with a patient reminder card in the outer carton. Complete the patient reminder card and give it to the patient, after insertion.

[…]

4.6 Fertility, pregnancy and lactation

[…]

Pregnancy

[…]

If a woman becomes pregnant while using Jaydess ectopic pregnancy should be excluded and the system should be removed as soon as possible,timely removal of the system is recommended since any intrauterine contraceptive left in situ may increase the risk of abortion and preterm labor.

[…]

In addition, an increased risk of virilising effects in a female foetus because of the intrauterine exposure to levonorgestrel cannot be excluded. There have been isolated cases of masculinization of the external genitalia of the female foetus following local exposure to levonorgestrel during pregnancy with an LNG-IUS in place.

Because of the intrauterine administration and the local exposure to LNG, the possible occurrence of virilizing effects in a female fetus should be taken into consideration. Clinical experience of the outcomes of pregnancies under Jaydess treatment is limited due to the high contraceptive efficacy. Women should be informed that, to date, there is no evidence of birth defects caused by a levonorgestrel-releasing intrauterine system use in cases where pregnancy has continued to term with the LNG-IUS in place.

[…]

10. DATE OF REVISION OF THE TEXT

July 2020July 2021

(BP21013+BP21031):

• Content updates were made to extend the duration of use of Mirena to 6 years, for the indication contraception.
• Additional information has been included on the pearl index and ectopic pregnancy rates, as observed in clinical trials and included in the respective SmPCs for Mirena, Jaydess and Kyleena.
• 2D and 3D ultrasound pictures were updated.

‘Patient’s/ Doctor’s Details’ at the top of the Leaflet have been deleted.

The revision date of the PIL has been updated to September 2020. 

The following information has been added:

"Other sources of information

Detailed and updated information on this medicine is available by scanning the QR Code included in the package leaflet, outer carton and patient reminder card with a smartphone. The same information is also available on the following URL: www.pi.bayer.com/jaydess/ie-mt and on the HPRA website: www.hpra.ie."

A QR Code has been added to the bottom of the Leaflet.

A QR Code has been added to the bottom of the Insertion Instructions.

The following has been added to the bottom of the Insertion Instructions:

“Summary of Product Characteristics for Jaydess online at www.pi.bayer.com/jaydess/ie-mt”

New document combining information from previous HCP educational materials

Reason for update:

Implement the outcome of the finished PSUSA procedure of all levonorgestrel-containing products (PSUSA/00001856/201905).

Reporting of suspected adverse reactions details updated for Ireland.

Section 4.8: Undesirable effects:

[.....]

Tabulated summary of adverse events

'Deceased libido' added as a common side effect under System Organ Class: Psychiatric disorders.

'Dizziness' added as an uncommon side effect under added System organ Class: Vascular disorders.

'Increased weight' added as a common side effect under added System Organ Class: Investigations

[.....]

Section 4.8: Reporting of suspected adverse reactions

[.....]

HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. website: www.hpra.ie.; e-mail: medsafety@hpra.ie.

[.....]

Section 10 Date of revision of the text:

12^th June 2019 July 2020

Reason for update:

Implement the outcome of the finished PSUSA procedure of all levonorgestrel-containing products (PSUSA/00001856/201905), addition of the adverse reactions: dizziness, libido decrease and weight increase and adding information on the use of menstrual cups.

Section 2: Warnings and Precautions

[.....]

Use of sanitary pads is recommended. If tampons or menstrual cups are used, you should change them with care so as not to pull the threads of Jaydess.

[.....]

Section 4: Possible side effects

[.....]

Common side effects: may affect up to 1 in 10 people

[.....]

<Common side effects added:>

'decreased libido'

'increased weight'

<'hair loss' re-located to maintain the same order of the adverse events as in the SmPC.>

[.....]

Uncommon side effects: may affect up to 1 in 100 people

[.....]

<Uncommon side effects added:>

'Dizziness'

[.....]

Section 4: Reporting of side effects:

[.....]

<Reporting of Side Effects details updated for Ireland and added for Malta>:

HPRA Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.

Ireland

HPRA Pharmacovigilance

Website: www.hpra.ie

Malta

ADR Reporting

Website: www.medicinesauthority.gov.mt/adrportal

[.....]

Section 6: Revision date

[.....]

This leaflet was last revised in June 2019 July 2020

Added            Deleted

3. PHARMACEUTICAL FORM

[…]

The white T-body has a loop at one end of the vertical stem and two horizontal arms at the other end. Removal Brown coloured removal threads are attached to the loop.

4.2 Posology and method of administration

[…]

Physical examination alone may not be sufficient to exclude partial perforation, which may have occurred even if the threads are still visible.

Jaydess can be distinguished from other IUSs by the combination of the visibility of the silver ring on ultrasound and the brown colour of the removal threads.

[…]

Patients with hepatic impairment

Jaydess has not been studied in women with hepatic impairment. Jaydess is contraindicated in women with acute liver disease or liver tumor tumour (see section 4.3).

4.4. Special warnings and precautions for use

[…]

·         marked increase of in blood pressure

[…]

Pelvic infection

While Jaydess and the inserter as such are sterile they may, due to bacterial contamination during insertion, become a vehicle for microbial transport in the upper genital tract.

[…]

Perforation

[…]

4.8 Undesirable effects

[…]

5.1 Pharmacodynamic properties

[…]

Pharmacodynamic effects

[…]

Evidence of ovulation was seen in 34 out of 35 women in the first year, in 26 out of 27 women in the second year, and in all 27 26 women in the third year.

5.2 Pharmacokinetic properties

[…]

Distribution

Within one The concentration of SHBG declined on average by about 15% during the first month after insertion of Jaydess, the concentration of SHBG declines by about 30%. Thereafter, plateau-like SBHG concentrations are observed with a tendency to increase towards baseline values and remained stable over time the 3 year period of use.

[…]

Linearity/ non-linearity

[…]

During the first month of use of Jaydess, a mean SBHG A decrease of about 30% is observed which SHBG concentration leads to a decrease of total levonorgestrel concentration in serum indicating non-linear pharmacokinetics of levonorgestrel with regard to time.

[…]

Paediatric population

In a one-year phase III study in post-menarcheal female adolescents (mean age 16.2, range 12 to 18 years) pharmacokinetic analysis of 283 subjects adolescents showed estimated LNG serum concentrations slightly higher (approximately 10%) in adolescents compared to adults.

[…]

No differences in the pharmacokinetics of LNG are expected between adolescents and adults following insertion of Jaydess.

Ethnic differences

A three-year phase III study in the Asian-Pacific region (93% Asian women, 7% other ethnicities) using Jaydess has been performed. A comparison of pharmacokinetic characteristics of LNG of the Asian population in this study with that of the Caucasian population from another phase III study showed no clinically relevant difference in systemic exposure and other pharmacokinetic parameters. In addition, the daily release rate of Jaydess was the same in both populations.

No differences in the pharmacokinetics of LNG are expected between Caucasian and Asian women following insertion of Jaydess.

10. DATE OF REVISION OF THE TEXT

July 2016 February 2017

Jaydess – PA 1410/68/1
14101
BEC 7153 + 6960
www.medicines.ie

(Inserted Text; Deleted Text)

4.2          Posology and method of administration

…

Paediatric population

Safety and efficacy has not been studied in women aged below 18. Use of this product before menarche is not indicated. For data on safety and efficacy in adolescents, see section 5.1.

4.8          Undesirable effects

Summary of the safety profile

…

Table 1 2: Bleeding patterns reported with Jaydess in clinical trials

…

Paediatric population

The safety profile of Jaydess observed in a study of 304 adolescents was consistent with that in the adult population.

5.1          Pharmacodynamic properties

Clinical efficacy and safety

…

The safety profile of Jaydess observed in a study of 304 adolescents was consistent with that in the adult population. Efficacy is expected to be the same for adolescents under the age of 18 as for users 18 years and older.

5.2          Pharmacokinetic properties

…. Estimated in vivo delivery rates for different time points are provided in Table 2 3.

Table 2 3: Estimated in vivo release rates based on observed ex vivo residual content data

…

Paediatric population

In a one-year phase III study in post-menarcheal female adolescents (mean age 16.2, range 12 to 18 years) pharmacokinetic analysis of 283 subjects showed estimated LNG serum concentrations slightly higher (10%) in adolescents compared to adults. This correlates to the generally lower body weight in adolescents. The ranges estimated for adolescents lie, however, completely within the ranges estimated for adults, showing high similarity.

10           Date of revision of the text

Jaydess 13.5 mg intrauterine delivery system (PA 1410/68/1);

BP14043

Changes for www.medicines.ie

(Inserted text; Deleted text)

4.2 Posology and method of administration

Insertion and removal/ replacement

In case of a difficult insertion and/ or exceptional pain or bleeding during or after insertion, appropriate steps should be taken immediately to exclude perforation, such as physical examination and ultrasound.
Physical examination may not be sufficient to exclude partial perforation.

4.4 Special Warning and Precautions for Use

Medical examination/ consultation

Before insertion, a woman must be informed of the benefits and risks of Jaydess, including the signs and symptoms of perforation and the risk of ectopic pregnancy, see below.

Perforation

Perforation or penetration of the uterine corpus or cervix by an intrauterine contraceptive may occur rarely, most often during insertion, although it may not be detected until sometime later, and may decrease the effectiveness of Jaydess. In case of a difficult insertion and/ or exceptional pain or bleeding during or after insertion, appropriate steps should be taken immediately to exclude perforation, such as physical examination and ultrasound. Such a system must be removed; surgery may be required. The risk of perforations is increased in breast feeding women and may be increased in post partum insertions (see section 4.2) and in women with a fixed retroverted uterus.

In a large prospective comparative non-interventional cohort study in users of other IUDs (N=61,448 women), the incidence of perforation was 1.3 (95% CI: 1.1 - 1.6) per 1000 insertions in the entire study cohort; 1.4 (95% CI: 1.1 - 1.8) per 1000 insertions in the cohort of another LNG- IUS and 1.1 (95% CI: 0.7 - 1.6) per 1000 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 (see Table 1). These risk factors were independent of the type of IUD inserted.

Table 1: Incidence of perforation per 1000 insertions for the entire study cohort, stratified by breastfeeding and time since delivery at insertion (parous women)

The risk of perforations may be increased in women with fixed retroverted uterus.

Re-examination after insertion should follow the guidance given under the heading "Medical examination/consultation" which may be adapted as clinically indicated in women with risk factors for perforation.

Lost threads

If the removal threads are not visible at the cervix on follow-up examinations, unnoticed expulsion and pregnancy must be excluded. The threads may have been drawn up into the uterus or cervical canal and may reappear during the next menstrual period. If pregnancy has been excluded, the threads may usually be located by gently probing the cervical canal with a suitable instrument. If they cannot be found, the possibility of expulsion or perforation should be considered the system may have been expelled. Ultrasound exam may be used to ascertain the position of the system. If ultrasound is not available or is not successful, X-ray may be used to locate Jaydess.

4.8 Undesirable effects

Summary of the safety profile

The majority of women experience changes in menstrual bleeding pattern after insertion of Jaydess. Over time, the frequency of amenorrhoea and infrequent bleeding increases, and the frequency of both prolonged and frequent bleeding decreases. The following bleeding patterns were observed in clinical trials:

Table 1 2: Bleeding patterns reported with Jaydess in clinical trials…..

….

* In clinical trials ovarian cysts had to be reported as AEs if they were abnormal, non-functional cysts and/or had a diameter > 3 cm on ultrasound examination.
** This frequency is based on clinical trials that excluded breastfeeding women. In a large prospective comparative non-interventional cohort study with women using another LNG-IUS and copper IUDs, the frequency of perforation in women who were breastfeeding or had an insertion up to 36 weeks after delivery was “uncommon” (see section 4.4 under Perforation).

Description of selected adverse events

With the use of another LNG-IUS, cases of hypersensitivity including rash, urticaria and angioedema have been reported.

If a woman becomes pregnant while using Jaydess, the relative likelihood of this pregnancy being ectopic is increased (see section 4.4 under Ectopic Pregnancy).

The removal threads may be felt by the partner during intercourse.

Clinical trials with Jaydess excluded breast feeding women. A large post authorization safety study with other IUDs/IUSs shows an increased risk of perforation in breast feeding women (see section 4.4. under Perforation).

5.2 Pharmocokinetic properties

Levonorgestrel is released locally into the uterine cavity. The in vivo release curve is characterized by an initial steep decline that slows down progressively resulting in little change after 1 year until the end of the intended 3-year period of use. Estimated in vivo delivery rates for different time points are provided in Table 23.

Table 23: Estimated in vivo release rates based on observed ex vivo residual content data

10. Date of Revision of the Text

April 2014 April 2015

years.
In Section 6.3, the shelf-life has been changed from 2 to 3 years.

Date of revision has been changed from February 2014 to April 2014

SUMMARY OF PRODUCT CHARACTERISTICS

   (Please insert "Inverted Black Triangle" symbol here.This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 for how to report adverse reactions.

4.8         Undesirable effects

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via IMB Pharmacovigilance, Earlsfort Terrace, IRL - Dublin 2; Tel: +353 1 6764971;  Fax: +353 1 6762517. Website: www.imb.ie; e-mail: imbpharmacovigilance@imb.ie.

the national reporting system listed in Appendix V.

10.     DATE OF REVISION OF THE TEXT

February 2014