Added            Deleted

3. PHARMACEUTICAL FORM

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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

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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.

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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

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·         marked increase of in blood pressure

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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.

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Perforation

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4.8 Undesirable effects

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5.1 Pharmacodynamic properties

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Pharmacodynamic effects

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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

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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.

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Linearity/ non-linearity

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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.

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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

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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…..

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* 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