Adverse reactions : תופעות לוואי

4.8    Undesirable effects

Summary of the safety profile

The majority of women experience changes in menstrual bleeding pattern after insertion of Kyleena. Over time, the frequency of amenorrhoea and infrequent bleeding increases, and the frequency of prolonged, irregular and frequent bleeding decreases. The following bleeding patterns were observed in clinical trials: 
Table 3: Bleeding patterns reported with Kyleena in clinical trials

Kyleena                 First 90 days   Second 90 days       End of year 1   End of year 3   End of year 5 Amenorrhoea             < 1%            5%                   12%             20%             23% Infrequent bleeding     10%             20%                  26%             26%             26% Frequent bleeding       25%             10%                  4%              2%              2% Prolonged bleeding*     57%             14%                  6%              2%              1% Irregular bleeding      43%             25%                  17%             10%             9% *Subjects with prolonged bleeding may also be included in one of the other categories (excluding amenorrhoea)
Tabulated summary of adverse events

The frequencies of Adverse Drug Reactions (ADRs) reported with Kyleena are summarized in the table below. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Frequencies are defined as:
 very common (≥ 1/10),
common (≥ 1/100 to < 1/10),
uncommon (≥ 1/1,000 to < 1/100),
rare (≥ 1/10,000 to < 1/1,000),
very rare (< 1/10,000).

System Organ           Very Common             Common                 Uncommon Class

Psychiatric                                    Depressed disorders                                      mood/Depression
Decreased libido
Nervous system         Headache                Migraine disorders
Vascular disorders                             Dizziness

Gastrointestinal       Abdominal/pelvic        Nausea disorders              pain
Skin and               Acne/Seborrhoea         Alopecia               Hirsutism subcutaneous tissue disorders


Reproductive           Bleeding changes        Upper genital tract    Uterine system and breast      including increased     infection              perforation** disorders              and decreased           Dysmenorrhoea menstrual bleeding,     Breast spotting, infrequent    pain/discomfort bleeding and            Device expulsion amenorrhoea             (complete and
Ovarian cyst*           partial)
Vulvovaginitis          Genital discharge

Investigations                                  Increased weight

* 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 a large prospective comparative non-interventional cohort study with women using another levonorgestrel-IUS and copper IUDs which showed that breastfeeding at the time of insertion and insertion up to 36 weeks after giving birth are independent risk factors for perforation (see section 4.4 under Perforation). In clinical trials with Kyleena that excluded breastfeeding women the frequency of perforation was "rare".


Description of selected adverse reactions

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

If a woman becomes pregnant while using Kyleena, 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.

The following ADRs have been reported in connection with the insertion or removal procedure of Kyleena: Procedural pain, procedural bleeding, insertion-related vasovagal reaction with dizziness or syncope. The procedure may precipitate a seizure in an epileptic patient.

Cases of sepsis (including group A streptococcal sepsis) have been reported following IUD insertion (see section 4.4 under Pelvic Infection).

Paediatric population

The safety profile of Kyleena is expected to be the same for adolescents under the age of 18 as for users 18 years and older. For data on safety in adolescents, see section 5.1.

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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il