Adverse reactions : תופעות לוואי

4.8   Undesirable effects
The adverse effects of this product most commonly reported in patients who were treated with drydrogesterone during clinical trials into indications without the use of oestrogen were metrorrhagia, painful/ sensitive breasts and migraine/headache.

The following adverse effects, with the frequencies indicated, were observed during clinical trials with dydrogesterone (n=3,483) for indications without the use of oestrogen, and were reported spontaneously:

Organ class according to     Common                  Uncommon                  Rare MedDRA database              ≥1/100, <1/10           ≥1/1,000, <1/100          ≥1/10,000, <1/1,000 
Neoplasms, benign,                                                            Growth of progestogen- malignant and non-                                                            dependent neoplasms specified (including cysts                                                    (e.g. meningioma)* and polyps)
Blood and lymphatic                                                           Haemolytic anaemia* system disorders
Psychiatric disorders                                Depression
Immune system disorders                                                        Hypersensitivity Nervous system disorders     Migraine/               Dizziness                 Somnolence headache
Gastrointestinal disorders   Nausea                  Vomiting


Hepatobiliary disorders                              Disturbed liver function (with icterus,
asthenia or malaise,
and abdominal pain)
Skin and subcutaneous                                Allergic dermatitis     Angiooedema* tissue disorders                                     (e.g. rash, pruritus, urticaria)
Reproductive system and      Disturbed                                        Swelling of the breasts breast disorders             menstruation
(including metrorrhagia,
menorrhagia, oligo-
/amenorrhoea,
dysmenorrhoea and irregular menstruation)
Painful/ sensitive breasts
General disorders and                                                          Oedema administration site conditions
Investigations                                       Weight gain

* Adverse effects reported spontaneously but not observed during clincal trials are classified as “rare” in view of the fact that the upper limit of the 95% confidence interval of the estimated frequency is not higher than 3/x, where x=3,483 (the total number of patients in the clinical trials).

LOTUS I study for luteal support as part of an Assisted Reproductive Technology (ART) treatment (see section 5.1):

The most frequently reported events are vaginal hemorrhage, nausea, procedural pain, headache, abdominal pain and biochemical pregnancy.
The only related treatment emergent adverse event (TEAE) reported in ≥ 2% of subjects in either treatment group is vaginal hemorrhage.
Adverse effects that may occur during treatment with oestrogen-progestogen (see also the section 4.4 and the product information for the oestrogen formulation): 
-       Breast cancer, endometrial hyperplasia, endometrial carcinoma, ovarian cancer -       Venous thromboembolism
-       Myocardial infarction, coronary heart disease, ischemic CVA

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 http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=AdversEffectMedic @moh.gov.il.