Adverse reactions : תופעות לוואי

4.8     Undesirable effects

Clinical studies with Belara have shown that the most common side- effects (> 20%) were breakthrough bleeding, spotting, headache and breast discomfort. Irregular bleeding usually decreases with continuation of the intake of Belara.

The following side-effects have been reported after administration of Belara in a clinical study with 1,629 women.

Very      Common           Uncommon         Rare (≥1 / 10,000 Very rare      Not known common      (≥1/100 -        (≥1/1000 -       - <1 / 1,000)     (<1/10,000)    (cannot be Frequency of              (≥1/10)    <1/10)           <1/100)                                           estimated undesirable effects                                                                                     from the /                                                                                                       available Organ system                                                                                            data) (MedDRA)
Infections and                                        vaginal         vulvovaginitis infestations                                          candidiasis
Neoplasms benign,                                     fibroadenoma of malignant and                                         the breast unspecified
(including cysts and polyps)


Immune system                                         drug                                              exacerbation disorders                                             hypersensitivity,                                 of symptoms including                                         of hereditary allergic skin                                     and acquired reactions                                         angioedema
Metabolism and                                        changes in        increased appetite nutrition disorders                                   blood lipid levels, including hypertriglycerid aemia
Psychiatric                          depressed        reduced libido disorders                            mood,
nervousness,
irritability
Nervous system                       dizziness,
disorders                            migraine
(and/or aggravation of migraine)
Eye disorders                        visual                            conjunctivitis, disturbance                       contact lens intolerance
Ear and labyrinth                                                      sudden hearing disorders                                                              loss, tinnitus 16
Frequency of        Very common Common                 Uncommon           Rare (≥ 1 / 10,000 Very rare undesirable effects (≥1/10)     (≥1/100 -              (≥1/1000 -         - <1 / 1,000)      (<1/10,000) /                               <1/10)                 <1/100)
Organ system
(MedDRA)
Vascular disorders                                                        hypertension, hypotension,
cardiovascular collapse, varicose vein, venous thrombosis,
venous/arterial thromboembolism
(VTE/ATE)* feeling sick      vomiting         abdominal pain,
Gastrointestinal    (nausea)                           abdominal disorders                                              distension,
Skin and                              acne             diarrhoea pigmentation       urticaria, eczema, erythema subcutaneous tissue                                    disorder,          erythema,          nodosum disorders                                              chloasma,          pruritus, alopecia, dry      aggravated skin, increased    psoriasis,
sweating, hair     hypertrichosis loss
Musculoskeletal and                   sensation of     back pain,
connective tissue                     heaviness        muscle disorders disorders

Reproductive system vaginal        lower               galactorrhoea,     breast and breast disorders discharge,    abdominal                              enlargement, dysmenorrhoea pain                                   vulvovaginitis,
, amenorrhoea                                        menorrhagia,
premenstrual
General disorders                     fatigue,                            syndrome and administration                    oedema,
site conditions                       increased weight

Investigations                        elevated blood pressure

*See Description of selected adverse reactions
In addition, the following adverse reactions have been reported in the post-marketing period with ethinylestradiol and chlormadinone acetate: weakness and other allergic skin reactions not related to immune system diseases.

Description of selected adverse reactions
The following side-effects have also been reported on administration of combined hormonal contraceptives including 0.030 mg ethinylestradiol and 2 mg chlormadinone acetate: 17
•     An increased risk of arterial and venous thrombotic and thrombo-embolic events, including myocardial infarction, stroke, transient ischemic attacks, venous thrombosis and pulmonary embolism has been observed in women using combined hormonal contraceptives. These are discussed in more detail in section 4.4.
•     An increased risk of biliary tract diseases has been reported in some studies on the long-term administration of CHCs.
•     In rare cases benign, and even more rarely, malignant liver tumours have been observed after the administration of hormonal contraceptives, and in isolated cases have resulted in life-threatening intra-abdominal haemorrhage (see section 4.4).
•     Aggravation of chronic inflammatory bowel disease (Crohn´s disease, ulcerative colitis; see section 4.4).

For other serious side-effects such as cancer of the cervix or breast see section 4.4.

Interactions
Breakthrough bleeding and/or contraceptive failure can occur because of interactions with other drugs (causing enzyme-induction) (see section 4.5).

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important, because it allows continued monitoring of the benefit/risk profile 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/.