Adverse reactions : תופעות לוואי

4.8.     Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions in clinical trials were headache, nausea, and breast tenderness, occurring in approximately 21.0%, 16.6%, and 15.9% of patients, respectively. Adverse reactions that may occur at the beginning of treatment but usually diminish after the first three cycles include spotting, breast tenderness and nausea.

Description of selected adverse reactions
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 CHCs, which are discussed in more detail in section 4.4.

Tabulated list of adverse reactions
Safety was evaluated in 3,322 sexually active women who participated in three Phase III clinical trials, which were designed to evaluate contraceptive efficacy. These subjects received six or 13 cycles of contraception (EVRA or oral contraceptive comparator), took at least one dose of study medicinal product and provided safety data. Table 1 below reflects the adverse reactions reported in clinical trials and from post-marketing experience. Frequency MedDRA convention: 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); not known (cannot be estimated from the available data).

Table 1: Frequency of adverse reactions
System Organ Class                   Adverse reaction
Frequency
Infections and infestations
Common                               (Vulvo) vaginal fungal infection Vaginal candidiasis
 rare                                  Rash pustular*
Application site pustules
Neoplasms benign, malignant and unspecified (incl cysts and polyps) rare                               Hepatic neoplasm*†
Breast cancer*†
Cervix carcinoma*†
Hepatic adenoma*†
Uterine leiomyoma
Fibroadenoma of breast
Immune system disorders uncommon                           Hypersensitivity rare                               Anaphylactic reaction*
Metabolism and nutrition disorders
Uncommon                           Hypercholesterolaemia
Fluid retention
Increased appetite
 rare                                 Hyperglycaemia*
Insulin resistance*
Psychiatric disorders
Common                               Mood, affect and anxiety disorders 
Uncommon                             Insomnia
Libido decreased
 rare                                 Anger*
Frustration*
Libido increased
Nervous system disorders very common                          Headache common                               Migraine
Dizziness

Rare                                 Cerebrovascular accident**†
Cerebral haemorrhage*†
Abnormal taste*
Eye disorders rare                                 Contact lens intolerance*
Cardiac disorders rare                                 Arterial thromboembolism
(Acute) myocardial infarction*†
Vascular disorders
Uncommon                             Hypertension
 rare                                  Hypertensive crisis*
Arterial thrombosis**†
Venous thrombosis**†
Thrombosis*†
Venous thromboembolism
Respiratory, thoracic and mediastinal disorders rare                                  Pulmonary (artery) thrombosis*† Pulmonary embolism†
Gastrointestinal disorders very common                           Nausea
 common                               Abdominal pain
Vomiting
Diarrhoea
Abdominal distension
 rare                                  Colitis*
Hepatobiliary disorders rare                                 Cholecystitis
Cholelithiasis†
Hepatic lesion*
Jaundice cholestatic*†
Cholestasis*†
Skin and subcutaneous tissue disorders
Common                               Acne
Rash
Pruritus
Skin reaction
Skin irritation
Uncommon                              Alopecia
Dermatitis allergic
Eczema
Photosensitivity reaction
Dermatitis contact
Urticaria
Erythema
 rare                                  Angioedema*
Erythema (multiforme, nodosum)*
Chloasma†
Exfoliative rash*
Pruritus generalised
Rash (erythematous, pruritic)
Seborrhoeic dermatitis*
Musculoskeletal and connective tissue disorders common                                Muscle spasms
Reproductive system and breast disorders very common                           Breast tenderness
 common                                Dysmenorrhoea
Vaginal bleeding and menstrual disorders**†
Uterine spasm
Breast disorders
Vaginal discharge uncommon                              Galactorrhoea
Premenstrual syndrome
Vulvovaginal dryness
 rare                                  Cervical dysplasia*
Suppressed lactation*
Genital discharge
General disorders and administration site conditions
Common                                Malaise
Fatigue
Application site reactions (erythema,
irritation, pruritus, rash)

uncommon                                 Generalised oedema
Oedema peripheral
Application site reactions**
 rare                                     Face oedema*
Pitting oedema*
Swelling
Application site reactions* (e.g., abscess,
erosion)
Localised oedema*
Investigations
Common                                   Weight increased

Uncommon                                 Blood pressure increased
Lipid disorders**
Rare                                     Blood glucose decreased*†
Blood glucose abnormal*†
* Post-marketing reports.
** Includes adverse reactions reported in clinical trials and post-marketing reports.
† See section 4.4.

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
Can also be reported by email: safety@trima.co.il