Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
The safety of anagrelide has been examined in 4 open label clinical studies. In 3 of the studies 942 patients who received anagrelide at a mean dose of approximately 2 mg/day were assessed for safety.
In these studies, 22 patients received anagrelide for up to 4 years.

In the later study 3660 patients who received anagrelide at a mean dose of approximately 2 mg/day were assessed for safety. In this study 34 patients received anagrelide for up to 5 years.

The most commonly reported adverse reactions associated with anagrelide were headache occurring at approximately 14%, palpitations occurring at approximately 9%, fluid retention and nausea both occurring at approximately 6% and diarrhoea occurring at 5%. These adverse drug reactions are expected based on the pharmacology of anagrelide (inhibition of PDE III). Gradual dose titration may help diminish these effects (see section 4.2).

Tabulated list of adverse reactions
Adverse reactions arising from clinical studies, post-authorisation safety studies and spontaneous reports are presented in the table below. Within the system organ classes they are listed under the following headings: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.


MedDRA                                            Frequency of adverse reactions System Organ       Very         Common             Uncommon             Rare                   Not known Class              common
Blood and                       Anaemia            Pancytopenia lymphatic                                          Thrombocytopenia system                                             Haemorrhage disorders                                          Ecchymosis

Metabolism and                Fluid          Oedema                Weight gain nutrition                     retention      Weight loss disorders
Nervous system     Headache   Dizziness      Depression            Migraine           Cerebral disorders                                    Amnesia               Dysarthria         infarction* Confusion             Somnolence
Insomnia              Abnormal
Paraesthesia          coordination
Hypoaesthesia
Nervousness
Dry mouth
Eye disorders                                                      Diplopia Vision abnormal
Ear and                                                            Tinnitus labyrinth disorders
Cardiac                       Tachycardia    Ventricular           Myocardial         Torsade de disorders                     Palpitations   tachycardia           infarction         pointes Congestive heart      Cardiomyopathy failure               Cardiomegaly
Atrial fibrillation   Pericardial
Supraventricular      effusion tachycardia           Angina pectoris
Arrhythmia            Postural
Hypertension          hypotension
Syncope               Vasodilatation
Prinzmetal angina
Respiratory,                                 Pulmonary             Pulmonary          Interstitial lung thoracic and                                 hypertension          infiltrates        disease including mediastinal                                  Pneumonia                                pneumonitis and disorders                                    Pleural effusion                         allergic alveolitis Dyspnoea
Epistaxis
Gastrointestinal              Diarrhoea      Gastrointestinal      Colitis disorders                     Vomiting       haemorrhage           Gastritis Abdominal      Pancreatitis          Gingival pain           Anorexia              bleeding
Nausea         Dyspepsia
Flatulence     Constipation
Gastrointestinal disorder

Hepatobiliary                                Hepatic enzymes                         Hepatitis disorders                                    increased


Skin and                      Rash           Alopecia              Dry skin subcutaneous                                 Pruritus tissue disorders                             Skin discoloration


Musculoskeletal                              Arthralgia and connective                               Myalgia tissue disorders                             Back pain

Renal and                                              Impotence         Renal failure       Tubulointerstitial urinary                                                                  Nocturia            nephritis disorders


General                               Fatigue          Chest pain        Flu-like disorders and                                          Fever             syndrome administration                                         Chills            Pain site conditions                                        Malaise           Asthenia Weakness
Investigations                                                           Blood creatinine increased



* Cerebral infarction (see section 4.4 Thrombotic Risk)

Paediatric population
48 patients aged 6 through17 years (19 children and 29 adolescents) have received anagrelide for up to
6.5 years either in clinical studies or as part of a disease registry (see section 5.1).
The majority of adverse events observed were among those listed in the SmPC. However, safety data are limited and do not allow a meaningful comparison between adult and paediatric patients to be made (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/