Adverse reactions : תופעות לוואי

4.8   Undesirable effects

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 drug related adverse reactions 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 summary 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).

MedDRA                                        Frequency of Adverse Reactions System Organ       Very         Common         Uncommon           Rare                  Not known Class              common
Blood and                       Anaemia        Thrombocytopenia lymphatic                                      Pancytopenia system                                         Ecchymosis disorders                                      Haemorrhage
Metabolism and                  Fluid          Oedema           Weight gain nutrition                       retention      Weight loss disorders
Nervous system     Headache Dizziness          Paraesthesia         Somnolence disorders                                      Insomnia             Abnormal Depression           coordination
Confusion            Dysarthria
Hypoaesthesia        Migraine
Nervousness
Dry mouth
MedDRA                                   Frequency of Adverse Reactions System Organ       Very     Common        Uncommon           Rare                 Not known Class              common
Amnesia
Eye disorders                                                  Vision abnormal Diplopia
Ear and                                                        Tinnitus labyrinth disorders
Cardiac                     Palpitations Congestive heart      Angina pectoris    Torsade de disorders                   Tachycardia failure                Myocardial         pointes Hypertension          infarction
Arrhythmia            Cardiomegaly
Atrial fibrillation   Cardiomyopathy
Supraventricular      Pericardial tachycardia           effusion
Ventricular           Vasodilatation tachycardia           Postural
Syncope               hypotension
Respiratory,                             Dyspnoea              Pulmonary          Allergic thoracic and                             Epistaxis             hypertension       alveolitis, mediastinal                              Pleural effusion      Pulmonary          including disorders                                Pneumonia             infiltrates        interstitial lung disease and pneumonitis
Gastrointestinal            Nausea        Dyspepsia            Colitis disorders                   Diarrhoea     Anorexia             Gastritis Abdominal     Pancreatitis         Gingival pain          Constipation         bleeding
Flatulence    Gastrointestinal
Vomiting      haemorrhage
Gastrointestinal disorder
Hepatobiliary                             Hepatic enzymes                         Hepatitis disorders                                 increased
Skin and                    Rash          Alopecia             Dry skin subcutaneous                              Skin discoloration tissue disorders                          Pruritus
Musculoskeletal                           Myalgia and connective                            Arthralgia tissue disorders                          Back pain
Renal and                                 Impotence            Nocturia           Tubulointerstitial urinary                                                        Renal failure      nephritis disorders
General                     Fatigue       Chest pain           Asthenia disorders and                             Weakness             Pain administration                            Chills               Flu-like site conditions                           Malaise              syndrome Fever
Investigations                                                 Blood creatinine increased