Adverse reactions : תופעות לוואי

4.8 Undesirable effects
Adverse reactions have been ranked under heading of system-organ class and frequency using the following convention: very common (≥1/10); common (≥1/100, ≤1/10); uncommon (≥1/1,000, ≤1/100); rare (≥1/10,000, ≤1/1,000); very rare (≤1/10,000); not known (cannot be estimated from the available data).
Blood and lymphatic system disorders:
• Uncommon: Thrombocytopenia*
• Not known: Reduction of red blood count and/or haemoglobin concentration * In infants and children, risk of thrombocytopenia increased significantly with duration of infusion. Clinical data suggest that milrinone-related thrombocytopenia is more common in children than in adults (see section 4.4).
Immune system disorders:
• Very rare: Anaphylactic shock
Metabolism and nutrition disorders:
• Uncommon: Hypokalaemia
Nervous system disorders:
• Common: Headaches, usually mild to moderate in severity
• Uncommon: Tremor Cardiac disorders:
• Common:
- Ventricular ectopic activity
- Non-sustained or sustained ventricular tachycardia (see section 4.4) - Supraventricular arrhythmias
- Hypotension
• Uncommon:
- Ventricular fibrillation
- Angina/chest pain
• Very rare: Torsades de pointes
The incidence of arrhythmias has not been related to dose or plasma levels of milrinone. These arrhythmias are rarely life-threatening. If present, they are often associated with certain underlying factors such as pre- existing arrhythmias, metabolic abnormalities (e.g. hypokalaemia), abnormal digoxin levels and catheter insertion. Clinical data suggest that milrinone-related arrhythmias are less common in children than in adults.
Respiratory, thoracic and mediastinal disorders:
• Very rare: Bronchospasm Hepato-biliary disorders:
• Uncommon: Liver function tests abnormality Skin and subcutaneous tissue disorders:
• Very rarely: Skin reactions such as rash Renal and urinary disorders:
• Not known: Renal failure, secondary to a concomitant hypotension General disorders and administration site reactions:
• Not known: Infusion site reaction Paediatric population:
Nervous system disorders
Not known: Intraventricular haemorrhage (see section 4.4)
Congenital, familial, and genetic disorders
Not known: patent ductus arteriosus*** (see sections 4.2, 4.4, 5.2 and 5.3) *** The critical consequences of the patent ductus arteriosus are related to a combination of pulmonary overcirculation with consecutive pulmonary oedema and haemorrhage and of reduced organ perfusion with consecutive intraventricular haemorrhage and necrotizing enterocolitis with possible fatal outcome as described in literature.
Long-term safety data for paediatric population are not yet available.
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://sideeffects.health.gov.il.