Pedea · 4.4 Special warnings and precautions for use · 1

HOS-093812 · has-adverse-reaction-information · PDF-Seite 4

Data are currently available on approximately 1,000 preterm newborn from both the literature concerning ibuprofen and clinical trials with Pedea. Causality of adverse events reported in the preterm newborn is difficult to assess since they may be related to the haemodynamic consequences of the patent ductus arteriosus as well as to direct effects of ibuprofen. Reported adverse reactions are listed below, by system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), common (≥1/100, <1/10) and uncommon (≥1/1,000, <1/100). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Blood and lymphatic system disorders Very common: Thrombocytopenia, Neutropenia Nervous system disorders Common: Intraventricular haemorrhage, Periventricular leukomalacia Respiratory, thoracic and mediastinal Very common: Bronchopulmonary dysplasia* disorders Common: Pulmonary haemorrhage Uncommon: Hypoxemia* Gastrointestinal disorders Common: Necrotizing enterocolitis, Intestinal perforation Uncommon: Gastrointestinal haemorrhage Unknown: Gastric perforation Renal and urinary disorders Common: Oliguria, Fluid retention, Haematuria Uncommon: Acute renal failure Investigations Very Common: Blood creatinine increased, Blood sodium decreased Skin and subcutaneous tissue disorders Not known: Acute generalised exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) 4 * see below In a clinical curative trial involving 175 preterm newborn infants less than 35 weeks of gestational age, the incidence of bronchopulmonary dysplasia at 36 weeks post-conceptional age was 13/81 (16%) for indomethacin versus 23/94 (24%) for ibuprofen. In a clinical trial where Pedea was administered prophylactically during the first 6 hours of life, severe hypoxemia with pulmonary hypertension was reported

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HOS-093808 · has-contraindication-information · PDF-Seite 3

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1; - Life-threatening infection; - Active bleeding, especially intracranial or gastrointestinal haemorrhage; - Thrombocytopenia or coagulation defects; - Significant impairment of renal function; - Congenital heart disease in which patency of the ductus arteriosus is necessary for satisfactory pulmonary or systemic blood flow (e.g. pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta); - Known or suspected necrotising enterocolitis;

HOS-093807 · has-indication-information · PDF-Seite 2

Treatment of a haemodynamically significant patent ductus arteriosus in preterm newborn infants less than 34 weeks of gestational age.

HOS-093810 · has-interaction-information · PDF-Seite 4

The concomitant use of Pedea with the following medicinal products is not recommended: - diuretics: ibuprofen may reduce the effect of diuretics; diuretics can increase the risk of nephrotoxicity of NSAIDs in dehydrated patients. - anticoagulants: ibuprofen may increase the effect of anticoagulants and enhance the risk of bleeding. - corticosteroids: ibuprofen may increase the risk of gastrointestinal bleeding. - nitric oxide: since both medicinal products inhibit platelet function, their combination may in theory increase the risk of bleeding. - other NSAIDs: the concomitant use of more than one NSAID should be avoided because of the increased risk of adverse reactions. - aminoglycosides: since ibuprofen may decrease the clearance of aminoglycosides, their co- administration may increase the risk of nephrotoxicity and ototoxicity (see section 4.4).

HOS-093811 · has-pregnancy-information · PDF-Seite 4

Not relevant

HOS-093809 · has-warning-information · PDF-Seite 3

Before administration of Pedea an adequate echocardiographic examination should be performed in order to detect a haemodynamically significant patent ductus arteriosus and to exclude pulmonary hypertension and ductal-dependent congenital heart disease. Since prophylactic use in the first 3 days of life (starting within 6 hours of birth) in preterm newborn infants less than 28 weeks of gestational age was associated with increased pulmonary and renal adverse events, Pedea should not be used prophylactically at any gestational age (see sections 4.8 and 5.1). In particular, severe hypoxemia with pulmonary hypertension was reported in 3 infants within one hour of the first infusion and was reversed within 30 min after start of inhaled nitric oxide therapy. If hypoxaemia occurs during or following Pedea infusion, close attention should be paid to pulmonary pressure. Since ibuprofen was shown in vitro to displace bilirubin from its binding site to albumin, the risk of bilirubin encephalopathy in premature newborn infants may be increased (see section 5.2). Therefore, ibuprofen should not be used in infants with marked elevated bilirubin concentration. As a non-steroidal anti-inflammatory drug (NSAID), ibuprofen may mask the usual signs and symptoms of infection. Pedea must therefore be used cautiously in the presence of an infection (see also section 4.3). Pedea should be administered carefully to avoid extravasation and potential resultant irritation to tissues. As ibuprofen may inhibit platelet aggregation, premature neonates should be monitored for signs of bleeding. As ibuprofen may decrease the clearance of aminoglycosides, strict surveillance of their serum levels is recommended during co-administration with ibuprofen. Careful monitoring of both renal and gastrointestinal function is recommended. Severe skin reactions Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis have been reported rarely in association with the use of NSAIDSs (see section 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) have been reported in relation to ibuprofen-containing products. Ibuprofen should be discontinued, at the firs

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