Pedea

Treatment with Pedea should only be carried out in a neonatal intensive care unit under the supervision of an experienced neonatologist. Posology A course of therapy is defined as three intravenous injections of Pedea given at 24-hour intervals.

The first injection should be given after the first 6 hours of life. The ibuprofen dose is adjusted to the body weight as follows: - 1st injection: 10 mg/kg, - 2nd and 3rd injections: 5 mg/kg. If anuria or manifest oliguria occurs after the first or second dose, the next dose should be withheld until urine output returns to normal levels.

If the ductus arteriosus does not close 48 hours after the last injection or if it re-opens, a second course of 3 doses, as above, may be given. If the condition is unchanged after the second course of therapy, surgery of the patent ductus arteriosus may then be necessary.

Method of administration For intravenous use only. Pedea should be administered as a short infusion over 15 minutes, preferably undiluted. 9%) solution for injection or glucose 50 mg/ml (5%) solution for injection. Any unused portion of the solution should be discarded.

The total volume of solution injected should take into account the total daily fluid volume administered. 3

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 disorders Very common: Bronchopulmonary dysplasia* 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) 5 * 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 in 3 newborn infants less than 28 weeks of gestational age. This occurred within one hour of the first infusion and was reversed within 30 minutes after the inhalation of nitric oxide.

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.

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.

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. 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. 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 first appearance of signs and symptoms of severe skin reactions, such as skin rash, mucosal lesions, or any other sign of hypersensitivity.

1). e. essentially ‘sodium- free’.

g. pulmonary atresia, severe tetralogy of Fallot, severe coarctation of the aorta); - Known or suspected necrotising enterocolitis;