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1 ml X 0.5 mg/ml
For administration by intravenous drip or constant rate infusion pump.
In infants with lesions restricting pulmonary blood flow (blood is flowing through the ductus arteriosus from the aorta to the pulmonary artery), Prostin VR may be administered by continuous infusion through an umbilical artery catheter placed at or just above the junction of the descending aorta and the ductus arteriosus, or intravenously. Adverse effects have occurred with both routes of administration, but the types of reactions are different. A higher incidence of flushing has been associated with intra-arterial than with intravenous administration.
The infusion is generally initiated at a rate of 0.05 to 0.1 micrograms alprostadil per kilogram of body weight per minute. The most experience has been with 0.1 micrograms/kg/min. After a therapeutic response (an increase in pO2 in neonates with restricted pulmonary blood flow or an increase in systemic blood pressure and blood pH in neonates with restricted systemic blood flow) has been obtained, the infusion rate should be reduced to the lowest possible dosage that will maintain the desired response.
For palliative therapy to maintain the patency of the ductus arteriosus.
Hypersensitivity to the active substance or to any of the excipients.
Prostin VR should be administered only by well trained healthcare professionals and in facilities with immediate access to paediatric intensive care.
Apnoea may occur in about 10-12% of neonates with congenital heart defects treated with alprostadil. There is some evidence that apnoea is dose related. Apnoea is most often seen in neonates weighing less than 2 kg at birth and usually appears during the first hour of drug infusion. Therefore Prostin VR should be used where ventilatory assistance is immediately available.
Prostin VR should be infused for the shortest time possible and at the lowest dose that will produce the desired effects. The risk of long-term infusion of Prostin VR should be weighed against the possible benefits that critically ill infants may derive from its administration.
Pathologic studies of the ductus arteriosus and pulmonary arteries of infants treated with prostaglandin E1 have disclosed histologic changes related with the weakening effect upon these structures. The specificity or clinical relevance of these results is not known.
Cortical proliferation of the long bones has followed long-term infusions of alprostadil in infants and dogs. The proliferation in infants regressed after withdrawal of the drug.
Since prostaglandin E1 is a potent inhibitor of platelet aggregation, use Prostin VR cautiously in neonates with histories of bleeding tendencies.
Alprostadil should not be used in neonates (or infants) with respiratory distress syndrome (hyaline membrane disease). A differential diagnosis should always be made between respiratory distress syndrome and cyanotic heart disease (restricted pulmonary blood flow). In the event that full diagnostic facilities are not immediately available, the diagnosis should be based on the presence of cyanosis (pO2 less than 40 torr) and x-ray evidence of a restricted pulmonary blood flow.
Arterial pressure should be monitored by umbilical artery catheter, auscultation or with a Doppler transducer. Should arterial pressure fall significantly, the rate of infusion should be immediately decreased
Weakening of the ductus arteriosus wall and pulmonary artery has been reported, particularly during prolonged administration.
The administration of alprostadil to neonates may result in gastric outlet obstruction secondary to antral hyperplasia. This effect appears to be related to duration of therapy and cumulative dose of the drug. Neonates receiving alprostadil at recommended doses for more than 120 hours should be closely monitored for evidence of antral hyperplasia and gastric outlet obstruction.
In neonates (or infants) with decreased pulmonary blood flow, the oxygenation increase is inversely proportional to the previous pO2 values; ie, better responses are obtained in patients with low pO2 values (less than 40 mmHg), whereas patients with high pO2 values (more than 40 mmHg) have usually a minimal response. In neonates (or infants) with decreased pulmonary blood flow, alprostadil efficacy is measured by monitoring blood oxygenation increase. In neonates (or infants) with decreased systemic blood flow the efficacy is determined by monitoring the increase in systemic blood pressure and blood pH.
The most frequent adverse reactions observed with Prostin VR infusion in neonates with ductal-dependent congenital heart defects are related to the drug’s known pharmacological effects.
Very common: Apnoea, Transient pyrexia.
Common: Seizures, Bradycardia, hypotension, tachycardia, Hypokalaemia,
Diarrhoea, Cutaneous vasodilatation (flushing)*.
*This is the only adverse event directly related to the route of administration, being more frequent with intra-arterial administration.
See prescribing information for full details.
No drug interactions have been reported to occur between Prostin VR and the standard therapy employed in neonates with congenital heart defects. Standard therapy includes antibiotics, such as penicillin or gentamicin; vasopressors, such as dopamine or isoproterenol; cardiac glycosides; and diuretics, such as frusemide.
Pregnancy and Lactation
Apnoea, bradycardia, pyrexia, hypotension and flushing may be signs of drug overdose. If apnoea or bradycardia occur, the infusion should be discontinued and the appropriate medical treatment initiated. Caution should be used if the infusion is restarted. If pyrexia or hypotension occur, the infusion rate should be reduced until these symptoms subside. Flushing is usually attributed to incorrect intra-arterial catheter placement and is usually alleviated by repositioning the tip of the catheter.
Incompatibilities: Diluted solutions of Prostin VR should be infused from glass or hard plastic containers, or PVC infusion bags. If undiluted Prostin VR comes in direct contact with a plastic container, plasticisers are leached from the sidewalls. This appears to be a concentration-dependent phenomenon.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Shelf life: Diluted solutions should be used within 24 hours.
Storage: Store in a refrigerator (2-8°C).