Special Warning : אזהרת שימוש

4.4 Special warnings and precautions for use

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 Pfleet 2021-0069764                       Page 2 of 8
Prostin VR LPD CC 040821 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.

Excipient information

Each 1 ml vial of Prostin VR contains 790 mg anhydrous ethanol (see section 2), which is equivalent to less than 20 ml beer or 8 ml wine.

An example of ethanol exposure based on maximum single dose (see section 4.2) is as follows: Administration of 0.576ml of this medicine to a child 1 month of age and weighing 2 kg would result in exposure to 227.52 mg/kg of ethanol which may cause a rise in blood alcohol concentration (BAC) of about 37.9 mg/100 ml.

For comparison, for an adult drinking a glass of wine or 500 ml of beer, the BAC is likely to be about 50 mg/100 ml.

The ethanol content in this preparation is likely to affect children. These effects may include somnolence and changes in behaviour.

Because this medication is administered slowly over 24 hours the effects of ethanol may be reduced (see section 4.2).

Co-administration with medicines containing e.g. propylene glycol or ethanol may lead to accumulation of ethanol and induce adverse effects, particularly in young children with low or immature metabolic capacity.


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Prostin VR LPD CC 040821
The ethanol content in this medicinal product should be carefully considered in the following patient groups who may be at higher risk of ethanol-related adverse effects: - Patients with liver disease
- Patients with epilepsy

The amount of ethanol in this medicinal product may alter the effects of other medicines.

Effects on Driving

4.7 Effects on ability to drive and use machines

Not relevant.