PROSTIN VR Concentrate for solution for infusion Ref.[8672] Active ingredients: Alprostadil

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; i.e. 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.

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).

Not relevant.

Not relevant.

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.

The following undesirable effects have been observed and reported during treatment with alprostadil (436 neonates treated) with the following frequencies: Very common (≥1/10); Common (≥1/100 to <1/10); Uncommon (≥1/1,000 to <1/100); Rare (≥1/10,000 to <1/1,000); Very rare (<1/10,000).

Nervous system disorders

Common: Seizures

Cardiac disorders

Common: Bradycardia, hypotension, tachycardia

Vascular disorders

Uncommon: Vascular fragility

Respiratory, thoracic and mediastinal disorders

Very common: Apnoea

Metabolism and nutrition disorders

Common: Hypokalaemia

Gastrointestinal disorders

Common: Diarrhoea

Uncommon: Gastric obstruction, gastric mucosal hypertrophy

Musculoskeletal and connective tissue disorders

Uncommon: Exostosis

General disorders and administration site conditions

Very common: Transient pyrexia

Common: Cutaneous vasodilatation (flushing)*

* This is the only adverse event directly related to the route of administration, being more frequent with intra-arterial administration.

The relationship of the following adverse events to the drug, in decreasing frequency, is unknown: sepsis, cardiac arrest, disseminated intravascular coagulation, and oedema.

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. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme: www.mhra.gov.uk/yellowcard.

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. See section 6.6.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.