Precautions and Warnings

Alprostadil should only be administered by a specialist in hospital or another setting where paediatric intensive care facilities are immediately available.

Heart rate, blood pressure, respiratory rate and core body temperature must be monitored during the infusion.

Apnoea may occur in 10-12% of neonates treated with alprostadil, evidence suggests that this effect is dose related. This effect generally appears in neonates weighing less than 2kg at birth and usually occurs during the first hour of administration. Ventilatory assistance should be immediately available.

The infusion should be temporarily stopped in neonates experiencing complications such as apnoea, profound bradycardia or severe hypotension. Once the complication is resolved, the infusion may be reintroduced at a lower dose.

The lowest effective dose and shortest effective infusion time should be used. The risks of prolonged infusion times should be weighed against the possible benefits to the critically ill infant.

Prolonged administration of alprostadil has produced cortical proliferation of the long bones in infants and animals. This effects appear to reverse following cessation of therapy.

Use with caution in neonates with bleeding tendencies or a history of haemorrhage.

Avoid the use of alprostadil in neonates with hyaline membrane disease (respiratory distress syndrome). This condition can sometimes be confused with cyanotic cardiac disease. If full diagnostic facilities are unavailable, cyanosis (pO2 less than 40mmHg) and restricted pulmonary blood flow apparent on X-ray are good indicators of the presence of congenital heart defects.

Arterial pressure should be monitored regularly throughout the infusion by umbilical artery catheter, auscultation, or with a Doppler transducer. The infusion rate should be decreased immediately if arterial pressure falls significantly.

The walls of the ductus arteriosus and pulmonary artery may be weakened by treatment, especially during prolonged administration.

Gastric outlet obstruction secondary to antral hyperplasia may occur following alprostadil administration in neonates. This effect appears to be related to the duration of therapy and the cumulative dose administered. Neonates receiving alprostadil at the recommended dosage for more than 120 hours should be closely monitored for evidence of antral hyperplasia and gastric outlet obstruction.

Long-term carcinogenicity and fertility studies have not been conducted. The Ames and Alkaline Elution assays reveal no potential for mutagenesis.

The efficacy of alprostadil in neonates with decreased pulmonary blood flow is measured by monitoring the blood oxygenation increase.

In neonates with decreased systemic blood flow, the efficacy of alprostadil should be measured by monitoring the increase in systemic blood pressure and blood pH.

Presentation

Concentrate for solution for infusion containing alprostadil 500micrograms in 1ml

Drugs List

alprostadil 500microgram/1ml concentrate for solution for infusion

PROSTIN VR 500microgram/1ml concentrate for solution for infusion

Therapeutic Indications

Uses

Used to maintain the patency of the ductus arteriosus until corrective or palliative surgery can be performed in infants who have congenital heart defects who depend upon the patent ductus for survival.

Such congenital heart defects include:
Pulmonary atresia
Pulmonary stenosis
Tricuspid atresia
Tetralogy of Fallot
Interruption of the aortic arch
Co-arctation of the aorta
Aortic stenosis
Aortic atresia
Mitral atresia
Transposition of the great vessels with or without other defects.

Dosage

Neonates

50 to 100 nanograms/kg/minute. However, doses as low as 5 nanograms/kg/minute have been used successfully.

After a therapeutic response has been obtained, the infusion rate should be reduced to the lowest possible dosage that will maintain the desired response.

Administration

For administration by intravenous drip or constant rate infusion.

In infants with lesions restricting pulmonary blood flow (blood flow through the ductus arteriosus from the aorta to the pulmonary artery), alprostadil 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.

Types of adverse reaction encountered differ between the routes of administration used.
There is a higher incidence of flushing with arterial administration than with intravenous administration.

Contraindications

Respiratory distress syndrome (hyaline membrane disease)