Phospholipid (beractant) is a sterile, non-pyrogenic pulmonary surfactant intended for intratracheal use only. It is a natural bovine lung extract containing phospholipids, neutral lipids, fatty acids, and surfactant-associated proteins to which colfosceril palmitate (dipalmitoyl phosphatidylcholine), palmitic acid and tripalmitin are added to standardize the composition and to mimic the surface-tension lowering properties of natural lung surfactant. It is dispersed in 0.9% sodium chloride solution and heat-sterilized. Phospholipid contains no preservatives. It contains two, hydrophobic, low molecular weight, surfactant-associated proteins commonly known as SP-B and SP-C. It does not contain the hydrophilic, large molecular weight surfactant-associated protein known as SP-A.

Pharmacology

Endogenous pulmonary surfactant lowers surface tension on alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting transpulmonary pressures. Deficiency of pulmonary surfactant causes Respiratory Distress Syndrome (RDS) in premature infants. Phospholipid replenishes surfactant and restores surface activity to the lungs of these infants.

In vitro, Phospholipid reproducibly lowers minimum surface tension to less than 8 dynes/cm on the pulsating bubble surfactometer and Wilhelmy Surface Balance.

In vivo, single Phospholipid doses improve lung pressure-volume measurements, lung compliance, and oxygenation in premature rabbit and sheep.

Phospholipids is indicated for prevention and treatment of Respiratory Distress Syndrome (RDS) (hyaline membrane disease) in premature infants.

Prevention: In premature infants less than 1250 g birthweight, or with evidence of surfactant deficiency, give Phospholipids as soon as possible, preferably within 15 minutes of birth.

Rescue: To treat infants with RDS confirmed by X-ray and requiring mechanical ventilation, give Phospholipids as soon as possible, preferably by 8 hours of age.

Results from clinical studies suggest that little benefit is likely to be gained from giving Phospholipids to infants who have completed a prenatal course of corticosteroids, unless they develop RDS within the first 6-8 hours of life.

The results of outborn compared to inborn infants were not analysed separately in the clinical trials.Outborn infants were distributed equally between the treatment groups and were not considered likely to bias the estimation of treatment effect. Therefore, there does not appear to be any evidence to suggest that outborn infants respond less well to treatment with Phospholipids.

For Intratracheal Administration Only. Survanta should be administered by or under the supervision of clinicians experienced in intubation, ventilator management and general care of premature infants.

Marked improvements in oxygenation may occur within minutes of administration of Survanta. Therefore, frequent and careful clinical observation and monitoring of systemic oxygenation are essential to avoid hyperoxia.

Each dose of Survanta is 100 mg of phospholipid/kg birth weight (4 mL/kg). The Survanta Dosage Chart shows the total dosage for a range of birth weights.

Four doses of Survanta can be administered in the first 48 hours of life. Doses should be given no more frequently than every 6 hours.

Administration

Directions for Use: Phospholipid should be inspected visually for discolouration prior to administration. The colour of Phospholipid is off-white to light brown. If settling occurs during storage, swirl the vial gently (DO NOT SHAKE) to redisperse. Some foaming at the surface may occur during handling and is inherent in the nature of the product.

Phospholipids is stored refrigerated (2-8°C). Before administration, Phospholipids should be warmed by standing at room temperature for at least 20 minutes or warmed in the hand for at least 8 minutes. If a prevention dose is to be given, preparation of Phospholipids should begin before the infant’s birth.

Unopened, unused vials of Phospholipids that have been warmed to room temperature may be returned to the refrigerator within 8 hours of warming and stored for future use. Drug should not be warmed and returned to the refrigerator more than once. Each single-use vial of Phospholipids should be entered only once. Used vials with residual drug should be discarded.

Dosing Precautions: If an infant experiences bradycardia or oxygen desaturation during the dosing procedure, stop the dosing procedure and initiate appropriate measures to alleviate the condition. After the infant has stabilised, resume the dosing procedure. Rales and moist breath sounds can occur transiently after administration of Phospholipids. Endotracheal suctioning or other remedial action is unnecessary unless clear-cut signs of airway obstruction are present.

Methods of Administration:

• Method A outlined below was the original method of administration in all the controlled clinical studies that established the efficacy and safety of Phospholipid. The two additional methods of administering Phospholipid were compared to the original method in a multi-centre, randomised clinical trial involving 299 infants weighing 600g or more with RDS requiring mechanical ventilation. There were no significant differences among the three methods in average FiO2 a/A PO2 or MAP at 72 hours of age, or in the incidence of pulmonary air leaks, pulmonary interstitial emphysema, patent ductus arteriosus, or mortality at 72 hours of age.
• Method B keeping the infant on the ventilator is considered the delivery method of choice as it was associated with less clinical deterioration (expressed as falls in heart rate and in oxygen saturation) during and immediately following treatment. Method B was associated with a greater degree of Phospholipid reflux than the other methods. This reflux was not associated with any clinical consequence.
• Method C: Phospholipids can be administered by inserting the 5 French catheter through the endotracheal tube while the endotracheal tube is briefly disconnected from the ventilator. The half doses were administered in the two positions described as for Method B. The procedure for dosing is similar to Method A, the only difference being the use of two half doses instead of four quarter doses. With the infant supine, the head and body of the infant were turned approximately 45° to the right. The infant is removed from the ventilator and the primed catheter inserted into the endotracheal tube. The first half of the Phospholipids is then delivered and the catheter withdrawn. The infant is then returned to the ventilator for at least 30 seconds of mechanical ventilation. The head and body of the infant is turned approximately 45° to the left. The second half dose of Phospholipids is delivered in the same manner as the first. The catheter is withdrawn and the infant returned to mechanical ventilation.

• Respiratory: lung consolidation, blood from the endotracheal tube, deterioration after weaning, respiratory decompensation, subglottic stenosis, paralyzed diaphragm, respiratory failure.
• Cardiovascular: hypotension, hypertension, tachycardia, ventricular tachycardia, aortic thrombosis, cardiac failure, cardio-respiratory arrest, increased apical pulse, persistent foetal circulation, air embolism, total anomalous pulmonary venous return.
• Gastrointestinal: abdominal distension, haemorrhage, intestinal perforations, volvulus, bowel infarct, loading intolerance, hepatic failure, stress ulcer.
• Renal: renal failure, haematuria.
• Haematologic: coagulopathy, thrombocytopenia, disseminated intravascular coagulation
• Central Nervous System: seizures.
• Endocrine/Metabolic: adrenal haemorrhage, inappropriate ADH secretion, hyperphosphataemia.
• Musculoskeletal: inguinal hernia.
• Systemic: fever, deterioration.

Overdose Effects

Overdosage with Phospholipids has not been reported. Based on animal data, overdosage might result in acute airway obstruction. Treatment should be symptomatic and supportive. Rales and moist breath sounds can transiently occur after Phospholipids is given, and do not indicate overdosage. Endotracheal suctioning or other remedial action is not required unless clear-cut signs of airway obstruction are present.

Phospholipids are intended for intratracheal use only. Phospholipids can rapidly affect oxygenation and lung compliance. Therefore, its use should be restricted to a highly supervised clinical setting with immediate availability of clinicians experienced with intubation, ventilator management and general care of premature infants. Infants receiving Phospholipids should be frequently monitored with arterial or transcutaneous measurement of systemic oxygen and carbon dioxide.

During the dosing procedure, transient episodes of bradycardia and decreased oxygen saturation have been reported. If these occur, stop the dosing procedure and initiate appropriate measures to alleviate the condition. After stabilization, resume the dosing procedure.

General: Rales and moist breath sounds can occur transiently after administration. Endotracheal suctioning or other remedial action is not necessary unless clear-cut signs of airway obstruction are present.

Increased probability of post-treatment nosocomial sepsis in Phospholipids-treated infants was observed in the controlled clinical trials (See Table). The increased risk for sepsis among Phospholipids-treated infants was not associated with increased mortality among these infants. The causative organisms were similar in treated and control infants. There was no significant difference between groups in the rate of post-treatment infections other than sepsis.

Use of Phospholipids in infants less than 600 g birth weight or greater than 1750 g birth weight has not been evaluated in controlled trials. There is no controlled experience with use of Phospholipids in conjunction with experimental therapies for RDS (eg. high-frequency ventilation or extracorporeal membrane oxygenation).

No information is available on the effects of doses other than 100 mg Phospholipidss / kg, more than four doses, dosing more frequently than every 6 hours, or administration after 48 hours of age.