Phospholipids (beractant) is indicated for the prevention and treatment of Respiratory Distress Syndrome (RDS), also known as hyaline membrane disease, in premature infants.

Prevention: In premature infants with birth weight less than 1250 g or with evidence of surfactant deficiency, Phospholipids should be administered as early as possible, preferably within 15 minutes of birth.

Rescue treatment: For infants with confirmed RDS by chest X-ray who require mechanical ventilation, Phospholipids should be given as early as possible, preferably within 8 hours of age.

Clinical studies suggest limited additional benefit in infants who have received antenatal corticosteroids, unless they develop RDS within the first 6–8 hours of life.

No separate adverse bias was observed between inborn and outborn infants in clinical trials; both groups responded similarly to treatment.

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 standardize composition and mimic natural lung surfactant, additives such as colfosceril palmitate (dipalmitoyl phosphatidylcholine), palmitic acid, and tripalmitin are included. It is dispersed in 0.9% sodium chloride solution and heat-sterilized. It contains hydrophobic surfactant-associated proteins SP-B and SP-C, but does not contain the hydrophilic protein SP-A. No preservatives are added.

Endogenous pulmonary surfactant reduces surface tension in the alveoli during respiration and prevents alveolar collapse at normal breathing pressures. Deficiency of surfactant leads to Respiratory Distress Syndrome (RDS) in premature infants.

Phospholipids replace deficient surfactant and restore normal lung surface activity.

In vitro, it reduces surface tension to less than 8 dynes/cm. In vivo studies show improvement in lung compliance, pressure-volume measurements, and oxygenation in premature animal models such as rabbits and sheep after a single dose.

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.

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 600 g 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 in endotracheal tube, deterioration after weaning, respiratory decompensation, subglottic stenosis, diaphragmatic paralysis, respiratory failure.
• Cardiovascular: Hypotension, hypertension, tachycardia, ventricular tachycardia, aortic thrombosis, cardiac failure, cardio-respiratory arrest, increased apical pulse, persistent fetal circulation, air embolism, total anomalous pulmonary venous return.
• Gastrointestinal: Abdominal distension, hemorrhage, intestinal perforation, volvulus, bowel infarction, feeding intolerance, hepatic failure, stress ulcer.
• Renal: Renal failure, hematuria.
• Hematologic: Coagulopathy, thrombocytopenia, disseminated intravascular coagulation (DIC).
• Central Nervous System: Seizures.
• Endocrine/Metabolic: Adrenal hemorrhage, inappropriate ADH secretion, hyperphosphatemia.
• Musculoskeletal: Inguinal hernia.
• Systemic: Fever, clinical deterioration.

Phospholipids are for intratracheal use only and can rapidly improve oxygenation and lung compliance. Therefore, it should be used only in a highly specialized and closely monitored clinical setting with immediate availability of skilled staff for intubation and ventilator management.

Infants should be continuously monitored using arterial or transcutaneous measurements of oxygen and carbon dioxide.

During administration, temporary bradycardia and oxygen desaturation may occur. If this happens, dosing should be stopped and appropriate supportive measures taken. Once the condition stabilizes, treatment may be resumed.

Transient rales and moist breath sounds may occur after administration and do not usually require suctioning unless airway obstruction is evident.

Clinical trials showed a slightly increased risk of nosocomial sepsis in treated infants, though without increased mortality. Infection patterns were similar between treated and control groups.

Use has not been evaluated in infants <600 g or >1750 g birth weight. There is also no controlled data with high-frequency ventilation or extracorporeal membrane oxygenation.

No data are available regarding dosing beyond 100 mg/kg, more than four doses, dosing more frequently than every 6 hours, or use after 48 hours of age.

No cases of overdose have been reported. Based on animal studies, excessive dosing may lead to acute airway obstruction. Treatment should be supportive and symptomatic. Post-administration rales or moist breath sounds are not signs of overdose unless clear airway obstruction is present. Suctioning is required only if clinically indicated.

Cholagogues, cholelitholytics & hepatic protectors, pulmonary surfactants

Store unopened vials at 2–8°C under refrigeration. Protect from light and keep in the carton until use. Vials are for single use only; discard any unused portion after opening.