BLES

BLES is indicated for treatment of Respiratory Distress Syndrome (RDS) (hyaline membrane disease) in new born premature infants with a birth weight of 700g or greater and who are intubated and are receiving mechanical ventilation.

BLES is also indicated for the prophylactic treatment of premature infants <32 weeks gestational age at risk of developing RDS.

Posology

Paediatric population

100 mg phosholipid/kg birth weight in a volume not exceeding 4ml/kg.

Treatment: BLES should be administered early in the course of RDS, i.e. preferably less than 8 hours of age. Depending on clinical course, this dose may be repeated within 48 hours at intervals of at least six hours for up to 4 doses.

Prophylaxis: The first dose of BLES should be administered as soon as possible after birth, preferably within 15 minutes. Depending on clinical course, this dose may be repeated within 48 hours at intervals of at least six hours for up to 4 doses.

Method of Administration

BLES should be administered by intratracheal administration (i.e. drug should be conducted into the lungs via an endotracheal tube) using a 5 Fr catheter. The tip of the catheter should lie at the end of the endotracheal tube. Infants should not be intubated solely for the administration of BLES.

BLES should be warmed to room temperature before administration (see Precautions).

Before administering BLES to infants on mechanical ventilation, set the respiratory frequency at 60/minute - with inspiration time 0.5s and F_i0₂ at 1.0. Inspiratory pressure needs no change at this point.

To ensure distribution of BLES throughout the lungs, each dose is divided into fractional doses. Each dose can be administered as either two half-doses or four quarter-doses. Each fractional dose is administered with the infant in different positions as given below. Between each position the infant should be ventilated for 30 seconds.

For Four quarter-doses, the recommended positions are :

Right Lateral Position with the head lowered (i.e. head and body slanting down at an angle of approximately 15°).

Left Lateral Position with the head lowered (i.e. head and body slanting down at an angle of approximately 15°).

Right Lateral Position with head elevated (i.e. head and body slanting up at an angle of approximately 15°).

Left Lateral Position with head elevated (i.e. head and body slanting up at an angle of approximately 15°).

For administration of each quarter dose, the ventilator is disconnected, the catheter inserted, the dose administered then the ventilator reconnected. Between each quarter dose the infant is ventilated for 30 seconds.

For two half-doses, the recommended positions are :

- With infant supine, the head and body turned approximately 45° to the right.

- With infant supine, the head and body turned approximately 45° to the left.

When two half-doses of BLES are being administered there are 2 alternative methods of administration:

Installation with disconnection from the ventilator

Each half dose is administered by disconnecting the endotracheal tube from the ventilator, inserting the catheter and administering the half dose. Between the half doses, the ventilator is reconnected for 30 seconds.

Alternatively,

Instillation without disconnection from the ventilator (through a suction port connector).

The first half dose is administered by inserting the catheter through a suction port connector without disconnection from the ventilator. There should be at least 30 seconds between the half doses during which time the catheter is retracted from the endotracheal tube but not removed from the connector. The catheter is then reinserted into the endotracheal tube and the second half dose administered. The catheter is then withdrawn completely.

Dosage in Adults

Not applicable.

Dosage in Older People

Not applicable.

No specific contraindications for BLES have been defined by the clinical studies.

BLES should only be administered with adequate facilities for ventilation and monitoring of babies with RDS.

Marked improvements in oxygenation may occur within minutes of the administration of BLES. Therefore, frequent and careful monitoring of systemic oxygenation is essential to avoid hyperoxia. Following BLES administration, monitoring of the arterial blood gases, the fraction of inspired oxygen and ventilatory change is required to ensure appropriate adjustments.

During the dosing procedure, transient episodes of bradycardia and/or oxygen desaturation have been reported. If these occur, dosing should be stopped and appropriate measures to alleviate the condition should be initiated. After stabilisation, the dosing procedure should be resumed.

Not relevant.

Paediatric population

Summary of the safety profile

Intracranial haemorrhage has been observed in patients who received either beractant or placebo. The incidence of intracranial haemorrhage in all patients is similar to that reported in the literature in this patient population. Pulmonary haemorrhage has also been reported. Blockage of the endotracheal tube by mucous secretions has been reported. No other serious adverse reactions have been reported.

These are presented in the following table:

The following frequency categories are used: Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100).

No antibody production to BLES proteins has been observed.

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:

Website: www.mhra.gov.uk/yellowcard

Paediatric Population

If an excessively large dose of BLES is given, observe the infant for signs of acute airway obstruction. Treatment should be symptomatic and supportive. Rales and moist breath sounds can transiently occur after BLES is given, and do not indicate overdosage. Endotracheal suction or other remedial action is not required unless clear-cut signs of airway obstruction are present.

Pharmacotherapeutic group: Lung Surfactant

ATC Code R07AA02

The mode of action of BLES is biophysical rather than biochemical, i.e. it reduces surface tension and concomitantly increases lung compliance.

Intratracheally administered BLES distributes rapidly to the alveolar surfaces and stabilises the alveoli against collapse during respiration thereby increasing alveolar ventilation.

In clinical studies of premature infants with Respiratory Distress Syndrome (RDS), a significant improvement in oxygenation was demonstrated after treatment with a single dose of BLES.

These infants showed a decreased need for supplemental oxygen and an increase in the arterial/alveolar oxygen ratio (a/Ap0₂). Significantly decreased need for respiratory support, as indicated by a lower mean airway pressure, was also observed. In most cases these effects were maintained for at least 72 hours after the administration of the single dose of BLES.

In preclinical studies using radiolabelled phosphatidylcholine, the clearance rate of BLES in the lung of three day old rabbits has been shown to be similar to that of natural calf and sheep surfactants (approximately 13% within 24 hours). In addition some re-uptake and secretion of BLES was shown, implying its entry into a metabolically active surfactant pool.

Since an exogenous preparation of BLES is delivered directly to the lung, classical clinical pharmocokinetic parameters (blood levels, plasma half-life etc.) have not been studied.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

None experienced to date, as product administration is unique.

Each vial of BLES is for single use only. Used vials with residual drug should be discarded.

BLES should be inspected visually for discolouration prior to administration. The colour of BLES is off-white to light brown. Some settling may occur during storage. If this occurs, gently invert the vial several times (DO NOT SHAKE) to redisperse.

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.