This information is intended for use by health professionals

1. Name of the medicinal product

Survanta 25mg/ml suspension

2. Qualitative and quantitative composition

Each ml contains beractant equivalent to:

Phospholipids

25 mg/ml

(including disaturated phosphatidylcholines 11.0 - 15.5 mg/ml)

Triglycerides

Free Fatty Acids

Protein

0.5 - 1.75 mg/ml

1.4 - 3.5 mg/ml

0.1 - 1.0 mg/ml

Excipient with known effect: 3.54mg/ml Sodium

For the full list of excipients, see section 6.1

3. Pharmaceutical form

Sterile suspension for intratracheal administration

4. Clinical particulars
4.1 Therapeutic indications

Survanta 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.

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

4.2 Posology and method of administration

Posology

Paediatric population

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

Treatment: Survanta 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 Survanta 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

Survanta 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 Survanta.

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

Before administering Survanta to infants on mechanical ventilation, set the respiratory frequency at 60/minute - with inspiration time 0.5s and Fi02 at 1.0. Inspiratory pressure needs no change at this point.

To ensure distribution of Survanta 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 Survanta 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.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Survanta 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 Survanta. Therefore, frequent and careful monitoring of systemic oxygenation is essential to avoid hyperoxia. Following Survanta 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.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6 Fertility, pregnancy and lactation

Not applicable.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

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:

System Organ Class

Frequency

Adverse Reactions

Vascular disorders

Very common

Intracranial haemorrhage

Respiratory

Common

Pulmonary haemorrhage

Surgical and Medical Procedures

Uncommon

Blockage of endotracheal tube by mucous secretions

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 Survanta 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

4.9 Overdose

Paediatric Population

If an excessively large dose of Survanta 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 Survanta 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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Lung Surfactant

ATC Code R07AA02

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

Intratracheally administered Survanta 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 Survanta.

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 Survanta.

5.2 Pharmacokinetic properties

In preclinical studies using radiolabelled phosphatidylcholine, the clearance rate of Survanta 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 Survanta was shown, implying its entry into a metabolically active surfactant pool.

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

5.3 Preclinical safety data

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

6. Pharmaceutical particulars
6.1 List of excipients

Sodium chloride

Palmitic acid

Dipalmitoyl Phosphatidylcholine

Tripalmitin

Sodium Hydroxide (for pH adjustment)

Hydrochloric acid (for pH adjustment)

Water for injection

6.2 Incompatibilities

None experienced to date, as product administration is unique.

6.3 Shelf life

18 months

Before administration, Survanta should be warmed by standing at room temperature for 20 minutes or warmed in the hand for 8 minutes. ARTIFICIAL WARMING METHODS SHOULD NOT BE USED. Discard each vial if not used within 8 hours of warming to room temperature. Vials should not be returned to the refrigerator once warmed.

6.4 Special precautions for storage

Store under refrigerated conditions (2-8°C) protected from light. Do not freeze. Any inadvertently frozen product should be discarded. For storage conditions after product is removed from the refrigerator before opening, see section 6.3.

6.5 Nature and contents of container

21ml glass bottle with a 20mm rubber stopper and a 20mm aluminium seal finish containing 8ml of product.

Pack sizes: 1, 3 and 10

6.6 Special precautions for disposal and other handling

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

Survanta should be inspected visually for discolouration prior to administration. The colour of Survanta 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.

7. Marketing authorisation holder

AbbVie Ltd.

Maidenhead,

SL6 4UB

UK

8. Marketing authorisation number(s)

PL 41042/0003

9. Date of first authorisation/renewal of the authorisation

13th October 1998

10. Date of revision of the text

30 October 2015