For Healthcare Professionals

SAFETY CONSIDERATIONS1

  • SURVANTA is intended for intratracheal use only.
  • SURVANTA 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 SURVANTA 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.
  • In controlled clinical trials, an increased probability of post-treatment nosocomial sepsis was observed in SURVANTA-treated infants, which was not associated with increased mortality among these infants.

Efficacy data

RDS Prevention1,2

SURVANTA was studied for prevention of RDS in two multiple-dose, randomized, multicenter, controlled studies of very premature infants.*

Study Objective: To assess the incidence of death due to RDS in the neonatal period (28 days of age), death due to all causes, and death or bronchopulmonary dysplasia (BPD) due to RDS. Incidence of RDS, acute oxygen and ventilatory outcomes, concurrent complications of prematurity, and adverse experiences were also assessed.

RDS Treatment/Rescue1,3

SURVANTA was studied for RDS rescue in two multiple-dose, randomized, multicenter, controlled studies in low birth weight infants.

Study Objective: To assess the incidence of death due to RDS in the neonatal period (28 days of age) and the incidence of death or BPD due to RDS. Acute oxygen and ventilatory outcomes, concurrent complications of prematurity, and adverse experiences were also assessed.

Efficacy data: RDS prevention. SURVANTA® (beractant) significantly reduced the incidence of RDS at day 28 compared with a sham air placebo in 2 studies of RDS prevention. 28% for Survanta and 64% for placebo (P<0.001, Study 1). 29% for Survanta and 48% for placebo (P=0.007, Study 2). Study 2 was discontinued when treatment IND was initiated. Survanta significantly decreased the risk of death due to RDS at 28 days compared with placebo in 2 studies of RDS prevention. 3% for Survanta and 20% for placebo (P<0.001, Study 1). 1% for Survanta and 11% for placebo (P=0.006, Study 2). There was no statistically significant difference between Survanta and placebo in the 2 studies of RDS prevention for death or BPD (bronchopulmonary dysplasia) due to RDS at day 28: P=NS, not significant, Study 1. P=0.018, Study 2.
Efficacy data: RDS treatment/rescue. SURVANTA® (beractant) significantly reduced the incidence of death due to RDS at day 28 compared with a sham air placebo in one of 2 studies of RDS treatment/rescue. 12% for Survanta and 18% for placebo (P=NS, Study 3). 6% for Survanta and 2% for placebo (P<0.001, Study 4). Survanta significantly reduced the incidence of for death or BPD due to RDS at day 28 compared with placebo in one of 2 studies of RDS treatment/rescue. P=NS, not significant, Study 3. P<0.001, Study 4. Survanta significantly reduced air leaks (pneuomothorax or pneumopericardium) at 28 days compared with placebo in 2 studies of RDS treatment/rescue. 12% for Survanta and 30% for placebo (P<0.001, Study 3). 11% for Survanta and 22% for placebo (P=0.005, Study 4).

a Sham air placebo. b Study discontinued when treatment IND was initiated. c Pneumothorax or pneumopericardium.

*Study design: Infants of 600 to 1250 g birth weight and 23 to 29 weeks estimated gestational age were randomized at birth to receive either SURVANTA or sham air placebo in two multiple-dose studies. A dose of SURVANTA was given within 15 minutes of birth to prevent the development of RDS. Up to 3 additional doses in the first 48 hours, as often as every 6 hours, were given if infants subsequently developed RDS and infants required mechanical ventilation with an FiO2 ≥0.30.

Study design: Infants of 600 to 1750 g birth weight with RDS requiring mechanical ventilation and an FiO2 ≥0.40 were randomized at birth to receive either SURVANTA or sham air placebo in two multiple-dose rescue studies. The initial dose of SURVANTA was given after RDS developed and before 8 hours of age. Infants could receive up to three additional doses in the first 48 hours, as often as every 6 hours, if they required mechanical ventilation with an FiO2 ≥0.30.

SAFETY CONSIDERATIONS1

In the multiple-dose controlled clinical trials, transient bradycardia occurred with 11.9% of doses. Oxygen desaturation occurred with 9.8% of doses. Other reactions during the dosing procedure occurred with fewer than 1% of doses and included endotracheal tube reflux, pallor, vasoconstriction, hypotension, endotracheal tube blockage, hypertension, hypocarbia, hypercarbia, and apnea. No deaths occurred during the dosing procedure and all reactions resolved with symptomatic treatment.

INDICATION AND IMPORTANT SAFETY INFORMATION1

INDICATION

SURVANTA® (beractant) is indicated for prevention and treatment (“rescue”) of Respiratory Distress Syndrome (RDS) (hyaline membrane disease) in premature infants. SURVANTA significantly reduces the incidence of RDS, mortality due to RDS and air leak complications.

Prevention: In premature infants less than 1250 g birth weight or with evidence of surfactant deficiency, give SURVANTA 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 SURVANTA as soon as possible, preferably by 8 hours of age.

IMPORTANT SAFETY INFORMATION

Warnings: SURVANTA is intended for intratracheal use only.

SURVANTA 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 SURVANTA 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.

Precautions: 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 SURVANTA-treated infants was observed in the controlled clinical trials. The increased risk for sepsis among SURVANTA-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 SURVANTA in infants less than 600 g birth weight or greater than 1750 g birth weight has not been evaluated in controlled trials.

Adverse Reactions: The most commonly reported adverse experiences were transient bradycardia and oxygen desaturation; both were associated with the dosing procedure.

Other reactions during the dosing procedure occurred with fewer than 1% of doses and included endotracheal tube reflux, pallor, vasoconstriction, hypotension, endotracheal tube blockage, hypertension, hypocarbia, hypercarbia, and apnea. No deaths occurred during the dosing procedure, and all reactions resolved with symptomatic treatment.

The occurrence of concurrent illnesses common in premature infants was evaluated in the controlled trials. The rates in all controlled studies are in the table below.

Concurrent event SURVANTA (%) Control (%) P-valuea
Patent ductus arteriosus 46.9 47.1 0.814
Intracranial hemorrhage 48.1 45.2 0.241
Severe intracranial hemorrhage 24.1 23.3 0.693
Pulmonary air leaks 10.9 24.7 <0.001
Pulmonary interstitial emphysema 20.2 38.4 <0.001
Necrotizing enterocolitis 6.1 5.3 0.427
Apnea 65.4 59.6 0.283
Severe apnea 46.1 42.5 0.114
Post-treatment sepsis 20.7 16.1 0.019
Post-treatment infection 10.2 9.1 0.345
Pulmonary hemorrhage 7.2 5.3 0.166

aP-value comparing groups in controlled studies.

References: 1. SURVANTA [package insert]. 2. Hoekstra RE, Jackson JC, Myers TF, et al. Improved neonatal survival following multiple doses of bovine surfactant in very premature neonates at risk for respiratory distress syndrome. Pediatrics. 1991;88(1):10-18. 3. Liechty EA, Donovan E, Purohit D, et al. Reduction of neonatal mortality after multiple doses of bovine surfactant in low birth weight neonates with respiratory distress syndrome. Pediatrics. 1991;88(1):19-28.

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