Survanta: Indications, Dosage, Precautions, Adverse Effects
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Survanta - Product Information

Manufacture: AbbVie
Country: Canada
Condition: Respiratory Distress Syndrome
Class: Lung surfactants
Form: Syrup
Ingredients: beractant, proteins, sodium chloride

SURVANTA

beractant, intratracheal suspension

Summary Product Information

Route of AdministrationDosage Form / StrengthClinically Relevant Nonmedicinal Ingredients
Intratracheal100 mg phospholipids / 4 mL suspension
200 mg phospholipids / 8 mL suspension
Sodium Chloride 0.9%

For a complete listing see DOSAGE FORMS, COMPOSITION AND PACKAGING section.

Description

SURVANTA (beractant, intratracheal suspension) is a sterile, non-pyrogenic pulmonary surfactant and natural bovine lung extract. It is supplemented with three synthetically derived lipids; colfosceril palmitate (dipalmitoylphosphatidylcholine), palmitic acid and tripalmitin. These latter lipids are added to standardize the composition and to mimic the surface-tension lowering properties of natural lung surfactant. The resulting composition provides an average concentration of 25 mg/mL phospholipids and less than 1.0 mg/mL protein. The formulation is an off-white to light brown opaque liquid.

Indications and Clinical Use

SURVANTA (beractant, intratracheal suspension) is indicated for:

  • Prevention (prophylaxis) and
  • Treatment (rescue) of Respiratory Distress Syndrome (RDS/Hyaline Membrane Disease) in premature infants

Prevention

For prophylactic treatment of infants at risk of developing RDS or who have evidence of pulmonary immaturity.

In premature infants less than 1250 g birth weight or with evidence of surfactant deficiency, give SURVANTA as soon as possible after an airway has been established, preferably within 15 minutes of birth.

Rescue Treatment

For rescue treatment of infants who have developed RDS.

To treat infants with RDS confirmed by X-ray and who require mechanical ventilation, give SURVANTA as soon as possible after an airway has been established, preferably by eight hours of age.

SURVANTA significantly reduces the incidence of RDS, mortality due to RDS and air leak complications.

The use of SURVANTA (beractant, intratracheal suspension) 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 the use of SURVANTA in conjunction with experimental therapies for RDS (e.g., high frequency ventilation or extra-corporeal membrane oxygenation).

Contraindications

There are no known contraindications to treatment with SURVANTA (beractant, intratracheal suspension).

Warnings and Precautions

Serious Warnings and Precautions

  • Administer in a highly supervised clinical setting SURVANTA can rapidly affect oxygenation and lung compliance. Therefore, frequent and careful clinical observation and monitoring of systemic oxygenation are essential to avoid hyperoxia.
  • Transient episodes of bradycardia and decreased oxygen saturation may occur during dosing.

General

SURVANTA (beractant, intratracheal suspension) is intended for intratracheal use only (see DOSAGE AND ADMINISTRATION).

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

Usage of SURVANTA should be restricted to a highly supervised clinical setting with immediate availability of experienced neonatologists and other clinicians experienced with intubation, ventilator management, and general care of premature infants. Vigilant clinical attention should be given to all infants prior to, during, and after administration of SURVANTA. 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 (see ADVERSE REACTIONS). If these occur, stop the dosing procedure and initiate appropriate measures to alleviate the condition. After stabilization, resume the dosing procedure.

The 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. There is no controlled experience with the use of SURVANTA in conjunction with experimental therapies for RDS (e.g., high frequency ventilation or extra-corporeal membrane oxygenation).

Intracranial Hemorrhage

In one of the single-dose rescue studies and one of the multi-dose prevention studies, the rate of intracranial hemorrhage was significantly higher in SURVANTA patients than in control patients (63.3% vs. 30.8%, p=0.001 and 48.8% vs. 34.2%, p=0.047, respectively). However, when all controlled studies were pooled, there was no difference between treatment groups in incidences of intracranial hemorrhage.

Carcinogenesis and Mutagenesis

Mutagenicity studies were negative. Carcinogenicity studies were not conducted with SURVANTA.

Immune

Increased probability of post-treatment nosocomial sepsis in SURVANTA-treated infants was observed in clinical trials (see Table 2). The increased risk for sepsis among SURVANTA-treated infants was not associated with increased mortality among these infants.

Respiratory

Endotracheal Tube Blockage Due to Mucous Plugs

Infants whose ventilation becomes markedly impaired during or shortly after dosing may have mucous plugging of the endotracheal tube, particularly if pulmonary secretions were prominent prior to drug administration. Suctioning of all infants prior to dosing may lessen the chance of mucous plugs obstructing the endotracheal tube. If endotracheal tube obstruction from such plugs is suspected, and suctioning is unsuccessful in removing the obstruction, the blocked endotracheal tube should be replaced immediately. In the multiple-dose studies performed with SURVANTA, there were 4 reports of endotracheal tube blockage out of 1,691 doses (0.2%).

Oxygenation

SURVANTA can rapidly affect oxygenation and lung compliance. In some infants, hyperoxia may occur within minutes of administration of SURVANTA. If hyperoxia develops, and transcutaneous oxygen saturation is in excess of 95%, FiO2 should be reduced until saturation is 90 to 95%. If the improvement in chest expansion seems excessive, peak ventilator inspiratory pressures should be immediately reduced. Failure to reduce inspiratory ventilatory pressures rapidly can result in lung overdistention and fatal pulmonary air leaks.

Hyperoxia, cyanosis and reflux through the endotracheal tube, additionally to bradycardia and decreased oxygen saturation, have been the most frequently reported complications in clinical trials. If reflux occurs, drug administration should be stopped and if necessary, peak inspiratory pressure on the ventilator should be increased by 4 to 5 cm H2O until clearing of the endotracheal tube occurs.

Rales

Rales and moist breath sounds can occur transiently after administration. Endotracheal suctioning or other remedial action is necessary if clear-cut signs of airway obstruction are present.

Sexual Function/Reproduction

Beractant up to 500 mg phospholipids/kg/day, approximately one-third the premature infant dose based on mg/m2/day, was administered subcutaneously to newborn rats for five days. These rats reproduced normally and there were no observable adverse effects in their offspring.

Monitoring and Laboratory Tests

Vigilant clinical attention should be given to all infants prior to, during, and after administration of SURVANTA. Infants receiving SURVANTA should be frequently monitored with arterial or transcutaneous measurement of systemic oxygen and carbon dioxide.

Adverse Reactions

Adverse Drug Reaction Overview

Adverse Drug Reaction Overview

The most commonly reported adverse experiences were associated with the dosing procedure.

In the multiple-dose controlled clinical trials, each dose of SURVANTA (beractant, intratracheal suspension) was divided into four quarter-doses. Each quarter dose was instilled through a catheter inserted into the endotracheal tube by briefly disconnecting the endotracheal tube from the ventilator.

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.

Clinical Trial Adverse Drug Reactions

Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates.

Table 1 summarizes all adverse experiences reported during controlled clinical trials.

There were no statistically significant differences between treatments in the type or number of events reported.

Table 1 Number of Infants with Adverse Events (All Controlled Studies) (Events with an incidence ≥ 0.2% are specified)
Body System/EventSURVANTASham Air 
N=840%N=851% 
Respiratory 
Decreased oxygenation91.130.4 
Problems with ET tube40.510.1 
Blood from ET tube30.400.0 
Pulmonary hemorrhage20.910.1 
N = 225 for SURVANTA 
N = 238 for Sham Air 
Other respiratory adverse events40.530.4
Cardiovascular 
Aortic thrombosis30.400.0 
Hypotension30.400.0 
Bradycardia20.210.1 
Other cardiovascular adverse events70.891.0 
Gastrointestinal 
Intestinal perforations20.250.6 
Volvulus20.200.0 
Other gastrointestinal adverse events40.550.6 
Renal 
Renal failure20.220.2 
Other renal adverse events20.210.1 
Hematologic 
Coagulopathy20.200.0 
Other hematologic adverse events0030.4 
Central Nervous System 
Seizure60.760.7 
Other CNS adverse events00.010.1 
Systemic 
Sepsis20.210.1 
Other systemic adverse events20.230.4 
Other Adverse Events30.430.4 
At Least 1 Event495.8404.7 

A clinical study compared the above quarter-dose administration regimen to the same procedure using two half-doses and another two half-dose procedure with uninterrupted ventilation accomplished by passing the catheter through a neonatal suction valve in the endotracheal tube. With the first dose there was significantly less endotracheal tube reflux observed in the group with the quarter-dose regimen (p=0.007) than in the group with uninterrupted ventilation. With the first dose there was significantly less oxygen desaturation in the group with uninterrupted ventilation (p=0.008) than in the other group receiving two half doses. There were no differences in these events after later doses and no differences in heart rate after any doses (see DOSAGE AND ADMINISTRATION, Administration, Dosing Procedures).

The occurrence of concurrent illnesses common in premature infants was evaluated in the controlled trials. The rates in all controlled studies are in Table 2.

Table 2 Percentage of Infants with Concurrent Events
SURVANTA (%)Control (%)
Patent ductus arteriosus46.947.1
Intracranial hemorrhage48.145.2
Severe intracranial hemorrhage24.123.3
Pulmonary air leaks10.924.7 *
Pulmonary interstitial emphysema20.238.4 *
Necrotizing enterocolitis6.15.3
Apnea65.459.6
Severe apnea46.142.5
Post-treatment sepsis20.716.1 **
Post-treatment infection10.29.1
Pulmonary hemorrhage7.25.3

* p < 0.001 ** p < 0.05

In one of the single-dose rescue studies and one of the multi-dose prevention studies, the rate of intracranial hemorrhage was significantly higher in SURVANTA patients than in control patients (63.3% vs. 30.8%, p=0.001 and 48.8% vs. 34.2%, p=0.047, respectively). However, when all controlled studies were pooled, there was no difference between treatment groups in incidences of intracranial hemorrhage.

Follow-up Evaluations

To date, no long-term complications or sequelae of SURVANTA therapy have been found.

Single-Dose Studies

Six-month adjusted-age follow-up evaluations of 232 infants (115 treated) demonstrated no clinically important differences between treatment groups in pulmonary and neurologic sequelae, incidence or severity of retinopathy of prematurity, rehospitalizations, growth, or allergic manifestations.

Multiple-Dose Studies

Six-month adjusted-age follow-up evaluations have been completed in 631 (345 treated) of 916 surviving infants. There was significantly less cerebral palsy and need for supplemental oxygen in SURVANTA infants than controls. Wheezing at the time of examination was more frequent among SURVANTA infants, although there was no difference in bronchodilator therapy.

Final twelve-month follow-up data from the multiple-dose studies are available from 521 (272 treated) of 909 surviving infants. There was significantly less wheezing in SURVANTA infants than controls in contrast to the six-month results. There was no difference in the incidence of cerebral palsy at twelve months.

Twenty-four month adjusted-age evaluations were completed in 429 (226 treated) of 906 surviving infants. There were significantly fewer SURVANTA infants with rhonchi, wheezing, tachypnea or neurological findings, compared to infants treated with Sham Air, at the time of examination. No other differences were found.

Abnormal Hematologic and Clinical Chemistry Findings

In the controlled clinical trials, there was no effect of SURVANTA on results of common laboratory tests: white blood cell count, serum sodium, potassium, bilirubin, and creatinine. IgG or IgM antibodies to surfactant–associated proteins SP-B and SP-C were not detected.

Post-Market Adverse Drug Reactions

No new adverse reactions have been reported, nor has there been an increase in the incidence of known adverse reactions identified in the clinical trials completed to date.

Drug Interactions

No formal drug-drug interaction studies were conducted.

Dosage and Administration

Dosing Considerations

For Intratracheal Administration Only

SURVANTA (beractant, intratracheal suspension) should be administered by or under the supervision of clinicians experienced in intubation, ventilator management, and general care of premature infants.

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

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.

Review of audiovisual instructional materials describing dosage and administration procedures is recommended before using SURVANTA. Materials are available upon request.

Recommended Dose and Dosage Adjustment

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

Each dose of SURVANTA is 100 mg of phospholipids/kg birth weight (4 mL/kg). The SURVANTA Dosing Chart (Table 3) shows the total dosage for a range of birth weights.

Table 3 SURVANTA Dosing Chart
Weight
(grams)
Total Dose
(mL)
Weight
(grams)
Total Dose
(mL)
600-6502.61301-13505.4
651-7002.81351-14005.6
701-7503.01401-14505.8
751-8003.21451-15006.0
801-8503.41501-15506.2
851-9003.61551-16006.4
901-9503.81601-16506.6
951-10004.01651-17006.8
1001-10504.21701-17507.0
1051-11004.41751-18007.2 *
1101-11504.61801-18507.4 *
1151-12004.81851-19007.6 *
1201-12505.01901-19507.8 *
1251-13005.21951-20008.0 *

* suggested dosages based on limited clinical experience in uncontrolled trials

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

Administration

Directions for Use

SURVANTA should be inspected visually for discolouration prior to administration. The colour of SURVANTA 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 to the nature of the product. SURVANTA does not require sonication before use.

SURVANTA is stored refrigerated (2 to 8°C). Before administration, SURVANTA should be warmed by standing at room temperature for at least 20 minutes or warmed in the hand for at least eight minutes.

Artificial warming methods should not be used. If a prevention dose is to be given, preparation of SURVANTA should begin before the infant's birth.

Unopened, unused vials of SURVANTA that have been warmed to room temperature may be returned to the refrigerator within 24 hours of warming, and stored for future use. SURVANTA should not be warmed and returned to the refrigerator more than once. Each single-use vial of SURVANTA should be entered only once. Used vials with residual drug should be discarded.

Dosing Procedures

General

SURVANTA is administered intratracheally. It can be instilled through a 5 French end-hole catheter inserted into the infant's endotracheal tube by briefly disconnecting the endotracheal tube from the ventilator OR by inserting the catheter through a neonatal suction valve without disconnecting the endotracheal tube from the ventilator or by instillation through the secondary lumen of a double lumen endotracheal tube.

If the drug is instilled through an end-hole catheter, the length of the catheter should be shortened so that the tip of the catheter protrudes just beyond the endotracheal tube above the infant's carina. SURVANTA should not be instilled into a mainstem bronchus.

To ensure homogenous distribution of SURVANTA throughout the lungs, each dose is divided into fractional doses. Each dose can be administered in two half-doses or in four quarter-doses. Each fractional dose is administered with the infant in a different position.

To administer SURVANTA in two half-doses, the recommended positions are:

  • Head and body turned approximately 45° to the right
  • Head and body turned approximately 45° to the left

To administer SURVANTA in four quarter-doses, the recommended positions are:

  • Head and body inclined 5 to 10° down, head and body turned to the right
  • Head and body inclined 5 to 10° down, head and body turned to the left
  • Head and body inclined 5 to 10° up, head and body turned to the right
  • Head and body inclined 5 to 10° up, head and body turned to the left

The positions for four quarter-doses are illustrated below:


The dosing procedure is facilitated if one person administers the dose while another person positions and monitors the baby.

The different methods of administering SURVANTA were evaluated in clinical trials. In the six single-dose and four multiple-dose controlled clinical trials that established safety and efficacy, SURVANTA was instilled through a catheter that was inserted into the infant's endotracheal tube by briefly disconnecting the endotracheal tube from the ventilator. Each dose was administered in four quarter-doses as described above.

This method of administering SURVANTA was compared to two other methods in a multi-centre, randomized clinical study involving 299 infants weighing 600 g or more with RDS requiring mechanical ventilation. The other methods evaluated were:

  • Two half-doses administered by inserting the catheter through the endotracheal tube while the endotracheal tube was briefly disconnected from the ventilator. The half-doses were administered in the two positions described above.
  • Two half-doses administered without disconnecting the endotracheal tube from the ventilator by inserting the catheter through a neonatal suction valve into the endotracheal tube. The half-doses were administered in the two positions described above.

There were no significant differences among the three groups in average FiO2, a/APO2, 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.

Administration of SURVANTA using a double-lumen endotracheal tube is functionally equivalent to the use of the neonatal suction valve; i.e., delivery of SURVANTA at the distal end of the endotracheal tube without interrupting mechanical ventilation. If an infant is already intubated with a single-lumen endotracheal tube, the infant should not be reintubated with a double-lumen endotracheal tube solely for the purpose of administering SURVANTA.

First Dose

Instillation Through End-Hole Catheter

Determine the total dose of SURVANTA from the SURVANTA Dosing Chart (Table 3) based on the infant's birth weight. Slowly withdraw the entire contents of the vial into a plastic syringe through a large-gauge needle (e.g., at least 20 gauge). Do not filter SURVANTA and avoid shaking.

Attach the pre-measured 5 French end-hole catheter to the syringe. Fill the catheter with SURVANTA. Discard excess SURVANTA through the catheter so that only the total dose to be given remains in the syringe.

Before administering SURVANTA, assure proper placement and patency of the endotracheal tube. At the discretion of the clinician, the endotracheal tube may be suctioned before administering SURVANTA. The infant should be allowed to stabilize before proceeding with dosing.

First Fractional Dose – Prevention Strategy

In the prevention strategy, weigh, intubate and stabilize the infant. Administer the dose as soon as possible after birth, preferably within 15 minutes. Position the infant appropriately and gently inject the first fractional dose through the catheter over two to three seconds.

After administration of the first fractional dose, remove the catheter from the endotracheal tube.

Manually ventilate with a hand-bag with sufficient oxygen to prevent cyanosis, at a rate of 60 breaths/minute and sufficient positive pressure to provide adequate air exchange and chest wall excursion.

First Fractional Dose – Rescue Strategy

In the rescue strategy, the first dose should be given as soon as possible after the infant is placed on a ventilator for management of RDS. In the clinical trials, immediately before instilling the first fractional dose, the infant's ventilator settings were changed to rate 60/minute, inspiratory time 0.5 second, and FiO2 1.0.

Position the infant appropriately and gently inject the first fractional dose through the catheter over two to three seconds. After administration of the first fractional dose, remove the catheter from the endotracheal tube. Return the infant to the mechanical ventilator.

Remaining Fractional Doses – Prevention and Rescue Strategies

In both strategies, ventilate the infant for at least 30 seconds or until stable. Reposition the infant for instillation of the next fractional dose.

Instill the remaining fractional doses using the same procedures. After instillation of each fractional dose, remove the catheter and ventilate for at least 30 seconds or until the infant is stabilized. After instillation of the final fractional dose, remove the catheter without flushing it.

Do not suction the infant for one hour after dosing unless signs of significant airway obstruction occur.

After completion of the dosing procedure, resume usual ventilator management and clinical care.

Instillation Through Secondary Lumen of a Double-Lumen Endotracheal Tube

Ensure that the infant is intubated with the appropriate size double-lumen endotracheal tube. Determine the total dose of SURVANTA from the SURVANTA Dosing Chart (Table 3) based on the infant's birth weight. Slowly withdraw the total dose from the vial into a plastic syringe through a large-gauge needle (e.g., at least 20 gauge). Do not filter SURVANTA and avoid shaking.

Before administering SURVANTA, assure proper placement and patency of the endotracheal tube. At the discretion of the clinician, the endotracheal tube may be suctioned before administering SURVANTA. The infant should be allowed to stabilize before proceeding with dosing.

First Fractional Dose – Prevention Strategy

In the prevention strategy, weigh, intubate and stabilize the infant. Administer the dose as soon as possible after birth, preferably within 15 minutes. Attach the syringe containing SURVANTA to the secondary lumen. Position the infant appropriately and gently inject the first fractional dose through the secondary lumen over two to three seconds without interrupting ventilation. If manually ventilated, ventilate with a hand-bag with sufficient oxygen to prevent cyanosis, at a rate of 60 breaths/minute, and sufficient positive pressure to provide adequate air exchange and chest wall excursion.

First Fractional Dose – Rescue Strategy

In the rescue strategy, the first dose should be given as soon as possible after the infant is placed on a ventilator for management of RDS. Immediately before instilling the first fractional dose, change the infant's ventilator settings to rate 60/minute, inspiratory time 0.5 second, and FiO2 1.0.

Position the infant appropriately and gently inject the first fractional dose through the secondary lumen over two to three seconds without interrupting mechanical ventilation.

Remaining Fractional Doses – Prevention and Rescue Strategies

In both strategies, ventilate the infant for at least 30 seconds or until stable. Reposition the infant for instillation of the next fractional dose.

Instill the remaining fractional doses using the same procedures. After instillation of each fractional dose, ventilate for at least 30 seconds or until the infant is stabilized. After instillation of the final fractional dose, remove the syringe from the secondary lumen, inject 0.5 mL of air to flush the secondary lumen and cap it.

After completion of the dosing procedure, resume usual ventilator management and clinical care.

Repeat Doses

The need for additional doses of SURVANTA is determined by evidence of continuing respiratory distress.

  • Dose no sooner than six hours after the preceding dose if the infant remains intubated and requires at least 30% inspired oxygen to maintain a PaO2 less than or equal to 80 torr. In controlled clinical trials, 60% of patients (prevention) and 79% of patients (rescue) required more than one dose of SURVANTA. 34.8% of patients (prevention) and 52.2% of patients (rescue) required four doses.
  • Radiographic confirmation of RDS should be obtained before administering additional doses to those who received a prevention dose.

The dosage of SURVANTA for each repeat doses is also 100 mg phospholipids/kg and is based on the infant's birth weight. The infant should not be reweighed for determination of the SURVANTA dosage. Use the SURVANTA Dosing Chart to determine the total dosage.

Prepare SURVANTA and position the infant for administration of each fractional dose as previously described. After instillation of each fractional dose, remove the dosing catheter from the endotracheal tube and ventilate the infant for at least 30 seconds or until stable.

In the clinical studies, ventilator settings used to administer repeat doses were different than those used for the first dose. For repeat doses, the FiO2 was increased by 0.20 or an amount sufficient to prevent cyanosis. The ventilator delivered a rate of 30/minute with an inspiratory time less than 1.0 second. If the infant's pretreatment rate was 30 or greater, it was left unchanged during SURVANTA instillation.

Manual hand-bag ventilation should not be used to administer repeat doses. During the dosing procedure, ventilator settings may be adjusted at the discretion of the clinician to maintain appropriate oxygenation and ventilation.

After completion of the dosing procedure, resume usual ventilator management and clinical care.

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 stabilized, resume the dosing procedure.

Rales and moist breath sounds can occur transiently after administration of SURVANTA. Endotracheal suctioning or other remedial action is necessary if clear-cut signs of airway obstruction are present.

Overdosage

Overdosage with SURVANTA (beractant, intratracheal suspension) has not been reported. Based on animal data, overdosage might result in acute airway obstruction. Treatment should be symptomatic and supportive.

Action and Clinical Pharmacology

Mechanism of Action

Deficiency of pulmonary surfactant is an important factor in the development of Respiratory Distress Syndrome (RDS) in premature infants. SURVANTA (beractant, intratracheal suspension) replenishes surfactant and restores surface activity to the lungs of these infants. It reduces surface tension and concomitantly increases lung compliance.

Pharmacodynamics

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

In clinical studies of premature infants with 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/ApO2). Significantly decreased need for respiratory support, as indicated by a lower mean airway pressure, was also observed.

In prophylactic studies of premature infants at high risk of RDS, multiple doses (up to four doses within 48 hours) of SURVANTA reduced the incidence and mortality of RDS, reduced the incidence of pulmonary air leaks and pulmonary interstitial emphysema, improved a/ApO2 and FiO2 (Fraction of inspired oxygen) at 72 hours of age, and reduced mortality from any cause.

No information is available about the metabolic fate of the surfactant–associated proteins in SURVANTA. The metabolic disposition in humans has not been studied.

Storage and Stability

Store unopened vials at refrigeration temperature (2 to 8°C). Protect from light. Store vials in carton until ready for use.

Unopened, unused vials of SURVANTA that have been warmed to room temperature may be returned to the refrigerator within twenty-four 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 SURVANTA should be entered with a needle only once. Used vials with residual drug should be discarded.

Dosage Forms, Composition and Packaging

Availability of Dosage Forms

SURVANTA (beractant, intratracheal suspension) is supplied in single-use glass vials containing 4 mL or 8 mL of SURVANTA.

4 mL:Each milliliter contains 25 mg of phospholipids (100 mg phospholipids/4 mL) suspended in 0.9% sodium chloride solution.
8 mL:Each milliliter contains 25 mg of phospholipids (200 mg phospholipids/8 mL) suspended in 0.9% sodium chloride solution.

The colour is off-white to light brown.

Composition

Table 4 Composition of SURVANTA by Chemical Class
ComponentsQuantities (mg/mL)
Total Phospholipids25
Disaturated Phosphatidylcholine11.0-15.5
Triglycerides0.5-1.75
Free Fatty Acids1.4-3.5
Protein0.1-0.4
Sodium Chloride9.0

Fortification lipids are added to standardize the composition and to mimic surface-tension lowering properties of natural lung surfactant.

SURVANTA is heat-sterilized and does not contain preservatives. Its protein content includes two hydrophobic surfactant-associated proteins of low molecular weight, commonly known as SP-B and SP-C. It does not contain the hydrophilic, large molecular weight surfactant-associated protein know as SP-A.