SURVANTA

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Other Administration Route(s)
Intratracheal Administration
-Beractant is only for intratracheal administration by or under the supervision of clinicians experienced in intubation, ventilator management, and intensive care.
-Perform arterial or transcutaneous measurement of systemic oxygen frequently in neonates receiving beractant. Employ measures to avoid hyperoxia.
-Prior to administration of beractant it is recommended that metabolic acidosis, anemia, hypoglycemia, hypotension, and hypothermia be corrected.
-Beractant is suspended in 0.9% Sodium Chloride Injection, contains no preservatives, and is heat-sterilized. Sodium hydroxide or hydrochloric acid may be added to adjust the pH. The pH is approximately 6.2 to 7.6.

Preparation
-Beractant does not require reconstitution before use. Do not filter or dilute.
-Warm beractant by standing at room temperature for at least 20 minutes or warmed in the hand for at least 8 minutes. Do not artificially warm before use.
-Record the date and time of warming on the vial carton.
-Prior to withdrawing a dose, gently swirl the vial to ensure a uniform suspension. Do not shake, this may denature the proteins; avoid excessive foaming. Visible foaming at the surface of the solution are normal.
-Use a 20-gauge or larger needle to withdraw the required dose from the vial; do not filter.
-Discard any unused portion.
-Storage: Unopened, unused vials may be returned to refrigeration within 24 hours of warming. Do not return vials that have been warmed to room temperature after 24 hours or returned more than once. Protect from light.

Intratracheal instillation
-Carefully follow the detailed dosage and administration instructions in the FDA-approved product label.
-At the discretion of the clinician, the endotracheal tube may be suctioned prior to administration.
-Administration is via a 5 French end-hole catheter into the endotracheal tube with the tip of the catheter protruding just beyond the end of the endotracheal tube above the infant's carina. Alternatively, beractant can be instilled through the endotracheal tube by using the neonatal suction valve or by briefly disconnecting the endotracheal tube from the ventilator.
-Divide the total dose into 4 equal aliquots; administer each aliquot with the neonate in a different position to ensure homogenous distribution throughout the lungs. The product label recommends that 1 person administer the dose while another person positions the neonate.
-Between the administration of each aliquot, remove the catheter and ventilate for at least 30 seconds or until stabilized.
-Do not suction infant for 1 hour after dosing unless signs of significant airway obstruction occur.
-On completion of the dosing procedure, resume usual ventilator management and clinical care.

Premature birth is naturally associated with a number of adverse reactions producing a high incidence of morbidity and mortality. The distinction between adverse reactions attributable to beractant and those that are a natural result of premature birth is not always clear.

Adverse reactions associated with the use of beractant are divided into those that can occur during the dosing procedure and those that can occur after the procedure. During clinical trials with beractant, a transient sinus bradycardia was evident in 11.9% of doses, and oxygen desaturation occurred in 9.8% of doses. A state of hypoxia can follow oxygen desaturation. These events can occur during the dosing procedure, which should be stopped and appropriate measures taken to relieve the condition. Once the patient is stabilized, the procedure can be resumed. Rales and moist-breath sounds can occur transiently after beractant administration and require no action unless there is obvious blockage of the airways, which may require endotracheal suctioning or other remedial action.

In addition to bradycardia and hypoxia, reported adverse reactions occurring during the beractant dosing procedure in < 1% of doses include endotracheal tube reflux, pallor, peripheral vasoconstriction, hypotension, hypertension, sinus tachycardia, endotracheal tube blockage, hypocarbia, hypercarbia, and apnea. All reactions were resolved with symptomatic treatment, and there were no fatalities. Following the lowering of surface tension by beractant administration, a rapid restoration of pulmonary function can produce hyperoxia and hypocarbia. Decreased carbon dioxide can reduce blood flow to the brain. Steps to avoid this possibility should be taken by careful monitoring of oxygenation and clinical observation. Frequent monitoring of arterial blood gases (ABG) is required. Throughout beractant treatment, ventilation must be maintained to ensure correct oxygenation. Adjustments in the fraction of inspired oxygen (FiO2) and other ventilator settings may be necessary during treatment to prevent cyanosis or hyperoxia.

Following treatment with beractant, there was no significant difference in the incidence of post-treatment infection other than sepsis (10.2% vs. 9.1%, p=0.345). There is the possibility of an increase in nosocomial sepsis after treatment with beractant. In clinical trials evaluating the occurrence of common illnesses in premature infants, post-treatment sepsis occurred in 20.7% of patients receiving beractant compared to 16.1% of control patients (p=0.019). The increased incidence of sepsis was not associated with increased mortality in the treated infants.

When all controlled studies of beractant were pooled, there was no difference in intracranial bleeding in treated vs. untreated patients (48.1% vs 45.2% intracranial hemorrhage; 24.1% vs 23.3% severe intracranial hemorrhage). However, in one of the single-dose rescue studies and one of the multiple-dose prevention studies, the rate of intracranial hemorrhage was significantly higher in beractant-treated patients vs. control patients (63.3% vs. 30.8%, and 48.8% and 34.2%, respectively). The rate of these events in a treatment IND in 8100 infants was lower than that which occurred in controlled clinical trials.

Beractant is extracted from bovine lung surfactant. Immunogenic sensitization has not been documented in newborns after the use of beractant. However, because surfactants might be used in investigational settings, beractant should be used with caution in those with known bovine protein hypersensitivity.

Rales and moist breath sounds can occur transiently after beractant administration; endotracheal suctioning or other remedial action is not necessary unless clear-cut signs of airway obstruction are present. During the surfactant dosing procedure, episodes of bradycardia, decreased oxygen saturation, reflux of the drug into the endotracheal tube (ETT), and airway/ETT obstruction have been reported. If these occur, stop the dosing procedure and initiate appropriate measures to alleviate the condition. Suctioning of the ETT may be required if the obstruction is persistent or severe. After stabilization, the dosing procedure may be resumed. The administration of exogenous surfactants, including beractant, can rapidly affect oxygenation and lung compliance. Therefore, infants receiving beractant should receive frequent clinical and laboratory assessments so that oxygen and ventilatory support can be modified to respond to respiratory changes. Beractant administration requires an experienced clinician trained in the care, resuscitation, and stabilization of preterm neonates.

In clinical trials, a higher probability of nosocomial sepsis was associated with beractant use; however, there was no increase in mortality. Carefully monitor newborn infants who receive beractant for signs of early sepsis.

Description: Beractant is a bovine-derived suspension that is administered intratracheally for the prevention and treatment of neonatal respiratory distress syndrome (RDS) in premature infants. Beractant is derived from minced bovine lung tissue while calfactant is obtained by lavaging bovine lungs. Beractant contains phospholipids, neutral lipids, fatty acids and surfactant-associated proteins with the addition of colfosceril palmitate, palmitic acid and tripalmitin. Beractant contains two low molecular weight, hydrophobic surfactant-associated proteins, SP-B and SP-C. It does not contain the hydrophilic large molecular weight surfactant-associated protein SP-A and contains no preservatives. During clinical trials, nosocomial sepsis was associated with beractant use; however, there was no increase in mortality. Neonates receiving beractant should be carefully monitored for signs of early sepsis. A review of head-to-head comparative studies of natural vs synthetic surfactants revealed that oxygen requirements and ventilator settings were lower following treatment with beractant (natural) compared with colfosceril (synthetic), however, this conclusion was based on the early clinical response. Most clinicians feel there is little difference between natural and synthetic surfactant products based on long-term clinical response. Surfactants as a group are being investigated for use in other respiratory distress syndromes in both children and adults, including acute respiratory distress syndrome (ARDS) and burn-inhalation injuries. Beractant is approved for pediatric patients, as young as premature neonates.

For neonatal respiratory distress syndrome prophylaxis in premature neonates and for the treatment of neonatal respiratory distress syndrome (RDS):
NOTE: Controlled trials examining the use of beractant in premature neonates with a birth weight of less than 600 g or more than 1,750 g have not been conducted; however, dosage recommendations based on weight ranges for premature neonates weighing from 600 g up to 2,000 g are included in the full prescribing information.
Intratracheal dosage:
Premature Neonates: 4 mL/kg/dose (100 mg of phospholipids/kg/dose) of birth weight intratracheally divided in 4 equal aliquots. May administer up to 3 subsequent doses of 4 mL/kg/dose (100 mg/kg/dose) at 6-hour intervals if needed. Due to the long half-life, the American Academy of Pediatrics (AAP) recommends redosing every 12 hours, unless surfactant is being inactivated by an infectious process, meconium, or blood. When beractant is administered as prophylaxis, administer subsequent only if RDS is confirmed by radiographic examination. In premature neonates weighing less than 1,250 g birth weight or with evidence of surfactant deficiency, administer beractant as soon as possible, preferably within 15 minutes of birth. To treat neonates with RDS confirmed by X-ray and requiring mechanical ventilation, administer beractant as soon as possible, preferably by 8 hours of age.

Maximum Dosage Limits:
-Neonates
100 mg/kg birth weight (4 ml/kg birth weight)/dose intratracheally.
-Infants
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Adolescents
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Beractant is administered directly to the lungs and can rapidly restore lung compliance. This composite material is designed to mimic surface-tension lowering properties of natural lung surfactant. This is achieved by reducing the surface tension on alveolar surfaces during respiration and stabilizing alveoli against collapse at resting transpulmonary pressures. A rapid increase in oxygenation may follow treatment; rapid restoration of lung compliance may lead to hyperoxia and hypocarbia. Conversely, hypoxia may occur during therapy, possibly as a result of airway obstruction and oxygen desaturation. Frequent monitoring of arterial blood gases (ABG) is required. Throughout the treatment, ventilation must be maintained to ensure correct oxygenation. An increase in the fraction of inspired oxygen (FiO2) may be necessary during repeat doses to prevent cyanosis.

Premature infants are deficient in natural pulmonary surfactant which may reduce surface activity in the lungs and induce respiratory distress syndrome. Restoration of surface tension is achieved by the lipids present in beractant, and rapid spreading and absorption by the proteins. Surfactant therapy in combination with nasal continuous positive airway pressure (CPAP) has been shown to be superior to nasal CPAP alone in a small study of neonates with RDS.

Natural human pulmonary surfactant is secreted by the lamellar bodies of alveolar type-II cells, and is first synthesized in the fetus after 24-28 weeks of gestation. Natural human pulmonary surfactant contains a mixture of roughly 90% phospholipids (e.g., phosphatidylcholine and phosphatidylglycerol) and 10% associated surfactant proteins (i.e., SP-A, SP-B, SP-C and SP-D). The exact role of all of the components of natural human pulmonary surfactant is uncertain, and of great scientific interest. Phospholipids adsorb rapidly to the surface of the air:liquid interface of the lung lumen and modify the surface tension within the alveoli. Surfactant-associated proteins, particularly SP-B, appear to be essential in binding, stabilizing, spreading, and recycling phospholipids on the alveolar surfaces. It has been recently discovered that some infants who develop fatal RDS have a genetic deficiency or a genetic mutation of the SP-B protein. Proteins SP-A and SP-D, which are not currently components of exogenous surfactant products, appear to have additional functions relating to host defenses in the lung.

Pharmacokinetics: Beractant is administered intratracheally. It is delivered directly to the site of action, and only a small amount reaches the systemic circulation. Distribution is improved by positioning the infant to allow gravity to help distribute surfactant to the distal airways. Clearance is a local phenomenon that involves type II alveolar cells. No information is available about the metabolic fate of the surfactant-associated proteins in the product; metabolic disposition in humans has not been studied.

Affected cytochrome P450 isoenzymes: none