Infasurf (antistress)

Overdose

There have been no reports of overdosage with Infasurf. While there are no known adverse effects of excess lung surfactant, overdosage would result in overloading the lungs with an isotonic solution. Ventilation should be supported until clearance of the liquid is accomplished.

Contraindications

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Undesirable effects

The most common adverse reactions associated with Infasurf dosing procedures in the controlled trials were cyanosis (65%), airway obstruction (39%), bradycardia (34%), reflux of surfactant into the endotracheal tube (21%), requirement for manual ventilation (16%), and reintubation (3%). These events were generally transient and not associated with serious complications or death. The incidence of common complications of prematurity and RDS in the four controlled Infasurf trials are presented in Table 3. Prophylaxis and treatment study results for each surfactant are combined.

Table 3 : Common Complications of Prematurity and RDS in Controlled Trials

Two-year follow-up data of neurodevelopmental outcomes in 415 infants enrolled in 5 centers that participated in the Infasurf vs. Exosurf Neonatal® controlled trials demonstrated significant developmental delays in equal percentages of Infasurf and Exosurf Neonatal® patients.

Therapeutic indications

Infasurf is indicated for the prevention of Respiratory Distress Syndrome (RDS) in premature infants at high risk for RDS and for the treatment (“rescue”) of premature infants who develop RDS. Infasurf decreases the incidence of RDS, mortality due to RDS, and air leaks associated with RDS.

Prophylaxis therapy at birth with Infasurf is indicated for premature infants <29 weeks of gestational age at significant risk for RDS. Infasurf prophylaxis should be administered as soon as possible, preferably within 30 minutes after birth.

Infasurf therapy is indicated for infants ≤72 hours of age with RDS (confirmed by clinical and radiologic findings) and requiring endotracheal intubation.

Date of revision of the text

Qualitative and quantitative composition

Infasurf (calfactant) Intratracheal Suspension is supplied sterile in single-use, rubber-stoppered glass vials containing 3 mL (NDC 61938-456-03) and 6 mL (NDC 61938-456-06) off-white suspension.

Store Infasurf (calfactant) Intratracheal Suspension at refrigerated temperature 2° to 8°C (36° to 46°F) and protect from light. THE 3 Ml VIAL MUST BE STORED UPRIGHT. Vials are for single use only. After opening, discard unused drug.

Manufactured by: ONY, Inc.,Amherst, NY 14228. Revised: Jun 2011

Special warnings and precautions for use

Infasurf is intended for intratracheal use only.

THE ADMINISTRATION OF EXOGENOUS SURFACTANTS, INCLUDING INFASURF, OFTEN RAPIDLY IMPROVES OXYGENATION AND LUNG COMPLIANCE. Following administration of Infasurf, patients should be carefully monitored so that oxygen therapy and ventilatory support can be modified in response to changes in respiratory status.

Infasurf therapy is not a substitute for neonatal intensive care. Optimal care of premature infants at risk for RDS and new born infants with RDS who need endotracheal intubation requires an acute care unit organized, staffed, equipped, and experienced with intubation, ventilator management, and general care of these patients.

TRANSIENT EPISODES OF REFLUX OF INFASURF INTO THE ENDOTRACHEAL TUBE, CYANOSIS, BRADYCARDIA, OR AIRWAY OBSTRUCTION HAVE OCCURRED DURING THE DOSING PROCEDURES. These events require stopping Infasurf administration and taking appropriate measures to alleviate the condition. After the patient is stable, dosing can proceed with appropriate monitoring.

When repeat dosing was given at fixed 12-hour intervals in the Infasurf vs. Exosurf Neonatal® trials, transient episodes of cyanosis, bradycardia, reflux of surfactant into the endotracheal tube, and airway obstruction were observed more frequently among infants in the Infasurf-treated group.

An increased proportion of patients with both intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) was observed in Infasurf-treated infants in the Infasurf-Exosurf Neonatal® controlled trials. These observations were not associated with increased mortality.

No data are available on the use of Infasurf in conjunction with experimental therapies of RDS, e.g., high-frequency ventilation. Data from controlled trials on the efficacy of Infasurf are limited to doses of approximately 100 mg phospholipid/kg body weight and up to a total of 4 doses.

Carcinogenesis studies and animal reproduction studies have not been performed with Infasurf. A single mutagenicity study (Ames assay) was negative.

Dosage (Posology) and method of administration

FOR INTRATRACHEAL ADMINISTRATION ONLY

Infasurf should be administered under the supervision of clinicians experienced in the acute care of newborn infants with respiratory failure who require intubation.

Rapid and substantial increases in blood oxygenation and improved lung compliance often follow Infasurf instillation. Close clinical monitoring and surveillance following administration may be needed to adjust oxygen therapy and ventilator pressures appropriately.

Each dose of Infasurf is 3 mL/kg body weight at birth. Infasurf has been administered every 12 hours for a total of up to 3 doses.

Infasurf is a suspension which settles during storage. Gentle swirling or agitation of the vial is often necessary for redispersion. DO NOT SHAKE. Visible flecks in the suspension and foaming at the surface are normal for Infasurf. Infasurf should be stored at refrigerated temperature 2° to 8°C (36° to 46°F). THE 3mL VIAL MUST BE STORED UPRIGHT. Date and time need to be recorded on the carton when Infasurf is removed from the refrigerator. Warming of Infasurf before administration is not necessary. Unopened, unused vials of Infasurf that have warmed to room temperature can be returned to refrigerated storage within 24 hours for future use. Infasurf should not be removed from the refrigerator for more than 24 hours. Infasurf should not be returned to the refrigerator more than once. Repeated warming to room temperature should be avoided. Each single-use vial should be entered only once and the vial with any unused material should be discarded after the initial entry.

INFASURF DOES NOT REQUIRE RECONSTITUTION. DO NOT DILUTE OR SONICATE.

Infasurf should only be administered intratracheally through an endotracheal tube. The dose of Infasurf is 3 mL/kg birth weight. The dose is drawn into a syringe from the single-use vial using a 20-gauge or larger needle with care taken to avoid excessive foaming. Administration is made by instillation of the Infasurf suspension into the endotracheal tube.

When used to treat RDS, Infasurf may be administered using either of the following 2 methods:

In the Infasurf vs. Exosurf® trials, Infasurf was administered intratracheally through a side-port adapter into the endotracheal tube. Two attendants, one to instill the Infasurf, the other to monitor the patient and assist in positioning, facilitated the dosing. The dose (3 mL/kg) was administered in two aliquots of 1.5 mL/kg each. After each aliquot was instilled, the infant was positioned with either the right or the left side dependent. Administration was made while ventilation was continued over 20-30 breaths for each aliquot, with small bursts timed only during the inspiratory cycles. A pause followed by evaluation of the respiratory status and repositioning separated the two aliquots. Repeat doses of 3 mL/kg of birth weight, up to a total of 3 doses 12 hours apart, were given if the patient was still intubated.

In the Infasurf vs. Survanta® trials, Infasurf was administered through a 5 French feeding catheter inserted into the endotracheal tube. The total dose was instilled in four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes. Each of the aliquots was administered with the patient in one of four different positions (prone, supine, right, and left lateral) to facilitate even distribution of the surfactant. Repeat doses were administered as early as 6 hours after the previous dose for a total of up to 4 doses if the infant was still intubated and required at least 30% inspired oxygen to maintain a PaO2 ≤ 80 torr.

Dosing procedures are described under Administration for Treatment of RDS. The amount of a prophylaxis dose of Infasurf should bebased on the infant's birth weight. Administration of Infasurf for prophylaxis should be given as soon as possible after birth. Usually the immediate care and stabilization of the premature infant born with hypoxemia and/or bradycardia should precede Infasurf prophylaxis.

During administration of Infasurf liquid suspension into the airway, infants often experience bradycardia, reflux of Infasurf into the endotracheal tube, airway obstruction, cyanosis, dislodgement of the endotracheal tube, or hypoventilation. If any of these events occur, the administration should be interrupted and the infant's condition should be stabilized using appropriate interventions before the administration of Infasurf is resumed. Endotracheal suctioning or reintubation is sometimes needed when there are signs of airway obstruction during the administration of the surfactant.

Interaction with other medicinal products and other forms of interaction

The most common adverse reactions associated with Infasurf dosing procedures in the controlled trials were cyanosis (65%), airway obstruction (39%), bradycardia (34%), reflux of surfactant into the endotracheal tube (21%), requirement for manual ventilation (16%), and reintubation (3%). These events were generally transient and not associated with serious complications or death. The incidence of common complications of prematurity and RDS in the four controlled Infasurf trials are presented in Table 3. Prophylaxis and treatment study results for each surfactant are combined.

Table 3 : Common Complications of Prematurity and RDS in Controlled Trials

Two-year follow-up data of neurodevelopmental outcomes in 415 infants enrolled in 5 centers that participated in the Infasurf vs. Exosurf Neonatal® controlled trials demonstrated significant developmental delays in equal percentages of Infasurf and Exosurf Neonatal® patients.

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