calfactant 35 MG/ML Intratracheal Suspension

INDICATIONS AND USAGE INFASURF is indicated: to reduce the risk of respiratory distress syndrome (RDS) in preterm neonates <29 weeks of gestational age at risk for RDS. for the rescue treatment of RDS in preterm neonates ≤72 hours of age with RDS who require endotracheal intubation. INFASURF ® is a surfactant indicated: to reduce the risk of respiratory distress syndrome (RDS) in preterm neonates < 29 weeks gestational age at risk for RDS. (1) for the rescue treatment of preterm neonates ≤72 hours of age with RDS who require endotracheal intubation. (1)

DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage The recommended dose of INFASURF is 3 mL/kg body weight at birth administered intratracheally through an endotracheal tube. INFASURF can be administered every 12 hours for a total of up to three doses. To reduce the risk of RDS in preterm neonates <29 weeks of gestational age at risk for RDS, administer INFASURF within 30 minutes after birth. 2.2 Preparation Instructions INFASURF does not require reconstitution. Do not dilute or sonicate. INFASURF does not need to reach room temperature before administration. Gently swirl or agitate the INFASURF intratracheal suspension vial for redispersion. Do not shake. Visually inspect the INFASURF intratracheal suspension for discoloration prior to administration. The color of the INFASURF intratracheal suspension should be off-white. Discard the INFASURF vial if the intratracheal suspension is discolored. Visible flecks in the intratracheal suspension and foaming at the surface are normal. Using a 20-gauge or larger needle and syringe to avoid excessive foaming, withdraw INFASURF from the vial. Discard unopened INFASURF vials stored at room temperature for more than 24 hours. Discard unused INFASURF after the initial vial entry. 2.3 Administration Instructions INFASURF should be administered by healthcare providers who are experienced in the acute care of neonates with RDS who require intubation. Two attendants should be present to facilitate dosing; one to instill the INFASURF, the other to monitor the neonate. Administer INFASURF intratracheally through an endotracheal tube using the prepared syringe [ see Dosage and Administration (2.2) ] using either of the following two methods. Instill the INFASURF dose through a: Side-port adapter into the endotracheal tube as two equal aliquots of 1.5 mL/kg each. During and after each aliquot that is instilled, position the neonate with either the right or the left side dependent and maintain ventilation over 20 to 30 breaths for each aliquot, with small bursts timed only during the inspiratory cycles. Between aliquot administration evaluate the respiratory status and reposition to the other side. 5-French feeding catheter inserted into the endotracheal tube as four equal aliquots of 0.75 mL/kg each. During and after each aliquot is instilled, position the neonate in four different positions (i.e., prone, supine, right, and left lateral) to facilitate even distribution of INFASURF. Remove the catheter between each of the instillations and resume mechanical ventilation for 0.5 to 2 minutes. After INFASURF administration, frequently monitor neonate oxygenation and ventilatory status [ see Warnings and Precautions (5.1) ]. For intratracheal administration only (2) The recommended dose of INFASURF is 3 mL/kg body weight at birth. (2.2) Up to 3 doses of INFASURF can be administered. (2.2) Doses should not be given more frequently than every 12 hours. (2.2) Administration instructions: (2.3) Side-port adapter into the endotracheal tube : two equal aliquots while ventilation is continued over 20 to 30 breaths for each aliquot. 5-French feeding catheter inserted into the endotracheal tube : four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes.

WARNINGS AND PRECAUTIONS 5.1 Acute Changes in Oxygenation and Lung Compliance The administration of exogenous surfactants, including INFASURF, can rapidly affect oxygenation and lung compliance. Frequently monitor neonates who receive INFASURF so that oxygen and ventilatory support can be modified in response to changes in respiratory status. INFASURF should only be administered by those trained and experienced in the care, resuscitation, and stabilization of preterm neonates with RDS who require intubation. 5.2 Administration-Related Adverse Reactions Administration-related adverse reactions associated with INFASURF use included cyanosis, bradycardia, airway obstruction, and reflux of INFASURF into the endotracheal tube. These adverse reactions occurred more frequently in neonates who received repeat doses of INFASURF at 12-hour intervals than neonates that received colfosceril palmitate, the comparator, in randomized controlled trials (Trials 1 and 3) [ see Clinical Studies (14) ]. If these adverse reactions occur during INFASURF administration, stop INFASURF and institute appropriate measures to alleviate these adverse reactions and resume INFASURF with appropriate monitoring. 5.3 Intraventricular Hemorrhage and Periventricular Leukomalacia An increased proportion of INFASURF-treated neonates compared to colfosceril palmitate-treated neonates in randomized clinical trials (Trials 1 and 3) [ see Clinical Studies (14) ] developed intraventricular hemorrhage and periventricular leukomalacia. These adverse reactions were not associated with increased mortality in those studies. In contrast, the same proportion of INFASURF-treated neonates compared to beractant-treated neonates in randomized clinical trials (Trials 2) developed intraventricular hemorrhage and periventricular leukomalacia [ see Adverse Reactions (6.2) ]. While there is no specific treatment for these complications, affected infants may be at increased risk for neurologic complications, including seizures and neurodevelopmental impairment, and should be monitored as per local guidelines. Acute Changes in Oxygenation and Lung Compliance: INFASURF administration can rapidly affect oxygenation and lung compliance. Frequently monitor neonates after administration of INFASURF to adjust oxygen therapy and ventilator pressures appropriately. (5.1) Administration-Related Adverse Reactions: Adverse reactions associated with INFASURF include cyanosis, bradycardia, airway obstruction, and reflux of INFASURF into the endotracheal tube. In the event of these adverse reactions, stop INFASURF administration, and take appropriate measures to alleviate the adverse reactions and resume INFASURF with appropriate monitoring. (5.2) Intraventricular Hemorrhage and Periventricular Leukomalacia: Some INFASURF-treated neonates developed intraventricular hemorrhage and periventricular leukomalacia in randomized clinical trials. (5.3)

CONTRAINDICATIONS None. None.

CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Endogenous lung surfactant is essential for effective ventilation because it modifies alveolar surface tension thereby stabilizing the alveoli. Lung surfactant deficiency is the cause of Respiratory Distress Syndrome (RDS) in preterm neonates. INFASURF is a lung surfactant that restores lung surface activity in preterm neonates with RDS by adsorbing to the surface of the air:liquid interface and modifying surface tension similarly to natural lung surfactant. 12.2 Pharmacodynamics Calfactant dose-response relationships and the time course of pharmacodynamic response are unknown. In vitro, INFASURF lowered minimum surface tension to ≤ 3 mN/m as measured on a pulsating bubble surfactometer. Ex vivo, INFASURF restored the pressure volume mechanics and compliance of surfactant-deficient rat lungs. In vivo, INFASURF improved lung compliance, respiratory gas exchange, and survival in preterm lambs with profound surfactant deficiency. 12.3 Pharmacokinetics The absorption, distribution, metabolism, and excretion of calfactant in humans following intratracheal administration of INFASURF is unknown. 12.6 Immunogenicity The immunogenicity of INFASURF is unknown.