ng can proceed with appropriate monitoring.

ed 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. i nfasurf 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. dosing procedures general 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. administration for treatment of rds when used to treat rds, infasurf may be administered using either of the following 2 methods: exosurf active control trials: initial and repeat dosing 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. survanta active control trials: initial and repeat dosing 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 less than or equal to 80 torr. administration for prophylaxis of rds at birth dosing procedures are described under administration for treatment of rds. the amount of a prophylaxis dose of infasurf should be based 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. dosing precautions 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.

stitial emphysema 7 17 10 10 pulmonary hemorrhage 7 7 7 6 necrotizing enterocolitis 5 5 17 18 a grade iii and iv by the method of papile. b patients with both intraventricular hemorrhage and periventricular leukomalacia. follow-up evaluations 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.

ransformation, or excretion of infasurf have been performed. the administration of infasurf with radiolabeled phospholipids into the lungs of adult rabbits results in the persistence of 50% of radioactivity in the lung alveolar lining and25% of radioactivity in the lung tissue 24 hours later. less than 5% of the radioactivity is found in other organs. in premature lambs with lethal surfactant deficiency, less than 30% of instilled infasurf is present in the lung lining after 24 hours.

l bursts over 20-30 inspiratory cycles. after each aliquot was instilled, the infant was positioned with either the right or the left side dependent. results for efficacy parameters evaluated at 28 days or to discharge for all treated patients from this treatment trial are shown in table 1. table 1- infasurf vs exosurf neonatal® treatment trial efficacy parameter infasurf (n=570) % exosurf neonatal® (n=556) % p-value incidence of air leaks a 11 22 less than or equal to 0.001 death due to rds 4 4 0.95 any death to 28 days 8 10 0.21 any death before discharge 9 12 0.07 bpd b 5 6 0.41 crossover to other surfactant c 4 4 1 a pneumothorax and/or pulmonary interstitial emphysema. b bpd is bronchopulmonary dysplasia, diagnosed by positive x-ray and oxygen dependence at 28 days. c protocol permitted use of comparator surfactant in patients who failed to respond to therapy with the initial randomized surfactant if the infant was less than 96 hours of age, had received a full course of the randomized surfactant, and had an a/a po2 ratio less than 0.10 prophylaxis trial a total of 853 infants less than 29 weeks gestation were enrolled into a multiple-dose, randomized, double-blind prophylaxis trial comparing infasurf (3 ml/kg) and exosurf neonatal® (5 ml/kg). the initial dose was administered within 30 minutes of birth. repeat doses were administered at 12 and 24 hours if the patient remained intubated. each dose was administered divided in 2 equal aliquots, and given through a side port adapter into the proximal end of the endotra cheal tube. each aliquot was given in small bursts over 20-30 inspiratory cycles. after each aliquot was instilled, the infant was positioned with either the right or the left side dependent. results for efficacy parameters evaluated to day 28 or to discharge for all treated patients from this prophylaxis trial are shown in table 2. table 2- infasurf vs exosurf neonatal® prophylaxis trial efficacy parameter infasurf (n=431) % exosurf neonatal® (n=422) % p-value incidence of rds 15 47 less than or equal to 0.001 incidence of air leaks a 10 15 0.01 death due to rds 2 5 less than or equal to 0.01 any death to 28 days 12 16 0.10 any death before discharge 18 19 0.56 bpd b 18 17 0.60 crossover to other surfactant c 0.2 3 less than or equal to 0.001 a pneumothorax and/or pulmonary interstitial emphysema. b bpd is bronchopulmonary dysplasia, diagnosed by positive x-ray and oxygen dependence at 28 days. c protocol permitted use of comparator surfactant in patients who failed to respond to therapy with the initial randomized surfactant if the infant was less than 72 hours of age, had received a full course of the randomized surfactant, and had an a/a po2 ratio less than 0.10 infasurf versus survanta® treatment trial a total of 662 infants with rds who required endotracheal intubation and had an a/a po2 less than 0.22 were enrolled into a multiple-dose, randomized, double-blind treatment trial comparing infasurf (4 ml/kg of a formulation that contained 25 mg of phospholipids/ml rather than the 35 mg/ml in the marketed formulation) and survanta® (4 ml/kg). repeat doses were allowed greater than or equal to 6 hours following the previous treatment (for up to three doses before 96 hours of age) if the patient required greater than or equal to 30% oxygen. the surfactant was given through a 5 french feeding catheter inserted into the endo tracheal 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. results for the major efficacy parameters evaluated at 28 days or to discharge (incidence of air leaks, death due to respiratory causes or to any cause, bpd, or treatment failure) for all treated patients from this treatment trial were not significantly different between infasurf and survanta®. prophylaxis trial a total of 457 infants less than or equal to 30 weeks gestation and less than 1251 grams birth weight were enrolled into a multiple-dose, randomized, double-blind trial comparing infasurf (4 ml/kg of a formulation that contained 25 mg of phospholipids/ml rather than the 35 mg/ml in the marketed formulation) and survanta® (4 ml/kg). the initial dose was administered within15 minutes of birth and repeat doses were allowed greater than or equal to 6 hours following the previous treatment (for up to three doses before 96 hours of age) if the patient required greater than or equal to 30% oxygen. the surfactant was given 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). results for efficacy endpoints evaluated at 28 days or to discharge for all treated patients from this prophylaxis trial showed an increase in mortality from any cause at 28 days (p=0.03) and in death due to respiratory causes (p=0.005) in infasurf-treated infants. for evaluable patients (patients who met the protocol-defined entry criteria), mortality from any cause and mortality due to respiratory causes were also higher in the infasurf group (p = 0.07 and 0.03, respectively). however, these observations have not been replicated in other adequate and well-controlled trials and their relevance to the intended population is unknown. all other efficacy outcomes (incidence of rds, air leaks, bpd, and treatment failure) were not significantly different between infasurf and survanta® when analyzed for all treated patients and for evaluable patients. acute clinical effects: as with other surfactants, marked improvements in oxygenation and lung compliance may occur shortly after the administration of infasurf. all controlled clinical trials with infasurf demonstrated significant improvements in fraction of inspired oxygen (fio2) and mean airway pressure (map) during the first 24 to 48 hours following initiation of infasurf therapy.