2 DOSAGE AND ADMINISTRATION Before administering CUROSURF, assure proper placement and patency of endotracheal tube (2.1) Administer intratracheally either in (2.1): Two divided aliquots after briefly disconnecting endotracheal tube from ventilator; or A single aliquot through secondary lumen of a dual lumen endotracheal tube without interrupting mechanical ventilation Initial recommended dose is 2.5 mL/kg birth weight (2.2) Up to two repeat doses of 1.25 mL/kg birth weight may be administered at approximately 12-hour intervals (2.2) Maximum total dose (initial plus repeat doses) is 5 mL/kg (2.2) See Full Prescribing Information for instructions on preparation and administration of the CUROSURF suspension (2.3, 2.4) 2.1 Important Administration Instructions For intracheal administration only. CUROSURF should be administered by, or under the supervision of clinicians experienced in intubation, ventilator management, and general care of premature infants. Before administering CUROSURF, assure proper placement and patency of the endotracheal tube. At the discretion of the clinician, the endotracheal tube may be suctioned before administering CUROSURF. Allow the infant to stabilize before proceeding with dosing. Administer CUROSURF either: Intratracheally by instillation in two divided aliquots through a 5 French end-hole catheter after briefly disconnecting the endotracheal tube from the ventilator; or Intratracheally in a single aliquot through the secondary lumen of a dual lumen endotracheal tube without interrupting mechanical ventilation. 2.2 Recommended Dosage The initial recommended dose is 2.5 mL/kg birth weight (see Table 1), administered as one or two aliquots depending upon the instillation procedure [see Dosage and Administration (2.3)]. Up to two repeat doses of 1.25 mL/kg birth weight each may be administered at approximately 12-hour intervals in infants who remain intubated and in whom RDS is considered responsible for their persisting or deteriorating respiratory status. The maximum recommended total dosage (sum of the initial and up to two repeat doses) is 5 mL/kg. Table 1: CUROSURF Weight-Based Dosing Chart for Rescue Treatment of RDS Weight (grams) Initial Dose 2.5 mL/kg Repeat Dose 1.25 mL/kg Weight (grams) Initial Dose 2.5 mL/kg Repeat Dose 1.25 mL/kg Each Dose (mL) Each Dose (mL) 600-650 1.60 0.80 1301-1350 3.30 1.65 651-700 1.70 0.85 1351-1400 3.50 1.75 701-750 1.80 0.90 1401-1450 3.60 1.80 751-800 2.00 1.00 1451-1500 3.70 1.85 801-850 2.10 1.05 1501-1550 3.80 1.90 851-900 2.20 1.10 1551-1600 4.00 2.00 901-950 2.30 1.15 1601-1650 4.10 2.05 951-1000 2.50 1.25 1651-1700 4.20 2.10 1001-1050 2.60 1.30 1701-1750 4.30 2.15 1051-1100 2.70 1.35 1751-1800 4.50 2.25 1101-1150 2.80 1.40 1801-1850 4.60 2.30 1151-1200 3.00 1.50 1851-1900 4.70 2.35 1201-1250 3.10 1.55 1901-1950 4.80 2.40 1251-1300 3.20 1.60 1951-2000 5.00 2.50 2.3 Preparation of the CUROSURF Suspension Remove the vial of CUROSURF suspension from a refrigerator at +2 to +8°C (36 to 46°F) and slowly warm the vial to room temperature before use. Visually inspect the CUROSURF suspension for discoloration prior to administration. The color of the CUROSURF suspension should be white to creamy white. Discard the CUROSURF vial if the suspension is discolored. Gently turn the vial upside-down, in order to obtain a uniform suspension. DO NOT SHAKE. Locate the notch (FLIP UP) on the colored plastic cap and lift the notch and pull upwards. Pull the plastic cap with the aluminum portion downwards. Remove the whole ring by pulling off the aluminum wrapper. Remove the rubber cap to extract content. Unopened, unused vials of CUROSURF suspension that have warmed to room temperature can be returned to refrigerated storage within 24 hours for future use. Do not warm to room temperature and return to refrigerated storage more than once. Protect from light. 2.4 Administration For endotracheal tube instillation using a 5 French end-hole catheter Slowly withdraw the entire contents of the vial of CUROSURF suspension into a 3 or 5 mL plastic syringe through a large-gauge needle (e.g., at least 20 gauge). Enter each single-use vial only once. Attach the pre-cut 8-cm 5 end-hole French catheter to the syringe. Fill the catheter with CUROSURF suspension. Discard excess CUROSURF through the catheter so that only the dose to be given remains in the syringe. When administering CUROSURF using a 5 French end-hole catheter, administer in two divided aliquots: For the first dose: 1.25 mL/kg (birth weight) per aliquot For each repeated dose: 0.635 mL/kg (birth weight) per aliquot First aliquot of CUROSURF suspension: Position the infant in a neutral position (head and body in alignment without inclination), with either the right or left side dependent. Immediately before CUROSURF administration, change the infant’s ventilator settings to a rate of 40-60 breaths/minute, inspiratory time 0.5 second, and supplemental oxygen sufficient to maintain SaO2 > 92%. Briefly disconnect the endotracheal tube from the ventilator. Insert the pre-cut 5 French catheter into the endotracheal tube and instill the first aliquot of CUROSURF suspension. After the first aliquot is instilled, remove the catheter from the endotracheal tube and manually ventilate the infant with 100% oxygen at a rate of 40-60 breaths/minute for one minute. Second aliquot of CUROSURF suspension: When the infant is stable, reposition the infant such that the other side is dependent. Administer the remaining aliquot using the same procedures as the first aliquot. After completion of the dosing procedure, resume usual ventilator management and clinical care. Do not suction airways for 1 hour after surfactant instillation unless signs of significant airway obstruction occur. Post dosing, consider maintenance of PaO2 of about 55 mmHg, PaCO2 of 35-45, and pH > 7.3 [see Clinical Studies (14.1)]. For endotracheal instillation using the secondary lumen of a dual lumen endotracheal tube Slowly withdraw the entire contents of the vial of CUROSURF suspension into a 3 or 5 mL plastic syringe through a large-gauge needle (e.g., at least 20 gauge). Do not attach 5 French end-hole catheter. Remove the needle and discard excess CUROSURF so that only the dose to be given remains in the syringe. Keep the infant in a neutral position (head and body in alignment without inclination). Administer CUROSURF suspension through the proximal end of the secondary lumen of the endotracheal tube as a single dose, given over 1 minute, and without interrupting mechanical ventilation. After completion of this dosing procedure, ventilator management may require transient increases in FiO2 , ventilator rate, or PIP. Do not suction airways for 1 hour after surfactant instillation unless signs of significant airway obstruction occur.