Poractant Alfa

Contraindications

None listed by the manufacturer

Cautions

Pulmonary hemorrhage may occur in premature birth and very low birth-weight

Rales, moist breathing sounds may occur normally with administration

Infant may exhibit bradycardia, reflux, cyanosis, airway obstruction

Use for intratracheal administration only

Correct hypotension, hypothermia, hypoglycemia, acidosis, and anemia before use

Mechanism of Action

Replaces deficient endogenous lung surfactant in neonates with respiratory distress syndrome

Surfactant prevents the alveoli from collapsing during expiration by lowering surface tension between alveolar surfaces and air

• Advise patient’s parent(s) or guardian that other complications of prematurity (e.g., pneumonia, septicemia, intracranial hemorrhage, patent ductus arteriosus) will not be eliminated by poractant therapy.1

• Importance of informing parent(s) or guardian of other important precautionary information. (See Cautions.)1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

There are no dosage adjustments provided in the manufacturer’s labeling.

Prior to administration, warm suspension to room temperature. Gently turn the vial over to obtain a uniform suspension; do not shake.

Take from refrigerator and warm to room temperature. Inspect for discoloration. The color should be white to creamy white. Gently turn the vial upside down to get a uniform suspension. Do not shake. Slowly withdraw the entire contents into a 3 mL or 5 mL plastic syringe through a large gauge needle (at least 20 gauge); discard the excess through the catheter so that only the total dose to be given remains in the syringe.

Before administering, assure proper placement and patency of the endotracheal tube. The endotracheal tube may be suctioned before administering the poractant alpha. The drug is administered intratracheally through a 5-French end-hole catheter cut to a standard length of 8 cm or through a secondary lumen of a dual-lumen endotracheal tube (without interrupting mechanical ventilation). Up to 2 repeated doses may be administered, using the same technique at 12-hour intervals.

Administration using a 5-French end-hole catheter: The infant should be stable before proceeding with administration. Keep the head and body of the infant in alignment without inclination and with either the right or left side dependent. Prior to administration, the infant's ventilator settings should be changed to a rate of 40-60 breaths/minute, inspiratory time 0.5 seconds, and supplemental oxygen to maintain SaO2 >92%. Briefly disconnect the endotracheal tube from the ventilator, insert the 5-French catheter. Administer dose in equally 2 divided aliquots. Instill the first aliquot (1.25 mL/kg birth weight for the initial dose; 0.635 mL/kg birth weight for repeat doses), remove the catheter and manually ventilate the infant with 100% oxygen at a rate of 40-60 breaths/minute for 1 minute. When the infant is stable, reposition the infant such that the other side is dependent and administer the remaining aliquot (1.25 mL/kg birth weight for the initial dose; 0.635 mL/kg birth weight for repeat doses) using the same technique. Do not suction the airways for 1 hour after instillation unless signs of significant airway obstruction occur. Resume ventilator management and clinical care.

Insert the first aliquot (1.25 mL/kg birth weight) and position the infant so that either the right or left side is dependent for the aliquot. Remove the catheter and manually ventilate the infant with 100% oxygen at a rate of 40-60 breaths/minute for 1 minute. When the infant is stable, reposition the infant such that the other side is dependent and administer the remaining aliquot using the same technique. Remove the catheter without flushing. Do not suction the airways for 1 hour after instillation unless signs of significant airway obstruction occur. Resume ventilator management and clinical care.

Administration using the secondary lumen of a dual-lumen endotracheal tube: The infant should be stable before proceeding with dosing. Keep the head and body of the infant in alignment without inclination. Administer poractant alfa through the proximal end of the secondary lumen of the endotracheal tube as a single dose over 1 minute (without interrupting mechanical ventilation); transient increases in F1O2, ventilatory rate, or peak inspiratory pressure (PIP) may be required. Do not suction airways for 1 hour after instillation unless signs of significant airway obstruction occur.

Store under refrigeration at defined temperature of 2°C to 8°C (36°F to 46°F). Unopened, unused vials that have been warmed to room temperature can be returned to refrigerator storage within 24 hours for future use. Do not warm and then refrigerate more than once. Vials are for single use only. Protect from light. Do not shake.

Mechanism of Action

Endogenous pulmonary surfactant reduces surface tension at the air-liquid interface of the alveoli during ventilation and stabilizes the alveoli against collapse at resting transpulmonary pressures. A deficiency of pulmonary surfactant in preterm infants results in Respiratory Distress Syndrome (RDS) characterized by poor lung expansion, inadequate gas exchange, and a gradual collapse of the lungs (atelectasis). CUROSURF compensates for the deficiency of surfactant and restores surface activity to the lungs of these infants.

Activity

In vitro --CUROSURF lowers minimum surface tension to </=4mN/m as measured by the Wilhelmy Balance System.

In vivo --In several pharmacodynamic studies, CUROSURF improved lung compliance, pulmonary gas exchange, or survival in premature rabbits.

FOR INTRATRACHEAL ADMINISTRATION ONLY.

General

CUROSURF is administered intratracheally by instillation through a 5 French end-hole catheter, and briefly disconnecting the endotracheal tube from the ventilator. Alternatively, CUROSURF may be administered through the secondary lumen of a dual lumen endotracheal tube without interrupting mechanical ventilation.

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. The infant should be allowed to stabilize before proceeding with dosing.

Initial Dose

The initial recommended dose of CUROSURF is 2.5 mL/kg birth weight. This dose may be determined from the CUROSURF dosing chart below.

For endotracheal tube instillation using a 5 French end-hole catheter

Slowly withdraw the entire contents of the vial of CUROSURF into a 3 or 5 mL plastic syringe through a large-gauge needle (e.g., at least 20 gauge). Attach the pre-cut 8-cm 5 end-hole French catheter to the syringe. Fill the catheter with CUROSURF. Discard excess CUROSURF through the catheter so that only the total dose to be given remains in the syringe.

Immediately before CUROSURF administration, the infant's ventilator settings should be changed to a rate of 40-60 breaths/minute, inspiratory time 0.5 second, and supplemental oxygen sufficient to maintain SaO 2 >92%. Keep the infant in a neutral position (head and body in alignment without inclination). Briefly disconnect the endotracheal tube from the ventilator. Insert the pre-cut 5 French catheter into the endotracheal tube and instill the first aliquot (1.25 mL/kg birth weight) of CUROSURF. The infant should be positioned such that either the right or left side is dependent for this aliquot. 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. When the infant is stable, reposition the infant such that the other side is dependant and administer the remaining aliquot using the same procedures. Do not suction airways for 1 hour after surfactant instillation unless signs of significant airway obstruction occur.

After completion of the dosing procedure, resume usual ventilator management and clinical care. In the clinical trials, ventilator management was modified to maintain a PaO 2 of about 55 mmHg, PaCO 2 of 35-45, and pH >7.3.

For endotracheal instillation using the secondary lumen of a dual lumen endotracheal tube

Slowly withdraw the entire contents of the vial of CUROSURF 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. Keep the infant in a neutral position (head and body in alignment without inclination). Administer CUROSURF 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, ventilatory management may require transient increases in FiO 2 , ventilatory rate, or PIP.

Repeat doses

Up to two repeat doses of 1.25 mL/kg birth weight each may be administered, using the same techniques described for the initial dose. Repeat doses should 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 dose (sum of the initial and up to two repeat doses) is 5 mL/kg.

Directions for Use

CUROSURF should be inspected visually for discoloration prior to administration. The color of CUROSURF is white to creamy white. CUROSURF should be stored in a refrigerator at +2 to +8°C (36-46°F). Before use, the vial should be slowly warmed to room temperature and gently turned upside-down, in order to obtain a uniform suspension. DO NOT SHAKE.

Unopened, unused vials of CUROSURF 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. Each single-use vial should be entered only once and the vial with any unused material should be discarded after the initial entry.

Dosing Precautions

Transient episodes of bradycardia, decreased oxygen saturation, reflux of the surfactant into the endotracheal tube, and airway obstruction have occurred during the dosing procedure of CUROSURF. These events require interrupting the administration of CUROSURF and taking the appropriate measures to alleviate the condition. After stabilization, dosing may resume with appropriate monitoring.