CUROSURF

General Administration Information
For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Other Administration Route(s)
Intratracheal Administration
-Poractant alfa is only for intratracheal administration by or under the supervision of clinicians experienced in intubation, ventilator management, and general care of premature infants.
-Prior to administration of poractant alfa, it is recommended that metabolic acidosis, anemia, hypoglycemia, hypotension, and hypothermia be corrected.

Preparation
-Poractant alfa is ready-to-use; no reconstitution or dilution is necessary.
-Slowly warm vial to room temperature and gently turn upside-down in order to obtain a uniform suspension. DO NOT SHAKE.
-Record the date and time of warming on the vial carton.
-Use a 20-gauge or larger needle to withdraw the required dose from the vial into a 3 or 5 ml syringe.
-Storage: Unopened, unused vials may be returned to refrigeration within 24 hours of warming. Vials that have been warmed to room temperature should not be returned after 24 hours or returned more than once. Protect from light.

Intratracheal Instillation
-NOTE: FOR INTRATRACHEAL ADMINISTRATION ONLY.
-Carefully follow the detailed dosage and administration instructions from the manufacturer.
-At the discretion of the clinician, the endotracheal tube may be suctioned prior to administration. Allow the patient to stabilize before proceeding with dosing.
-Administration is via a 5 French end-hole catheter; alternatively it can be instilled using the secondary lumen of a dual lumen endotracheal tube.
-If a 5 French catheter is used, immediately before 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 SaO2>92%. Keep the infant in a neutral position (head and body in alignment without inclination).
-The manufacturer recommends that the total dose be divided into two equal aliquots. Each aliquot is administered into one of the two main bronchi by positioning with either the right or left side dependent. This ensures homogenous distribution throughout the lungs.
-On completion of the dosing procedure the usual ventilator management and clinical care should be resumed. In clinical trials, ventilator management was modified to maintain a PaO2 of approximately 55 mmHg, PaCo2 of 35-45, and pH > 7.3.

Premature birth is naturally associated with a number of adverse reactions producing a high incidence of morbidity and mortality. The distinction between adverse reactions attributable to poractant alfa and those that are a natural result of premature birth is not always clear.

Adverse reactions associated with the use of poractant alfa are divided into those that can occur during administration and those that can occur following the procedure. Transient episodes of hypotension, sinus bradycardia, oxygen desaturation, endotracheal tube blockage/reflux of the surfactant into the endotracheal tube, and airway obstruction have occurred during the dosing procedure of poractant alfa. A state of hypoxia can follow oxygen desaturation. These adverse events are not usually associated with serious complications when appropriately managed. If these events occur, the surfactant administration procedure should be stopped, and appropriate measures taken to relieve the condition. In some cases, manual ventilation or reintubation will be required. Once the patient is stabilized, the administration procedure can be resumed.

Following poractant alfa administration, a rapid increase in oxygenation and lung compliance may lead to hyperoxia and hypocarbia. Hypocarbia may reduce blood flow to the brain. Steps to avoid this possibility should be taken by careful monitoring of oxygenation and clinical observation. Frequent monitoring of arterial blood gases (ABG) is required. Throughout poractant alfa treatment, ventilation must be maintained to ensure correct oxygenation. Adjustments in the fraction of inspired oxygen (FiO2) and other ventilator settings may be necessary during treatment to prevent cyanosis or hyperoxia.

Bleeding in the lungs (i.e. pulmonary hemorrhage) has been reported both in clinical trials and in post-marketing adverse event reports in infants who received poractant alfa. Pulmonary hemorrhage is a known complication of premature birth, especially in very low birth-weight infants, and therefore, it is difficult to determine whether these events were related to drug administration or to premature birth. In controlled clinical trials, patent ductus arteriosus was diagnosed in 60% of patients receiving poractant alfa versus 48% of controls. The groups did not differ in regard to the incidence of any other common complication of RDS or prematurity, including rates of intracranial bleeding.

Poractant alfa is extracted from porcine lung surfactant. Immunogenic sensitization has not been documented in newborns after the use of poractant alfa. However, because surfactants might be used in investigational settings, poractant alfa should be used with caution in those with known porcine protein hypersensitivity.

During surfactant administration, transient episodes of bradycardia, hypotension, endotracheal tube blockage, and decreased oxygen saturation have been reported. If these occur, stop the dosing procedure and initiate appropriate measures to alleviate the condition. After stabilization, the dosing procedure may be resumed. The administration of exogenous surfactants, including poractant alfa, can rapidly affect oxygenation and lung compliance. Therefore, patients receiving poractant alfa should receive frequent clinical and laboratory assessments so that oxygen and ventilatory support can be modified to respond to respiratory changes. Prior to administration of poractant alfa, it is recommended that acidosis, anemia, hypoglycemia, hypotension, and hypothermia be corrected. Poractant alfa administration requires an experienced clinician trained in the care, resuscitation, and stabilization of preterm neonates.

Description: Poractant alfa is a porcine-derived lung surfactant that is indicated for the treatment of neonatal respiratory distress syndrome (RDS) in premature infants. Poractant alfa replaces pulmonary surfactant, which is deficient in some premature neonates. It also increases lubrication within the alveoli, thus improving expansion and ventilation. The administration of poractant alfa, as well as other exogenous surfactants, is expected to reduce the severity of RDS but not eliminate the mortality and morbidity associated with other complications in premature neonates. Poractant alfa has also been used in cases of acute respiratory distress syndrome (ARDS) after fresh-water near-drowning. Compared to other commercial pulmonary surfactants, poractant alfa is the most concentrated product on the market; it contains 76 mg phospholipids and 1 mg protein per ml. Poractant alfa is approved for pediatric patients, as young as premature neonates.

For the rescue treatment of neonatal respiratory distress syndrome (RDS):
Intratracheal dosage:
Premature neonates: 2.5 mL/kg/dose of birth weight intratracheally divided in 1 or 2 aliquots. May administer up to 2 subsequent doses of 1.25 mL/kg/dose at 12-hour intervals if needed. The maximum recommended total dose (sum of all aliquots) is 5 mL/kg. The safety and efficacy of administering poractant alfa more than 15 hours after the initial diagnosis of neonatal RDS has not been established. Adequate data are not available on the use of poractant alfa in conjunction with experimental therapies of RDS (e.g., high-frequency ventilation).

For the treatment of acute respiratory distress syndrome (ARDS)* due to near-drowning:
Intratracheal dosage:
Neonates: 100 mg/kg intratracheally as a single aliquot and repeated 4 hours later for improving but ongoing hypoxemia.
Infants, Children, and Adolescents: 40 or 50 mg/kg intratracheally as a single aliquot.

Maximum Dosage Limits:
-Neonates
2.5 ml/kg (birth weight)/dose intratracheally.
-Infants
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Adolescents
Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that dosage adjustments are not needed.

Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that dosage adjustments are not needed.

*non-FDA-approved indication

Monograph content under development

Mechanism of Action: Poractant alfa exhibits actions similar to natural pulmonary surfactant. Poractant alfa reduces the surface tension at the air-liquid interface on alveolar surfaces during ventilation and stabilizes the alveoli against collapse at resting transpulmonary pressures. This leads to an improvement in lung compliance and respiratory gas exchange. Additionally, in vitro data suggest that poractant alfa causes a substantial reduction in tumor necrosis factor output from human monocytes, thereby producing antiinflammatory effects within the alveolar space.

Natural pulmonary surfactant contains a mixture of roughly 90% phospholipids (e.g., phosphatidylcholine and phosphatidylglycerol) and 10% associated surfactant proteins (i.e., SP-A, SP-B, SP-C, and SP-D). Poractant alfa consists of about 99% phospholipids and 1% surfactant associated proteins (SP-B and SP-C only). The exact role of all the components of natural human pulmonary surfactant is uncertain, and of great scientific interest. Phospholipids adsorb rapidly to the surface of the air:liquid interface of the lung lumen and modify the surface tension within the alveoli. Surfactant-associated proteins, particularly SP-B, appear to be essential in binding, stabilizing, spreading, and recycling phospholipids on the alveolar surfaces. It has been recently discovered that some infants who develop fatal RDS have a genetic deficiency or a genetic mutation of the SP-B protein. Proteins SP-A and SP-D, which are not currently components of exogenous surfactant products, appear to have additional functions relating to host defenses in the lung.

Pharmacokinetics: Poractant Alfa is administered intratracheally. It is delivered directly to the site of action, and only a small amount reaches the systemic circulation. Distribution is improved by positioning to allow gravity to help distribute surfactant to the distal airways. Clearance is a local phenomenon that appears to involve type II alveolar cells.