Infasurf

Lung Surfactants

Intratracheal Administration
Calfactant is only for intratracheal administration by or under the supervision of clinicians experienced in intubation, ventilator management, and intensive care of premature infants.
Arterial blood gases (ABGs) should be performed frequently in neonates receiving calfactant.
 
Preparation:
Calfactant does not require reconstitution before use. Do not filter or dilute.
Calfactant does not require warming prior to administration.
Record the date and time of removal from refrigerator.
Prior to withdrawing a dose, the calfactant vial should be gently swirled to ensure a uniform suspension. Do not shake the vial, as this may denature the proteins. Avoid excessive foaming. Visible flecks or foaming at the surface of the solution are normal for Infasurf.
Use a 20-gauge or larger needle to withdraw the required dose from the vial; do not filter.
Discard any unused portion.
Storage: The 3mL vial MUST be stored upright. 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 hour 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.
Administration is via a side port adapter or a 5 French end-hole catheter inserted into the proximal end of the endotracheal tube.
Divide the total dose into 2 equal aliquots; administer each aliquot with the patient in a different position to ensure homogenous distribution throughout the lungs.
On completion of the dosing procedure usual ventilator management and clinical care should be resumed.

cyanosis / Rapid / 65.0-65.0
bradycardia / Rapid / 34.0-34.0
intraventricular hemorrhage / Delayed / Incidence not known
intracranial bleeding / Delayed / Incidence not known
hypocarbia / Rapid / Incidence not known

hypoxia / Rapid / Incidence not known
hyperoxia / Rapid / Incidence not known

Infasurf

Rx

Bovine-derived lung surfactant.
Used to prevent and treat RDS in premature neonates.

3 mL/kg/dose (approximately 100 mg of phospholipids/kg/dose) of birth weight intratracheally divided in 2 or 4 aliquots. May administer up to 2 subsequent doses of 3 mL/kg/dose every 12 hours. Repeat doses have been administered as early as 6 hours for a total of up to 4 doses if the neonate is still intubated and requiring at least 30% inspired oxygen to maintain a PaO2 of 80 torr or less. Due to the long half-life, the American Academy of Pediatrics (AAP) recommends redosing every 12 hours, unless surfactant is being inactivated by an infectious process, meconium, or blood. Calfactant is FDA-approved for RDS prophylaxis in premature infants younger than 29 weeks of gestational age at birth who are at significant risk for RDS and for RDS treatment in neonates 72 hours of age or younger requiring endotracheal intubation. Administer calfactant for RDS prophylaxis as soon as possible, preferably within 30 minutes after birth.[44352]

80 mL/m2 per dose intratracheally, divided and administered in 2 equal aliquots. Repeat doses may be given according to clinical response every 12 hours; total dosage has not exceeded 4 doses. Two trials in 195 children (aged 1 month to 21 years) reported that calfactant administration was associated with a dramatic improvement in oxygenation. One study found a decrease in mortality, but no decrease in intensive care unit stay or duration of ventilator therapy. The second study found no change in mortality, but earlier extubation and decreased length of intensive care unit stays versus no treatment. The authors recommended that calfactant be further studied in pediatric patients with respiratory failure.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Amikacin: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant. Use the combination of amikacin and surfactants with caution.
Amphotericin B: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as amphotericin B.
Gentamicin: (Major) Aminoglycosides are commonly given via nebulization to the airway for the prevention and treatment of pneumonia and are known to be at risk for inactivation of their antibiotic activity, mainly due to their susceptibility for changes in pH. A reduced activity of gentamicin may occur in the presence of surfactant.
Neomycin: (Major) Some surfactant antiinfective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation.
Streptomycin: (Moderate) A reduced activity of streptomycin may occur in the presence of surfactant when given via nebulization.
Tobramycin: (Major) Some surfactant anti infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. A reduced activity of tobramycin, a commonly nebulized aminoglycoside, has been reported in the presence of surfactant.
Vancomycin: (Major) Some surfactant-anti-infective mixtures have been shown to affect the in vivo activity of exogenous pulmonary surfactants when they are administered via inhalation. Pulmonary surfactants should not be mixed with anti-infectives that are commonly administered via nebulization such as vancomycin.

Infasurf Endotracheal Susp

Safe and effective use has not been established.

Safe and effective use has not been established.

Safe and effective use has not been established; 80 ml/m2/dose intratracheally has been used off-label for pediatric acute respiratory distress syndrome (ARDS).

Safe and effective use has not been established; 80 ml/m2/dose intratracheally has been used off-label for pediatric acute respiratory distress syndrome (ARDS).

Safe and effective use has not been established; 80 ml/m2/dose intratracheally has been used off-label for pediatric acute respiratory distress syndrome (ARDS).

100 mg/kg birth weight (3 mL/kg birth weight)/dose intratracheally.

Calfactant exhibits actions similar to natural pulmonary surfactant. Calfactant reduces the surface tension on alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting transpulmonary pressures. This leads to an improvement in lung compliance and respiratory gas exchange. The exact mechanisms of calfactant are still uncertain.
 
Natural human pulmonary surfactant is secreted by the lamellar bodies of alveolar type-II cells, and is first synthesized in the fetus after 24—28 weeks of gestation. 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). The exact role of all of 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.

Calfactant 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 the infant to allow gravity to help distribute surfactant to the distal airways. Calfactant distributes primarily to the alveolar linings and lung tissues; only 5% of the administered dose is detected in other organs.[44352] Metabolism of calfactant in humans is uncertain, as pharmacokinetic studies have not been performed. Pharmacokinetic studies in surfactant-deficient animals indicate that calfactant has little effect on the endogenous production of surfactant by the lungs. Clearance is a local phenomenon that appears to involve type II alveolar cells.[51659] In animals, less than 30% of an administered calfactant dose is present in the lung tissues 24 hours after the administration of a single dose.[44352]
 
Affected cytochrome P450 isoenzymes: none

Intratracheal Route
Absorption of calfactant in humans is uncertain, as pharmacokinetic studies have not been performed. Based on clinical studies of aerosolized surfactant administration versus endotracheal bolus administration, bolus administration provides for faster onset of action and clinical efficacy.

Clinical studies in women or animals during pregnancy are not available. Calfactant should only be administered to pregnant women where the potential benefit of the medication would outweigh the unknown risks to the fetus.

There are no data on the use of Calfactant (Infasurf) during lactation. Since data are not available, calfactant should be administered with caution during breast-feeding.