Calfactant is a bovine-derived lung surfactant suspension. It is administered intratracheally and is indicated for the prevention and treatment of respiratory distress syndrome (RDS) in premature infants. Many different surfactants are available commercially; they can be derived from natural sources or synthesized. Infasurf and Survanta are bovine-derived while colfosceril-cetyl alcohol-tyloxapol (Exosurf Neonatal) and lucinactant are synthetic (see separate monographs). Calfactant is obtained by lavaging bovine lungs, while beractant is derived from minced bovine lung tissue. Similar to beractant, calfactant contains phospholipids, neutral lipids, fatty acids and two low-molecular weight, hydrophobic surfactant-associated proteins, SP-B and SP-C. It does not contain the hydrophilic large molecular weight surfactant-associated protein SP-A. Based on clinical response and outcomes in neonates, most clinicians feel there is little difference between the currently available natural and synthetic exogenous surfactant products. Surfactants are being investigated for use in other respiratory distress syndromes in both children and adults, including acute respiratrory distress syndrome (ARDS) and burn-inhalation injuries. Final FDA approval of calfactant was granted in 1997. However, the FDA delayed marketing of Infasurf until the orphan drug status for Survanta expired in July 1998. The Infasurf product was made available after 2000.
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
-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.
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 calfactant and those that are a natural result of premature birth is not always clear.
In controlled trials of calfactant prophylaxis and treatment, there was an increased incidence of both intraventricular hemorrhage and periventricular leukomalacia in calfactant-treated patients versus those who received colfosceril-cetyl alcohol-tyloxapol. The incidences for calfactant and colfosceril-cetyl alcohol-tyloxapol were 7% and 3%, respectively. The treatment groups did not differ regarding the incidence of severe intracranial bleeding, mortality, or other complications common in premature infants with RDS. In clinical trials of calfactant compared to beractant, treatment groups did not differ regarding the incidence of any common complication of RDS or prematurity.
Adverse reactions associated with the use of calfactant are divided into those that can occur during calfactant administration and those that can occur after the procedure. During administration, transient episodes of reflux of calfactant into the endotracheal tube may occur. During clinical trials with calfactant, reflux occurred in 21% of infants treated. Transient cyanosis (65%), sinus bradycardia (34%), airway obstruction (39%), and oxygen desaturation are other common adverse events. 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 calfactant administration procedure should be stopped, and appropriate measures taken to relieve the condition. In some cases, manual ventilation (16%) or reintubation (3%) will be required. Once the patient is stabilized, the administration procedure can be resumed.
After calfactant 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 calfactant 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.
Immunogenic sensitization has not been documented in neonates following the use of calfactant (Infasurf), which is derived from bovine sources. However, because surfactants might be used investigationally in other populations (e.g., children or adults), calfactant should be used with caution in those with known bovine protein hypersensitivity.
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.
During the surfactant dosing procedure, transient episodes of bradycardia 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 calfactant, can rapidly affect oxygenation and lung compliance. Therefore, infants receiving calfactant should receive frequent clinical and laboratory assessments so that oxygen and ventilatory support can be modified to respond to respiratory changes. Calfactant should only be administered by those trained and experienced in the care, resuscitation, and stabilization of preterm infants. Prior to administration of calfactant, it is recommended that acidosis, anemia, hypoglycemia, hypotension, and hypothermia be corrected.
For neonatal respiratory distress syndrome prophylaxis in premature neonates and for the treatment of neonatal respiratory distress syndrome (RDS):
Intratracheal dosage:
Premature and Term 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.
For the treatment of pediatric acute respiratory distress syndrome (ARDS)* in pediatric patients needing ventilator support:
Intratracheal dosage (Infasurf):
Infants, Children, and Adolescents: 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.
Maximum Dosage Limits:
-Adults
Safe and effective use has not been established.
-Geriatric
Safe and effective use has not been established.
-Adolescents
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).
-Children
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).
-Infants
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).
-Neonates
100 mg/kg birth weight (3 mL/kg birth weight)/dose intratracheally.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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.
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. 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. 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.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Other Route(s)
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.