Professional Information
Calfactant (Intratracheal-Local)
VA CLASSIFICATION
Primary: RE700
Commonly used brand name(s): Infasurf.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).
Category:
Pulmonary surfactant—
Indications
Accepted
Respiratory distress syndrome, neonatal (prophylaxis and treatment)—Calfactant intratracheal suspension is indicated for the prophylaxis (prevention strategy) and treatment (rescue strategy) of respiratory distress syndrome (RDS) in premature infants {01}.
—Prophylaxis is indicated in premature infants younger than 29 weeks of gestational age as soon as possible after birth, preferably within 30 minutes. {01}
—Treatment is indicated for infants less than 72 hours of age who have RDS (confirmed by clinical and radiological findings) and require endotracheal intubation {01}.
Pharmacology/Pharmacokinetics
Physicochemical characteristics:
Source—
Natural. Extract of natural surfactant from calf lungs {01}.
pH
5 to 6 {01}.
Mechanism of action/Effect:
Calfactant is a natural surfactant from calf lungs, which includes phospholipids, neutral lipids, and hydrophobic surfactant-associated proteins B and C (SP-B and SP-C) {01}.
Endogenous surfactant modifies alveolar surface tension, thereby stabilizing the alveoli, which makes it essential for effective ventilation. Calfactant restores surface activity to the lungs of premature infants who have respiratory distress syndrome (RDS) caused by a deficiency of lung surfactant. It decreases the incidence of RDS, mortality due to RDS, and air leaks associated with RDS. {01}
Calfactant adsorbs rapidly to the surface of the air:liquid interface and modifies surface tension in a manner similar to that of natural surfactant. Ex vivo , calfactant has been found to restore the pressure volume mechanics and compliance of surfactant-deficient rat lungs. In vivo , it improves lung compliance, respiratory gas exchange, and survival in preterm lambs with profound surfactant deficiency. {01}
Absorption:
No studies have been done {01}.
Biotransformation:
No studies have been done {01}.
Onset of action:
Significant improvements in fraction of inspired oxygen (F iO 2) and mean airway pressure (MAP) occur during the first 24 to 48 hours following initiation of therapy {01}.
Elimination:
No studies have been done {01}.
Precautions to Consider
Carcinogenicity
Studies have not been done {01}.
Mutagenicity
Calfactant was not found to be mutagenic in the Ames assay {01}.
Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).
Risk-benefit should be considered when the following medical problem exists
Sensitivity to calfactant
Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
» Respiratory status{01} (careful monitoring is recommended following calfactant administration, in order to modify oxygen therapy and ventilatory support in response to rapid improvement in oxygenation and lung compliance {01})
Side/Adverse Effects
Note: Intraventricular hemorrhage and periventricular leukomalacia have been observed in patients treated with calfactant, although they were not associated with increased mortality {01}.
Common complications of prematurity and respiratory distress syndrome (RDS) noted in clinical trials have included apnea, patent ductus arteriosus, intracranial hemorrhage, sepsis, pulmonary air leaks, pulmonary interstitial emphysema, pulmonary hemorrhage, and necrotizing enterocolitis {01}.
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
Those indicating need for medical attention
Incidence more frequent
Airway obstruction{01}
bradycardia{01}
cyanosis{01}
reflux of calfactant into the endotracheal tube{01}
Note: Transient episodes of cyanosis, bradycardia, reflux of calfactant into the endotracheal tube, and airway obstruction have been observed during dosing {01}. These effects usually are transient and not associated with serious complications or death {01}.
Overdose
Clinical effects of overdose
There have been no reports of overdosage with calfactant {01}. Although there are no known adverse effects, excess lung surfactant would result in overloading the lungs with an isotonic solution {01}.
Treatment of overdose
Support of ventilation until the excess fluid has been cleared is recommended {01}.
General Dosing Information
Calfactant should be used only by neonatologists and other clinicians who are experienced in neonatal intubation and ventilatory management. Adequate facilities, personnel, equipment, and medications are required to optimize the perinatal outcome in these premature infants. In addition, continuous clinical attention should be given to all infants prior to, during, and after administration of this medication. {01}
To ensure homogeneous distribution of calfactant throughout the lungs, the total dose (3 mL per kg of birth weight) is divided into two aliquots (1.5 mL per kg of birth weight). Following the instillation of each aliquot, the patient should be positioned with either the right or the left side dependent. {01}
The dose is drawn into a syringe through a 20-gauge or larger needle, taking care to avoid excessive foaming {01}. Remove needle before instilling calfactant into the endotracheal tube. {02}
The dose is administered intratracheally through a side-port adapter into the endotracheal tube. Two attendants, one to instill the calfactant, the other to monitor the patient and assist in positioning and facilitating the dosing, are present. After each dose, the infant is placed in the appropriate position. Ventilation is continued during administration over 20 to 30 breaths for each aliquot, with small bursts timed only during the inspiratory cycles. The two aliquots should be separated by a pause followed by evaluation of the respiratory status and repositioning. {01}
Infants frequently experience bradycardia, reflux of calfactant into the endotracheal tube, airway obstruction, cyanosis, dislodgement of the endotracheal tube, or hypoventilation during administration of calfactant. If any of these occur, it is recommended that administration be interrupted and the infant's condition stabilized using appropriate interventions before resuming the calfactant administration. Endotracheal suctioning or reintubation may be needed when there are signs of airway obstruction during administration. {01}
Close clinical monitoring and surveillance may be necessary following calfactant administration to adjust oxygen therapy and ventilator pressures appropriately in response to potential rapid and substantial increases in blood oxygenation and improved lung compliance {01}.
Intratracheal Dosage Forms
CALFACTANT INTRATRACHEAL SUSPENSION
Usual pediatric dose
Respiratory distress syndrome (prophylaxis or treatment)
Intratracheal (instilled into the endotracheal tube), the equivalent of 105 mg of phospholipids (3 mL of suspension) per kg of birth weight for the first dose (administered as two 1.5-mL aliquots) {01}. A total of three doses given at twelve hour intervals has been used in clinical trials when the patient was still intubated {01}.
Note: It is recommended that the prophylactic dose be given as soon as possible after birth {01}. Prior to initiating calfactant prophylaxis, the immediate care and stabilization of the infant born with hypoxemia and/or bradycardia are usually recommended. {01}
Strength(s) usually available
U.S.—
35 mg of total phospholipids per mL (Rx) [Infasurf (sodium chloride 0.9%)]
Note: Each mL contains 35 mg of total phospholipids, including 26 mg phosphatidylcholine (of which 16 mg is disaturated phosphatidylcholine), and 0.65 mg proteins, including 0.25 mg of surfactant-associated protein B (SP-B). {01}
Packaging and storage:
Store unopened vials between 2 and 8 °C (36 and 46 °F) {01}. Protect from light {01}.
Unopened, unused vials that have warmed to room temperature may be returned to the refrigerator within 24 hours of warming and stored for future use {01}. However, warmed, unopened vials should not be returned to the refrigerator more than once {01}.
Preparation of dosage form:
If the suspension appears to have separated, gentle swirling (not shaking) may be used to resuspend any particles that may have settled during storage {01}.
Warming is not necessary before use of calfactant intratracheal suspension {01}.
Calfactant suspension does not require reconstitution. It should not be diluted or sonicated. {01}
Stability:
Calfactant suspension does not contain preservatives {01}.
Visible flecks in the suspension and foaming at the surface of the suspension are normal {01}.
A vial should be entered with a needle only once and any unused suspension should be discarded {01}.
Auxiliary labeling:
• Do not shake.
• For intratracheal use only.
Developed: 10/16/1998
References
- Infasurf package insert (Forest—US), Rev 7/98, Rec 8/17/98.
- Panel comment, 9/30/98.
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