Calfactant

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# Overview
Calfactant is a Lung Surfactant that is FDA approved for the prevention of of respiratory distress syndrome(RDS) in premature infants at high risk for RDS and for the treatment (rescue) of premature infants who develop RDS.   Common adverse reactions include cyanosis, airway obstruction, bradycardia, reflux of surfactant into the endotracheal tube, requirement for manual ventilation, and reintubation.

# Adult Indications and Dosage

## FDA-Labeled Indications and Dosage (Adult)
- Calfactant is indicated for the prevention of Respiratory Distress Syndrome (RDS) in premature infants at high risk for RDS and for the treatment (rescue) of premature infants who develop RDS. Calfactant decreases the incidence of RDS, mortality due to RDS, and air leaks associated with RDS.
- Prophylaxis therapy at birth with Calfactant is indicated for premature infants less than 29 weeks of gestational age at significant risk for RDS. Calfactant prophylaxis should be administered as soon as possible, preferably within 30 minutes after birth.
- Calfactant therapy is indicated for infants less than or equal to 72 hours of age with RDS (confirmed by clinical and radiologic findings) and requiring endotracheal intubation.

## Off-Label Use and Dosage (Adult)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Calfactant in adult patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Calfactant in adult patients.

# Pediatric Indications and Dosage

## FDA-Labeled Indications and Dosage (Pediatric)
There is limited information regarding FDA-Labeled Use of Calfactant in pediatric patients.

## Off-Label Use and Dosage (Pediatric)

### Guideline-Supported Use
There is limited information regarding Off-Label Guideline-Supported Use of Calfactant in pediatric patients.

### NonGuideline-Supported Use
There is limited information regarding Off-Label NonGuideline-Supported Use of Calfactant in pediatric patients.

# Contraindications
None

# Warnings
- Calfactant is intended for intratracheal use only.
- THE ADMINISTRATION OF EXOGENOUS SURFACTANTS, INCLUDING Calfactant, OFTEN RAPIDLY IMPROVES OXY GENATION AND LUNG COMPLIANCE. Following administration of Calfactant, patients should be carefully monitored so that oxygen therapy and ventilatory support can be modified in response to changes in respiratory status. Calfactant therapy is not a substitute for neonatal intensive care. Optimal care of premature infants at risk for RDS and new born infants with RDS who need endotracheal intubation requires an acute care unit organized, staffed, equipped, and experienced with intubation, ventilator management, and general care of these patients.
- TRANSIENT EPISODES OF REFLUX OF Calfactant INTO THE ENDOTRACHEAL TUBE, CYANOSIS, BRADYCARDIA, OR AIRWAY OBSTRUCTION HAVE OCCURRED DURING THE DOSING PROCEDURES. These events require stopping Calfactant administration and taking appropriate measures to alleviate the condition. After the patient is stable, dosing can proceed with appropriate monitoring.

### Precautions
- DescriptionWhen repeat dosing was given at fixed 12-hour intervals in the Calfactant vs. Exosurf Neonatal trials, transient episodes of cyanosis, bradycardia, reflux of surfactant into the endotracheal tube, and airway obstruction were observed more frequently among infants in the Calfactant-treated group.
- An increased proportion of patients with both intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL) was observed in Calfactant-treated infants in the Calfactant-Exosurf Neonatal controlled trials. These observations were not associated with increased mortality.
- No data are available on the use of Calfactant in conjunction with experimental therapies of RDS, e.g., high-frequency ventilation. Data from controlled trials on the efficacy of Calfactant are limited to doses of approximately 100 mg phospholipid/kg body weight and up to a total of 4 doses.

# Adverse Reactions

## Clinical Trials Experience
- The most common adverse reactions associated with Calfactant dosing procedures in the controlled trials were cyanosis (65%), airway obstruction (39%), bradycardia (34%), reflux of surfactant into the endotracheal tube (21%), requirement for manual ventilation (16%), and reintubation (3%). These events were generally transient and not associated with serious complications or death. The incidence of common complications of prematurity and RDS in the four controlled Calfactant trials are presented in Table3.Prophylaxis and treatment study results for each surfactant are combined.
- Follow-up Evaluations
- Two-year follow-up data of neurodevelopmental outcomes in 415 infants enrolled in 5 centers that participated in the Calfactant vs Exosurf Neonatal controlled trials demonstrated significant developmental delays in equal percentages of Calfactant and Exosurf Neonatal patients.

## Postmarketing Experience
There is limited information regarding Postmarketing Experience of Calfactant in the drug label.

# Drug Interactions
There is limited information regarding Calfactant Drug Interactions in the drug label.

# Use in Specific Populations

### Pregnancy
Pregnancy Category (FDA): 
There is no FDA guidance on usage of Calfactant in women who are pregnant.
Pregnancy Category (AUS): 
There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Calfactant in women who are pregnant.

### Labor and Delivery
There is no FDA guidance on use of Calfactant during labor and delivery.

### Nursing Mothers
There is no FDA guidance on the use of Calfactant with respect to nursing mothers.

### Pediatric Use
There is no FDA guidance on the use of Calfactant with respect to pediatric patients.

### Geriatic Use
There is no FDA guidance on the use of Calfactant with respect to geriatric patients.

### Gender
There is no FDA guidance on the use of Calfactant with respect to specific gender populations.

### Race
There is no FDA guidance on the use of Calfactant with respect to specific racial populations.

### Renal Impairment
There is no FDA guidance on the use of Calfactant in patients with renal impairment.

### Hepatic Impairment
There is no FDA guidance on the use of Calfactant in patients with hepatic impairment.

### Females of Reproductive Potential and Males
There is no FDA guidance on the use of Calfactant in women of reproductive potentials and males.

### Immunocompromised Patients
There is no FDA guidance one the use of Calfactant in patients who are immunocompromised.

# Administration and Monitoring

### Administration
- Intrathecal

### Monitoring
There is limited information regarding Monitoring of Calfactant in the drug label.

# IV Compatibility
There is limited information regarding IV Compatibility of Calfactant in the drug label.

# Overdosage
- There have been no reports of overdosage with Calfactant. While there are no known adverse effects of excess lung surfactant, overdosage would result in overloading the lungs with an isotonic solution. Ventilation should be supported until clearance of the liquid is accomplished.

# Pharmacology
There is limited information regarding Calfactant Pharmacology in the drug label.

## Mechanism of Action
- Endogenous lung surfactant is essential for effective ventilation because it modifies alveolar surface tension thereby stabilizing the alveoli. Lung surfactant deficiency is the cause of Respiratory Distress Syndrome (RDS) in premature infants. Calfactant restores surface activity to the lungs of these infants.

## Structure
- Calfactant (calfactant) Intratracheal Suspension is a sterile, non-pyrogenic lung surfactant intended for intratracheal instillation only. It is an extract of natural surfactant from calf lungs which includes phospholipids, neutral lipids, and hydrophobic surfactant-associated proteins B and C (SP-B and SP-C). It contains no preservatives.
- Calfactant is an off-white suspension of calfactant in 0.9% aqueous sodium chloride solution. It has a pH of 5.0 - 6.2 (target pH 5.7). Each milliliter of Calfactant contains 35 mg total phospholipids (including 26 mg phosphatidylcholine of which 16 mg is disaturated phosphatidylcholine) and 0.7 mg proteins including 0.26 mg of SP-B.

## Pharmacodynamics
- Calfactant adsorbs rapidly to the surface of the air:liquid interface and modifies surface tension similarly to natural lung surfactant. A minimum surface tension of less than or equal to 3 mN/m is produced in vitro by Calfactant as measured on a pulsating bubble surfactometer. Ex vivo, Calfactant restores the pressure volume mechanics and compliance of surfactant-deficient rat lungs. In vivo, Calfactant improves lung compliance, respiratory gas exchange, and survival in preterm lambs with profound surfactant deficiency

## Pharmacokinetics
- Animal Metabolism: Calfactant is administered directly to the lung lumen surface, its site of action. No human studies of absorption, biotransformation, or excretion of Calfactant have been performed. The administration of Calfactant with radiolabeled phospholipids into the lungs of adult rabbits results in the persistence of 50% of radioactivity in the lung alveolar lining and25% of radioactivity in the lung tissue 24 hours later. Less than 5% of the radioactivity is found in other organs. In premature lambs with lethal surfactant deficiency, less than 30% of instilled Calfactant is present in the lung lining after 24 hours.

## Nonclinical Toxicology
- Carcinogenesis studies and animal reproduction studies have not been performed with Calfactant. A single mutagenicity study (Ames assay) was negative.

# Clinical Studies
- Clinical Studies: The efficacy of Calfactant was demonstrated in two multiple-dose controlled clinical trials involving approximately 2,000 infants treated with Calfactant (approximately 100 mg phospholipid/kg) or Exosurf Neonatal. In addition, two controlled trials of Calfactant versus Survanta, and four uncontrolled trials were conducted that involved approximately 15,500 patients treated with Calfactant.
- Treatment Trial
- A total of 1,126 infants less than or equal to 72 hours of age with RDS who required endotracheal intubation and had an a/A PO2 less than  0.22 were enrolled into a multiple-dose, randomized, double-blind treatment trial comparing Calfactant (3 mL/kg) and Exosurf Neonatal (5 mL/kg). Patients were given an initial dose and one repeat dose 12 hours later if intubation was still required. The dose was instilled in two aliquots through a side port adapter into the proximal end of the endotracheal tube. Each aliquot was given in small bursts over 20-30 inspiratory cycles. After each aliquot was instilled, the infant was positioned with either the right or the left side dependent. Results for efficacy parameters evaluated at 28 days or to discharge for all treated patients from this treatment trial are shown in Table 1.
- Prophylaxis Trial
- A total of 853 infants less than 29 weeks gestation were enrolled into a multiple-dose, randomized, double-blind prophylaxis trial comparing Calfactant (3 mL/kg) and Exosurf Neonatal (5 mL/kg). The initial dose was administered within 30 minutes of birth. Repeat doses were administered at 12 and 24 hours if the patient remained intubated. Each dose was administered divided in 2 equal aliquots, and given through a side port adapter into the proximal end of the endotra cheal tube. Each aliquot was given in small bursts over 20-30 inspiratory cycles. After each aliquot was instilled, the infant was positioned with either the right or the left side dependent. Results for efficacy parameters evaluated to day 28 or to discharge for all treated patients from this prophylaxis trial are shown in Table 2.
- Treatment Trial
- A total of 662 infants with RDS who required endotracheal intubation and had an a/A PO2 less than 0.22 were enrolled into a multiple-dose, randomized, double-blind treatment trial comparing Calfactant (4 mL/kg of a formulation that contained 25 mg of phospholipids/mL rather than the 35 mg/mL in the marketed formulation) and Survanta (4 mL/kg). Repeat doses were allowed Greater than or equal to 6 hours following the previous treatment (for up to three doses before 96 hours of age) if the patient required Greater than or equal to 30% oxygen. The surfactant was given through a 5 French feeding catheter inserted into the endo tracheal tube. The total dose was instilled in four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes. Each of the aliquots was administered with the patient in one of four different positions (prone, supine, right, and left lateral) to facilitate even distribution of the surfactant. Results for the major efficacy parameters evaluated at 28 days or to discharge (incidence of air leaks, death due to respiratory causes or to any cause, BPD, or treatment failure) for all treated patients from this treatment trial were not significantly different between Calfactant and Survanta.
- Prophylaxis Trial
- A total of 457 infants less than or equal to 30 weeks gestation and less than 1251 grams birth weight were enrolled into a multiple-dose, randomized, double-blind trial comparing Calfactant (4 mL/kg of a formulation that contained 25 mg of phospholipids/mL rather than the 35 mg/mL in the marketed formulation) and Survanta (4 mL/kg). The initial dose was administered within15 minutes of birth and repeat doses were allowed Greater than or equal to 6 hours following the previous treatment (for up to three doses before 96 hours of age) if the patient required Greater than or equal to 30% oxygen. The surfactant was given through a 5 French feeding catheter inserted into the endotracheal tube. The total dose was instilled in four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes. Each of the aliquots was administered with the patient in one of four different positions (prone, supine, right, and left lateral). Results for efficacy endpoints evaluated at 28 days or to discharge for all treated patients from this prophylaxis trial showed an increase in mortality from any cause at 28 days (p=0.03) and in death due to respiratory causes (p=0.005) in Calfactant-treated infants. For evaluable patients (patients who met the protocol-defined entry criteria), mortality from any cause and mortality due to respiratory causes were also higher in the Calfactant group (p = 0.07 and 0.03, respectively). However, these observations have not been replicated in other adequate and well-controlled trials and their relevance to the intended population is unknown. All other efficacy outcomes (incidence of RDS, air leaks, BPD, and treatment failure) were not significantly different between Calfactant and Survanta when analyzed for all treated patients and for evaluable patients.
- Acute Clinical Effects: As with other surfactants, marked improvements in oxygenation and lung compliance may occur shortly after the administration of Calfactant. All controlled clinical trials with Calfactant demonstrated significant improvements in fraction of inspired oxygen (FiO2) and mean airway pressure (MAP) during the first 24 to 48 hours following initiation of Calfactant therapy.

# How Supplied
- Calfactant Intratracheal Suspension is supplied sterile in single-use, rubber-stoppered glass vials containing 3 mL (NDC 61938-456-03) and 6 mL (NDC 61938-456-06) off-white suspension.

## Storage
- Store Calfactant (calfactant) Intratracheal Suspension at refrigerated temperature 2 to 8C (36 to 46F) and protect from light. THE 3mL VIAL MUST BE STORED UPRIGHT. Vials are for single use only. After opening, discard unused drug.

# Images

## Drug Images

## Package and Label Display Panel

# Patient Counseling Information
There is limited information regarding Patient Counseling Information of Calfactant in the drug label.

# Precautions with Alcohol
- Alcohol-Calfactant interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

# Brand Names
- Calfactant

# Look-Alike Drug Names
There is limited information regarding Calfactant Look-Alike Drug Names in the drug label.

# Drug Shortage Status

# Price