INFASURF

Calfactant is a sterile, non-pyrogenic lung surfactant intended for intratracheal instillation.

It is an off-white suspension of an extract of natural surfactant from calf lungs suspended in 0.9% saline.

Each milliliter of calfactant contains 35 mg of phospholipids (including 26 mg phosphatidylcholine of which 16 mg is disaturated phosphatidylcholine) and 0.65 mg of proteins including surfactant-associated proteins B and C. Calfactant is approved for use in the United States of America.

It is used to prevent or treat respiratory distress syndrome in premature infants with lung surfactant deficiency.

Calfactant has been shown to decrease the incidence of respiratory distress syndrome, mortality due to respiratory distress syndrome, and air leaks associated with respiratory distress syndrome in clinical trials.

It adsorbs to the air:fluid interface in the lungs and works to reduce surface tension, in a manner similar to endogenous pulmonary surfactant.

Calfactant is indicated for prophylaxis therapy to prevent respiratory distress syndrome (RDS) in premature infants <29 weeks of gestational age with low lung surfactant and at high risk for RDS.

Calfactant therapy is also indicated for the treatment of respiratory distress syndrome in infants 72 hours or less of age with RDS confirmed by clinical and radiologic findings and requiring endotracheal intubation.

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 preterm neonates.

INFASURF is a lung surfactant that restores lung surface activity in preterm neonates with RDS by adsorbing to the surface of the air:liquid interface and modifying surface tension similarly to natural lung surfactant. 12.2 Pharmacodynamics Calfactant dose-response relationships and the time course of pharmacodynamic response are unknown.

In vitro, INFASURF lowered minimum surface tension to ≤ 3 mN/m as measured on a pulsating bubble surfactometer.

Ex vivo, INFASURF restored the pressure volume mechanics and compliance of surfactant-deficient rat lungs.

In vivo, INFASURF improved lung compliance, respiratory gas exchange, and survival in preterm lambs with profound surfactant deficiency. 12.3 Pharmacokinetics The absorption, distribution, metabolism, and excretion of calfactant in humans following intratracheal administration of INFASURF is unknown. 12.6 Immunogenicity The immunogenicity of INFASURF is unknown.

Pulmonary surfactant is an endogenous substance produced in the lungs that functions to decrease surface tension at the air:fluid interface on the alveolar surface.

In premature infants with pulmonary surfactant deficiency, surface tension can increase to the point where sections of lung collapse and respiratory distress syndrome (RDS) develops.

Calfactant adsorbs rapidly to the surface of the alveolar air:fluid interface and modifies surface tension to a minimum of less than 3 mN/m.

It acts in a manner similar to natural lung surfactant, thus preventing or treating respiratory distress syndrome.

Calfactant is administered directly to the lung lumen surface where it acts.

No human studies on absorption have been completed.

No human studies on the distribution of calfactant have been performed.

Endogenous lung surfactant is produced and excreted by Type II alveolar pneumocytes to form a surface monolayer across the alveoli through adsorption.

Through repeated contraction and expansion of an alveolus, this monolayer degrades and the surfactant is taken back up into the Type II alveolar pneumocyte for re-packaging.

No human studies on the metabolism of calfactant have been completed, but it is likely metabolized through a similar mechanism to endogenous pulmonary surfactant.

No human studies on elimination of calfactant have been completed.

Half time clearance from the lung lumen was reported as 12 hours in a study of normal rabbits.

No human studies on the metabolism and elimination of calfactant have been performed.

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Carcinogenesis and animal reproduction studies have not been performed with calfactant.

A single mutagenicity study produced a negative Ames assay.

Overdose with calfactant has not yet been reported, but it is recommended that in the case of an overdose ventilation should be supported until all excess fluid is cleared from the lungs.

Cyanosis, bradycardia and airway obstruction have been reported with administration of calfactant.

Recommended Dosage The recommended dose of

INFASURF is 3 mL/kg body weight at birth administered intratracheally through an endotracheal tube.

INFASURF can be administered every 12 hours for a total of up to three doses.

To reduce the risk of

RDS in preterm neonates <29 weeks of gestational age at risk for RDS, administer INFASURF within 30 minutes after birth. 2.2 Preparation Instructions INFASURF does not require reconstitution.

Do not dilute or sonicate.

INFASURF does not need to reach room temperature before administration.

Gently swirl or agitate the

INFASURF intratracheal suspension vial for redispersion.

Do not shake.

Visually inspect the

INFASURF intratracheal suspension for discoloration prior to administration.

The color of the

INFASURF intratracheal suspension should be off-white.

Discard the

INFASURF vial if the intratracheal suspension is discolored.

Visible flecks in the intratracheal suspension and foaming at the surface are normal.

Using a 20-gauge or larger needle and syringe to avoid excessive foaming, withdraw INFASURF from the vial.

Discard unopened

INFASURF vials stored at room temperature for more than 24 hours.

Discard unused

INFASURF after the initial vial entry. 2.3 Administration Instructions INFASURF should be administered by healthcare providers who are experienced in the acute care of neonates with RDS who require intubation.

Two attendants should be present to facilitate dosing; one to instill the INFASURF, the other to monitor the neonate.

INFASURF intratracheally through an endotracheal tube using the prepared syringe using either of the following two methods.

Instill the INFASURF dose through a

Side-port adapter into the endotracheal tube as two equal aliquots of 1.5 mL/kg each.

During and after each aliquot that is instilled, position the neonate with either the right or the left side dependent and maintain ventilation over to 30 breaths for each aliquot, with small bursts timed only during the inspiratory cycles.

Between aliquot administration evaluate the respiratory status and reposition to the other side. 5-French feeding catheter inserted into the endotracheal tube as four equal aliquots of 0.75 mL/kg each.

During and after each aliquot is instilled, position the neonate in four different positions (i.e., prone, supine, right, and left lateral) to facilitate even distribution of INFASURF.

Remove the catheter between each of the instillations and resume mechanical ventilation for 0.5 to 2 minutes.

INFASURF administration, frequently monitor neonate oxygenation and ventilatory status.

For intratracheal administration only The recommended dose of INFASURF is 3 mL/kg body weight at birth.

Up to 3 doses of INFASURF can be administered.

Doses should not be given more frequently than every 12 hours.

Administration instructions

Side-port adapter into the endotracheal tube: two equal aliquots while ventilation is continued over to 30 breaths for each aliquot. 5-French feeding catheter inserted into the endotracheal tube: four equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5 to 2 minutes.

(calfactant) intratracheal suspension is an off-white suspension available in a sterile, rubber-stoppered glass single-dose vial packaged as one vial per carton: 105 mg/3 mL (35 mg/mL) (NDC 61938-456-03) 210 mg/6 mL (35 mg/mL) (NDC 61938-456-06) Refrigerate INFASURF (calfactant) intratracheal suspension at 2°C to 8°C (36°F to 46°F) and protect from light.

Must store the 105 mg/3 mL (35 mg/mL) vial upright.

Do not remove

INFASURF from the refrigerator for more than 24 hours.

Unopened, unused INFASURF vials that have reached room temperature within 24 hours can be refrigerated for future use; however, do not re-refrigerate INFASURF more than once.

Record the date and time on the carton when INFASURF is removed from the refrigerator.