NEODOSE

INDICATIONS

• Prevention of respiratory distress syndrome (RDS): in premature infants: Routine continuous positive airway pressure (CPAP) is considered superior to prophylactic surfactant therapy. It is strongly recommended that CPAP immediately after birth with subsequent selective surfactant administration be considered as an alternative to routine intubation with prophylactic or early surfactant administration in preterm infants. Lucinactant reduced the occurrence of RDS among premature neonates (32 weeks gestational age or younger) at high risk for developing RDS more effectively than colfosceril palmitate (47.2% vs 39.1%; p=0.005) and also reduced the number of RDS-related deaths compared with colfosceril palmitate and beractant treatment groups (4.7% vs 9.4% (p=0.002) vs 10.5% (p=0.001), respectively) in a multicenter, randomized comparison trial (n=1294) . Lucinactant and poractant alfa were similar in terms of efficacy in premature infants (24 to 28 weeks gestation) at high risk for developing RDS in a multicenter randomized noninferiority trial (n=252). The rate of survival without BPD at 28 days (primary outcome) was 37.8% vs 33.1%, respectively. In a one-year follow-up of these 2 studies (n=1546), lucinactant had similar efficacy to the animal-derived and synthetic exogenous surfactant products for decreasing mortality and morbidity rates in premature neonates at risk for RDS. Neurologic function was similar in infants who received lucinactant and those that received other surfactants.
• Meconium aspiration syndrome: Infants (gestational age, 35 weeks or more) treated with lucinactant lavage within 72 hours of birth, compared with no lavage, experienced more rapid and more sustained improvement in oxygenation and shorter ventilation times (median 4.6 vs 7.6 days); however, these outcomes were not statistically significant in an open-label, randomized trial (n=22). Lucinactant (2.5 mg/mL) 8 mL/kg per lung was instilled over approximately 20 seconds followed by suctioning after 5 ventilator breaths. This was repeated followed by a third treatment of lucinactant (10 mg/mL) 8 mL/kg per lung and suctioned at the discretion of the physician.

FDA APPROVED INDICATION

Lucinactant intratracheal suspension is indicated for the prevention of respiratory distress syndrome (RDS) in premature infants at high risk for RDS.

CONTRAINDICATIONS / PRECAUTIONS

Bradycardia, hypoxemia, airway obstruction, and reflux of drug into the endotracheal tube (ETT) may occur; if reactions occur, interrupt treatment until resolved. Suctioning of the ETT or reintubation may be necessary for persistent airway obstruction. Respiratory status may change rapidly with administration; monitoring recommended, oxygen and ventilatory support modifications may be required

ADVERSE EFFECTS

Bradycardia, hypoxemia, airway obstruction, and reflux of drug into the endotracheal tube are common adverse events. In clinical trials, rates of bradycardia and oxygen desaturation have ranged from 3% to 23% and 8% to 58%, respectively. Endotracheal tube reflux occurred at an incidence of 18% to 27% . The incidence of pulmonary hemorrhage, pulmonary leaks, patent ductus arteriosus, sepsis, intraventricular hemorrhage, necrotizing enterocolitis (grade 2 or higher), retinopathy of prematurity (grade 3 or 4), and periventricular leukomalacia was not significantly different between lucinactant and the comparators in clinical trials. Gagging (20%) and coughing (27%) occurred in infants (gestational age, 35 weeks or more) treated with lucinactant lavage within 72 hours of birth. Oxygen desaturation, probably related to lavage therapy, occurred in 1 infant with herpes simplex virus infection.

ADMINISTRATION

Preparation: Prior to administration, warm the lucinactant intratracheal suspension vial for 15 minutes in a preheated dry block heater set at 44 degrees C (111 degrees F). Remove the vial from the heater and shake vigorously until the suspension is uniform and free-flowing. After withdrawn into a syringe for administration, the temperature of the suspension will be about 37 degrees C (99 degrees F). Warmed vials should not be refrigerated after warming but may be stored in the carton at room temperature for no more than 2 hours. Administration: For intratracheal administration only. Using a 16- or 18-gauge needle, slowly draw up the dose of warmed and vigorously shaken lucinactant intratracheal suspension into an appropriately sized syringe. Before administration of the suspension, ensure patency and proper placement of the endotracheal tube. The endotracheal tube may be suctioned before lucinactant administration if necessary. Allow the infant to stabilize before administration. The infant should be positioned in the right lateral decubitus position with head and thorax at a 30 degree upward inclined position. A 5-French end-hole catheter with the syringe of lucinactant attached should be threaded through a Bodai valve (or equivalent device) to allow maintenance of positive end-expiratory pressure. The tip of the catheter should be advanced into the endotracheal tube and positioned so that it is slightly distal to the end of the endotracheal tube. The lucinactant dose should be delivered in 4 equal aliquots (each aliquot equal to one-fourth of the total dose). Administer the first aliquot while continuing positive pressure mechanical ventilation and maintaining a positive end-expiratory pressure of 4 to 5 cm Hg2O. Adjust ventilator settings as necessary to maintain appropriate oxygenation and ventilation until the infant is stable (oxygen saturation of at least 90% and heart rate greater than 120 beats/minute). Maintain adequate positive pressure ventilation, move the infant to the left decubitus position, and repeat the administration procedure for the second aliquot. Pause between administration of each aliquot to evaluate the infant’s respiratory status. Move the infant to the right decubitus position for administration of the third aliquot, and to the left decubitus position for administration of the fourth aliquot. Remove the catheter after administration of the fourth aliquot, and resume usual ventilator management. Keep the head of the infant’s bed elevated at least 10 degrees for at least 1 to 2 hours. Unless the infant develops significant airway obstruction, do not suction the infant for the first hour after dosing.

MONITORING

Monitor oxygen saturation and ventilatory support frequently and modify according to changes in respiratory status.