Infasurf

Infasurf Mechanism of Action

Manufacturer:

ONY Biotech

Distributor:

Transmedic
Full Prescribing Info
Action
Pharmacology: 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. Infasurf restores surface activity to the lungs of these infants.
Activity: Infasurf adsorbs rapidly to the surface of the air:liquid interface and modifies surface tension similarly to natural lung surfactant. A minimum surface tension of ≤3 mN/m is produced in vitro by Infasurf as measured on a pulsating bubble surfactometer. Ex vivo, Infasurf restores the pressure volume mechanics and compliance of surfactant-deficient rat lungs. In vivo, Infasurf improves lung compliance, respiratory gas exchange, and survival in preterm lambs with profound surfactant deficiency.
Animal Metabolism: Infasurf is administered directly to the lung lumen surface, its site of action. No human studies of absorption, biotransformation, or excretion of Infasurf have been performed. The administration of Infasurf with radiolabeled phospholipids into the lungs of adult rabbits results in the persistence of 50% of radioactivity in the lung alveolar lining and 25% of radioactivity in the lung tissue 24 hrs later. Less than 5% of the radioactivity is found in other organs. In premature lambs with lethal surfactant deficiency, <30% of instilled Infasurf is present in the lung lining after 24 hrs.
Clinical Studies: The efficacy of Infasurf was demonstrated in 2 multiple-dose controlled clinical trials involving approximately 2000 infants treated with Infasurf (approximately phospholipid 100 mg/kg) or Exosurf Neonatal. In addition, 2 controlled trials of Infasurf versus Survanta, and 4 uncontrolled trials were conducted that involved approximately 15,500 patients treated with Infasurf.
Infasurf versus Exosurf Neonatal: Treatment Trial: A total of 1126 infants ≤72 hrs of age with RDS who required endotracheal intubation and had an a/A PO2 <0.22 were enrolled into a multiple-dose, randomized, double-blind treatment trial comparing Infasurf (3 mL/kg) and Exosurf Neonatal (5 mL/kg). Patients were given an initial dose and 1 repeat dose 12 hrs later if intubation was still required. The dose was instilled in 2 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.

Click on icon to see table/diagram/image

Prophylaxis Trial: A total of 853 infants <29 weeks gestation were enrolled into a multiple-dose, randomized, double-blind prophylaxis trial comparing Infasurf (3 mL/kg) and Exosurf Neonatal (5 mL/kg). The initial dose was administered within 30 min of birth. Repeat doses were administered at 12 hrs and 24 hrs 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 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 to day 28 or to discharge for all treated patients from this prophylaxis trial are shown in Table 2.

Click on icon to see table/diagram/image

Infasurf versus Survanta: Treatment Trial: A total of 662 infants with RDS who required endotracheal intubation and had an a/A PO2 <0.22 were enrolled into a multiple-dose, randomized, double-blind treatment trial comparing Infasurf (4 mL/kg of a formulation that contained phospholipids 25 mg/mL rather than the 35 mg/mL in the marketed formulation) and Survanta (4 mL/kg). Repeat doses were allowed ≥6 hours following the previous treatment (for up to 3 doses before 96 hrs of age) if the patient required ≥30% oxygen. The surfactant was given through a 5 French feeding catheter inserted into the endotracheal tube. The total dose was instilled in 4 equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5-2 min. Each of the aliquots was administered with the patient in 1 of 4 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 Infasurf and Survanta.
Prophylaxis Trial: A total of 457 infants ≤30 weeks gestation and <1251 grams birth weight were enrolled into a multiple-dose, randomized, double-blind trial comparing Infasurf (4 mL/kg of a formulation that phospholipids 25 mg/mL rather than the 35 mg/mL in the marketed formulation) and Survanta (4 mL/kg). The initial dose was administered within15 min of birth and repeat doses were allowed ≥6 hrs following the previous treatment (for up to 3 doses before 96 hrs of age) if the patient required ≥30% oxygen. The surfactant was given through a 5 French feeding catheter inserted into the endotracheal tube. The total dose was instilled in 4 equal aliquots with the catheter removed between each of the instillations and mechanical ventilation resumed for 0.5-2 min. Each of the aliquots was administered with the patient in 1 of 4 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 Infasurf-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 Infasurf 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 Infasurf 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 Infasurf. All controlled clinical trials with Infasurf demonstrated significant improvements in fraction of inspired oxygen (FiO2) and mean airway pressure (MAP) during the first 24-48 hrs following initiation of Infasurf therapy.
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