"The U.S. Food and Drug Administration today approved Breo Ellipta (fluticasone furoate and vilanterol inhalation powder) for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary di"...
Mechanism of Action
Endogenous pulmonary surfactant lowers surface tension at the air-liquid interface of the alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting transpulmonary pressures. A deficiency of pulmonary surfactant in premature infants results in RDS. SURFAXIN compensates for the deficiency of surfactant and restores surface activity to the lungs of these infants.
Lucinactant lowers minimum surface tension to ≤ 6 dynes per cm, as assessed by the pulsating bubble surfactometer.
Lucinactant improves lung compliance and respiratory gas exchange in premature fetal rabbits, lambs and non-human primates with RDS under experimental conditions with controlled airflow and oxygen pressure. The clinical relevance of these animal findings to humans is unknown.
SURFAXIN is administered directly to the lung, where biophysical effects occur at the terminal airways and alveolar surface. No human pharmacokinetic studies have been performed to characterize the absorption, distribution, metabolism, or elimination of SURFAXIN.
Prevention of Neonatal Respiratory Distress Syndrome
The efficacy and safety of SURFAXIN for the prevention of RDS in premature infants was demonstrated in a single randomized, double-blind, multicenter, active-controlled, multi-dose study involving 1294 premature infants (Study 1). This study included 646 males and 648 females who weighed between 600 g and 1250 g at birth and were 32 weeks or less in gestational age. Seventy-eight percent of the infants were white, 1% black, and 21% classified as other. Study participants were from Europe and Latin America. Within the first 30 minutes after birth, infants were randomized to receive 1 of 3 surfactants, SURFAXIN (N = 527), colfosceril palmitate (N = 509), or beractant (N = 258). SURFAXIN was administered at a dose of 5.8 mL per kg, colfosceril palmitate at a dose of 5.0 mL per kg, and beractant at a dose of 4.0 mL per kg. Infants in the SURFAXIN and beractant groups could be given up to 3 additional doses between 6 and 24 hours of birth, as often as every 6 hours, if they subsequently developed RDS and required mechanical ventilation with an FiO2 ≥ 0.30 and a mean airway pressure (MAP) ≥ 6 cm H2O. Infants in the colfosceril palmitate group could receive up to 2 additional doses at least 12 hours apart if they met the retreatment criteria. Some infants received sham air to maintain blinding of the study. All doses were calculated based on birth weight. Infants were followed through 12-months corrected age.
Co-primary endpoints were the incidence of RDS (defined as having a chest x-ray consistent with RDS and an FiO2 ≥ 0.30) at 24 hours and RDS-related mortality at 14 days. The primary comparison of interest was between SURFAXIN and colfosceril palmitate with the intent of demonstrating superiority. Beractant served as an additional active comparator. Compared to colfosceril palmitate, SURFAXIN demonstrated a statistically significant improvement in both RDS at 24 hours and RDS-related mortality through Day 14. Results for the primary endpoint comparisons and other relevant endpoints are shown in Table 4.
Table 4: Results from a Controlled Prophylaxis Study in
Preterm Infants (Study 1)
(N = 527)
(N = 509)
|P-value SURFAXIN vs. Colfosceril palmitate|
|RDS at 24 hours||206 (39)||240 (47)||< 0.01|
|RDS-related mortality through Day 14||25 (5)||48 (9)||< 0.01|
|Non-RDS-related mortality through Day 14||59 (11)||37 (7)||0.04|
|Sepsis-related mortality through Day 14||21 (4)||17 (3)||0.70|
|Through Day 28||100 (19)||108 (21)||0.23|
|Through 36-weeks PCA||111 (21)||121 (24)||0.18|
|Pulmonary air leak through Day 7, all types||82 (16)||93 (18)||0.15|
|At Day 28||304 (58)||316 (62)||0.06|
|At 36-weeks PCA||210 (40)||227 (45)||0.05|
A second multicenter, double-blind, active-controlled study involving 252 premature infants was also conducted (Study 2). The study included 126 males and 126 females who weighed between 600 g and 1250 g at birth with a gestational age ≥ 24 weeks but < 29 weeks. Eighty-three percent of the infants were white and 5% black. Study participants were from North America and Europe. Within the first 30 minutes after birth, infants were randomized to receive 1 of 2 surfactants, SURFAXIN (N = 124) or poractant alfa (N = 128). SURFAXIN was administered at a dose of 5.8 mL per kg and poractant alfa was dosed at 2.2 mL per kg for the first dose and 1.25 mL per kg for subsequent doses. Infants in each group could be given up to 2 additional doses during the first 48 hours of life if they continued to require mechanical ventilation with an FiO2 ≥ 0.30 to maintain arterial PaO2 ≥ 50 mmHg or an oxygen saturation ≥ 90% and a chest radiograph consistent with RDS. The primary endpoint was the incidence of being alive without bronchopulmonary dysplasia at Day 28 of life. Bronchopulmonary dysplasia was defined as a requirement for mechanical ventilation or use of supplemental oxygen in order to maintain oxygen saturation ≥ 90%. The study was designed with the intent of demonstrating non-inferiority between SURFAXIN and poractant alfa with a planned sample size of 248 infants per treatment group. However, the basis of the non-inferiority margin could not be justified; the study was also terminated prematurely. As such, Study 2 can only be used to support the safety of SURFAXIN relevant to another surfactant product.
There is no controlled experience with the use of SURFAXIN in conjunction with experimental therapies for RDS (e.g., high-frequency ventilation or extracorporeal membrane oxygenation).
Last reviewed on RxList: 3/16/2012
This monograph has been modified to include the generic and brand name in many instances.
Additional Surfaxin Information
Report Problems to the Food and Drug Administration
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.
Find out what women really need.