Survanta (Beractant) Drug Information: Clinical Pharmacology

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May 27, 2012

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Survanta

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CLINICAL PHARMACOLOGY

Endogenous pulmonary surfactant lowers surface tension on alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting trans-pulmonary pressures. Deficiency of pulmonary surfactant causes Respiratory Distress Syndrome (RDS) in premature infants. SURVANTA (beractant) replenishes surfactant and restores surface activity to the lungs of these infants.

Activity

In vitro, SURVANTA (beractant) reproducibly lowers minimum surface tension to less than 8 dynes/cm as measured by the pulsating bubble surfactometer and Wilhelmy Surface Balance. In situ, SURVANTA (beractant) restores pulmonary compliance to excised rat lungs artificially made surfactant-deficient. In vivo, single SURVANTA (beractant) doses improve lung pressure-volume measurements, lung compliance, and oxygenation in premature rabbits and sheep.

Animal Metabolism

SURVANTA (beractant) is administered directly to the target organ, the lungs, where biophysical effects occur at the alveolar surface. In surfactant-deficient premature rabbits and lambs, alveolar clearance of radio-labelled lipid components of SURVANTA (beractant) is rapid. Most of the dose becomes lung-associated within hours of administration, and the lipids enter endogenous surfactant pathways of reutilization and recycling. In surfactant-sufficient adult animals, SURVANTA (beractant) clearance is more rapid than in premature and young animals. There is less reutilization and recycling of surfactant in adult animals.

Limited animal experiments have not found effects of SURVANTA (beractant) on endogenous surfactant metabolism. Precursor incorporation and subsequent secretion of saturated phosphatidylcholine in premature sheep are not changed by SURVANTA (beractant) treatments.

No information is available about the metabolic fate of the surfactant-associated proteins in SURVANTA (beractant) . The metabolic disposition in humans has not been studied.

Clinical Studies

Clinical effects of SURVANTA (beractant) were demonstrated in six single-dose and four multiple-dose randomized, multi-center, controlled clinical trials involving approximately 1700 infants. Three open trials, including a Treatment IND, involved more than 8500 infants. Each dose of SURVANTA (beractant) in all studies was 100 mg phospho-lipids/kg birth weight and was based on published experience with Surfactant TA, a lyophilized powder dosage form of SURVANTA (beractant) having the same composition.

Prevention Studies

Infants of 600-1250 g birth weight and 23 to 29 weeks estimated gestational age were enrolled in two multiple-dose studies. A dose of SURVANTA (beractant) was given within 15 minutes of birth to prevent the development of RDS. Up to three additional doses in the first 48 hours, as often as every 6 hours, were given if RDS subsequently developed and infants required mechanical ventilation with an FiO₂ ≥ 0.30. Results of the studies at 28 days of age are shown in Table 1.

TABLE 1

Study 1	SURVANTA	Control	P-Value
Number infants studied	119	124
Incidence of RDS (%)	27.6	63.5	<0.001
Death due to RDS (%)	2.5	19.5	<0.001
Death or BPD due to RDS (%)	48.7	52.8	0.536
Death due to any cause (%)	7.6	22.8	0.001
Air Leaks^a (%)	5.9	21.7	0.001
Pulmonary interstitial emphysema (%)	20.8	40	0.001
Study 2^b	SURVANTA	Control	P-Value
Number infants studied	91	96
Incidence of RDS (%)	28.6	48.3	0.007
Death due to RDS (%)	1.1	10.5	0.006
Death or BPD due to RDS (%)	27.5	44.2	0.018
Death due to any causec (%)	16.5	13.7	0.633
Air Leaks^a(%)	14.5	19.6	0.374
Pulmonary interstitial emphysema (%)	26.5	33.2	0.298
^aPneumothorax or pneumopericardium ^bStudy discontinued when Treatment IND initiated c ^cNo cause of death in the SURVANTA (beractant) group was significantly increased; the higher number of deaths in this group was due to the sum of all causes.

Rescue Studies

Infants of 600-1750 g birth weight with RDS requiring mechanical ventilation and an FiO₂ ≥ 0.40 were enrolled in two multiple-dose rescue studies. The initial dose of SURVANTA (beractant) was given after RDS developed and before 8 hours of age. Infants could receive up to three additional doses in the first 48 hours, as often as every 6 hours, if they required mechanical ventilation and an FiO₂ ≥ 0.30. Results of the studies at 28 days of age are shown in Table 2.

TABLE 2

Study 3^a	SURVANTA	Control	P-Value
Number infants studied	198	193
Death due to RDS (%)	11.6	18.1	0.071
Death or BPD due to RDS (%)	59.1	66.8	0.102
Death due to any cause (%)	21.7	26.4	0.285
Air Leaks^b(%)	11.8	29.5	<0.001
Pulmonary interstitial emphysema (%)	16.3	34.0	<0.001
Study 4	SURVANTA	Control	P-Value
Number infants studied	204	203
Death due to RDS (%)	6.4	22.3	<0.001
Death or BPD due to RDS (%)	43.6	63.4	<0.001
Death due to any cause (%)	15.2	28.2	0.001
Air Leaks^b (%)	11.2	2.2	0.005
Pulmonary interstitial emphysema (%)	20.8	44.4	<0.001
^a Study discontinued when Treatment IND initiated ^b Pneumothorax or pneumopericardium

Acute Clinical Effects

Marked improvements in oxygenation may occur within minutes of administration of SURVANTA (beractant) . 00All controlled clinical studies with SURVANTA (beractant) provided information regarding the acute effects of SURVANTA (beractant) on the arterial-alveolar oxygen ratio (a/APO₂), FiO₂, and mean airway pressure (MAP) during the first 48 to 72 hours of life. Significant improvements in these variables were sustained for 48-72 hours in SURVANTA (beractant) -treated infants in four single-dose and two multiple-dose rescue studies and in two multiple-dose prevention studies. In the single-dose prevention studies, the FiO₂ improved significantly.

Last reviewed on RxList: 9/9/2008
This monograph has been modified to include the generic and brand name in many instances.