"The U.S. Food and Drug Administration today approved Dotarem (gadoterate meglumine) for use in magnetic resonance imaging (MRI) of the brain, spine and associated tissues of patients ages 2 years and older.
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Endogenous pulmonary surfactant lowers surface tension on alveolar surfaces during respiration and stabilizes the alveoli against collapse at resting transpulmonary pressures. Deficiency of pulmonary surfactant causes Respiratory Distress Syndrome (RDS) in premature infants. SURVANTA replenishes surfactant and restores surface activity to the lungs of these infants.
In vitro, SURVANTA 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 restores pulmonary compliance to excised rat lungs artificially made surfactantdeficient. In vivo, single SURVANTA doses improve lung pressure-volume measurements, lung compliance, and oxygenation in premature rabbits and sheep.
SURVANTA 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 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 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 on endogenous surfactant metabolism. Precursor incorporation and subsequent secretion of saturated phosphatidylcholine in premature sheep are not changed by SURVANTA treatments.
No information is available about the metabolic fate of the surfactant-associated proteins in SURVANTA. The metabolic disposition in humans has not been studied.
Clinical effects of SURVANTA 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 in all studies was 100 mg phospholipids/kg birth weight and was based on published experience with Surfactant TA, a lyophilized powder dosage form of SURVANTA having the same composition.
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 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.
|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 Leaksa (%)||5.9||21.7||0.001|
|Pulmonary interstitial emphysema (%)||20.8||40.0||0.001|
|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
cNo cause of death in the SURVANTA group was significantly increased; the higher number of deaths in this group was due to the sum of all causes.
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 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.
|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 Leaksb (%)||11.8||29.5||< 0.001|
|Pulmonary interstitial emphysema (%)||16.3||34.0||< 0.001|
|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 Leaksb (%)||11.2||22.2||0.005|
|Pulmonary interstitial emphysema (%)||20.8||44.4||< 0.001|
|aStudy discontinued when Treatment IND
bPneumothorax or pneumopericardium
Acute Clinical Effects
Marked improvements in oxygenation may occur within minutes of administration of SURVANTA.
All controlled clinical studies with SURVANTA provided information regarding the acute effects of SURVANTA 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-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: 4/25/2013
This monograph has been modified to include the generic and brand name in many instances.
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