Survanta Adverse Reactions

Clinical Trials: Mechanically Ventilated Patients: The most commonly reported adverse experiences were associated with the dosing procedure.
In the multiple-dose controlled clinical trials, each dose of SURVANTA was divided into four quarter- doses. Each quarter dose was instilled through a catheter inserted into the endotracheal tube by briefly disconnecting the endotracheal tube from the ventilator. Transient bradycardia occurred with 11.9% of doses. Oxygen desaturation occurred with 9.8% of doses.
Other reactions during the dosing procedure occurred with fewer than 1% of doses and included endotracheal tube reflux, pallor, vasoconstriction, hypotension, endotracheal tube blockage, hypertension, hypocarbia, hypercarbia, and apnea. No deaths occurred during the dosing procedure, and all reactions resolved with symptomatic treatment.
A clinical study compared the previously noted quarter-dose administration regimen to the administration of two half-doses with interrupted ventilation as described previously and the administration of two half-doses accomplished by passing the catheter through a neonatal suction valve in the endotracheal tube, with uninterrupted ventilation. With the first dose, there was significantly less endotracheal tube reflux observed in the group with the quarter-dose regimen (p=.007) than in the group with uninterrupted ventilation. With the first dose there was significantly less oxygen desaturation in the group with uninterrupted ventilation (p=.008) than in the other group receiving two half-doses. There were no differences in these events after later doses and no differences in heart rate after any doses (see General Dosing Procedures under Dosage & Administration).
The occurrence of concurrent illnesses common in premature infants was evaluated in the controlled trials. The rates in all controlled studies are in Table 3. (See Table 3.)

Click on icon to see table/diagram/image

When all controlled studies were pooled, there was no difference in intracranial hemorrhage. However, in one of the single-dose rescue studies and one of the multiple-dose prevention studies, the rate of intracranial hemorrhage was significantly higher in SURVANTA patients than control patients (63.3% versus 30.8%, P = 0.001; and 48.8% versus 34.2%, P = 0.047, respectively). The rate in a Treatment IND involving approximately 8100 infants was lower than in the controlled trials.
In the controlled clinical trials, there was no effect of SURVANTA on results of common laboratory tests: white blood cell count and serum sodium, potassium, bilirubin, and creatinine.
More than 4300 pre-treatment and post-treatment serum samples from approximately 1500 patients were tested by Western Blot immunoassay for antibodies to surfactant-associated proteins SP-B and SP-C. No IgG or IgM antibodies were detected.
Several other complications are known to occur in premature infants. The following conditions were reported in the controlled clinical studies. The rates of the complications were not different in treated and control infants, and none of the complications were attributed to SURVANTA.
Blood and lymphatic system disorders: Coagulopathy, thrombocytopenia, disseminated intravascular coagulation.
Endocrine disorders: Adrenal hemorrhage, inappropriate ADH secretion.
Metabolism and nutrition disorders: Hyperphosphatemia, feeding intolerance.
Nervous system disorders: Seizures.
Cardiac disorders: Tachycardia, ventricular tachycardia, cardiac failure, cardio-respiratory arrest, increased apical pulse, persistent fetal circulation, total anomalous pulmonary venous return.
Vascular disorders: Hypotension, hypertension, aortic thrombosis, air embolism.
Respiratory, thoracic and mediastinal disorders: Lung consolidation, blood from the endotracheal tube, deterioration after weaning, respiratory decompensation, subglottic stenosis, paralyzed diaphragm, respiratory failure.
Gastrointestinal disorders: Abdominal distension, gastrointestinal hemorrhage, intestinal perforations, volvulus, bowel infarct, stress ulcer, inguinal hernia.
Hepatobiliary disorders: Hepatic failure.
Renal and urinary disorders: Renal failure, haematuria.
General disorders and administration site conditions: Fever, deterioration.
Post Marketing Experience: To date, no long-term complications or sequelae of SURVANTA therapy have been found.
Single-Dose Studies: Six-month adjusted-age follow-up evaluations of 232 infants (115 treated) demonstrated no clinically important differences between treatment groups in pulmonary and neurologic sequelae, incidence or severity of retinopathy of prematurity, rehospitalizations, growth, or allergic manifestations.
Multiple-Dose Studies: Six-month adjusted-age follow-up evaluations have been completed in 631 (345 treated) of 916 surviving infants. There was significantly less cerebral palsy and need for supplemental oxygen in SURVANTA infants than controls. Wheezing at the time of examination was more frequent among SURVANTA infants, although there was no difference in bronchodilator therapy.
Final twelve-month follow-up data from the multiple-dose studies are available from 521 (272 treated) of 909 surviving infants. There was significantly less wheezing in SURVANTA infants than controls in contrast to the six-month results. There was no difference in the incidence of cerebral palsy at twelve months.
Twenty-four month adjusted age evaluations were completed in 429 (226 treated) of 906 surviving infants. There were significantly fewer SURVANTA infants with rhonchi, wheezing, and tachypnea at the time of examination. No other differences were found.
INSURE and LISA Techniques: Safety results with the INSURE and LISA techniques were comparable to those of the control groups, although bradycardia and hypoxemia were reported more frequently in some cases with LISA.