talisation was 16 of 612 (2.6%) in the palivizumab group.
5.2 Pharmacokinetic properties
Lyophilised formulation of palivizumab
In studies in adult volunteers, palivizumab had a pharmacokinetic profile similar to a human IgG1 antibody with regard to volume of distribution (mean 57 ml/kg) and half-life (mean 18 days). In prophylactic studies in premature and bronchopulmonary dysplasia paediatric populations, the mean half-life of palivizumab was 20 days and monthly intramuscular doses of 15 mg/kg achieved mean 30 day trough serum active substance concentrations of approximately 40 μg/ml after the first injection, approximately 60 μg/ml after the second injection, approximately 70 μg/ml after the third injection and fourth injection. In the congenital heart disease study, monthly intramuscular doses of 15 mg/kg achieved mean 30 day trough serum active substance concentrations of approximately 55 µg/ml after the first injection and approximately 90 µg/ml after the fourth injection.
Among 139 children in the congenital heart disease study receiving palivizumab who had cardio-pulmonary bypass and for whom paired serum samples were available, the mean serum palivizumab concentration was approximately 100 μg/ml pre-cardiac bypass and declined to approximately 40 μg/ml after bypass.
Liquid formulation of palivizumab
The pharmacokinetics and safety of palivizumab liquid formulation and palivizumab lyophilised formulation, following 15 mg/kg intramuscular administration, were compared in a cross-over trial of 153 infants less than or equal to 6 months of age with a history of prematurity (less than or equal to 35 weeks gestational age). The results of this trial indicated that the trough serum concentrations of palivizumab were similar between the liquid formulation and the lyophilised formulation and bioequivalence of the liquid and the lyophilised formulation was demonstrated.
5.3 Preclinical safety data
Single dose toxicology studies have been conducted in cynomolgus monkeys (maximum dose 30 mg/kg), rabbits (maximum dose 50 mg/kg) and rats (maximum dose 840 mg/kg). No significant findings were observed.
Studies carried out in rodents gave no indication of enhancement of RSV replication, or RSV-induced pathology or generation of virus escape mutants in the presence of palivizumab under the chosen experimental conditions.
6. Pharmaceutical particulars
6.1 List of excipients
Histidine
Glycine
Water for injections
6.2 Incompatibilities
This medicinal product should not be mixed with other medicinal products.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in a refrigerator (2°C to 8°C).
Do not freeze.
Keep the vial in the carton in order to protect from light.
6.5 Nature and contents of container
Single-use vials: 3 ml capacity, clear, colourless type I glass vial with a chlorobutyl stopper and flip-off seal containing either 0.5 ml or 1 ml of solution for injection.
Pack size of 1.
6.6 Special precautions for disposal and other handling
Do not mix the palivizumab liquid and lyophilised formulations.
Do not dilute the product.
Do not shake the vial.
Both the 0.5 ml and 1 ml vials contain an overfill to allow the withdrawal of 50 mg or 100 mg, respectively.
To administer, remove the tab portion of the vial cap and clean the stopper with 70 % ethanol or equivalent. Insert the needle into the vial and withdraw into the syringe an appropriate volume of sol |
