ted pharmacokinetic parameters of sugammadex by age group and renal function based on compartmental modelling (using three compartments) are presented below:
Mean and coefficient of variation (CV in %) are presented.
Gender:
No gender differences were observed.
Race:
In a study in healthy Japanese and Caucasian subjects no clinically relevant differences in pharmacokinetic parameters were observed. Limited data does not indicate differences in pharmacokinetic parameters in Black or African Americans.
Body weight:
Population pharmacokinetic analysis of adult and elderly patients showed no clinically relevant relationship of clearance and volume of distribution with body weight.
5.3 Preclinical safety data
Preclinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity potential, and toxicity to reproduction, local tolerance or compatibility with blood.
Sugammadex is rapidly cleared from most organs; however some retention of compound occurs in bone and teeth in the rat. The most likely component involved in the reversible binding is hydroxy apatite, the inorganic matrix in these tissues. Preclinical studies in young adult and mature rats have shown that this retention does not adversely affect tooth colour or bone quality, structure, turnover and development. In juvenile rats whitish discoloration was observed in the incisors and disturbance of enamel formation was observed upon repeated dosing, however at exposure levels of 48-480 times the clinical exposure at 4 mg/kg.
6. Pharmaceutical particulars
6.1 List of excipients
Hydrochloric acid 3.7% (to adjust pH) and/or sodium hydroxide (to adjust pH)
Water for injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
Physical incompatibility has been reported with verapamil, ondansetron and ranitidine
6.3 Shelf life
3 years
After first opening and dilution chemical and physical in-use stability has been demonstrated for 48 hours at 2°C to 25°C. From a microbiological point of view, the diluted product should be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and would normally not be longer than 24 hours at 2°C to 8°C, unless dilution has taken place in controlled and validated aseptic conditions.
6.4 Special precautions for storage
Store below 30°C.
Do not freeze.
Keep the vial in the outer carton in order to protect from light.
For storage conditions of the diluted medicinal product, see section 6.3.
6.5 Nature and contents of container
2 ml or 5 ml of solution in type I glass vial closed with chlorobutyl rubber stoppers with aluminium crimp-cap and flip-off seal.
Pack sizes: 10 vials of 2 ml or 10 vials of 5 ml.
Not all pack-sizes may be marketed.
6.6 Special precautions for disposal and other handling
If Bridion is administered via the same infusion line that is also used for other medicinal products, it is important that the infusion line is adequately flushed (e.g. with sodium chloride 9 mg/ml (0.9%solution)) between administration of Bridion and medicinal products for which incompatibility with Bridion has been demonstrated or for which compatibility with Bridion has not been established.
Sugammadex can be injected into the intravenous line of a running infusion with the following |
