ical trials indicated that the clearance of enfuvirtide is 20% lower in females than males irrespective of weight and is increased with increased body weight irrespective of gender (20% higher in a 100 kg and 20% lower in a 40 kg body weight patient relative to a 70 kg reference patient). However, these changes are not clinically significant and no dose adjustment is required.
Race: Analysis of plasma concentration data from patients in clinical trials indicated that the clearance of enfuvirtide was not different in Afro-Americans compared to Caucasians. Other PK studies suggest no difference between Asians and Caucasians after adjusting exposure for body weight.
Paediatric population: The pharmacokinetics of enfuvirtide have been studied in 37 paediatric patients. A dose of 2 mg/kg bid (maximum 90 mg bid) provided enfuvirtide plasma concentrations similar to those obtained in adult patients receiving 90 mg bid dosage. In 25 paediatric patients ranging in age from 5 to 16 years and receiving the 2 mg/kg bid dose into the upper arm, anterior thigh or abdomen, the mean steady-state AUC was 54.3 ± 23.5 μg*h/ml, Cmax was 6.14 ± 2.48 μg/ml, and Ctrough was 2.93 ± 1.55 μg/ml.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity and late embryonal development. Long-term animal carcinogenicity studies have not been performed.
Studies in guinea pigs indicated a potential for enfuvirtide to produce delayed contact hypersensitivity. In a rat model on the resistance to influenza infection, an impairment of IFN-γ production was observed. The resistance to influenza and streptococcal infection in rats was only weakly compromised. The clinical relevance of these findings is unknown.
6. Pharmaceutical particulars
6.1 List of excipients
Powder
Sodium carbonate
Mannitol
Sodium hydroxide
Hydrochloric Acid
Solvent
Water for Injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6.3 Shelf life
Powder
4 years
Solvent
4 years
Shelf life after reconstitution
After reconstitution: Store in a refrigerator (2°C – 8°C).
Chemical and physical in-use stability has been demonstrated for 48 hours at 5°C when protected from light.
From a microbiological point of view, the 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 reconstitution has taken place in controlled and validated aseptic conditions.
6.4 Special precautions for storage
Powder
Keep the vial in the outer carton in order to protect from light. For storage conditions after reconstitution of the medicinal product, see section 6.3
Solvent
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
Powder
Vial: 3 ml vial, colourless glass type 1
Closure: lyophilisate stopper, rubber (latex free)
Seal: aluminium seal with flip-off cap
Solvent
Vial: 2 ml vial, colourless glass type 1
Closure: rubber stopper (latex free)
Seal: aluminium seal with flip-off cap
Pack sizes
60 vials powder for |
