0 % higher in females than in males.
Race
There were no differences in the clearance of tigecycline based on race.
Weight
Clearance, weight-normalised clearance, and AUC were not appreciably different among patients with different body weights, including those weighing 125 kg. AUC was 24 % lower in patients weighing 125 kg. No data is available for patients weighing 140 kg and more.
5.3 Preclinical safety data
In repeated dose toxicity studies in rats and dogs, lymphoid depletion/atrophy of lymph nodes, spleen and thymus, decreased erythrocytes, reticulocytes, leukocytes, and platelets, in association with bone marrow hypocellularity, and adverse renal and gastrointestinal effects have been seen with tigecycline at exposures of 8 and 10 times the human daily dose based on AUC in rats and dogs, respectively. These alterations were shown to be reversible after two weeks of dosing.
Bone discolouring was observed in rats which was not reversible after two weeks of dosing.
Results of animal studies indicate that tigecycline crosses the placenta and is found in foetal tissues. In reproduction toxicity studies, decreased foetal weights in rats and rabbits (with associated delays in ossification) and foetal loss in rabbits have been observed with tigecycline. Tigecycline was not teratogenic in the rat or rabbit. Tigecycline did not affect mating or fertility in rats at exposures up to 4.7 times the human daily dose based on AUC. In female rats, there were no compound-related effects on ovaries or oestrus cycles at exposures up to 4.7 times the human daily dose based on AUC.
Results from animal studies using 14C-labelled tigecycline indicate that tigecycline is excreted readily via the milk of lactating rats. Consistent with the limited oral bioavailability of tigecycline, there is little or no systemic exposure to tigecycline in the nursing pups as a result of exposure via maternal milk.
Lifetime studies in animals to eva luate the carcinogenic potential of tigecycline have not been performed, but short-term genotoxicity studies of tigecycline were negative.
Bolus intravenous administration of tigecycline has been associated with a histamine response in animal studies. These effects were observed at exposures of 14 and 3 times the human daily dose based on the AUC in rats and dogs respectively.
No evidence of photosensitivity was observed in rats following administration of tigecycline.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose monohydrate
Hydrochloric acid, sodium hydroxide (for pH adjustment)
6.2 Incompatibilities
The following active substances should not be administered simultaneously through the same Y-site as Tygacil: Amphotericin B, amphotericin B lipid complex, diazepam esomeprazole, omeprazole and intravenous solutions that could result in an increase of pH above 7.
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6.3 Shelf life
2 years.
Once reconstituted and diluted in the bag or other suitable infusion container (e.g. glass bottle), tigecycline should be used immediately.
6.4 Special precautions for storage
Store below 25°C.
For storage conditions of the reconstituted product see section 6.3.
6.5 Nature and contents of container
5 ml Type 1 clear glass vials fitted with grey butyl rubber stoppers and snap-off aluminium crimp seals. Tygacil is distributed in a ten vial tray pack.
6.6 |
