ministration and consequent plasma concentration accumulation, the rate of elimination approached zero-order kinetics. As such, half-life was 8 hours (range: 2-32 hours) after the first 30 mg dose and was 6 days (range: 1-14 days) after the last 30 mg dose. Steady-state concentrations were reached after about 6 weeks of dosing. No apparent difference in pharmacokinetics between males and females was observed nor was any apparent age effect observed.
5.3 Preclinical safety data
Preclinical eva luation of alemtuzumab in animals has been limited to the cynomolgus monkey because of the lack of expression of the CD52 antigen on non-primate species.
Lymphocytopenia was the most common treatment-related effect in this species. A slight cumulative effect on the degree of lymphocyte depletion was seen in repeated dose studies compared to single dose studies. Lymphocyte depletion was rapidly reversible after cessation of dosing. Reversible neutropenia was seen following daily intravenous or subcutaneous dosing for 30 days, but not following single doses or daily dosing for 14 days. Histopathology results from bone marrow samples revealed no remarkable changes attributable to treatment. Single intravenous doses of 10 and 30 mg/kg produced moderate to severe dose related hypotension accompanied by a slight tachycardia.
MabCampath Fab binding was observed in lymphoid tissues and the mononuclear phagocyte system. Significant Fab binding was also observed in the male reproductive tract (epididymis, sperm, seminal vesicle) and the skin.
No other findings, in the above toxicity studies, provide information of significant relevance to clinical use.
No short or long term animal studies have been conducted with MabCampath to assess carcinogenic and mutagenic potential.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Disodium edetate
Polysorbate 80
Potassium chloride
Potassium dihydrogen phosphate
Sodium chloride
Dibasic sodium phosphate
Water for injections
6.2 Incompatibilities
This medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
There are no known incompatibilities with other medicinal products. However, other medicinal products should not be added to the MabCampath infusion or simultaneously infused through the same intravenous line.
6.3 Shelf life
Unopen vial: 3 years.
Reconstituted solution: MabCampath contains no antimicrobial preservative. MabCampath should be used within 8 hours after dilution. Solutions may be stored at 15°C-30°C or refrigerated. This can only be accepted if preparation of the solution takes place under strictly aseptic conditions and the solution is protected from light.
6.4 Special precautions for storage
Store in a refrigerator (2°C-8°C).
Do not freeze.
Store in the original package in order to protect from light.
For storage conditions of the reconstituted medicinal product, see section 6.3.
6.5 Nature and contents of container
Clear type I glass vial, closed with a rubber stopper, containing 1 ml of concentrate.
Pack size: carton of 3 vials.
6.6 Special precautions for disposal and other handling
The vial contents should be inspected for particulate matter and discolouration prior to administration. If particulate matter is present or the concentrate is coloured, then the vial should not be used.
MabCampath contains no antimicrobial preservatives, therefore, it is recomme |
