rment, and presence of co-morbid conditions.
Renal impairment
The effect of renal impairment on the pharmacokinetics of bezlotoxumab was eva luated in patients with mild (eGFR 60 to < 90 mL/min/1.73 m2), moderate (eGFR 30 to < 60 mL/min/1.73 m2), or severe (eGFR 15 to < 30 mL/min/1.73 m2) renal impairment, or with end stage renal disease (eGFR < 15 mL/min/1.73 m2), as compared to patients demonstrating normal (eGFR ≥ 90 mL/min/1.73 m2) renal function. No clinically meaningful differences in the exposure of bezlotoxumab were found between patients with renal impairment and patients with normal renal function.
Hepatic impairment
The effect of hepatic impairment on the pharmacokinetics of bezlotoxumab was eva luated in patients with hepatic impairment (defined as having two or more of the following: [1] albumin ≤ 3.1 g/dL; [2] ALT ≥ 2X ULN; [3] total bilirubin ≥ 1.3X ULN; or [4] mild, moderate or severe liver disease as reported by the Charlson Co-morbidity Index), as compared to patients with normal hepatic function. No clinically meaningful differences in the exposure of bezlotoxumab were found between patients with hepatic impairment and patients with normal hepatic function.
Elderly
The effect of age on the pharmacokinetics of bezlotoxumab was eva luated in patients ranging from 18 to 100 years of age. No clinically meaningful differences in the exposure of bezlotoxumab were found between elderly patients 65 years and older and patients under 65 years of age.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of repeated dose toxicity. Genotoxicity and carcinogenic potential have not been eva luated.
Animal reproduction or developmental toxicity studies have not been conducted with bezlotoxumab. There were no notable effects in the male and female reproductive organs in mice based on repeat dose toxicity studies and no binding to reproductive tissues was observed in tissue cross-reactivity studies.
6. Pharmaceutical particulars
6.1 List of excipients
Citric acid monohydrate (E330)
Diethylenetriaminepentaacetic acid
Polysorbate 80 (E433)
Sodium chloride
Sodium citrate dihydrate (E331)
Water for injections
Sodium hydroxide (E524) (for pH adjustment).
6.2 Incompatibilities
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products except those mentioned in section 6.6.
6.3 Shelf life
Unopened vial: 3 years.
Solution for infusion: Chemical and physical in-use stability has been demonstrated for 24 hours at 2°C – 8°C or 16 hours at room temperature (at or below 25°C). These time limits include storage of the infusion solution in the IV bag through the duration of infusion. From a microbiological point of view, the product must be used immediately. If not used immediately, in-use storage times and conditions prior to use are the responsibility of the user and must not be longer than a total of 24 hours at 2°C – 8°C or 16 hours at room temperature (at or below 25°C).
6.4 Special precautions for storage
Store in a refrigerator 2 °C to 8 °C. Do not freeze. Keep vial in the outer carton in order to protect from light.
For storage conditions after dilution of the medicinal product, see section 6.3.
6.5 Nature and contents of container
Type I glass vial containing 40 mL solution, with a chlorobutyl stopper, and a flip-off cap seal.
Each carton conta |
