Revised: May 2012
AN: 02138/2011
SUMMARY OF PRODUCT CHARACTERISTICS
1.
NAME OF THE VETERINARY MEDICINAL PRODUCT
Cevaxel 50 mg/ml Powder and Solvent for Solution for Injection for Cattle and
Pigs.
2.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Powder vials contains:
Active substance:
Ceftiofur (as sodium) ............................................................. 1 g
Or
Ceftiofur (as sodium) ............................................................. 4 g
Excipients qs ...................................................................... 1 vial
One ml solvent contains
Water for injections ...............................................................1 ml
1 ml of reconstituted solution contains:
Active substance:
Ceftiofur (as sodium) ........................................................ 50 mg
For a full list of excipients, see section 6.1.
3.
PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
Powder: white to off white powder.
Solvent: clear and colourless liquid.
Reconstituted solution: clear brownish yellow to yellow coloured solution.
4.
CLINICAL PARTICULARS
4.1 Target species
Cattle and pigs.
4.2 Indications for use, specifying the target species
Cattle:
- For the treatment of bacterial respiratory disease associated with Pasteurella
multocida andMannheimia haemolyticasensitive to ceftiofur.
- For the treatment of cattle with interdigital necrobacillosis (foot rot) in which
Fusobacterium necrophorum and Bacteroides melaninogenicus
(Porphyromonas asaccharolytica) sensitive to ceftiofur are involved.
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Pigs:
- For the treatment of bacterial respiratory disease in which Pasteurella
multocida, Actinobacillus pleuropneumonia and Streptococcus suis sensitive to
ceftiofur are involved.
4.3 Contraindications
Do not use in animals previously found to be hypersensitive to ceftiofur or other
beta-lactamines.
Do not use in poultry (including eggs) due to risk of spread of antimicrobial
resistance to humans.
4.4 Special warnings for each target species
None known.
4.5 Special precautions for use
i.
Special precautions for use in animals
In case of repeated administrations, precautions must be taken, such as
injections on both sides of the neck.
Cevaxel selects for resistant strains such as bacteria carrying extended
spectrum betalactamases (ESBL) and may constitute a risk to human
health if these strains disseminate to humans e.g. via food. For this
reason, Cevaxel should be reserved for the treatment of clinical conditions
which have responded poorly, or are expected to respond poorly (refers to
very acute cases when treatment must be initiated without bacteriological
diagnosis) to first line treatment. Official, national and regional
antimicrobial policies should be taken into account when the product is
used. Increased use, including use of the product deviating from the
instructions given in the SPC, may increase the prevalence of such
resistance. Whenever possible, Cevaxel should only be used based on
susceptibility testing.
Cevaxel is intended for treatment of individual animals. Do not use for
disease prevention or as a part of heard health programmes. Treatment of
groups of animals should be strictly restricted to ongoing disease
outbreaks according to the approved conditions of use.
ii.
Special precautions to be taken by the person administering the
veterinary medicinal product to animals
Penicillins and cephalosporins may cause hypersensitivity following
injection, inhalation, ingestion or skin contact. Hypersensitivity to
penicillins may lead to cross sensitivity to cephalosporins and vice versa.
Allergic reactions to these substances may occasionally be serious.
People with known hypersensitivity should avoid contact with the
veterinary medicinal product.
In case of development of a skin rash following exposure, seek medical
advice.
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Swelling of the face, lips or eyes or difficulty in breathing are more
serious symptoms and require urgent medical attention.
Wash hands after use.
4.6 Adverse reactions (frequency and seriousness)
Fleeting symptoms of pain may be observed at the injection site.
In local tolerance studies conducted in cattle and swine, mild and transient
swelling were observed at the injection site in a few pigs six hours after
injection. No signs of swelling at the palpation of the injection site were
observed 24 hours after injection.
Hypersensitivity reactions can occasionally occur. In the case of an allergic
reaction, treatment should be stopped.
4.7 Use during pregnancy, lactation or lay
Ceftiofur showed no reproductive or developmental toxicity at therapeutic doses
in rats. The safety of the product has not been assessed in pregnant and
lactating cows and sows. Use only according to the benefit/risk assessment by
the responsible veterinarian.
4.8 Interaction with other medicinal products and other forms of interaction
The use of ceftiofur with other ß-lactam antibiotics or cephalosporins may
induce in rare occasion a potential immunological cross-reaction.
4.9 Amounts to be administered and administration route
Intramuscular use.
The solution for injection is to be reconstituted with 20 ml of water for injections
for the 1 g presentation and with 80 ml of water for injections for the 4 g
presentation.
Rapid addition of solvent will give best results.
Cattle:
- For respiratory disease
1 mg ceftiofur (as sodium) per kg bodyweight per day for 3 to 5 days, i.e. 1 ml
of reconstituted solution per 50 kg bodyweight per day for 3 to 5 days.
- For interdigital necrobacillosis (foul in the foot rot)
1 mg ceftiofur (as sodium) per kg bodyweight per day for 3 days, i.e. 1 ml of
reconstituted solution per 50 kg bodyweight per day for 3 days.
Pigs:
3 mg ceftiofur (as sodium) per kg bodyweight per day for 3 days, i.e. 1 ml of
reconstituted solution per 16 kg bodyweight per day for 3 days.
The dose should be given once daily at 24 hour intervals.
Do not administer more than 10 ml per injection site.
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4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary
In cattle, no signs of systemic toxicity are observed after important overdose by
parenteral administrations.
In pigs, the lowest toxicity of ceftiofur was demonstrated at 8 times the
therapeutic dose for 15 days by intramuscular use.
4.11 Withdrawal period(s)
Meat and offal:
- Cattle: 2 days.
- Pigs: 2 days.
Milk: zero days.
5.
PHARMACOLOGICAL PROPERTIES
Pharmacotherapeutic group: third generation cephalosporins.
ATCvet code: QJ01DD90.
5.1 Pharmacodynamic properties
Ceftiofur is a cephalosporin, resistant to beta-lactamase. Ceftiofur is active
against Gram-positive and Gram-negative bacteria.
Ceftiofur has bactericidal properties, acting by inhibition of the bacteria cell wall
synthesis.
Cell wall synthesis is dependent on enzymes that are called penicillin-binding
proteins (PBP's). Bacteria develop resistance to cephalosporins by four basic
mechanisms: 1) altering or acquiring penicillin binding proteins insensitive to an
otherwise effective b-lactam; 2) altering the permeability of the cell to b-lactams;
3) producing b-lactamases that cleave the b-lactam ring of the molecule, or 4)
active efflux.
Ceftiofur is active against the following pathogenic bacteria:
- Mannheimia haemolytica, Pasteurella multocida, Actinobacillus somnus
responsible for bovine respiratory diseases
- Fusobacterium necrophorum and Bacteroides melaninogenicus
(Porphyromonas asaccharolytica) responsible for bovine interdigital
necrobacillosis
- Pasteurella multocida, Streptococcus suis and Actinobacillus
pleuropneumonia responsible for porcine respiratory diseases
The following Minimum Inhibitory Concentrations (MIC) have been determined
for ceftiofur in European isolates (France, United Kingdom, Netherlands,
Denmark, Germany, Belgium, Italy, Czech Republic, Ireland, Poland and Spain)
collected from diseased animals between 2000 to 2007:
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Bacteria species
Origin
Cattle
Pasteurella
multocida
Pigs
Mannheimia
haemolytica
Cattle
Haemophilus
somnus
Cattle
Actinobacillus
pleuropneumoniae
Pigs
Streptococcus suis
Pigs
Fusobacterium
necrophorum
Cattle
Year
2004
to
2006
2004
to
2006
2004
to
2006
2005
to
2007
2003
/
2004
2004
to
2006
2000
to
2006
Nb of
strains
82
66
72
62
58
CMI of ceftiofur
(µg/mL)
Range CMI50 CMI90
0.0019
–
0.003 0.005
0.0625
0.0019
–
0.003 0.006
0.0156
0.0019
–
0.005 0.008
0.0156
0.0019
–
0.004 0.02
0.125
0.0039
–
0.006 0.02
0.0312
44
0.0312
0.2
– 0.5
0.3
27
0.015
– 16
0.2
0.1
The following ceftiofur breakpoints are used:  2 µg/mL (Susceptible), 4 µg/mL
(Intermediate) and 8 µg/mL (Resistant).
5.2 Pharmacokinetic particulars
After administration by intramuscular route, biodisponibility of ceftiofur is total in
cattle and in pigs.
Ceftiofur is quickly metabolised into desfuroylceftiofur for which the maximal
concentration is reached in 2.5 hours in cattle and in less than one hour in pigs.
Half-life of desfuroylceftiofur is of 11.2 hours in cattle and of 15.2 hours in pigs.
Repeated administrations induce no accumulation in cattle and pigs.
6.
PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Powder:
Potassium dihydrogen phosphate.
Sodium carbonate.
Solvent:
Water for injections.
6.2 Incompatibilities
None known.
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6.3 Shelf life
- Shelf life of the veterinary medicinal product as packaged for sale: 2 years
- Shelf life of the product after reconstitution according to directions:
7 days, stored in a refrigerator (2 °C – 8 °C)
12 hours, stored below 25°C
6.4 Special precautions for storage
Store in a refrigerator (2 °C – 8 °C).
Keep the vial in the outer carton in order to protect from light.
6.5 Nature and composition of immediate packaging
Nature of container:
Powder:
- Glass vial type I
- Bromobutyl rubber stopper.
Solvent:
- Glass vial type II
- Chlorobutyl rubber stopper.
Pack sizes:
Box containing 1 vial of Cevaxel 50 mg/ml 1 g and box containing a vial of 20 ml
solvent
Box containing 1 vial of Cevaxel 50 mg/ml, 4 g and box containing a vial of 80
ml solvent
Not all pack sizes may be marketed.
6.6 Special precautions for the disposal of unused veterinary medicinal
product or waste materials derived from the use of such products
Dispose of any unused product and empty containers in accordance with guidance
from your local waste regulation authority.
7.
MARKETING AUTHORISATION HOLDER
Ceva Animal Health Ltd
Unit 3, Anglo Office Park
White Lion Road
Amersham
Buckinghamshire
HP7 9FB
8.
MARKETING AUTHORISATION NUMBER(S)
Vm 15052/4036
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9.
DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date: 18 March 2009
10
DATE OF REVISION OF THE TEXT
Date: May 2012
Approved by:
06/12/12
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