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Date: Friday, July 1, 2022 16:52

Release 3.215
Draxxin Plus 100 mg/ml + 120 mg/ml solution for injection for cattle
 
Species: Cattle
Therapeutic indication: Pharmaceuticals: Antimicrobials: Injections
Active ingredient: Ketoprofen, Tulathromycin
Product:Draxxin Plus 100 mg/ml + 120 mg/ml solution for injection for cattle
Product index: Draxxin Plus
Cattle - meat: 50 days
Withdrawal notes: Not authorised for use in cattle producing milk for human consumption.
Presentation
A clear colourless to yellow / green-yellow solution for injection containing tulathromycin 100 mg/ml and ketoprofen 120 mg/ml. Also contains the excipient monothioglycerol 5 mg/ml.
Uses
For the treatment of bovine respiratory disease (BRD) associated with pyrexia due to Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis susceptible to tulathromycin.
Dosage and administration
Subcutaneous use.
A single subcutaneous injection of 2.5 mg tulathromycin/kg bodyweight and 3 mg ketoprofen/kg bodyweight (equivalent to 1 ml/40 kg bodyweight). For treatment of cattle over 400 kg bodyweight, divide the dose so that no more than 10 ml are injected at one site.
To ensure correct dosage bodyweight should be determined as accurately as possible to avoid underdosing.
For any respiratory disease, it is recommended to treat animals in the early stages of the disease and to evaluate the response to treatment within 48 hours after injection. If clinical signs of respiratory disease persist or increase, or if relapse occurs, treatment should be changed, using another antibiotic, and continued until clinical signs have resolved.
If there is persistent elevated body temperature 24 hours after treatment initiation, the responsible veterinarian must evaluate the necessity of further anti-pyretic treatment. The stopper may be safely punctured up to 20 times. When treating groups of animals in one run, use a draw-off needle that has been placed in the vial stopper or an automatic syringe to avoid excessive broaching of the stopper. The draw-off needle should be removed after treatment.
Contra-indications, warnings, etc
Do not use in cases of hypersensitivity to the active substances or to any of the excipients.
Do not use simultaneously with other macrolides or lincosamides.
Do not administer to animals suffering from gastrointestinal lesions, haemorrhagic diathesis, blood dyscrasia or hepatic, renal or cardiac conditions.
Do not use concurrently with other diuretics, nephrotoxic veterinary medicinal products or anticoagulants.
Cross resistance occurs with other macrolides. Do not administer simultaneously with antimicrobials with a similar mode of action such as other macrolides or lincosamides.
This product does not contain any antimicrobial preservative.
Use of the product should be based on identification and susceptibility testing of the target pathogen(s). If this is not possible, therapy should be based on epidemiological information and knowledge of susceptibility of the target bacteria at farm level, or at local/regional level.
Use of the product should be in accordance with official, national and regional antimicrobial policies.
Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to tulathromycin and may decrease the effectiveness of treatment with other macrolides, lincosamides and group B streptogramins due to the potential for cross resistance (MLSB resistance).
Since many NSAIDs possess the potential to induce gastrointestinal ulceration, especially in aged cattle and young calves, concomitant use of the product with other anti-inflammatory drugs (NSAIDs) or steroidal anti-inflammatory drugs (e.g., corticosteroids) should be avoided within the first 24 hours of treatment. Afterwards concurrent treatment with NSAIDs and steroidal anti-inflammatory drugs should be closely monitored. The use of the product (that contains ketoprofen) in aged animals or animals less than 6 weeks should be based on a benefit/risk assessment of the responsible veterinarian.
Avoid use in dehydrated, hypovolaemic or hypotensive animals which require parenteral rehydration, as there may be a potential risk of renal toxicity.
Intra-arterial and intra-venous injection should be avoided.
Subcutaneous administration very commonly causes transient pain reactions and local swellings at the injection site that can persist for up to 32 days. Pathomorphological injection site reactions (including reversible changes of congestion, oedema, fibrosis and haemorrhage) are present for approximately 32 days after injection.
In common with all NSAIDs, due to their action of inhibition of prostaglandin synthesis, there can be the possibility in certain individuals of gastric or renal intolerance.
The frequency of adverse reactions is defined using the following convention:
- very common (more than 1 in 10 animals treated displaying adverse reaction(s))
- common (more than 1 but less than 10 animals in 100 animals treated)
- uncommon (more than 1 but less than 10 animals in 1,000 animals treated)
- rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports).
At dosages of 3 and 5 times the recommended dose transient signs of injection site pain and/or swelling which in some instances lasted until day 32. Additionally, transient signs attributed to injection site discomfort (pain) were observed and included restlessness, head-shaking, pawing the ground, and brief decrease in feed intake. Microscopic mucosal erosions of the pylorus of the abomasum were observed at 3 and 5 times the recommended dose. Repeated administration can result in gastric toxicity. Mild myocardial degeneration has been observed in cattle receiving 5 to 6 times the recommended dose.
Laboratory studies with tulathromycin in rats and rabbits have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. Studies with ketoprofen in laboratory species (rats, mice and rabbits) have not produced any evidence of teratogenic effects, but effects on fertility, maternal toxicity and embryotoxicity has been observed. There are known adverse class-effects of NSAIDS and other prostaglandin inhibitors on pregnancy and/or embryofoetal development. The safety of tulathromycin and ketoprofen combination in the target species has not been established during pregnancy and lactation. Use only according to the benefit/risk assessment by the responsible veterinarian.
Withdrawal periods
Meat and offal: 50 days
Not authorised for use in cattle producing milk for human consumption.
Do not use in pregnant animals, which are intended to produce milk for human consumption, within 2 months of expected parturition.
Operator warnings
This veterinary medicinal product may cause hypersensitivity (allergy). People with known hypersensitivity to tulathromycin, ketoprofen, or to non-steroidal anti-inflammatory drugs (NSAIDs) should avoid contact with the veterinary medicinal product. In case of accidental spillage onto skin, wash the skin immediately with soap and water.
This veterinary medicinal product may cause adverse effects after dermal exposure and self-injection. Take care to avoid skin contact and accidental self-injection. In case of accidental self-injection, seek medical advice immediately and show the package leaflet or the label to the physician.
NSAIDs, such as ketoprofen, may affect fertility and be harmful for the unborn child. Pregnant women, women intending to conceive and men planning to have children should use extreme caution while handling this veterinary medicinal product.
This veterinary medicinal product is irritating to eyes. Avoid contact with the eyes. In case of accidental eye exposure, flush the eyes immediately with clean water. If irritation persists, seek medical advice and show the package leaflet to the physician.
Wash hands after use.
Pharmaceutical precautions
Do not freeze.
In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.
Shelf life after first opening the immediate packaging: 56 days.
Keep out of the sight and reach of children.
Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. For animal treatment only.
Legal category
Legal category: POM-V
Packaging quantities
Amber glass vials containing 50 ml, 100 ml or 250 ml. Not all pack sizes may be marketed.
Marketing Authorisation Holder (if different from distributor)
Not applicable.
Further information
In addition to its antimicrobial properties, tulathromycin demonstrates immune-modulating and anti-inflammatory actions in experimental studies. In bovine polymorphonuclear cells (PMNs; neutrophils), tulathromycin promotes apoptosis (programmed cell death) and the clearance of apoptotic cells by macrophages. It lowers the production of the pro-inflammatory mediators leukotriene B4 and CXCL-8 and induces the production of anti-inflammatory and pro-resolving lipid lipoxin A4.
Ketoprofen is a substance belonging to the group non-steroidal anti-inflammatory drugs (NSAIDs). Ketoprofen has anti-inflammatory, analgesic and antipyretic properties. Not all aspects of its mechanism of action are known. Effects are obtained partially by the inhibition of prostaglandin and leukotriene synthesis by ketoprofen, acting on cyclooxygenase and lipoxygenase respectively. The formation of bradykinin is also inhibited. Ketoprofen inhibits thrombocyte aggregation.
When subcutaneously co-administered in the combination formulation, at 2.5 mg tulathromycin/kg bodyweight, the maximum concentration (Cmax) in plasma was approximately 0.4 μg/ml, this was achieved approximately 3 hours post-dosing (Tmax). Peak concentrations were followed by a slow decline in systemic exposure with an apparent elimination half-life (t1/2) of 85 hours in plasma.
Furthermore, after subcutaneous injection of the tulathromycin-ketoprofen combination, the AUC0-t of tulathromycin has been shown to be bioequivalent to the AUC0-t after subcutaneous injection of tulathromycin 100 mg/ml for cattle. The combination had a slightly lower tulathromycin Cmax and the rate of absorption was decreased in comparison with the administration of the compounds separately.
Regarding ketoprofen, following administration of the combination product, at 3 mg ketoprofen/kg bodyweight, the pharmacokinetics of ketoprofen are driven by flip-flop kinetics. The mean Cmax in plasma was 2 μg/ml, which was achieved at 4 hours on average. The terminal half-life of ketoprofen is dominated by the slow absorption and was estimated at 6.8 hours.
Furthermore, after subcutaneous injection of the tulathromycin-ketoprofen combination, there was a delay in the absorption, with a lower ketoprofen peak concentration, and a longer elimination half-live, as compared with the compound alone.
Marketing Authorisation Number
Vm 42058/4211
Significant changes
GTIN
GTIN description:50 ml:
GTIN:05414736050386
GTIN description:100 ml:
GTIN:05414736050393