Enrotron 25 Mg/Ml Solution For Injection For Dogs, Cats And Exotic Animals

Summary

Revised: November 2014

AN: 00947/2014

SUMMARY OF PRODUCT CHARACTERISTICS

Name of the Veterinary Medicinal Product

Enrotron 25 mg/ml Solution for injection for dogs, cats and exotic animals

2. QUALITATIVE aND QUANTITATIVE Composition

Each ml contains:

Active Substance

Enrofloxacin 25.0 mg

Excipients

1-Butanol 30.0 mg

For a full list of excipients, see section 6.1

3. Pharmaceutical Form

Solution for injection.

Clear, slightly yellowish to yellowish orange solution.

4. Clinical Particulars

4.1 Target Species

Dog.

Cat.

Exotic Animals (rodents, reptiles and ornamental birds).

4.2 Indications for use, specifying the target species

Dogs

Treatment of infections of the alimentary, respiratory and urogenital tracts (including prostatitis, adjunctive antibiotic therapy for pyometra), skin and wound infections, otitis (externa/media) caused by enrofloxacin susceptible strains of: Staphylococcus spp., Escherichia coli, Pasteurella spp., Klebsiella spp., Bordetella spp., Pseudomonas spp. and Proteus spp.

Cats

Treatment of infections of the alimentary, respiratory and urogenital tracts (as adjunctive antibiotic therapy for pyometra), skin and wound infections, caused by enrofloxacin susceptible strains of: Staphylococcus spp., Escherichia coli, Pasteurella spp., Klebsiella spp., Bordetella spp., Pseudomonas spp. and Proteus spp.

Exotic Animals (rodents, reptiles and ornamental birds)

Treatment of infections of the alimentary and respiratory tracts where clinical experience, if possible,

supported by susceptibility testing of the causal organism, indicates enrofloxacin as the substance of

choice.

4.3 Contraindications

Do not use in dogs less than 1 year of age or in exceptionally large breeds of dog with a longer growth period under 18 months of age.

Do not use for cats less than 8 weeks of age.

Do not use in cases of known hypersensitivity to fluoroquinolones or to any of the excipients.

Do not use when resistance / cross resistance to (fluoro)quinolones is known to occur. Refer to section 4.5.

4.4 Special warnings for each target species

Dogs:Not for use in dogs less than 1 year of age or in exceptionally large breeds of dogs with a longer growth period, under 18 months of age. In dogs enrofloxacin may affect articular cartilage during the period of rapid growth.

4.5 Special precautions for use

Special precautions for use in animals

Fluoroquinolones should be reserved for the treatment of clinical conditions which have responded poorly, or are expected to respond poorly, to other classes of antimicrobials.

Whenever possible, fluoroquinolones should only be used based on susceptibility testing.

Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to the fluoroquinolones and may decrease the effectiveness of treatment with other quinolones due to the potential for cross resistance.

Do not exceed the recommended dosage.

Repeat injections should be made at different sites.

Do not use in dogs and cats with CNS disturbances.

Enrofloxacin should be used with caution in epileptic animals or animals affected by renal dysfunction.

Special precautions to be taken by the person administering the veterinary medicinal product to animals

The product is an alkaline solution. Wash any splashes from skin or eyes immediately with water.

Do not eat, drink or smoke whilst using the product.

Care should be taken to avoid accidental self-injection. If accidental injection occurs, seek medical advice immediatelyand show the package leaflet to the doctor.

Direct contact with the skin should be avoided because of sensitisation, contact dermatitis and possible hypersensitivity reactions to (fluoro) quinolones.

Wear gloves.

4.6 Adverse reactions (frequency and seriousness)

In dogs enrofloxacin may affect articular cartilage during the period of rapid growth. Occasionally skin reactions have been seen after administration to kennelled greyhounds.

Local tissue reactions may occasionally occur at the injection site. Normal sterile precautions should be taken.

Exotic Animals:Muscle bruising after injection in reptiles and birds has been reported occasionally.

4.7 Use during pregnancy, lactation or lay

Do not use during pregnancy and lactation.

4.8 Interaction with other medicinal products and other forms of interaction

Antagonistic effects due to concurrent administration of macrolides and tetracyclines may occur. Enrofloxacin may interfere with the metabolism of theophylline, decreasing theophylline clearance resulting in increased plasma levels of theophylline.

Care should be taken during the concomitant use of flunixin and enrofloxacin in dogs to avoid adverse drug reactions. The decrease in drug clearances as a result of co-administration of flunixin and enrofloxacin indicates that these substances interact during the elimination phase. Thus, in dogs, the

co-administration of enrofloxacin and flunixin increased the AUC and the elimination half-life of flunixin and increased the elimination half-life and reduced the C_maxof enrofloxacin.

4.9 Amounts to be administered and administration route

Subcutaneous or intramuscular use.

Repeated injections should be made at different injection sites.

To ensure a correct dosage, body weight (bw) should be determined as accurately as possible to avoid underdosing.

Dogs and cats

5 mg of enrofloxacin/kg bw, corresponding to 1 ml/5 kg bw, daily by subcutaneous injection for up to 5 days.

Treatment may be initiated with injectable product and maintained with enrofloxacin tablets. Duration of treatment should be based on the duration of treatment approved for the appropriate indication in the product information of the tablet product.

Rodents

10 mg/kg bw, corresponding to 0.4 ml/kg bw, once daily by subcutaneous injection for 5 to 10 consecutive days. If necessary, depending on the severity of clinical signs, this dosage can be doubled.

Reptiles

Reptiles are ectothermic, relying on external heat sources to maintain their body temperature at the optimum level for correct function of all body systems. Metabolism of substances and activity of the immune system are, thus, critically dependent on the body temperature. Therefore, the veterinarian must be aware of the correct temperature requirements of the respective reptile species and the hydration status of the individual patient. Furthermore, it has to be considered that large differences exist in the pharmacokinetic behaviour of enrofloxacin among different species, which additionally will influence the decision about the correct dosage of Enrotron 25 mg/ml Solution for injection.

Therefore, the recommendations made here can only be used as a starting point for individual dose setting.

5–10 mg/kg bw, corresponding to 0.2–0.4 ml/kg bw, once daily by intramuscular injection for 5 consecutive days.

An extension of the treatment interval to 48 hours may be necessary in individual cases. In complicated infections, higher dosages and longer treatment courses may be necessary. The presenceof the renal portal system in reptiles means it is prudent to administer substances in the front half of the body wherever possible.

Ornamental birds

20 mg/kg bw, corresponding to 0.8 ml/kg bw, once daily by intramuscular injection for 5 to 10 consecutive days. In case of complicated infections higher doses may be necessary.

The use of a 0.5 ml (100 unit) insulin syringe should be considered for administration of the small volumes required by some species of small animals (mice, gerbils etc.) Treatment may be initiated with the injection and maintained with an enrofloxacin containing oral solution.

4.10 Overdose (symptoms, emergency procedures, antidotes), if necessary

Do not exceed the recommended dose. In accidental overdose there is no antidote and treatment should be symptomatic. In target animal studies, cats have been shown to suffer ocular damage after receiving doses of more than 15 mg/kg once daily for 21 consecutive days. Doses of 30 mg/kg given once daily for 21 consecutive days have been shown to cause irreversible ocular damage. At 50 mg/kg given once daily for 21 consecutive days, blindness can occur.

In dogs and cats, lack of appetite and nausea may occur following overdose.

Overdose may result in CNS and renal dysfunction.

Dogs: 10-fold over dosage results in neurological symptoms such as ataxia, tremor, nystagmus or convulsions. These symptoms are reversible on cessation of treatment.

Cats:Retinotoxic effects including blindness can occur when the recommended dose is exceeded.

4.11 Withdrawal Period

Do not use in birds intended for human consumption.

5. PHARMACOLOGICAL or IMMUNOLOGICAL PROPERTIES

Pharmacotherapeutic group:antibacterials for systemic use, fluoroquinolones.

ATC Vet Code:QJ01MA90.

5.1 Pharmacodynamic Properties

Mode of action

Two enzymes essential in DNA replication and transcription, DNA gyrase and topoisomerase IV, have been identified as the molecular targets of fluoroquinolones. Target inhibition is caused by noncovalent binding of fluoroquinolone molecules to these enzymes. Replication forks and translational complexes cannot proceed beyond such enzyme-DNA-fluoroquinolone complexes, and inhibition of DNA and mRNA synthesis triggers events resulting in a rapid, drug concentration-dependent killing of pathogenic bacteria. The mode of action of enrofloxacin is bactericidal and bactericidal activity is concentration dependent

Antibacterial spectrum

Enrofloxacin is active against many Gram-negative bacteria such as Escherichia coli, Klebsiella spp., Actinobacillus pleuropneumoniae, Pasteurella spp.(e.g. Pasteurella multocida), Bordetella spp., Proteus spp., Pseudomonas spp., against Gram-positive bacteria such as Staphylococcus spp. (e.g. Staphylococcus aureus) and against Mycoplasma spp. at the recommended therapeutic doses.

Types and mechanisms of resistance

Resistance to fluoroquinolones has been reported to arise from five sources, (i) point mutations in the genes encoding for DNA gyrase and/or topoisomerase IV leading to alterations of the respective enzyme, (ii) alterations of drug permeability in Gram-negative bacteria, (iii) efflux mechanisms, (iv) plasmid mediated resistance and (v) gyrase protecting proteins. All mechanisms lead to a reduced susceptibility of the bacteria to fluoroquinolones. Cross-resistance within the fluoroquinolone class of antimicrobials is common.

5.2 Pharmacokinetic Properties

The pharmacokinetics of enrofloxacin are such that oral and parenteral administration leads to similar serum levels. Enrofloxacin possesses a high distribution volume. Tissue levels 2-3 higher than that found in the serum, have been demonstrated in laboratory animals and target species. Organs in which high levels can be expected are the lungs, liver, kidney, skin, bone and lymphatic system. Enrofloxacin also distributes into the cerebrospinal fluid, the aqueous humour and the foetus in pregnant animals.

Molecular resistance to fluoroquinolones has been observed to arise from two principal sources, (i) alteration to DNA gyrase or topoisomerase IV and (ii) alterations in drug permeability of the bacterial cell. Both mechanisms lead to a reduced susceptibility of the bacteria to fluoroquinolones. Clinical resistance is dependent on several mutations accumulating in a step-wise manner.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

1-Butanol

Potassium Hydroxide (excipient and for pH adjustment)

Hydrochloric acid (for pH adjustment)

Water for Injection

6.2 lncompatibilities

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

6.3 Shelf-life

Shelf life of the product as packaged for sale: 3 years.

Shelf life after first opening the immediate packaging: 28 days.

6.4 Special precautions for storage

Keep the vial in the outer carton in order to protect from light.

6.5 Nature and composition of immediate packaging

Pack size:

50 ml clear glass vial type I with teflonised rubber stopper sealed with an aluminium cap.

Cartons of 1 x 50 ml or 12 x 50 ml available.

Not all pack sizes may be marketed.

6.6 Special precautions for the disposal of unused veterinary medicinal products or waste materials

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements.