Enrotron 100 Mg/Ml Solution For Injection For Cattle And Pigs

Summary

Revised: November 2014

AN: 00947/2014

SUMMARY OF PRODUCT CHARACTERISTICS

1. Name of the Veterinary Medicinal Product

Enrotron 100 mg/ml Solution for injection for cattle and pigs

2. QUALITATIVE aND QUANTITATIVE Composition

Each ml contains:

Active Substance

Enrofloxacin 100.0 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

Cattle.

Pig.

4.2 Indications for use, specifying the target species

Cattle

Treatment of infections of the respiratory tract caused by enrofloxacin susceptible strains of Pasteurella multocida, Mannheimia haemolyticaand Mycoplasma spp.

Treatment of acute severe mastitis caused by enrofloxacin susceptible strains of Escherichia coli.

Treatment of infections of the alimentary tract caused by enrofloxacin susceptible strains of Escherichia coli.

Treatment of septicaemia caused by enrofloxacin susceptible strains of Escherichia coli.

Treatment of acute mycoplasma-associated arthritis due to enrofloxacin susceptible strains of Mycoplasma bovisin cattle less than 2 years old.

Pigs

Treatment of infections of the respiratory tract caused by enrofloxacin susceptible strains of Pasteurella multocida, Mycoplasma spp. and Actinobacillus pleuropneumoniae.

Treatment of infections of the urinary tract caused by enrofloxacin susceptible strains of Escherichia coli.

Treatment of post-partum dysgalactiae syndrome, PDS (MMA syndrome) caused by enrofloxacin susceptible strains of Escherichia coliand Klebsiella spp.

Treatment of infections of the alimentary tract caused by enrofloxacin susceptible strains of Escherichia coli.

Treatment of septicaemia caused by enrofloxacin susceptible strains of Escherichia coli.

4.3 Contraindications

Do not use the product for prophylaxis.

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.

Do not use in growing horses because of possible deleterious damage on articular cartilage.

4.4 Special warnings for each target species

None known.

4.5 Special precautions for use

Special precautions for use in animals

The safety of the product has not been established in pigs or calves when administered by the intravenous route and use of this route of administration is not recommended in these animal groups.

Official and local antimicrobial policies should be taken into account when the product is used.

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, fluoroquinoones 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 dose.

Repeat injections should be made at different sites.

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

Degenerative changes of articular cartilage were observed in calves treated orally with 30 mg enrofloxacin/kg bw during 14 days.

The use of enrofloxacin in growing lambs at the recommended dose for 15 days caused histological

changes in the articular cartilage, not associated with clinical signs.

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 self 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.

Other precautions

None known.

4.6 Adverse reactions (frequency and seriousness)

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

4.7 Use during pregnancy, lactation or lay

There is no restriction on the use of this product 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.

4.9 Amounts to be administered and administration route

Intravenous, 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.

Cattle

5 mg of enrofloxacin/kg bw, corresponding to 1 ml/20 kg bw, once daily for 3-5 days.

Acute mycoplasma-associated arthritis due to enrofloxacin susceptible strains of Mycoplasma bovisin cattle less than 2 years old: 5 mg of enrofloxacin/kg bw, corresponding to 1 ml/20 kg bw, once daily for 5 days.

The product can be administered by slow intravenous or subcutaneous administration.

Acute mastitis caused by Escherichia coli: 5 mg enrofloxacin/kg bw, corresponding to 1 ml/20 kg bw, by slow intravenous injection once daily for two consecutive days.

The second dose may be administered by the subcutaneous route. In this case, the withdrawal period following subcutaneous injection applies.

Not more than 10 ml should be administered at one subcutaneous injection site.

Pigs

2.5 mg of enrofloxacin/kg bw, corresponding to 0.5 ml/20 kg bw, once daily by intramuscular injection for 3 days.

Alimentary tract infection or septicaemia caused by Escherichia coli: 5 mg of enrofloxacin/kg bw, corresponding to 1 ml/20 kg bw, once daily by intramuscular injection for 3 days.

In pigs, the injection should be made in the neck at the ear base.Not more than 3 ml should be administered at one intramuscular injection site.

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.

No signs of over dosage were observed in pigs following administration of the product at five times the recommended therapeutic dose.

4.11 Withdrawal Periods

Cattle:

Following intravenous injection:

Meat and offal: 5 days.

Milk: 3 days.

Following subcutaneous injection:

Meat and offal: 12 days.

Milk: 4 days.

Pigs:

Meat and offal: 13 days.

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, Mannheimia haemolytica, Pasteurella spp. (e.g. Pasteurella multocida), 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 times 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.

After an intravenous dose of 5 mg enrofloxacin per kg body weight (bw) to lactating dairy cattle, the total systemic exposure over the dosing interval of 24 h was at 7.1 mg*h/L. In cattle serum, approximately 30% of drug exposure (2.31 mg*h/L) consisted of ciprofloxacin, the active metabolite of enrofloxacin. The drug was well distributed into the body compartments (Venro = 1.5 L/kg, Vcipro = 8.51 L/kg). Total body clearance was 0.71 L/h/kg.

In milk, most of drug activity consisted of ciprofloxacin. Overall drug concentrations peaked at 4.1 mg/kg two hours after treatment. Overall drug exposure over 24 h was 22.1 mg*h/L. The actives were eliminated from milk with a mean exposure half-life of 2.8 h.

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 to protect from light.

6.5 Nature and composition of immediate packaging

Pack Size:

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

Cartons of 1 x 100 ml or 12 x 100 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.