SUMMARY OF PRODUCT CHARACTERISTICS

1. Name of the veterinary medicinal product

Combimox Injection Suspension for Injection

2. Qualitative and quantitative composition

Active Substances:

Amoxicillin (as Amoxicillin trihydrate) 140 mg/ml

Clavulanic acid (as Potassium clavulanate) 35 mg/ml

Excipients:

Butylated Hydroxyanisole 0.08 mg/ml

Butylated Hydroxytoluene 0.08 mg/ml

For a full list of excipients, see section 6.1

3. Pharmaceutical form

Suspension for Injection.

An off-white to creamy oil suspension.

4. Clinical Particulars

4.1 Target species

Cattle and dogs

4.2 Indications for use, specifying the target species

The combination product has a notably broad spectrum of bactericidal activity against the bacteria commonly found in cattle and dogs.

(a) In vitroCombimox Injection is active against a wide range of clinically important bacteria including:

Gram-positive: Staphylococci (including beta-lactamase producing strains), Streptococci, Corynebacteria, Clostridia, Bacillus anthracis, Actinomyces, Peptostreptococcusspp.

Gram-negative: Escherichia coli(including beta-lactamase producing strains), Salmonellaspp (including beta-lactamase producing strains), Campylobacterspp, Bordetella bronchiseptica, Klebsiellaspp, Proteusspp, Pasteurellaespp, Fusobacteriumnecrophorum, Bacteroides (including beta-lactamase producing strains), Haemophilusspp, Moraxellaspp and Actinobacillus lignieresi.

(b) Clinically Combimox Injection is effective in treating:

Cattle:

Respiratory infections

Soft tissue infections (e.g. joint/navel ill, abscesses etc.)

Metritis

Mastitis.

Dogs:

Respiratory tract infections

Urinary tract infections

Skin and soft tissue infections (e.g. abscesses, pyoderma, anal sacculitis and gingivitis.)

4.3 Contraindications

The product should not be administered to rabbits, guinea pigs, hamsters or gerbils. Caution is advised in its use in other very small herbivores.

4.4 Special Warnings for each target species

None

4.5 Special precautions for use

The suspension is not suitable for intravenous or intrathecal administration.

Care should be taken to avoid contaminating the remaining contents of a vial with water.

Clavulanic acid is moisture sensitive. It is very important therefore, that a completely dry needle and syringe is used when extracting suspension for injection in order to avoid contaminating the remaining contents of the vial with drops of water.

Contamination will result in obvious beads of dark, brown discolouration corresponding to the introduced water droplets. Material affected in this way should not be used as it may have significantly reduced potency.

Use of the product should be based on susceptibility testing of bacteria isolated from the animal. If this is not possible, therapy should be based on local (regional, farm level) epidemiological information about susceptibility of the target bacteria.

Care should be taken to avoid accidental self-injection.

Penicillins and cephalosporins may cause hypersensitivity (allergy) following injection, inhalation, ingestion or skin contact. Hypersensitivity to penicillins may lead to cross reactions to cephalosporins and vice versa. Allergic reactions to these substances may occasionally be serious.

1. Do not handle this product if you know you are sensitised, or if you have been advised not to work with such preparations.

2. Handle this product with great care to avoid exposure, taking all recommended precautions.

3. If you develop symptoms following exposure such as a skin rash, you should seek medical advice and show the doctor this warning. Swelling of the face, lips or eyes or difficulty with breathing are more serious symptoms and require urgent medical attention.

Wash hands after use.

4.6 Adverse reactions (frequency and seriousness)

Use of the product may occasionally result in pain on injection and/or local tissue reaction.

4.7 Use during pregnancy, lactation or lay

The product may be used in pregnant animals.

4.8 Interaction with other medicinal products and other forms of interaction

None known.

4.9 Amounts to be administered and administration route

The product is indicated for intramuscular administration to cattle and subcutaneous or intramuscular administration to dogs.

The recommended dosage rate is 8.75 mg/kg bodyweight (1 ml per 20 kg bodyweight) daily for 3-5 days. Shake the vial well before use. After injection, massage the injection site. Use a completely dry sterile needle and syringe. Swab the septum before removing each dose.

To ensure a correct dosage, bodyweight should be determined as accurately as possible to avoid underdosing.

The product has a low order of toxicity and is well tolerated by the parenteral route. Apart from occasional injection site reactions, which may occur at the recommended dose, no other adverse effects are to be expected from an accidental overdose.

Cattle (meat): 42 days

(milk): 60 hours

5. pharmacological properties

Pharmacotherapeutic group:Amoxicillin and Enzyme Inhibitor

ATC Vet Code:QJ01CR02

Mode of Action

Amoxicillin:

The mechanism by which ß-lactam antibiotics bind with proteins associated with developing the bacterial cell wall, resulting in the ultimate lysis of the cell, is well established. In the case of Gram-positive bacteria the ß-lactam can freely pass across the peptidoglycan layer in the aqueous phase to the site of activity at the cytoplasmic membrane. In the case of Gram-negative bacteria there is a hydrophobic barrier outside the peptidoglycan layer. Broad-spectrum ß-lactam antibiotics have the ability to cross this barrier by way of small pores in its structure.

There are three major mechanisms of resistance available to bacteria: the production of ß-lactamase enzymes, impermeability of the cell wall by modification of the small pores and by modifications of the amino acid sequences at the cytoplasmic membrane interface where the cell wall is constructed.

Clavulanic Acid:

In the absence of specific inhibitor enzymes with ß-lactamase activity, ß-lactamases either form complexes with the antibiotic or cause a breakdown of the ß-lactam ring. In either case the antibacterial activity is lost.

Clavulanic acid has a ß-lactam ring in its structure which is recognised by ß-lactamases as a type of “penicillin”. The enzyme/clavulanate interaction is irreversible and results in the depletion of enzymes molecules.

5.2 Pharmacokinetic properties

None

6. Pharmaceutical particulars

6.1 List of excipients

Butylated Hydoxyanisole

Butylated Hydroxytoluene

Propylene Glycol Octanoate Decanoate

None known.

Shelf life of the veterinary medicinal product as packaged for sale: 1 year

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

Do not store above 25ºC.

Discard unused material.

This product does not contain an antimicrobial preservative.

Once a vial has been broached the contents should be used within 28 days.

Supplied in clear colourless Type II glass vials of 50 ml and 100 ml, complete with nitryl bungs and aluminium caps.

Any unused product or waste material should be disposed of in accordance with national requirements.

7. MARKETING AUTHORISATION HOLDER

Norbrook Laboratories Limited

Station Works

Newry

Co. Down

BT35 6JP

Northern Ireland

8. MARKETING AUTHORISATION NUMBER

Vm: 02000/4235

9. DATE OF FIRST AUTHORISATION

Date: 9 May 2003

10. DATE OF REVISION OF THE TEXT

Date: January 2015

Approved: 09 January 2015