1. Name of the veterinary medicinal product

Combiclav Suspension for Injection

2. Qualitative and quantitative composition

Active Substance(s) % w/v

Amoxicillin (as Amoxicillin trihydrate) 14.0

Clavulanic acid (as Potassium clavulanate) 3.5

Excipients:

Butylated Hydroxyanisole 0.008

Butylated Hydroxytoluene 0.008

For a full list of excipients, see section 6.1

3. Pharmaceutical form

Suspension for injection.

An off-white to cream oily suspension.

4. Clinical Particulars

4.1 Target species

Cattle

4.2 Indications for use, specifying the target species

Combiclav Injection has a notably broad spectrum of bactericidal activity against the bacteria commonly found in cattle.

(a) In vitro Combiclav 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 bovis.

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

(b) Clinically Combiclav Injection is effective in treating:

Cattle:

Respiratory infections

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

Metritis

Mastitis.

Combined Therapy for the treatment of bovine mastitis. In the situation where systemic treatment as well as intramammary treatment is necessary, Combiclav Injection can be administered in combination with Combiclav Lactating Cow Intramammary Suspension.

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

Special precautions for use in animals

Use of the product should be based on susceptibility testing of the bacteria isolated from the animal. If this is not possible, therapy should be based on local epidemiological information.

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.

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

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 in 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 safely 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

For intramuscular injection at a dosage rate of 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.

For Combined therapy the following minimum treatment regime should be followed:

Combiclav Injection

Combiclav LC Intramammary

8.75 mg/kg bodyweight (7.0 mg amoxicillin, 1.75 mg clavulanic acid) i.e. 1 ml/20 kg bodyweight. 24 hours 8.75 mg/kg bodyweight (7.0 mg amoxicillin, 1.75 mg clavulanic acid) i.e. 1 ml/20 kg bodyweight. 24 hours 8.75 mg/kg bodyweight (7.0 mg amoxicillin, 1.75 mg clavulanic acid) i.e. 1 ml/20 kg bodyweight. Where necessary Combiclav Injection may be administered for an additional two days for a total of 5 daily injections.

One syringe gently infused into the teat of the infected quarter 12 hours One syringe gently infused into the teat of the infected quarter 12 hours One syringe gently infused into the teat of the infected quarter

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

Potentiated penicillin is of 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.

4.11 Withdrawal period

Animals must not be slaughtered for human consumption during treatment.

Meat: 42 days.

Milk for human consumption must not be taken during treatment.

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

6. Pharmaceutical particulars

6.1 List of excipients

Butylated Hydroxyanisole

Butylated Hydroxytoluene

Propylene Glycol Octanoate Decanoate

6.2 Incompatibilities

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.

6.4 Special precautions for storage

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.

6.5 Nature and composition of immediate packaging

50 and 100 ml siliconised, clear, colourless, glass (Type II) vials with nitryl bung secured with aluminium overseal.

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

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

7. MARKETING AUTHORISATION HOLDER

Norbrook Laboratories Limited,

Station Works,

Camlough Road,

Newry,

Co. Down, BT35 6JP,

Northern Ireland

8. MARKETING AUTHORISATION NUMBER

Vm: 02000/4238

9. DATE OF FIRST AUTHORISATION

24^th September 2003

January 2009