SUMMARY OF PRODUCT CHARACTERISTICS

Noroclav 250 mg Chewable Flavoured Tablets for Cats and Dogs (ROI [RMS], AT, BG, CY, HU, IT, EL, LV, LT, PL, RO, SK, SE, UK).

Noroclav 200 mg/50 mg Chewable Flavoured Tablets for Cats and Dogs (CZ).

Veclavam 250 mg Chewable Flavoured Tablets for Cats and Dogs (BE, ES, LU, NL, PT).

Veclavam vet., 200/50 mg Chewable Tablets for Cats and Dogs (DK).

VeclavamP 250 mg Chewable Tablets for Cats and Dogs (FR).

Veclavam vet., 200 mg/50 mg Chewable Tablets for Cats and Dogs (NO).

Veclavam vet., 200 mg/50 mg Chewable Tablets for Cats and Dogs (SE).

Each tablet contains:

Active ingredients:

Amoxicillin 200.00 mg

(as Amoxicillin Trihydrate)

Clavulanic acid 50.00 mg

(as Potassium Clavulanate)

Excipients:

For the full list of excipients, see section 6.1.

Chewable Tablet.

Pale brown circular tablet with two crossing score lines and embossed with '250' on opposing faces.

The tablets can be divided into equal halves.

4. CLINICAL PARTICULARS

4.1 Target Species

Cats and Dogs.

4.2 Indications for Use, Specifying the Target Species

Treatment of the following infections caused by beta-lactamase producing strains of bacteria sensitive to amoxicillin in combination with clavulanic acid:

Skin infections (including superficial and deep pyodermas) caused by susceptible Staphylococcus spp.

Urinary tract infections caused by susceptible Staphylococcus spp or Escherichia coli.

Respiratory tract infections caused by susceptible Staphylococcus spp.

Enteritis caused by susceptible Escherichia coll.

Dental infections (e.g. gingivitis)

It is recommended to carry out suitable tests for sensitivity when initiating the treatment. The treatment should only proceed if sensitivity is proven to the combination.

4.3 Contraindications

The product should not be given to rabbits, hamsters, guinea pigs or gerbils. Caution is advised in their use in any other small herbivores.

The product is not indicated for cases involving Pseudomonas spp.

Do not use in animals with known hypersensitivity to penicillin and other beta-lactams.

Do not use in animals with serious dysfunction of the kidneys accompanied by anuria or oliguria.

Do not use where resistance to this combination is known to occur.

Do not administer to horses and ruminating animals.

4.4 Special Warnings for Each Target Species

None known.

4.5 Special Precautions for Use

Whenever possible, the product 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 beta-lactam antimicrobials and may decrease the effectiveness of treatment with

other classes of antimicrobials due to the potential for cross resistance.

Official and regional antimicrobial policies should be taken into account.

In animals with hepatic and renal failure, the dosing regimen should be carefully evaluated.

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.

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

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

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)

Hypersensitivity reactions to penicillins may occur in treated animals.

Allergic reactions (e.g. skin reactions, anaphylaxis) may occasionally occur. In case of occurrence of allergic reaction, the treatment should be withdrawn.

Very rarely, use of the product may result in gastro-intestinal disorders (vomiting, diarrhoea, anorexia).

4.7 Use During Pregnancy, Lactation or Lay

To date, laboratory studies in animals have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. However, as no studies have been carried out in pregnant or lactating dogs and cats, it is recommended to use the product only according to the benefit/risk assessment by the

responsible veterinarian.

4.8 Interaction with other Medicinal Products and Other Forms of Interaction

Chloramphenicol, macrolides, sulfonamides and tetracyclines may inhibit the antibacterial effect of penicillins because of the rapid onset of bacteriostatic action. The potential for allergic crossreactivity with other penicillins should be considered.

Penicillins may increase the effect of aminoglycosides.

4.9 Amounts to be Administered and Administration

Administration: by the oral route.

Dosage rate: total 12.5 mg of combined actives/kg bw. (equal to 10 mg of amoxicillin + 2.5 mg of clavulanate/kg bw).

Dosage frequency: The following table is intended as a guide to dispensing at the standard dose rate of 12.5 mg/kg, twice daily.

To ensure a correct dosage, bodyweight should be determined as accurately

as possible.

Body weight (kg)	Number of tablets to be administered twice daily
< 8	Use 50 mg tablet
[8.1 —10.0]	½
[10.1 —20.0]	1
[20.1 — 30.0]	1 ½
[30.1 — 40.0]	2
>40	Use 500 mg tablet

If the dog or cat does not accept the tablet from hand or bowl, then the tablets may be crumbled and added to a little food.

The majority of routine cases respond after between 5 and 7 days therapy. If no improvement is observed after 5 — 7 days, the diagnosis should be re-assessed.

In chronic or refractory cases, a longer course of therapy may be required e.g. chronic skin disease 10 - 20 days, chronic cystitis 10 - 28 days, respiratory disease 8 - 10 days.

If no improvement is observed after two weeks, the diagnosis should be re-assessed.

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

The product is of low order toxicity to the target species. Mild gastrointestinal symptoms (diarrhoea, nausea and vomiting) may occur more frequently after overdose of the product.

4.11 Withdrawal Period(s)

Not applicable.

5. PHARMACOLOGICAL PROPERTIES

Pharmacotherapeutic group: Beta-lactam antibacterials, penicillins.

ATC Vet Code: QJOICR02.

5.1 Pharmacodynamic properties

Amoxicillin is a beta-lactam antibiotic and its structure contains the beta-lactam ring and thiazolidine ring common to all penicillins. Amoxicillin shows activity against susceptible Gram-positive bacteria

and Gram-negative bacteria.

Beta-lactam antibiotics prevent the bacterial cell wall from forming by interfering with the final stage of peptidoglycan synthesis. They inhibit the activity of transpeptidase enzymes, which catalyse crosslinkage

of the glycopeptide polymer units that form the cell wall. They exert a bactericidal action but cause lysis of growing cells only.

Clavulanic acid is one of the naturally occurring metabolites of the streptomycete Streptomyces clavuligerus. It has a structural similarity to the penicillin nucleus, including possession of a betalactam ring. Clavulanic acid is a beta-lactamase inhibitor acting initially competitively but ultimately

irreversibly. Clavulanic acid will penetrate the bacterial cell wall binding to both extracellular and intracellular beta-lactamases.

Amoxicillin is susceptible to breakdown by p-lactamase and therefore combination with an effective B-lactamase inhibitor (clavulanic acid) extends the range of bacteria against which it is active to include P-lactamase producing species.

In vitro potentiated amoxicillin is active against a wide range of clinically important aerobic and anaerobic bacteria including:

Gram-positive:

Staphylococcus spp. (including (3-lactamase producing strains)

Streptococcus spp

Gram-negative:

Escherichia coli (including most p-lactamase producing strains)

Pasteurella spp

Proteus spp

Resistance is shown among Enterobacter spp, Pseudomonas aeruginosa and methicillin-resistant

Staphylococcus aureus.

Dogs and cats diagnosed with Pseudomonas infections should not be treated with this antibiotic combination.

A trend in resistance of E. coli is reported.

Resistance

Acquired resistance prevalence may be high in E. coli.

Resistance notably develops through the production of inhibitor-resistant beta-lactamases or the hyperproduction of beta-lactamases.

In some strains of Staphylococcus aureus (methicillin-resistant S. aureus, MRSA), and of Staphylococcus pseudintermedius, resistance to all beta-lactams is conferred by the alteration of the cell wall target proteins (Penicillin-Binding Proteins). This is often associated to resistance to multiple

other antimicrobial compounds with cross resistance.

Pseudomonas aeruginosa and Enterobacter spp. can be regarded as intrinsically resistant to the combination.

5.2 Pharmacokinetic properties

Amoxicillin is well-absorbed following oral administration. In dogs the systemic bioavailability is 60-70%. Amoxicillin (pKa 2.8) has a relatively small apparent distribution volume, a low plasma protein binding (34% in dogs) and a short terminal half-life due to active tubular excretion via the kidneys.

Following absorption the highest concentrations are found in the kidneys (urine) and the bile and then in liver, lungs, heart and spleen. The distribution of amoxicillin to the cerebrospinal fluid is low unless the meninges are inflamed.

Clavulanic acid (pKl 2.7) is also well-absorbed following oral administration. The penetration to the cerebrospinal fluid is poor. The plasma protein binding is approximately 25% and the elimination halflife is short. Clavulanic acid is heavily eliminated by renal excretion (unchanged in urine).

After oral administration of the recommended dose of 12.5mg combined actives/kg to cats, the following parameters were observed: Cmax of 9.17 μg/ml and AUC of 53.2711g.h/m1 for amoxicillin and Cmax of 2.32 μg/ml, and AUC of 13.33 ug.h/m1 for clavulanic acid.

After oral administration of the recommended dose of 12.5mg combined actives/kg to dogs, the following parameters were observed: Cmax of 8.92 μg/ml and AUC of 46.29 u.g.h/m1 for amoxicillin and Cmax of 2.21 μg/ml, and AUC of 8.99 ug.h/m1 for clavulanic acid.

6. PHARMACEUTICAL PARTICULARS

6.1 List of Excipient(s)

Sodium Starch Glycolate, type A

Povidone K30

Spray Dried Pork Liver Powder

Yeast Extract

Silica Colloidal Hydrated

Magnesium Stearate

Microcrystalline Cellulose

6.2 Incompatibilities

Not applicable.

6.3 Shelf-Life

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

Discard any unused halved tablets immediately.

6.4 Special Precautions for Storage

Do not store above 30°C.

Store in a dry place.

6.5 Nature and Composition of Immediate Packaging

Blisters (aluminium/aluminium): 20, 50, 200, 250 and 500 tablets in outer packages with blister strips containing 5 tablets each.

Not all pack sizes may be marketed.

6.6 Special Precautions for the Disposal of Unused Veterinary Medicinal Products or Waste Materials Derived from the Use of Such Products, if appropriate

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product 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(S)

Vm02000/4318

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date: 22 June 2012

10. DATE OF REVISION OF THE TEXT

Date:June 2013

Approved: 20/06/2013