SUMMARY OF PRODUCT CHARACTERISTICS

1. Name of the Veterinary Medicinal Product

Noroclav 75 mg Chewable Flavoured Tablets for Cats and Dogs (IE [RMS], AT, BG, CY, HU, IT, EL, LV, LT, PL, RO, SK, UK).

Noroclav 60 mg/15 mg Chewable Flavoured Tablets for Cats and Dogs (CZ).

Veclavam 75 mg Chewable Flavoured Tablets for Cats and Dogs (BE, ES, LU, NL, PT)

Veclavam vet., 60 mg/15 mg chewable tablets (DK).

Veclavam P 75 mg Chewable Tablets for Cats and Dogs (FR).

Veclavam vet., 60 mg/15 mg Chewable Tablets (NO).

Veclavam vet 60 mg/15 mg Chewable Tablets for Cats and Dogs (SE).

2. Qualitative and Quantitative Composition

Each tablet contains:

Active ingredients:

Amoxicillin 60.00 mg (as Amoxicillin Trihydrate)

Clavulanic acid 15.00 mg (as Potassium Clavulanate)

Excipients:

For the full list of excipients, see section 6.1.

3. Pharmaceutical Form

Chewable Tablet.

Pale brown circular tablet with a score line and embossed with ‘75’ on opposing faces.

The tablets can be divided into equal halves.

4. Clinical Particulars

4.1 Target Species:

Cats and Dogs.

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 Staphylococcusspp.

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

Respiratory tract infections caused by susceptible Staphylococcusspp.

Enteritis caused by susceptible Escherichia coli.

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.

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.

Special precautions for use in animals

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.

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

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.

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.

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

Penicillins may increase the effect of aminoglycosides.

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
2	Use 50 mg tablets
[2.1- 3.0]	½
[3.1- 6.0]	1
[6.1- 9.0]	1 ½
[9.1- 12.0]	2
>12	Use 250 or 500 mg tablets

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 reassessed.

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:QJ01CR02.

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 cross-linkage 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 beta-lactam 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 b-lactamase and therefore combination with an effective ß-lactamase inhibitor (clavulanic acid) extends the range of bacteria against which it is active to include b-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 b-lactamase producing strains)

Streptococcus spp.

Gram-negative:

Escherichia coli(including most b-lactamase producing strains)

Pasteurellaspp.

Proteusspp.

Resistance is shown among Enterobacterspp., Pseudomonas aeruginosaand methicillin-resistantStaphylococcus aureus.

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

A trend in resistance of E. coliis 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 (pK1 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 half-life 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: C_maxof 9.17 µg/ml and AUC of 53.27 µg.h/ml foramoxicillin and C_maxof 2.32 µg/ml, and AUC of 13.33 µg.h/ml for clavulanic acid.

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

6. Pharmaceutical Particulars

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: 15 months

Discard any unused halved tablets immediately.

6.4 Special Precautions for Storage:

Do not store above 25°C.

Store in a dry place.

6.5 Nature and Composition of Immediate Packaging:

Blisters (aluminium/aluminium): 28, 56, 224 and 504 tablets in outer packages with blister strips containing 14 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

Vm 02000/4380

9. DATE OF FIRST AUTHORISATION

05 March 2014

March 2014

Approved: 05/03/2014