Cladaxxa 40 mg/10 mg chewable tablets for cats and dogs
Chewable tablet. Pink mottled tablets, round, with a break line on one side. The tablet can be divided into halves. Each tablet contains 40 mg Amoxicillin and 10 mg Clavulanic acid.

Chewable tablet. Pink mottled tablets, round, with a break line on one side. The tablet can be divided into halves. Each tablet contains 200 mg Amoxicillin and 50 mg Clavulanic acid.

Chewable tablet. Pink mottled tablets, round, with a break line on one side. The tablet can be divided into halves. Each tablet contains 400 mg Amoxicillin and 100 mg Clavulanic acid.

For the treatment of infections caused by bacteria susceptible to amoxicillin and clavulanic acid including: skin disease (including deep and superficial pyodermas); soft tissue infections (abscesses and anal sacculitis); dental infections (e.g. gingivitis); urinary tract infections; respiratory disease (involving upper and lower respiratory tract); enteritis.

FOR ORAL ADMINISTRATION

Dosage rate and frequency: 10 mg amoxicillin and 2.5 mg clavulanic acid/kg body weight (i.e. 12.5 mg of combined active substances per kg bodyweight), twice daily (corresponding to 25 mg of combined active substances per kg per day).

Cats and Dogs:

Dogs:

To ensure a correct dosage body weight should be determined as accurately as possible to avoid underdosing.

Duration of therapy:

The majority of routine cases respond to between 5 and 7 days therapy. In chronic cases, a longer course of therapy is recommended. In such circumstances, overall treatment length must be at the clinician’s discretion but should be long enough to ensure complete resolution of the bacterial disease.

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

Very rarely, hypersensitivity reactions to penicillins may occur in treated animals; in these cases, administration should be discontinued and a symptomatic treatment given.

Very rarely, gastro-intestinal disturbances (diarrhoea, vomiting, …) may occur after administration of the product. Treatment may be discontinued depending on the severity of the undesirable effects and a benefit/risk evaluation by the veterinary surgeon.

The frequency of adverse reactions is defined using the following convention: - very common (more than 1 in 10 animals treated displaying adverse reaction(s)) - common (more than 1 but less than 10 animals in 100 animals treated) - uncommon (more than 1 but less than 10 animals in 1,000 animals treated) - rare (more than 1 but less than 10 animals in 10,000 animals treated) - very rare (less than 1 animal in 10,000 animals treated, including isolated reports).

Laboratory studies in rats and mice have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. The safety of the product has not been assessed in pregnant and lactating bitches and queens. In pregnant and lactating animals, use only according to the benefit/risk assessment by the responsible veterinarian.

Do not administer to gerbils, guinea pigs, hamsters, rabbits and chinchillas. Do not use in horses and ruminants.

Do not use in cases of serious dysfunction of the kidneys accompanied by anuria and oliguria.

Do not use in cases of hypersensitivity to penicillins or other substances of the β-lactam group or to any excipients.

Do not use in cases of known resistance to the combination of amoxicillin and clavulanic acid.

This product is not indicated for cases involving Pseudomonas spp.

Special precautions for use in animals:

Whenever possible, the amoxicillin/clavulanic acid combination should only be used based on susceptibility testing.

Official, national and regional antimicrobial policies should be taken into account when the product is used.

Use of the product deviating from the instructions given in the package leaflet may increase the prevalence of bacteria resistant to amoxicillin/clavulanic acid and may decrease the effectiveness of treatment with other penicillins, due to the potential for cross-resistance.

A trend in resistance of E. coli is reported, including multidrug-resistant E. coli.

In animals with hepatic and renal dysfunction, the dosing regimen should be carefully evaluated and the use of the product based on a risk/benefit evaluation by the veterinary surgeon.

Caution is advised in the use in small herbivores other than those in section Contraindications.

The chewable tablets are flavoured. In order to avoid any accidental ingestion, store tablets out of reach of the animals.

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

Penicillins and cephalosporins may cause hypersensitivity (allergy) following 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 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.

To avoid accidental ingestion, particularly by a child, unused part-tablets should be returned to the open blister space, inserted back into the outer packaging and kept in a safe place out of the sight and reach of children.

Overdose (symptoms, emergency procedures, antidotes):

Mild gastrointestinal symptoms (diarrhoea, nausea and vomiting) may occur after overdose of the product and symptomatic treatment should be initiated when necessary.

Chloramphenicol, macrolides, sulfonamides and tetracyclines may inhibit the antibacterial effect of penicillins because of the rapid onset of bacteriostatic action. Penicillins may increase the effect of aminoglycosides.

Cellulose, microcrystalline Magnesium stearate Silica, colloidal anhydrous Sodium starch glycollate (type A) Issued: June 2021 AN: 00577/2020 Page 7 of 8 Dried autolyzed yeast Erythrosine aluminium lake, E127

Keep out of the sight and reach of children. Do not store above 25 °C.

Store in the original package in order to protect from light and moisture.

Do not use this veterinary medicinal product after the expiry date which is stated on the carton and the blister after {EXP}. The expiry date refers to the last day of that month.

Any unused half tablets should be returned to the blister pack and used within 12 hours.

3 years

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

Cladaxxa 40 mg/10 mg & 200 mg/50 mg chewable tablets for cats and dogs - Blister contains 10 tablets. Carton contains 10, 20, 100 or 500 tablets.

Cladaxxa 400 mg/100 mg chewable tablets for dogs - Blister contains 6 tablets. Carton contains 12, 60 or 300 tablets.

KRKA, d.d., Novo mesto

Šmarješka cesta 6

8501 Novo mesto

Slovenia

Pharmacotherapeutic group: antibacterials for systemic use, combinations of penicillins, incl. beta-lactamase inhibitors.

ATC vet code: QJ01CR02.

Amoxicillin is an aminobenzylpenicillin from the beta-lactam penicillin family. It interferes with the synthesis of peptidoglycan, an important component of bacterial cell walls. Therefore, it prevents bacterial cell wall formation. Clavulanic acid binds irreversibly with beta –lactamase and prevents it from inactivating amoxicillin. Therefore, amoxicillin/clavulanic acid combination has a notably broad spectrum of bactericidal activity against bacteria commonly found in cats and dogs. In vitro amoxicillin/clavulanic acid combination is active against a wide range of clinically important aerobic and anaerobic bacteria including: Gram-positive: Staphylococci (including ß-lactamase producing strains); Streptococci. Gram-negative: Escherichia coli (including most ß-lactamase producing strains); Klebsiellae; Pasteurellae.

Susceptibility and resistance for selected pathogens causing respiratory, urinary tract or skin infections and identified in European surveys can be referenced in full SmPC at https://www.vmd.defra.gov.uk/ProductInformationDatabase/search

The Clinical and Laboratory Standards Institute CLSI has set the MIC breakpoints based on disk-diffusion method (CLSI document VET01S, 5th ed, 2020) for amoxicillin-clavulanate against staphylococci and streptococci causing skin and soft tissue infections and urinary tract infections in cats and dogs as ≤0.25 / 0.12 µg/ml susceptible and ≥1 / 0.5 µg/ml resistant. For E. coli causing skin and soft tissue infections in cats and dogs, the susceptible breakpoint is set at ≤0.25 / 0.12 µg/ml and for urinary tract infections as ≤8 / 4 µg/ml. For P. multocida of feline origin, the susceptible breakpoint is set as ≤0.25 / 0.12 µg/ml and the resistant one as ≥1 / 0.5 µg/ml. The two main mechanisms of resistance to amoxicillin/clavulanic acid are: - Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D. Issued: June 2021 AN: 00577/2020 Page 6 of 8 - Alteration of Penicillin-Binding Proteins (PBP), which reduce the affinity of the antibacterial agent for the target (methicillin resistant S. aureus, MRSA and S. pseudintermedius, MRSP). Impermeability of bacteria or efflux pump mechanisms may cause or contribute to bacterial resistance, particularly in Gram-negative bacteria. Resistance genes can be located on chromosomes (mecA, MRSA) or plasmids (LAT, MIR, ACT, FOX, CMY family beta-lactamases) and a variety of resistance mechanisms have emerged. Pseudomonas aeruginosa and Enterobacter spp. may be regarded as intrinsically resistant to the combination. Resistance is shown among methicillin-resistant Staphylococcus aureus. A trend in resistance of E. coli is reported, including multidrug-resistant E. coli.

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.

Following the administration of the product in dogs, a mean Cmax of 7.31 μg/ml was achieved for amoxicillin at approximately 1.37 hours. The mean terminal half-life for amoxicillin was 1.21 hours.

In cats, a mean Cmax of 5.87 µg/ml was achieved for amoxicillin at approximately 1.59 hours. The mean terminal half-life for amoxicillin was 1.18 hours.

Clavulanic acid (pKa 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 mainly eliminated by renal excretion (unchanged in urine).

Following the administration of the product in dogs, a mean Cmax of 1.33 μg/ml was achieved for clavulanic acid at approximately 1.02 hours. The mean terminal half-life for clavulanic acid was 0.83 hours.

In cats, a mean Cmax of 3.16 μg/ml was achieved for clavulanic acid at approximately 0.70 hours. The mean terminal half-life for clavulanic acid was 0.81 hours.

Cladaxxa 40 mg/10 mg chewable tablets for cats and dogs - Vm 01656/4200

Cladaxxa 200 mg/50 mg chewable tablets for cats and dogs - Vm 01656/4021

Cladaxxa 400 mg/100 mg chewable tablets for dogs - Vm 01656/4202