50 and 62.5mg tablets: cats and dogs
250, 500 and 625mg tablets: dogs
Do not use in animals with known hypersensitivity to penicillins or other susbstances of the β-lactam group or to any excipients.
Do not use in animals with serious dysfunction of the kidneys accompanied by anuria and oliguria.
Do not administer to gerbils, guinea pigs, hamsters, rabbits and chinchillas. Do not use in horses and ruminating animals.
Do not use where resistance to this combination is known to occur.
Special precautions for use in animals
Official, national and regional antimicrobial policies with respect to the use of broad-spectrum antibiotics should be taken into account. Do not use in case of bacteria sensitive to narrow spectrum penicillins or to amoxicillin as single substance. It is advised that upon initiating therapy appropriate sensitivity testing is performed and that therapy is continued only after susceptibility to the combination has been established. Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to the amoxicillin/clavulanate, and may decrease the effectiveness of treatment with beta-lactam antibiotics.
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 indicated in 'Contraindications'.
The potential for allergic cross-reactions with other penicillin derivates and cephalosporins should be considered.
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 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.
Adverse reactions (Frequency and Seriousness)
Mild gastrointestinal signs (diarrhoea, and vomiting) have been reported in very rare cases (less than 1 animal in 10,000 animals, including isolated reports) 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.
Allergic reactions (skin reactions, anaphylaxis) have been reported in very rare cases (less than 1 animal in 10,000 animals, including isolated reports). In these cases, administration should be discontinued and a symptomatic treatment given.
Use during Pregnancy, Lactation or Lay
Laboratory studies in rats and mice have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects.
In pregnant and lactating animals, use only according to the benefit/risk assessment by the responsible veterinarian.
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.
Penicillins may increase the effect of aminoglycosides.
In case of overdose diarrhoea, allergic reactions or further symptoms like central nervous excitation manifestations or cramps could appear. Symptomatic treatment should be initiated when necessary.
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 ß-lactamase and therefore combination with an effective ß-lactamase inhibitor (clavulanic acid) extends the range of bacteria against which it is active to include ß-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), Pasteurella spp, Proteus spp
Resistance is shown among Enterobacter spp, Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus.
A trend in resistance of E. coli is reported.
After oral administration in dogs, amoxicillin and clavulanic acid are rapidly absorbed. 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 (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).
After single oral administration of 17 mg/kg amoxicillin and 4.3 mg/kg clavulanic acid in dogs:
-The maximal plasma concentration (Cmax) of amoxicillin (8.6 µg/mL) was observed 1.5 hour following administration.
-The maximal plasma concentration (Cmax) of clavulanic acid (4.9 µg/mL) was observed 54 minutes following administration.
After single oral administration of 13 mg/kg amoxicillin and 3.15 mg/kg clavulanic acid in cats:
-The maximal plasma concentration (Cmax) of amoxicillin (9.3 µg/mL) was observed 2 hours following administration.
-The maximal plasma concentration (Cmax) of clavulanic acid (4.1 µg/mL) was observed 50 minutes following administration
List of Excipient(s)
Pig liver powder, Yeast, Crospovidone (type A), Povidone K 25, Hypromellose, Microcrystalline cellulose, Silica, colloidal anhydrous, Magnesium stearate