Tsefalen 50mg/ml Powder for Oral Suspension for Dogs up to 20 kg and Cats

Composition

Each ml of reconstituted oral suspension contains:

Active substance:

Cefalexin 50 mg

(equivalent to cefalexin monohydrate 52.6 mg)

Excipients:

White-coloured powder.

Reconstituted suspension: red-coloured suspension.

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Pharmacological properties

4.1 ATCvet code: QJ01DB01

Pharmacotherapeutic group: other beta-lactam antibacterials. First-generation cephalosporins

4.2 Pharmacodynamics

Cefalexin is a broad spectrum cephalosporin antibiotic with bactericidal activity against a wide range of Gram-positive and Gram-negative bacteria.

Cefalexin is a semi-synthetic bactericidal broad spectrum antibiotic belonging to the cephalosporin group which acts by interfering with bacterial cell wall formation. This bactericidal activity is mediated by drug binding to bacterial enzymes known as penicillin binding proteins (PBPs). Such enzymes are located on the inner membrane of the cell wall and their transpeptidase activity is required for the terminal stages of assembling this essential structure of the bacterial cell. Inactivation of PBPs interferes with the cross-linkage of peptidoglycan chains necessary for bacterial cell wall strength and rigidity. The bactericidal effect of cefalexin is mainly time dependent.

Cefalexin is resistant to the action of staphylococcal penicillinase and is therefore active against the strains of Staphylococcus aureus that are not susceptible to penicillin (or related antibiotics such as ampicillin or amoxycillin) because of production of penicillinase.

Cefalexin is also active against the majority of ampicillin-resistant E.coli.

The following micro-organisms have been shown to be susceptible to Cefalexin in vitro: Corynebacterium spp, Staphylococcus spp (including penicillin-resistant strains), Streptococcus spp, Escherichia coli, Moraxella spp, Pasteurella multocida.

The following breakpoints are recommended by the CLSI (2018) in dogs for E.coli and Staphylococcus spp:

Organism, minimum inhibitory concentration breakpoints of cefalexin (µg/ml):

E.coli: Susceptible ≤2; Intermediate 4; Resistant ≥8

Staphylococcus spp: Susceptible ≤2; Intermediate 4; Resistant ≥8

Recent surveillance data from France, analysing bacteria isolated from dogs and cats in 2018 demonstrates the following susceptibility of key pathogens to cephalexin:

For cefalexin, susceptible ≤ 8 mg/L and Resistant > 32 mg/L. Based on the recommendations of the French Antibiogram Comity (CA-SFM 2019)

Resistance to cefalexin may be due to one of the following mechanisms of resistance. Firstly, the production of various extended-spectrum beta-lactamases (ESBLs), that inactivate the antibiotic, is the most prevalent mechanism among gram- negative bacteria. Secondly, a decreased affinity of the PBPs (penicillin-binding proteins) for beta-lactam drugs is frequently involved for beta-lactam resistant gram-positive bacteria. Staphylococci commonly harbour the methicillin resistance gene mecA encoding a penicillin binding protein (PBP2a) with low affinity for beta- lactams. Lastly, efflux pumps, extruding the antibiotic from the bacterial cell, and structural changes in porins, reducing passive diffusion of the drug through the cell wall, may contribute to improve the resistant phenotype of a bacterium.

Well-known cross-resistance (involving the same resistance mechanism) exists between antibiotics belonging to the beta-lactam group due to structural similarities. It occurs with beta-lactamase enzymes, structural changes in porins or variations in efflux pumps. Co-resistance (different resistance mechanisms involved) has been described in E.coli due to a plasmid harbouring various resistance genes.

4.3 Pharmacokinetics

Cefalexin is rapidly and almost completely absorbed in the gastrointestinal tract following oral administration. Cefalexin binds to a limited extent (10-20%) to plasma proteins.

Cefalexin is poorly metabolised. Elimination of the microbiologically active form is almost entirely via the kidneys by tubular excretion and glomerular filtration.

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Target species

Dogs up to 20kg and cats

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Indications

DOGS: For the treatment of infections of the respiratory system, urogenital system and skin, localised infections in soft tissue and gastrointestinal infections caused by bacteria susceptible to cefalexin.

CATS: For the treatment of infections of the respiratory system, urogenital system and skin and localised infections in soft tissue caused by bacteria susceptible to cefalexin.

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Dosage

Oral use.

The recommended dose is 15 mg of cefalexin per kg of body weight (0.3 ml of reconstituted product per kg of body weight), twice a day. In severe or acute conditions, the dose may be doubled to 30 mg/kg (0.6 ml/kg) twice daily.

The product must be administered for a minimum of 5 days.

- 14 days in cases of urinary tract infection,

- At least 15 days in cases of superficial infectious dermatitis,

- At least 28 days in cases of deep infectious dermatitis.

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

To facilitate the dosage and the administration, the syringe present in the package can be used.

The veterinary medicinal product can be added to food if necessary.

Prior to addition of water for reconstitution, the bottle should be inverted and tapped to loosen the powder before adding water.

Water is added to the respective fill line on the bottle. The bottle is then closed, inverted and vigorously shaken for 60 seconds. The level of solution will drop slightly therefore continue adding water up to the fill line marked on the bottle label prior to filling the dosing syringe.

After reconstitution, the volume of red-coloured suspension is 100 ml for the bottle containing 66.6 g of powder and 60 ml for the bottle containing 40.0 g of powder.

Shake vigorously before each use of the product for at least 60 seconds.

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Contraindications

Do not use in cases of hypersensitivity to the active substance or to any of the excipients.

Do not use in rabbits, gerbils, guinea pigs and hamsters.

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Adverse reactions

Cats:

Rare (1 to 10 animals / 10,000 animals treated): Vomiting1,2, Hypersensitivity reaction3.

Very rare (<1 animal / 10,000 animals treated, including isolated reports): Diarrhoea1,2, Nausea.

Dogs:

Rare (1 to 10 animals / 10,000 animals treated): Hypersensitivity reaction3.

Very rare (<1 animal / 10,000 animals treated, including isolated reports): Nausea, vomiting2, diarrhoea2.

1 Mild and transient, at the lowest recommended dosage regime. Symptoms were reversible in most cats without symptomatic treatment.

2 In case of recurrence, the treatment should be discontinued and the advice of the attending veterinarian sought

3 In cases of hypersensitivity reactions the treatment should be discontinued.

Reporting adverse events is important. It allows continuous safety monitoring of a veterinary medicinal product. Reports should be sent, preferably via a veterinarian, to either the marketing authorisation holder or the national competent authority via the national reporting system. See the package leaflet for respective contact details.

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Warnings

Special precautions for safe use in the target species:

Use of the product should be based on identification and susceptibility testing of the target pathogen(s). If this is not possible, therapy should be based on epidemiological information and knowledge of susceptibility of the target pathogens at farm level, or at local/regional level.

An antibiotic with a lower risk of antimicrobial resistance selection (lower AMEG category) should be used for first line treatment where susceptibility testing suggests the likely efficacy of this approach.

Narrow spectrum antibiotic therapy with a lower risk of antimicrobial resistance selection should be used for first line treatment where susceptibility testing suggests the likely efficacy of this approach.

Deviating from the instructions given in the SPC when using the product may increase the prevalence of bacteria resistant to cefalexin and may also decrease the effectiveness of other beta-lactam antimicrobial treatments, due to the potential for cross-resistance. Therefore, deviation from the instructions must only be undertaken according to a risk/benefit assessment by the responsible veterinarian.

Do not administer in cases of known resistance to cephalosporins and penicillin.

As with other antibiotics which are excreted mainly by the kidneys, systemic accumulation may occur when renal function is impaired. In case of known renal insufficiency the dose should be reduced and substances known to be nephrotoxic should not be administered concurrently.

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 penicillin may lead to cross-reactions to cephalosporin and vice versa. Allergic reactions to these substances may occasionally be serious. Do not handle this veterinary medicinal product if you know you are sensitised or if you have been advised not to be in contact with such substances.

Handle this veterinary medicinal product with great care to avoid exposure, taking all recommended precautions and take care to avoid prolonged skin contact. When preparing the reconstituted product, ensure lid is correctly closed before shaking to mix product. Take care when loading the syringe to avoid spillage.

If you develop symptoms following exposure such as skin rash, you should seek medical advice and show the doctor this warning. Swelling of the face, lips or eyes or difficulty breathing are more serious symptoms and require urgent medical attention.

Accidental ingestion may result in gastrointestinal disturbances. In order to reduce the risk of accidental ingestion by children, close the bottle immediately after use. Do not leave a syringe containing suspension unattended and ensure syringe is out of sight and reach of children at all times. In order to prevent children from getting access to the used syringe, store the bottle and syringe in the outer carton.

When stored in the refrigerator, the oral suspension should be kept in a safe place out of sight and reach of children.

In case of accidental ingestion, particularly by children, seek medical advice immediately and show the package leaflet or the label to physician.

Do not smoke, eat or drink while handling the medication.

Wash hands after use.

Special precautions for the protection of the environment:

Not applicable.

3.11 Special restrictions for use and special conditions for use, including restrictions on the use of antimicrobial and antiparasitic veterinary medicinal products in order to limit the risk of development of resistance

Not applicable.

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Use during pregnancy, lactation or lay

Laboratory studies in rats and mice have not produced any evidence of teratogenic, foetotoxic, or embryotoxic effects.

The safety of the veterinary medicinal product has not been established during pregnancy and lactation. Use only according to the benefit-risk assessment by the responsible veterinarian.

Cephalexin crosses the placental barrier in pregnant animals.

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Interactions

In order to ensure efficacy, the veterinary medicinal product should not be used in combination with bacteriostatic antibiotics.

Concurrent use of first generation cephalosporins with polypeptide antibiotics, aminoglycosides or some diuretics such as furosemide can enhance nephrotoxicity risks.

Refer to section 3.3.

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Overdose

Concerning acute toxicity, an LD50 > 0.5 g/kg has been recorded following oral administration of cefalexin to cats and dogs. The administration of cefalexin has been shown to produce no serious side effects at several times the recommended dose rate.

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Special warnings

Cross-resistance has been shown between antimicrobials in the beta-lactam group. Use of the cefalexin should be carefully considered when susceptibility testing has shown resistance to beta lactam group because its effectiveness may be reduced.

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Withdrawal period

Not applicable.

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Incompatibilities

None known.

In the absence of compatibility studies, this veterinary medicinal product must not be mixed with other veterinary medicinal products.

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Immediate packaging

High density polyethylene bottle and polypropylene child-resistant screw cap with liner.

Dosing syringe with 0.1 ml graduations in polyethylene and 5 ml polystyrene piston.

Package size:

Carton box with 1 bottle containing 66.6 g of powder providing 100 ml of suspension after reconstitution and 1 syringe of 5 ml.

Carton box with 1 bottle containing 40.0 g of powder providing 60 ml of suspension after reconstitution and 1 syringe of 5 ml.

Not all pack sizes may be marketed.

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Storage

Do not open the bottle until the veterinary medicinal product requires reconstitution. Store below 25° C.

After reconstitution, store the oral suspension in a refrigerator (2° C - 8° C) Do not freeze the reconstituted suspension.

Keep the bottle in the outer carton in order to protect from light.

Keep the bottle tightly closed.

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 3 years. Shelf life after reconstitution according to directions: 28 days.

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Disposal of unused product

Medicines should not be disposed of via wastewater.

Use take-back schemes for the disposal of any unused veterinary medicinal product or waste materials derived thereof in accordance with local requirements and with any national collection systems applicable to the veterinary medicinal product concerned.

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Additional information

Vm 58047/4002

8 DATE OF FIRST AUTHORISATION

08 March 2021

9 DATE OF THE LAST REVISION OF THE SUMMARY OF THE PRODUCT CHARACTERISTICS

November 2024

10 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCT

Veterinary medicinal product subject to prescription.

Find more product information by searching for the ‘Product Information Database’ on www.gov.uk.

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Registration holder

Nextmune Italy S.R.L.

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