Noroclav Intramammary Suspension for Lactating Cows

Composition

Each intramammary syringe of 3g contains:

Active substances:

Amoxicillin (as amoxicillin trihydrate) 200 mg

Clavulanic acid (as potassium clavulanate) 50 mg

Prednisolone 10 mg

Excipients:

Qualitative composition of excipients and other constituents

Aluminium Sodium Silicate

Cetostearyl Alcohol (Type B), emulsifying

Paraffin, White Soft

Paraffin, Light Liquid

Cream to buff oily suspension.

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Pharmacological properties

4.1 ATCvet code: QJ51RV01

4.2 Pharmacodynamics

Amoxicillin is a broad spectrum bactericidal β-lactam antibiotic. Clavulanic acid inactivates β-lactamases. This combination is effective against β-lactamase producing organisms.

Prednisolone is an anti-inflammatory corticosteroid.

In vitro, clavulanic acid and amoxicillin in combination are active against a wide range of clinically important bacteria including the following organisms which are commonly associated with bovine mastitis:

Staphylococci (including β-lactamase producing strains)

Streptococci (including S. agalactiae, S. dysgalactiae and S. uberis)

Escherichia coli (including β-lactamase producing strains)

The Minimum Inhibitory Concentrations (MICs) of these target organisms determined from samples collected in nine EU countries (namely Belgium, Czech Republic, Denmark, France, Germany, Italy, Netherlands, Spain, and the UK)1, show susceptibility to amoxicillin and clavulanic acid used in combination in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines2 on breakpoints (Table 1 and 2).

Table 1: Minimum Inhibitory Concentrations (mg/L) of Amoxicillin/Clavulanic Acid against strains from mastitis in dairy cattle in nine EU countries

Table 2: Clinical Laboratory Standards Institute (CLSI) resistance breakpoints (mg/L) for target bacteria

Amoxicillin/Clavulanic Acid: E. coli >32; S. aureus >8; CNS3 >8; S. uberis >32; S. agalactiae >8; S. dysgalactiae >32

1Antimicrobial susceptibility of mastitis pathogens isolated from diseased dairy cows across Europe: VetPath monitoring results, European society of clinical microbiology and infectious diseases (ECCMID), 2015.

2Clinical and Laboratory Standards Institute (2013). Approved standards- fourth edition, CLSI document VETO01-A4, Wayne, PA, USA.

3CNS – Coagulase Negative Staphylococci

The mechanisms underlying antimicrobial resistance in Streptococcus can be acquired through the mutation of intrinsic genes or horizontal exchange of genetic material encoding resistance determinants. Mastitic strains of E. coli and Staphylococcus, are known to acquire resistance through horizontal gene transfer and bacteriophages/plasmid transfer, and also through their ability to form a biofilm.

Acquired resistance prevalence in particular to be high in E. coli. In some strains of Staphylococcus aureus (methicillin-resistant S. aureus, MRSA), and of Staphylococcus pseudintermedius, resistance to all β-lactams is conferred by the alteration of the cell wall target proteins (penicillin-binding proteins). This is often associated with resistance to multiple other antimicrobial compounds with cross resistance.

Mastitic strains of E. coli and Staphylococcus are known to acquire resistance through horizontal gene transfer and bacteriophages/plasmid transfer, and also through their own ability to form a biofilm.

4.3 Pharmacokinetics

It has been documented that the pharmacokinetic characteristics of penicillins (including amoxicillin) after intramammary administration indicate rapid elimination of the drug from milk. The mean residence time has a several-fold lower value than the designated elimination half-life and amounts to only 3.4 hours. The concentration of the drug in the milk drops relatively quickly and the process is very dynamic.

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Target species

Cattle (lactating cows).

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Indications

For the treatment of clinical mastitis caused by the following bacteria susceptible to the combination of amoxicillin and clavulanic acid:

Staphylococci (including β-lactamase producing strains).

Streptococci (including S. agalactiae, S. dysgalactiae and S. uberis).

Escherichia coli (including β-lactamase producing strains).

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Dosage

Intramammary use.

The syringe must only be used once. Partly emptied syringes due to the unsuccessful use should be discarded.

The content of one syringe should be infused gently into the teat of the infected quarter every 12 hours after each of three consecutive milkings.

Milk out the infected quarters. After thoroughly cleaning and disinfecting the teat and teat orifice with the cleaning towels provided, gently infuse the contents of one syringe into each affected quarter. Disperse the product by gentle massage of the teat and udder of the affected animal.

In cases of infections caused by Staphylococcus aureus, a longer course of antibacterial therapy may be required. Therefore overall treatment length must be at the veterinarian’s discretion but should be long enough to ensure complete resolution of intramammary infection.

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Contraindications

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

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Adverse reactions

Very rare (<1 animal / 10,000 animals treated, including isolated reports): Hypersensitivity reaction

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 its local representative 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:

Swab teat end before treatment, with cleaning towels provided.

Recommendations for prudent use

The product should be used for treatment of clinical mastitis only.

Use of the product should be based on susceptibility testing of the bacteria isolated from the animal. If this is not possible, therapy should be based on local (regional, farm level) epidemiological information about susceptibility of the target bacteria. Official, national and regional antimicrobial policies should be taken into account when the product is used.

The combination of amoxicillin and clavulanic acid should be reserved for the treatment of clinical conditions which have responded poorly, or are expected to respond poorly, to other classes of antimicrobials.

Avoid use of the product in herds where no β-lactamase producing staphylococci strains have been isolated. Veterinarians should strive to use narrow spectrum antibiotics if possible. Inappropriate use of the product may increase the prevalence of bacteria resistant to β-lactam antibiotics and may decrease the effectiveness of treatment with β-lactam antibiotics, due to the potential for cross-resistance. The feeding of waste milk containing residues of antibiotics to calves should be avoided up to the end of the milk withdrawal period, except during colostral phase, because it could select antimicrobial resistant bacteria within the intestinal microbiota of the calf and increase the faecal shedding of these bacteria.

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

This product may cause skin and eye irritation. Avoid contact with the skin and eyes. In the event of skin or eye contact rinse with plenty of clean water.

The cleaning towels supplied with the product contain isopropyl alcohol, which may cause skin or eye irritation in some people.

The wearing of gloves is recommended during administration of the product and when handling the cleaning towels.

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 label or leaflet to the doctor.

Swelling of the face, lips or eyes or difficulty with breathing, are more serious symptoms and require urgent medical attention.

Wash hands after use.

Special precautions for the protection of the environment:

Due to the endocrine-disrupting potential of prednisolone, the product may be dangerous to fish and other aquatic organisms. Consequently, treated animals should not have access to watercourses during the first 12 hours after treatment.

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

Pregnancy and lactation:

Can be used during pregnancy and lactation.

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Interactions

None known.

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Overdose

No adverse reactions are to be expected from an accidental overdose.

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Special warnings

Do not use in cases associated with Pseudomonas.

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Withdrawal period

Meat and offal: 7 days

Milk: 84 hours.

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Incompatibilities

Not applicable.

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Immediate packaging

Single dose 3g white LDPE syringes with a white LDPE dual push-fit cap.

Cartons of 3, 12, and 24 syringes, including 3, 12 or 24 individually wrapped teat cleaning towels containing isopropyl alcohol or buckets of 120 syringes including 120 individually wrapped teat cleaning towels containing isopropyl alcohol.

Not all pack sizes may be marketed.

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Storage

Do not store above 25°C.

Store in a dry place.

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Shelf life

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

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Disposal of unused product

Medicines should not be disposed of via wastewater.

Extremely dangerous for fish and aquatic life. Do not contaminate ponds, waterways or ditches with the product or used container.

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

GB - Vm 02000/5018 NI - Vm 02000/3010

8 DATE OF FIRST AUTHORISATION

03 October 2018

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

December 2024

10 CLASSIFICATION OF VETERINARY MEDICINAL PRODUCTS

Veterinary medicinal product subject to prescription.

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

Gavin Hall Approved: 01 April 2025

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Registration holder

Norbrook Laboratories Limited

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