VETOQUINOL’S ANTI-INFECTIVE RANGE -...

VETOQUINOL’S ANTI-INFECTIVE RANGE

SERVICES

CONVENIENCE

TECHNICAL SUPPPORTEFFICACY

EASE OF ADMINISTRATION

DOSING ACCURACY

PALATABILITY

COMPLIANCE

INTRODUCTION

VETOQUINOL OVERVIEWVetoquinol is an independent, family owned company exclusively dedicated to animal health, established in 1933.

Vetoquinol is a truly global company with 9 manufacturing sites producing 29 million units a year, making us the 9th largest animal health company in the world.

A core part of the Vetoquinol business is new product development. With 159 employees dedicated to research & development, Vetoquinol launches an average of 2.5 products and contributes to, or commissions, over 120 scientific publications every year. 7% of our annual sales are re-invested into the R&D departments of Vetoquinol.

To ensure the products which we deliver to you are of the highest quality, Vetoquinol dedicates 1 person in every 3 employees to checking the quality of our products.

Making Vetoquinol your partner ofchoice for your anti-infective needs:Vetoquinol has over 80 years experience of providing a range of anti-infective medications to veterinary surgeons around the world. Throughout this time we have endeavoured to provide veterinary surgeons with the right medication for the right condition, at the right dose, at the right intervals, for the right time.

Alongside the versatile product range Vetoquinol offers, we are also committed to bringing a range of services to veterinary practices which help to improve the use of anti-infective medicines.

Appropriate use of anti-infectives:Vetoquinol strongly believes that veterinary surgeons should be able to make the appropriate choice of anti-infective to best treat their patient. Vetoquinol has introduced the following services and contributions to improve anti-infective use in veterinary practices:

Practice Infection Control Assessments and CPD.

Training in cytology.

Anti-infective protocol meetings.

Vet Touch app to aid client communication.

PROTECT Guidelines, produced by BSAVA, distributed by Vetoquinol.

REQUEST initiative, promoting an evidence-based approach to fluoroquinolone use.

Product formulations across 5 classes of anti-infectives with improved palatability,

dosing options and packaging; all of which help improve compliance.

Technical support service where all technical queries are responded to within 2 working hours.

See accompanying SPCs for further information. Active ingredients: Marbocyl - marbofloxacin, Aurizon - marbofloxacin, clotrimazole & dexamethasone, Clavaseptin - amoxicillin & clavulanic acid, Clindaseptin - clindamycin & Cefaseptin - cefalexin. Legal category: UK: All POM-V. ROI: All POM. Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117.Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

VETOQUINOL AND ANTI-INFECTIVE MEDICATIONS

ART6349


� Periodontal disease� Respiratory infections� Genitourinary infections� Orthopaedic infections� Dermatological infections� Aural infections

Cefaseptin Cefalexin

Marbocyl Marbofloxacin Clindaseptin Clindamycin

Clavaseptin Amoxicillin/ clavulanic acid

Aurizon Marbofloxacin, clotrimazole & dexamethasone

Vetoquinol’s brandsoffer solutions for the most commonly seen infections

in veterinary practice.

TIPS FOR USING ANTI-INFECTIVE MEDICINES RESPONSIBLY IN YOUR PRACTICE

Responsible use of anti-infective medications can optimize therapeutic effects whilst minimizing the risk of selection for resistant bacteria. Using anti-infective medications responsibly means using the correct anti-infective therapy, as little as possible but as much as necessary.

The following provides some steps you can take to increase the responsible use of anti-infective medications in your practice:

• Choose the right drug for the right bug.

Construct protocols for anti-infective medicine use that all members of staff adhere to.

Choose medications based on their pharmacodynamic properties.

Consider which bacteria are likely to be involved (anaerobes, aerobes, Gram positive vs Gram negative).

Use culture and sensitivity testing. • Culture promptly when it is likely a prolonged course of anti-infective medication will be prescribed (e.g. pyoderma, otitis externa, deep/surgical wound infection).

• Repeat culture after long courses of anti-infective medications.

• Work with pet owners to avoid the need for anti-infective medications.

Outline the benefits of regular health checks.

Use symptomatic relief or topical preparations where appropriate.

Isolate infected animals where possible.

• Avoid inappropriate use.

Do not use in uncomplicated viral infections.

Restrict use to diseased animals.

Advise clients on correct storage and use of products.

Avoid underdosing.

• Monitor anti-infective medication sensitivity.

Culture and sensitivity should be obtained whenever possible to ensure treatment is appropriate.

Monitor culture and sensitivity trends.

• Record use and justify deviations from practice protocols.

You should be able to justify your choice of anti-infective medication and the dosage you use.

Taking accurate records as a practice can help you to validate your anti-infective medication choices.

Further information: 1. BSAVA PROTECT Poster: https://www.bsava.com/Portals/4/knowledgevault/resources/files/Protect_Poster.pdf2. FECAVA Advice on Responsible Use of Antimicrobials: http://www.fecava.org/sites/default/files/files/2014_12_fecava_responsible%20use%20AM.pdf

Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117.Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

Do you know (or highly suspect)a bacterial infection is present?

YES

YES

NO (it might resolve)

YES NO

Is the use of anti-infectivemedication essential to

treat the infection?

Will delaying treatment threaten the animal’s

wellbeing?

Choose an anti-infective medication based on cytology and expected cause, current

recommendations and scientific literature

Consider use of other anti-infective agents if

recommended and supportedby scientific literature

If not resolving,take samples

for culture andsensitivity testing

If not resolving,take samples

for culture andsensitivity testing

Consider non-bacterial causes (viral, parasitic,

non-infectious)

NO

Take samples for cultureand sensitivity testing

Choose an anti-infective medication based on laboratory results,

recommendations and scientific literature

If indicated changetreatment according to laboratory results and

use the narrowestspectrum anti-infective

medication possible

If there is a poor response, review

your diagnosis and treatment plan

TIPS FOR USING ANTI-INFECTIVE MEDICINES RESPONSIBLY IN YOUR PRACTICE

Art6350

A STEP-BY-STEP GUIDEVetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

ART6384

A GUIDE TO WASHING HANDS

STEP 1Wet the hands with warm running water.

STEP 6Right palm overleft dorsum andleft palm over right dorsum.

STEP 2Apply enough antiseptic tocover hands.

STEP 7Rotational rubbing, backwards forwards with clasped fingers of right claspedin left palm andvice versa.

STEP 3Palm to palm fingers interlaced.

STEP 8Rotational rubbingof right thumb & hand in left palmand vice versa.

STEP 4Rub palm to palm.

STEP 9Finally rinse the hands with waterand dry thoroughly with a cleanpaper towel.

STEP 5Backs of fingers to opposing palms with fingers interlocked.

Follow this stepped process toensure antiseptic coverage ofall areas of the hands.

An antiseptic hand wash will remove debris and oil from the skin and kill bacteria on the skin surface.

References: 1. McKay L. et al (2007) Antimicrobial testing of selected fluoroquinolones against Pseudomonas aeruginasa isolated from canine otitis. Journal of American Animal Hospital Association 43:307-311. Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117. Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible


ART6358

LABORATORY GUIDE TO THE CYTOLOGICALINVESTIGATION OF OTITIS EXTERNA

STAGE 1. Sample collection:

STAGE 2. Sample preparation:

STAGE 3. Microscopic examination:

Is cytology normal?Normal features include: Absence or low numbers of leucocytes. Low numbers of Malassezia pachydermatis and Staphylococci may be observed attached to shed squames.

Is cytology abnormal?Abnormal features include: Leucocytes, Bacteria, Yeasts, Neoplastic cells.

Cytologic sample from a normal ear. Note the low cell content in the cerumen.

Increased numbersof squames, someof which are nucleated due to increasedcellular turnover.

Squames withsurroundingneutrophils.

Squames, proteinaceous debris, and dark, pyknotic neutrophils.

a) Sample prior to ear cleaning or commencing ear medication

b) Use a clean, dry swab c) Ideally sample horizontal canal of ears (in smaller dogs sample the vertical canal instead)

a) Roll collected material on to a clean, dry slide

b) Stain using a recognised staining system such as Diff-Quik

c) Air dry slide (N.B. If long-term storage of sample is required then heat fix)

Staphylococcus spp.Coccoid (circular shaped). The commonest ear pathogen. If in very low numbers and not associated with any leucocytes, may not be pathogenic. Culture and sensitivity may be required.

Pseudomonas spp.Bacilli (rod shaped). Culture and sensitivity highly recommended to establish a sensitivity profile and to differentiate from other Gram negative bacilli such as Escherichia coli and Proteus spp. Choose an anti-infective medication with a good sensitivity profile against Pseudomonas spp. e.g. marbofloxacin.1

Malassezia pachydermatis. Typically flask or peanut-shaped. If in very low numbers and not associated with any leucocytes, the presence of M.pachydermatis may not be pathogenic. If more prolific, then M.pachydermatis is considered a significant pathogen. Treatment with an ear preparation containing an anti-fungal agent suchas clotrimazole is required.

BACTERIOSTATIC VS BACTERICIDALANTIMICROBIALS: WHAT’S THE DIFFERENCE?

Understanding the difference between the mode of action of different anti-infective medications is critical when treating bacterial infections responsibly.

Bactericidal: an anti-infective medication which kills the bacteria. The host’s immune system is helpful but not essential. A bactericidal drug can become non-bactericidal if the concentration of antimicrobial in the tissue does not reach the required level.1

Bacteriostatic: an anti-infective medication which inhibits the growth of the bacteria as opposed to killing them. The bacteria must be killed by the host’s own immune system.1

The following shows different classes of anti-infective medication according to mechanism of action and as bacteriostatic or bactericidal agents2:

Anti-infectivemedication class Mechanism of action Bacteriostatic or

bactericidal action

Penicillins Cephalosporins

Either inhibit cell wall synthesis or activate enzymes which disrupt the cell wall

Bactericidal

Polymyxins

Act on the cell (plasma) membrane to modify permeability causing loss of intracellular molecules to the external environment

Bactericidal

Diaminopyrimidines (e.g. trimethoprim)Sulfonamides

Inhibit synthesis of nucleic acidsBacteriostatic but bactericidal when one agent from each group is combined

Fluoroquinolones Nitroimidazoles (e.g. metronidazole)

Inhibit the enzymes involved in DNA metabolism, including DNA gyrase and DNA-dependent RNA polymerase or cause disruption of the DNA template

Bactericidal

Macrolides* LincosamidesPhenicols*Fusidic acid

Bind to 50S subunit of ribosomes causing inhibition of bacterial protein synthesis

Bacteriostatic

TetracyclinesAminoglycosides

Bind to 30S ribosomal subunit of ribosomes leading either to misreading of mRNA code or to inhibition of the first step of protein synthesis

Bacteriostatic (tetracyclines*) or bactericidal (aminoglycosides)

* Please note that some agents which are bacteriostatic can be bactericidal against some species and at high concentrations, consult the product SPC for further information.


TIME-DEPENDENT VS CONCENTRATION-DEPENDENT: DOES THAT CHANGE ANYTHING?

Art6366

Understanding the difference between time or concentration-dependence of different anti-infective medications is important when treating bacterial infections responsibly.

Time-dependent anti-infective medications

Time-dependent anti-infective medications have a slow bactericidal action. The anti-infective medication’s plasma concentration should be over the MIC for at least 40-50% of the dosing interval for optimal efficacy.

Concentration dependent anti-infective medications

Concentration-dependent anti-infective medications eradicate bacteria at a higher concentration. Efficacy can be predicted by looking at the Cmax/MIC or the AUC/MIC ratios achieved by the anti-infective medication. To be successful in providing a cure with a single dose, the Cmax/MIC ratio needs to be greater than 8-10 and the AUC/MIC needs to be higher than 100-125.

Time versus concentration dependant antibiotics 3

Time dependantConcentration dependant

MIC

1 2 3 Administration

Pla

sma

Dog

Con

cent

ratio

n

Efficacy measures for concentration dependant antibiotics 3

0 2 4 6 8 10 12 14 16 18 20 22 24

0

10

20

30

40

50

Time (Hours)

Time above MIC

AUC

C(max)

C(max) / MIC Ratio

MIC

Pla

sma

Con

cent

ratio

n µg

/ml

References: 1. Loscher W, Ungemach FR, Kroker R (2003): Pharmacotherapie ei Haus und Nutztieren, 6. Aktuaslisierte Auflage, Parey. 2. Guardabassi L., Jensen L.B. & Kruse H. (2008) Guide to Antimicrobial Use in Animals. Blackwells Publishing. (6) 79. 3. Papich MG. Pharmacokinetics-pharmacodynamics Modelling and the Rational Selection of Dosage Regimes for the Prudent Use of Antimicrobial Drugs. Veterinary microbiology 2014 (171); 480-486.

HOW TO RECOGNISE BACTERIAUNDER THE MICROSCOPE

CytologyKnowledge of the bacterial species present when treating an infectious condition is important in selecting an appropriate anti-infective medication and therefore culture and sensitivity testing is often indicated. A combination of cytology and a knowledge of which pathogens are likely for a given situation can also help in selecting an appropriate antimicrobial.

Cytological Staining with Diff-QuikAlways take multiple samples to stain.How to stain:

1. Dip sample five times (or between 5-10 seconds) into the fixative (fast green in methanol – pale green colour).

2. Dip sample for 1 second, five times into Stain 1 (eosin G in phosphate buffer – red colour). Allow excess to drain after each dip.

3. Dip sample for 1 second, five times, into Stain 2 (thiazine dye in phosphate buffer – blue colour). Allow excess to drain after each dip.

4. Rinse sample in distilled/tap water or Weise’s buffer, being careful not to wash off the stains.

5. Leave the sample to dry before examining under microscope at x100 with oil immersion.

Stained Microbes

Gram StainThe Gram stain was discovered by H.C. Gram in 1884. It allows a large proportion of clinically important bacteria to be classified as either Gram positive or negative based on their morphology and differential staining properties.

How to Gram Stain a Slide1. Heat fix a thin smear by passing the slide through a Bunsen burner

multiple times for roughly 3 seconds, do not overheat the sample.2. Stain with crystal violet (0.5% aqueous solution) for 30 seconds.3. Wash with water briefly.4. Stain with Gram’s Iodine (Lugol’s Iodine) for 30 seconds.5. Wash with water briefly.6. Decolourise with acetone/alcohol (Gram decolouriser); allow to flow

over slide held at a 30° angle until colour begins to fade (should only take a few seconds).

7. Wash immediately with water for 5 seconds.8. Counterstain with safranin (0.5% aqueous solution) for 15 seconds.9. Wash with water, blot dry and examine under microscope at x100 with

oil immersion.10. Results: o Gram-positive bacteria = BLUE o Gram-negative bacteria = RED

Rod Cocci Yeast


DIFFERENT BACTERIAL TYPES1

Art6356

References: 1. http://www.columbia.edu/itc/hs/medical/pathophys/id/2009/introNotes.pdf

Gram Positive Gram NegativeStaphylococci Enterobacteriaceae CampylobacterStreptococci E.coli Yersina enterocoliticaEnterococci Klebsiella BordetellaBacillus Pseudomonas PasteurellaListeria Haemophilus BacteroidesNocardia Proteus FusobacteriumActinomyces Salmonella PorphyromonasClostridiumCorynebacterium

Veillonella

NeisseriaBranhamella

BacteroidesFusobacterium

Non-lactose fermentersSalmonella

Shigella

Lactose fermentersE.coli

Klebsiella

Enterobacteriaceae

AnaerobicAerobicAnaerobicAerobic

ActinomycesClostridium

BacillusListeria

Nocardia

PeptostreptococciStaphylococciStreptococciEnterococci

Cocci Rods

Intracellular Sacteria:ChlamydiaRickettsiaBorellia

Poorly Staining:MycoplasmaLegionella

Helicobacter

Acid Fast Stain:Mycobacterium

Nocardia (modified)

Miscellaneous/poorly stained species

PseudomonasVibrio

Hemophilus

Gram Positive Bacteria

AnaerobicAerobic andFacultative Anaerobic

AnaerobicAerobic andFacultative Anaerobic

Cocci Rods

Gram Negative Bacteria

CEFASEPTIN®

Cefaseptin is licensed for the treatment of bacterial skin infections (including deep and superficial pyoderma) and treatment of urinary tract infections (including nephritis and cystitis) in dogs.

Cefaseptin should be administered at a rate of 15 mg/kg BID (equivalent to 30 mg/kg/day) for the following durations dependent on the type of infection which is being treated:

Infection type Treatment period

Urinary tract infection 14 days

Superficial bacterial skin infection At least 15 days

Deep bacterial skin infection At least 28 days

Making accurate dosing easyCompliance and accurate dosing are critical to ensuring effective and responsible anti-infective medication treatment.

Cefaseptin is now available as a range of flavoured, multi-scored and crushable tablets. This makes the tablets easy to administer and provides accurate dosing.

Cefaseptin comes in 3 strengths:

Tablet size Pack size Split method

75 mg 250 tablets 2-way divisible

300 mg 250 tablets

4-way divisible

750 mg 150 tablets

CEFASEPTIN®

See accompanying SPC for further information. Active ingredient: cefalexin. Legal category: UK: POM-V. ROI: POM. Further information is also available on request from: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

In severe or acute conditions (except in cases of known renal insufficiency) the dose may be doubled to 30 mg/kg BID. Cefaseptin may be crushed or added to food if necessary.ART6340

75 mg 300 mg 750 mg

Body

wei

ght (

kg)

2.5

5.0

10.0

15.0

20.0

25.0

30.0

37.5

50.0

Cefaseptin Dosing GuideActual tablet size

75 mg 300 mg 750 mg

The following dose guide indicates the split of tablets for different weights using the dose rate of 15 mg/kg which should be administered twice a day:

CLAVASEPTIN®

ComplianceCompliance is one of the key success factors in effective treatment with anti-infective medications.Clavaseptin was the first amoxicillin/clavulanic acid to be awarded the ISFM ‘Easy to Give Award’ due to its palatable tablets and optimum shape.

Clavaseptin comes in4 different strengths:

Clavaseptin tablets have been improved to make them even easier to split in half.

500mg

50mg

62.5mg

250mg

Tablet Size Pack Size Active Ingredient Contents

50 mg100 tablets

40 mg amoxicillin and 10 mg clavulanic acid500 tablets

62.5 mg100 tablets

50 mg amoxicillin and 12.5 mg clavulanic acid500 tablets

250 mg100 tablets


500 mg100 tablets


CLAVASEPTIN®

See accompanying SPC for further information. Active ingredient: amoxicillin/clavulanic acid. Legal category: UK: POM-V. ROI: POM. Further information is also available on request from: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

50 mg Tablets1 tablet per 4 kg

Twice Daily

62.5 mg Tablets1 tablet per 5kg

Twice Daily

250 mg Tablets1 tablet per 20 kg

Twice Daily

500 mg Tablets 1 tablet per 40 kg

Twice Daily

Body

wei

ght (

kg)

4 kg

5 kg

10 kg

20 kg

30 kg

40 kg

OR

Improved packaging and tablet designClavaseptin has colour-coded packaging and blister packs which aids differentiationbetween sizes. This helps to improve the dispensing process and avoid confusion. Special dispensing packs are also available from Vetoquinol for Clavaseptin to help make dispensing even easier.

The packaging has also been improved to be PVC-free and environmentally friendly whilst including enhanced technology to protect tablets from moisture.

ART5908

AURIZON®

0%

20%

40%

60%

80%

100%

ReferenceAurizon

83.8%

95.8%

Sign

ifica

nt d

iffer

ence

(p=0

.01)

Products

Perc

enta

ge

0%

20%

40%

60%

80%

100%

Products

Perc

enta

ge

ReferenceAurizon ReferenceAurizon

DAY 7 DAY 1495.8%

79.7%

51.4%

37.5%

Clinical efficacy of treatmentPercentage of canine otitis externa cases that respondedsatisfactorily to treatment.

n rapid improvement n rapid improvementn cure n cure

Percentage of animals with a normal pain scoreIn the same comparative study, dogs treated with Aurizon were shown to be in significantly less pain during the course of treatment.

EfficacyTriple action for otitis externa of bacterial and fungal originA trial was carried out to compare the efficacy of Aurizon and a licensed preparation (containing polymixin B, miconazole and prednisolone) in the treatment of canine otitis externa. The results revealed a significantly better clinical outcome at day 14 when treating with Aurizon.1

Dexamethasone 1. anti-inflammatory

Marbofloxacin 2. antimicrobial

effective against grampositive and gram negative bacteria

Clotrimazole3. anti-fungaleffective against

Malasseziapachydermatitis

Tripleaction

AURIZON®

n Aurizon diffuses extensively through cerumen.2

n Marbofloxacin’s activity is not diminished in an abscess, contrary to aminoglycosides which are inactivated by pus.3,4

Multiple Indications*

For use in dogs for the treatment of otitis externa of both bacterial and fungal origin.

n Once daily administration for 7-14 days to aid owner compliance.

n Flexible nozzle for ease of administration.

n 2 available sizes (10 and 20ml) for your convenience.

Control

Aurizon®

Epiotic®

Easotic®

Panolog®

Posatex®

Otomax®

Surolan®

Otifree®

Time (minutes)

Diffu

sion

pat

hway

(cm

)

50000

2

4

6

1000 1500

Diffusion of several otic preparations through synthetic canine cerumen2

* For use in dogs for the treatment of otitis externa of both bacterial and fungal origin. References: 1. Rougier, S. et al (2005) A Comparative Study of Two Antimicrobial/Anti-inflammatory Formulations in the Treatment of Canine Otitis Externa, Veterinary Dermatology, Vol 16, pages 299-307. 2. Stahl, J. et al (2012) The In Vitro Diffusion of Several Antimicrobial Otic Preparations Through Canine Cerumen, 7th World Congress of Veterinary Dermatology, Vancouver. 3. Riviere, J. E. et al (2009), Veterinary Pharmacology and Therapeutics, 9th Edition, Wiley and Sons, page 990. 4. Maddison, J. E., et al, Small Animal Clinical Pharmacology, page 171.

See accompanying SPC for further information. Active ingredients: marbofloxacin, clortrimazole and dexamethasone. Legal category: UK: POM-V. ROI: POM.Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

Rods seen on cytology Purulent exudative otitis

ART5953

MARBOCYL®

0.5

0.00 12 24 36 48

Arithmetic plots of the mean plasma concentrations (ug/ml) versus time (h), after a single oraladministration of enrofloxacin or marbofloxacin at the nominal dose of 5 and 2 mg/kg, respectively:

Enrofloxacin Enrofloxacin metabolite (ciprofloxacin) Marbofloxacin

Time (Hours)

1.5

1.0

Plas

ma

Conc

entr

atio

n (u

g/m

l)

MIC E.coli WT(1)

Efficacyn A wide range of indications.*

n Pharmacokinetics support ONCE DAILY use.

SafetyMarbocyl is well tolerated.

n There is no need to adjust the dosage of Marbocyl in dogs with mild renal impairment.(4)

n No link with cases of retinal toxicity in cats.(5)

Marbocyl P Marbocyl SA Injection

n Skin and soft tissue infections.

n Urinary tract infections +/- prostatitis.

n Respiratory tract infections.

n Infected wounds and abscesses.

n Upper respiratory tract infections.


n Urinary tract infections.


Marbocyl(2) enrofloxacin(2) pradofloxacin(3)

Cmax (µg/ml) 2.53 1.75 1.2

Half-life (hours) 10.89 4.61 >8

AUC (µg/ml) 35.44 11.65 12.98

Maintains effective plasma concentration for longer .(1)

* caused by susceptible strains of organisms.

MARBOCYL®

Pasteurella multocida

0%

50%

100%

Escherichiacoli

Proteusmirablis

Pseudomonasaeruginosa

(otitis)

Bacteria

Perc

enta

ge o

fsu

scep

tible

bac

teri

a

Pseudomonasaeruginosa

(dermatological)

Staphylococcusintermedius

(otitis)

Staphylococcusintermedius

(dermatological)

Staphylococcusaureus(otitis)

Staphylococcusaureus

(dermatological)

Marbofloxacin Enrofloxacin

Graph showing susceptibility of bacteria to marbofloxacin and enrofloxacin, used in the treatment of cat and dog infections in Europe over a seven year period.*

* Based on CLSI registered breakpoints.

References: 1. Cester CC, Schneider M and Toutain PL Comparative kinetics of two orally administered fluoroquinolones in dog: Enrofloxacin versus Marbofloxacin. Revue de Médecine Vétérinaire 1996(147)10:703-716. 2. Frazier DL, Thompson L, Trettien A, Evans EI Comparison of fluoroquinolone pharmacokinetic parameters after treatment with marbofloxacin, enrofloxacin and difloxacin in dogs. J. Vet. Pharmacol. Therap. 23, 93-302, 2000. 3. Veraflox. EPAR- Scientific discussion. EMA/142130/2011. 4. Lefebvre HP, Dupouy V, Schneider M, Laroute V, Toutain PL. Effect of experimental renal impairment on disposition of marbofloxacin and its metabolites in the dog. Journal of Veterinary Pharmacology and Therapeutics. 1998, 21, 453-461. 5. Wiebe V, Hamilton P. Fluoroquinolone-induced retinal degeneration in cats. Dr Vet Med Today: Topics in Drug Therapy. JAVMA. Vol 221, 11 December 1, 2002. 6. Stephane Kroemer, Farid El Garch, Delphine Galland, Jean-Luc Petit, Frederique Woerhrle, Henri-Jean Boulouis. Antibiotic susceptibility oif bacteria isolated from infections in cats and dogs throughout Europe (2002-2009). ELSEVIER, Comparative Immunology, Microbiology and Infectious Diseases November 6-9, 2014 Germany, Bayern, Munich.

See accompanying SPC for further information. Active ingredient: marbofloxacin. Legal category: UK: POM-V. ROI: POM.Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

ART5777

Confidencen Bacteria remain sensitive to marbofloxacin over time.(6)

ConvenienceMarbocyl P has a palatable tablet formulation making it easier to administer and aid compliance. It is presented as: 5 mg x 100 tablets, 20 mg x 100 tablets and 80 mg x 72 tablets.

Indications and dosage: 2 mg/kg once daily.

Dogs: Skin and soft tissue infections: 5-40 days of treatment.Urinary tract infections: 10-28 days of treatment.Respiratory tract infections: 7-21 days of treatment.

Cats:Skin and soft tissue infections: 3-5 days of treatment.Upper respiratory tract infections: 5 days of treatment.

Marbocyl SA Injection* is the only licensed fluoroquinolone with an intravenous** indication and can also be administered subcutaneously. Indications and dosage: 2 mg/kg once daily.

Dogs:Infected wounds and subcutaneous abscesses: a single injection followed by 6 days of oral Marbocyl P.Lower urinary tract infections: a single injection followed by 10-28 daysof oral Marbocyl P.

Cats:Infected wounds and subcutaneous abscesses: a single SC or IV injection followed by 3-5 daysof SC injections.

* only available in the UK ** for cats and dogs in Europe

CLINDACYL® TABLETS Compliance is one of the key success factors in successful anti-infective medication treatment. Clindacyl Tablets and Clindaseptin Oral Solution offer the choice of tablets or oral solution clindamycin for easy dosing of dogs and cats*.

Clindacyl Tablets and Clindaseptin Oral Solution have multiple indications:

Clindacyl TabletsClindacyl Tablets come in 4 strengths: 25mg, 75mg, 150mg and 300mg, which are presented in 100 tablet boxes in blister strips of 10.

Clindacyl Tablets DosingInfected wounds, abscesses, oral cavity/dental infections: 5.5 mg/kg every 12 hours for 7-10 days. Treatment may be extendedto a maximum of 28 days based on clinical judgement.

25 mg 1 tablet per 4.5 kg twice daily75 mg 1 tablet per 13.5 kg twice daily

150 mg 1 tablet per 27 kg twice daily300 mg 1 tablet per 54 kg twice daily

Superficial pyoderma**: 11 mg/kg every 24 hours, treatment should continue for at least 21 days.

25 mg 2 tablets per 4.5 kg once daily75 mg 2 tablets per 13.5 kg once daily

150 mg 2 tablets per 27 kg once daily300 mg 2 tablets per 54 kg once daily

Osteomyelitis: 11 mg/kg every 12 hours for at least 28 days.

25 mg 1 tablet per 4.5 kg twice daily75 mg 2 tablets per 13.5 kg twice daily

150 mg 2 tablets per 27 kg twice daily300 mg 2 tablets per 54 kg twice daily

Providing antimicrobial cover during dental procedures: 5.5 mg/kg every 12 hours for 10 days. Treatment should commence 5 days before the procedure and continue for 5 days thereafter.

25 mg 1 tablet per 4.5 kg twice daily75 mg 1 tablet per 13.5 kg twice daily

150 mg 1 tablet per 27 kg twice daily300 mg 1 tablet per 54 kg twice daily

* Clindaseptin Oral Solution is licensed for use in dogs and cats, Clindacyl Tablets are licenced for use in dogs only. ** Clindacyl Tablets are licensed for this in the UK only.

Infected woundsand abscesses

Superficial pyoderma** Osteomyelitis Antimicrobial cover

during dental procedures

25mg 75mg 150mg 300mg

*

CLINDASEPTIN® ORAL SOLUTION

^Vetoquinol market research study number VTQUK121115.See accompanying SPC for further information. Active ingredient: clindamycin. Legal category: UK: POM-V. ROI: POM.Further information is also available on request from: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

Clindaseptin Oral Solution DosingClindaseptin Oral Solution is presented as a25 mg/ml solution and comes in 22 ml bottleswith a dosing syringe.

CatsInfected wounds and abscesses:11 mg/kg once per 24 hours or 5.5 mg/kg every 12 hours for 7-10 days.

DogsInfected wounds, abscesses and oral cavity/dental infections:11 mg/kg once per 24 hours or 5.5 mg/kg every 12 hours for 7-10 days.

Treatment of bone infections (osteomyelitis): 11 mg/kg every 12 hours for 28 days minimum.

ART6500

98% dose compliance in dogs and cats!^

Weight Volume if administering at 11 mg/kg Volume if administering at 5.5 mg/kg

1 kg 0.50 ml 0.25 ml

2 kg 1.00 ml 0.50 ml

3 kg 1.50 ml 0.75 ml

4 kg 2.00 ml 1.00 ml

5 kg 2.50 ml 1.25 ml

Weight Volume if administeringat 11 mg/kg

Volume if administeringat 5.5 mg/kg

1 kg 0.50 ml 0.25 ml

5 kg 2.50 ml 1.25 ml

10 kg 5.00 ml 2.50 ml

NAME OF THE VETERINARY MEDICINAL PRODUCT: Cefaseptin 75mg, 300 mg & 750 mg tablets for dogs. QUALITATIVE AND QUANTITATIVE COMPOSITION: One tablet contains: Active Ingredient: cefalexin (as cefalexin monohydrate) 75 mg, 300 mg or 750 mg respectively. PHARMACEUTICAL FORM: Beige oblong tablet. 75 mg tablets can be divided into equal halves. 300 mg and 750 mg tablets can be divided into equal halves and quarters. CLINICAL PARTICULARS: Target species: Dogs. Indications for use, specifying the target species: For the treatment of bacterial skin infections (including deep and superficial pyoderma) caused by organisms, including Staphylococcus spp., susceptible to cefalexin. For the treatment of urinary-tract infections (including nephritis and cystitis) caused by organisms, including Escherichia coli, susceptible to cefalexin. Contraindications: Do not use in cases of known hypersensitivity to the active substance, to other cephalosporins, to other substances of the β-lactam group or to any of the excipients. Do not use in the case of resistance to cephalosporins or penicillins. Do not use in rabbits, guinea pigs, hamsters and gerbils. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: The need for systemic antibiotics compared with non-antibiotic alternatives for the treatment of superficial pyoderma should be carefully considered by the responsible veterinarian. As with other antibiotics which are excreted mainly by the kidneys, systemic accumulation may occur in the body when renal function is impaired. In case of known renal insufficiency, the dose should be reduced and antimicrobials known to be nephrotoxic should not be administered concurrently. This product should not be used to treat puppies of less than 1 kg of bodyweight. 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 epidemiological information. Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to cefalexin and may decrease the effectiveness of treatment with other cephalosporins and penicillins, due to the potential for cross-resistance. Official, national and regional antimicrobial policies should be taken into account when the product is used. 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 cephalosporin 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. Wash hands after use. 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 in breathing are more-serious symptoms and require urgent medical attention. Adverse reactions (frequency and seriousness): In very rare cases, nausea, vomiting and/or diarrhoea have been observed in some dogs after administration. In rare cases hypersensitivity can occur. In cases of hypersensitivity reactions the treatment should be stopped. The frequency of adverse reactions is defined using the following convention: very common (more than 1 in 10 animals displaying adverse reaction(s) during the course of one treatment), common (more than 1 but less than 10 animals in 100 animals), uncommon (more than 1 but less than 10 animals in 1,000 animals), rare (more than 1 but less than 10 animals in 10,000 animals) & very rare (less than 1 animal in 10,000 animals, including isolated reports). Use during pregnancy, lactation or lay: The safety of the veterinary medicinal product has not been established in bitches during pregnancy and lactation. Use only according to the benefit/risk assessment by the responsible veterinarian. Interaction with other medicinal products and other forms of interaction: 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 aminoglycoside antibiotics or some diuretics such as furosemide can enhance nephrotoxicity risks. Amounts to be administered and administration route: For oral administration. 15 mg of cefalexin per kg of bodyweight twice daily (equivalent to 30 mg per kg of bodyweight per day) for a duration of: 14 days in case of urinary-tract infection, at least 15 days in case of superficial bacterial infection of the skin & at least 28 days in case of deep bacterial infection of the skin. To ensure correct dosage, bodyweight should be determined as accurately as possible to avoid underdosing. The product may be crushed or added to food if necessary. In severe or acute conditions, except in cases of known renal insufficiency, the dose may be doubled. Overdose (symptoms, emergency procedures, antidotes), if necessary: Trials performed on animals with up to 5 times the recommended twice daily dosage of 15 mg cefalexin/kg demonstrated that the product was well tolerated. Adverse reactions that may occur at the recommended dose are expected in the case of overdose. In the event of overdose, treatment should be symptomatic. Withdrawal period(s): Not applicable. PHARMACOLOGICAL PROPERTIES: Pharmacotherapeutic group:

Antibacterials for systemic use, first generation cephalosporins. ATC vet code: QJ01DB01. Pharmacodynamic properties: Cefalexin acts by inhibiting the nucleopeptide synthesis of the bacterial wall. Cephalosporins interfere with the enzymes of transpeptidation making it unable to cross-link the peptidoglycans of the bacterial cell wall. The glycan cross-linking is essential for the cell to build its cell wall. Inhibition of the biosynthesis results in a weakened cell wall, which eventually ruptures to osmotic pressure. The combined action results in cell lysis and filament formation. Cefalexin is active against a wide range of Gram-positive (e.g. Staphylococcus spp.) and Gram-negative (e.g. Escherichia coli) aerobic bacteria. The following breakpoints are recommended by the CLSI in dogs for E.coli and Staphylococcus spp:

MIC (µg/mL) Interpretation

≤2 Sensitive

4 Intermediate

≥8 Resistant

Resistance to cefalexin can be due to one of the following mechanisms of resistance. Firstly, the production of cephalosporinases, that inactivate the antibiotic by hydrolysis of the β-lactam ring, is the most prevalent mechanism among Gram-negative bacteria. This resistance is transmitted by plasmid or chromosomally. Secondly, a decreased affinity of the PBPs (penicillin-binding proteins) for beta-lactam drugs is frequently involved for beta-lactam resistant Gram-positive bacteria. 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. Pharmacokinetic particulars: After single oral administration of the recommended dosage of 15 mg of cefalexin per kg of bodyweight to Beagle dogs, plasma concentrations were observed within 30 minutes. The plasma peak was observed at 1.3 hour with a plasma concentration of 18.2 mg/ml. The bioavailability of the active was over 90 %. Cefalexin was detected until 24 hours after the administration. The first urine specimen was collected within 2 to 12 hours with peak concentrations of cefalexin measured at 430 to 2758 mg/ml within 12 hours. After repeated oral administration of the same dosage, twice a day for 7 days, plasma peaks occurred 2 hours later with a concentration of 20 mg/ml. Over the treatment period, concentrations were maintained above 1 mg/ml. The mean elimination half-life is 2 hours. Skin levels were around 5.8 to 6.6 mg/g, 2 hours after treatment. PHARMACEUTICAL PARTICULARS: List of excipients: Lactose monohydrate, Povidone K30, Croscarmellose sodium, Microcrystalline cellulose, Porcine liver powder, Yeast, Crospovidone & Sodium stearyl fumarate. Incompatibilities: Not applicable. Shelf life: Shelf life of the veterinary medicinal product as packaged for sale: 2 years. Shelf life after first opening the immediate packaging: 75 mg: 16 hours, 300 mg & 750 mg: 48 hours. Special precautions for storage: Store in the original package. Return any part used tablet to the opened blister-pack. Nature and composition of immediate packaging: PVC/aluminium/OPA blister, with an aluminium foil for sealing: cardboard box of 10 blisters of 10 tablets (75 mg & 300 mg), cardboard box of 25 blisters of 10 tablets (75 mg & 300 mg), cardboard box of 12 blisters of 6 tablets (750 mg) and cardboard box of 25 blisters of 6 tablets (750 mg). Not all pack sizes may be marketed. Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Ltd, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, Buckinghamshire, MK18 1PA. DATE OF FIRST AUTHORISATION: January 2016. LEGAL CATEGORY: UK: POM-V IE: POM

CEFASEPTIN®

NAME OF THE VETERINARY MEDICINAL PRODUCT: Clindacyl 25 mg, 75 mg, 150 mg & 300 mg Tablets. QUALITATIVE AND QUANTITATIVE COMPOSITION : Each tablet contains 25 mg, 75 mg, 150 mg or 300 mg Clindamycin (as Clindamycin Hydrochloride). PHARMACEUTICAL FORM: Tablet. CLINICAL PARTICULARS: Target species: Dogs. Indications for use, specifying the target species: Clindacyl 25 mg, 75 mg, 150 mg & 300 mg tablets are indicated for the treatment of infected wounds, abscesses, superficial pyoderma (superficial pyoderma is not indicated in 300 mg tablets in IE) and oral cavity/dental infections caused by or associated with clindamycin-sensitive staphylococci, streptococci, bacteroidaceae, Fusobacterium necrophorum, Clostridium perfringens and osteomyelitis caused by Staphylococcus aureus. Clindacyl 25 mg, 75 mg, 150 mg & 300 mg Tablets can also be used to help provide antimicrobial cover during dental procedures. Contra-indications: Do not administer to animals with hypersensitivity to clindamycin and lincomycin preparations. Do not administer to rabbits, guinea pigs, chinchillas, hamsters, horses or ruminants because ingestion of clindamycin by these species may result in severe gastro-intestinal disturbance. Special warnings for each target species: Before use of Clindacyl tablets, the identification of causative pathogenic micro-organisms should be carried out and their susceptibility to clindamycin should be established. Clindamycin and lincomycin show parallel-resistance. There is a partial cross-resistance to erythromycin and other macrolide-antibiotics. Special precautions for use: Special precautions for use in animals: During prolonged therapy of one month or greater, periodic liver and kidney function tests and blood counts should be performed. Patients with severe renal and/or hepatic disturbances accompanied by severe metabolic aberrations should be dosed with caution and should be monitored by serum examination during high dose clindamycin therapy. Wherever possible, the veterinary medicinal product should only be used based on susceptibility testing. Special precautions to be taken by the person administering the veterinary medicinal product to animals: Wash hands after the administration of this product. Persons with known hypersensitivity to Lincosamides (lincomycin, clindamycin) should not handle the product. Do not eat, drink or smoke while handling the product. Adverse reactions (frequency and seriousness): Clindamycin and lincomycin show parallel-resistance. There is partial cross-resistance to erythromycin and other macrolide-antibiotics. Clindamycin sometimes causes the overgrowth of non-sensitive organisms such as resistant clostridia and yeasts. In cases of superinfection or severe infection, appropriate measures should be taken according to the clinical situation. Vomiting and diarrhoea are observed occasionally. Use during pregnancy, lactation or lay: While high dose studies in rats suggests that clindamycin is not a teratogen and does not significantly affect the breeding performance of males and females, safety in gestating bitches or breeding male dogs has not been established. Therefore, the administration of the veterinary medicinal product during pregnancy and lactation should be the subject of a benefit/risk assessment by the veterinarian. Interaction with other medicinal products and other forms of interaction: Neuromuscular blocking effects have been observed with clindamycin possibly leading to an increase of efficacy of other neuromuscular blocking agents. The concomitant use of such drugs must be handled with care. Clindamycin should not be used concomitantly with chloramphenicol or macrolides because they may antagonise each other at the site of action. When clindamycin and aminoglycoside antibiotics (e.g. gentamicin) are used simultaneously adverse interactions (acute renal failure) cannot be fully excluded. Amounts to be administered and administration route: For oral administration. For treatment of infected wounds, abscesses, oral cavity/dental infections, administer 5.5 mg/kg bodyweight every 12 hours for 7 - 10 days. Treatment may be extended to a maximum of 28 days based on clinical judgement (not for 300 mg in IE). If no improvement is seen within 4 days, the sensitivity of the pathogens involved should be redetermined. For the treatment of superficial pyoderma (superficial pyoderma is not indicated in 300 mg tablets in IE) administer 11 mg/kg every 24 hours (i.e. 5.5 mg every 12 hours). Continue treatment for at least 21 days. For the treatment of osteomyelitis administer 11 mg/kg every 12 hours for at least 28 days. If no improvement is seen within 14 days, the sensitivity of the pathogens involved should be redetermined. To help provide antimicrobial cover during dental procedures, a 10 day course of 5.5 mg/kg every 12 hours is recommended. To ensure a correct dosage, bodyweight should be determined as accurately as possible. Overdose (symptoms, emergency procedures, antidotes), if necessary. Symptoms of overdose include vomiting, inappetency and diarrhoea (IE 75 mg: toxicosis has also been noted, IE 300 mg: occasional leukocytosis and increases in liver enzymes (AST, ALT) have been observed). In such cases, treatment should be stopped immediately and the dogs treated symptomatically. Withdrawal period(s): Not applicable. PHARMACOLOGICAL PROPERTIES: Pharmacotherapeutic group: Antiinfectives for systemic use: Lincosamides ATCvet code: QJ01FF01. Pharmacodynamic properties: Clindamycin, a chlorinated analogue of lincomycin, is an antibiotic with bacteriostatic action. Bactericidal actions have also been reported. Clindamycin is primarily a bacteriostatic antibiotic of the lincosamide group, which acts by inhibition of protein synthesis. The antibiotic activity of clindamycin is based on the inhibition of bacterial synthesis. Reversible coupling to the 50 s subunit of the bacterial ribosome inhibits inter alia the translation of tRNA-bound amino acids, thereby preventing elongation of the peptide chain. Because of this, the mode of action of clindamycin is predominantly bacteriostatic. Clindamycin has been shown to have in-vitro activity against the following organisms Staphylococcus spp; Streptococcus spp; Bacteroides spp; Fusobacterium spp; Clostridium spp. Clindamycin and lincomycin show cross-resistance, which is common also to erythromycin and other macrolide antibiotics. Acquired resistance can occur, by methylation of the ribosomal binding site via chromosomal mutation in gram positive organisms, or by plasmid-mediated mechanisms in gram negative organisms. Pharmacokinetic particulars: Clindamycin is rapidly absorbed; following oral administration up to 90% of the active ingredient is absorbed from the gastro-intestinal tract. After a single administration of one tablet to fasting dogs maximum plasma levels (Cmax) of 5 µg/ml are found compared to 3.4 µg/ml in non-fasting dogs. Bioavailability is greater in fasting dogs than fed dogs. Clindamycin crosses the placental barrier and can be detected in milk. PHARMACEUTICAL PARTICULARS: List of excipients: Microcrystalline cellulose, Sodium lauryl sulphate, Colloidal anhydrous silica, Magnesium stearate, Ludipress (Lactose monohydrate, povidone & crospovidone). Incompatibilities: None Known. Shelf life: Shelf-life of the veterinary medicinal product as packaged for sale: UK: 3 years (4 years for 300 mg). IE: 2 years (4 years for 300 mg). Special precautions for storage: The veterinary medicinal product does not require any special storage conditions. Nature and composition of immediate packaging: Polyethylene bottle with child resistant tamper evident closures containing 100 tablets. Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. IE 300mg: Chanelle Animal Health Ltd., 7 Rodney Street, Liverpool, L1 9HZ. DATE OF FIRST AUTHORISATION: 25 mg: UK: June 2002 IE: August 2010. 150 mg: UK: June 2002. IE: August 2010. 75 mg: UK: December 2001. IE: August 2010. 300 mg: UK: September 2010. IE: July 2008. DATE OF REVISION OF THE TEXT: 25 mg: UK: December 2007. IE: May 2011. 75 mg: UK: December 2007. IE: May 2011. 150 mg: UK: December 2007. IE: May 2011. 300 mg: UK: June 2015. IE: July 2013. LEGAL CATEGORY UK: POM-V. IE: POM.

NAME OF THE VETERINARY MEDICINAL PRODUCT: Clindaseptin 25 mg/ml oral solution for cats and dogs. QUALITATIVE AND QUANTITATIVE COMPOSITION: One ml contains: Active Ingredient: Clindamycin 25 mg (as Clindamycin Hydrochloride 27.15 mg) Excipients: Ethanol 96% 90.56 mg. PHARMACEUTICAL FORM: Oral solution. Clear, colourless solution. CLINICAL PARTICULARS: Target Species: Cats & Dogs. Indications for use, specifying the target species: In cats: For the treatment of infected wounds and abscesses caused by clindamycin-sensitive species of Staphylococcus spp. and Streptococcus spp. In dogs: For the treatment of infected wounds, abscesses and oral cavity/dental infections caused by or associated with clindamycin-sensitive species of Staphylococcus spp., Streptococcus spp., Bacteroides spp., Fusobacterium necrophorum, Clostridium perfringens. Adjunctive treatment of mechanical or surgical periodontal therapy in the treatment of infections of the gingival and periodontal tissues. For the treatment of osteomyelitis caused by Staphylococcus aureus. Contra-indications: Do not use in rabbits, hamsters, guinea pigs, chinchillas,

horses or ruminants because ingestion of clindamycin by these species may cause severe gastrointestinal disorders. Do not use in cases of hypersensitivity to either clindamycin or lincomycin, or to any of the excipients. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: Inappropriate use of the product may increase the prevalence of bacteria resistant to clindamycin. Whenever possible, clindamycin should only be used based on susceptibility testing. Official national and local antimicrobial policies should be taken into account when the product is used. Clindamycin shows parallel-resistance with lincomycin and co-resistance with erythromycin. There is a partial cross-resistance to erythromycin and other macrolides. In case of administration of high doses of clindamycin or during prolonged therapy of one month or greater, tests for liver and renal functions and blood counts should be performed periodically. In dogs and cats with kidney problems and/or liver problems, accompanied by severe metabolic aberrations, the dose to be administered should be carefully determined and their condition should be monitored by performing serum tests during treatment. Special precautions to be taken by the person administering the veterinary medicinal product to animals: Wash hands after administration. Persons with known hypersensitivity to lincosamides (lincomycin and clindamycin) should avoid contact with the veterinary medicinal product. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician. Other precautions: None. Adverse reactions (frequency and seriousness): Vomiting and diarrhoea are occasionally observed. Clindamycin sometimes causes the overgrowth of non-sensitive organisms such as resistant clostridia and yeasts. If superinfection occurs, the treatment should be stopped and appropriate measures should be taken based on the clinical situation. Use during pregnancy, lactation or lay: While high dose studies in rats suggests that clindamycin is not a teratogen and does not significantly affect the breeding performance of males and females, the safety of the veterinary medicinal product in gestating bitches/queens or breeding male dogs/cats has not been established. Use only according to the benefit/risk assessment by the responsible veterinarian. Clindamycin can pass the blood-milk barrier. As a consequence, treatment of lactating females can cause diarrhoea in puppies. Interaction with other medicaments and other forms of interaction: Neuromuscular blocking effects have been observed with clindamycin, which may possibly enhance the activity of neuromuscular blocking agents. The simultaneous use of such product must be made with caution. Do not use clindamycin together with chloramphenicol or macrolides as they share the same binding site on the ribosomes. During the simultaneous use of clindamycin and aminoglycosides (e.g. gentamicin), the risk of adverse interactions (acute renal failure) cannot be excluded. Clindamycin may reduce the levels of cyclosporine, concomitant use should be avoided. Amounts to be administered and administration route: For oral administration only. Recommended dosage: Cats: Infected wounds, abscesses: 11 mg clindamycin per kg of body weight per 24h or 5.5 mg/kg per 12h for 7 to 10 days. The treatment should be stopped if no therapeutic effect is observed after 4 days. Dogs: Infected wounds, abscesses and oral cavity/dental infections: 11 mg clindamycin per kg of body weight per 24h or 5.5 mg/kg per 12h for 7 to 10 days. The treatment should be stopped if no therapeutic effect is observed after 4 days. Treatment of bone infections (osteomyelitis): 11 mg clindamycin per kg of body weight every 12 hours during a period of 28 days minimum. The treatment should be discontinued if no therapeutic effect is observed in the first 14 days.

Dosage Volume to be administered per kg bodyweight

5.5 mg/kg Corresponding approximately to 0.25 ml per kg

11 mg/kg Corresponding approximately to 0.5 ml per kg

A 3 ml graduated syringe is provided to facilitate the administration of the veterinary medicinal product. Overdose (symptoms, emergency procedures, antidotes), if necessary: Doses of 300 mg/kg were tolerated by dogs without having adverse effects. Vomiting, loss of appetite, diarrhoea, leukocytosis and elevations in liver enzymes (AST, ALT) were observed occasionally. In such cases, discontinue treatment immediately and establish a symptomatic treatment. Withdrawal period(s): Not applicable. PHARMACOLOGICAL or IMMUNOLOGICAL PROPERTIES: Pharmacotherapeutic group: Anti-infectives for systemic use, lincosamides. ATC vet code: QJ01FF01. Pharmacodynamic properties: Clindamycin is mainly a bacteriostatic antibiotic belonging to the group of lincosamides. Clindamycin is a chlorinated analogue of lincomycin. It works by inhibiting bacterial protein synthesis. The reversible coupling to the sub-unit 50-S bacterial ribosome inhibits translation of amino acids linked to the tRNA, thereby preventing elongation of the peptide chain. That is why the mode of action of clindamycin is predominantly bacteriostatic. Clindamycin and lincomycin have cross-resistance, which is also common between erythromycin and other macrolides. Acquired resistance can occur, by methylation of the ribosomal binding site via chromosomal mutation in gram positive organisms, or by plasmid-mediated mechanisms in gram negative organisms. Clindamycin is active in vitro against many Gram-positive bacteria, Gram positive and Gram-negative anaerobic bacteria. Most aerobic or facultative Gram-negative bacteria are resistant to clindamycin. CLSI clindamycin veterinary breakpoints are available for dogs in Staphylococcus spp. in skin and soft tissue infections: S < 0.5 µg/ml; I = 1-2 µg/ml; R > 4 µg/ml (CLSI January 2010). Pharmacokinetic particulars: Clindamycin is almost completely absorbed after oral administration. Maximum serum concentrations of 8 µg/ml (without influence of the bolus) were obtained 1 hour after a dose of 11 mg/kg. Clindamycin is widely distributed and can concentrate in certain tissues. The half-life of clindamycin is about 4 hours. Approximately 70% of clindamycin is excreted in faeces and about 30% in urine. PHARMACEUTICAL PARTICULARS: List of excipients: Ethanol 96%, Sorbitol, liquid (non-crystallising), Disodium Edetate, Propylene Glycol, Sodium Saccharin, Citric Acid Monohydrate & Purified Water. Incompatibilities: Do not mix this product with any other veterinary medicinal products. Shelf life: Shelf life of the veterinary medicinal product as packaged for sale: 1 year (PET bottle). Shelf life of the veterinary medicinal product as packaged for sale: 3 years (Glass bottle) Shelf life after first opening the immediate packaging: 28 days. Special Precautions for storage: This veterinary medicinal product does not require any special storage conditions. Nature and composition of immediate packaging: Carton box containing clear polyethylene terephthalate (PET) bottle or Type III amber glass bottle of 22 ml with HDPE/LDPE or polypropylene tamper proof closure supplied with a low density polyethylene measuring syringe. Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. MARKETING AUTHORISATION HOLDER: Chanelle Pharmaceuticals Manufacturing Ltd., Loughrea, Co. Galway, Ireland. DATE OF FIRST AUTHORISATION: May 2012. DATE OF REVISION: September 2015. LEGAL CATEGORY: UK: POM-V IE: POM.

ART6

469

CLINDACYL® & CLINDASEPTIN®

Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK: Tel: 01280 814500 Fax: 01280 825460 IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected] Website: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible

NAME OF THE VETERINARY MEDICINAL PRODUCT: Clavaseptin 50 mg, 62.5 mg, 250 mg & 500 mg Palatable tablets for dogs and cats. QUALITATIVE AND QUANTITATIVE COMPOSITION: One tablet contains: Active Ingredients: Amoxicillin (as amoxicillin trihydrate) 40 mg, 50 mg, 200 mg & 400 mg respectively. Clavulanic acid (as potassium salt) 10 mg, 12.5 mg, 50 mg & 100 mg respectively. Excipients: Brown iron oxide (E172) 0.095 mg, 0.12 mg, 0.475 mg & 0.95 mg respectively. PHARMACEUTICAL FORM: Tablet. Beige scored tablet that can be divided into equal halves. CLINICAL PARTICULARS: Target species: Dogs and cats. Indications for use, specifying the target species: In dogs (50 mg, 62.5 mg, 250 mg & 500 mg): treatment or adjunctive treatment of periodontal infections caused by bacteria susceptible to amoxicillin in combination with clavulanic acid i.e. Pasteurella spp, Streptococcus spp and Escherichia coli. In cats (50 mg & 62.5 mg only): treatment of skin infections (including wounds and abscesses) caused by bacteria susceptible to amoxicillin in combination with clavulanic acid i.e. Pasteurella spp, Staphylococcus spp, Streptococcus spp and Escherichia coli. Contraindications: Do not use in animals with known hypersensitivity to penicillins or other substances of the β-lactam group. Do not administer to gerbils, guinea pigs, hamsters, rabbits and chinchillas. Do not administer to horses and ruminating animals. Do not use in animals with serious dysfunction of the kidneys accompanied by anuria or oliguria. Do not use in cases of known resistance to the combination of amoxicillin and clavulanic acid. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: In animals with impaired liver and kidney function, the use of the product should be subject to a risk/benefit evaluation by the veterinary surgeon and the posology evaluated carefully. Caution is advised in the use in small herbivores. Use of the product should be based on susceptibility testing. Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to amoxicillin/clavulanic acid and may decrease the effectiveness of treatment with other β-lactam antibiotics, due to the potential for cross resistance. Use of the product should take into account official and local antimicrobial policies. Do not use in cases of bacteria sensitive to narrow spectrum penicillins or to amoxicillin as a single substance. 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 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. Wash hands after handling the tablets. Adverse reactions (frequency and seriousness): Vomiting and diarrhoea may be observed. Treatment may be discontinued depending on the severity of the undesirable effects and a benefit/risk evaluation by the veterinary surgeon. Hypersensitivity reactions (allergic skin reactions, anaphylaxis) may be observed. In these cases, administration should be discontinued and a symptomatic treatment given. Use during pregnancy, lactation or lay: The safety of the product has not been established during pregnancy and lactation. Laboratory studies in rats have not produced any evidence of teratogenic, foetotoxic or maternotoxic effects. Use the product only according to the benefit/risk assessment of the responsible veterinarian. Interaction with other medicinal products and other forms of interaction: The bactericidal activity of amoxicillin may be reduced by the simultaneous use of bacteriostatic substances such as macrolides, tetracyclines, sulfonamides and chloramphenicol. The potential for allergic cross-reactivity with other penicillins should be considered. Penicillins may increase the effect of aminoglycosides. Amounts to be administered and administration route: The recommended dose of the product is 10 mg amoxicillin/2.5 mg clavulanic acid per kg body weight twice a day by the oral route in dogs and cats. In severe infections, the dose may be doubled to 20 mg amoxicillin/5 mg clavulanic acid/kg body weight twice daily. Duration of treatment: 7 days for the treatment of periodontal infections in dogs. 7 days for the treatment of skin infections in cats (including wounds and abscesses). The clinical status of animals should be re-evaluated after 7 days and the treatment prolonged for a further 7 days if necessary. Severe cases of skin infection may require an even longer duration of treatment and this should be at the discretion of the responsible veterinarian. To ensure the correct dosage, body weight should be determined as accurately as possible to avoid under-dosing. Overdose (symptoms, emergency procedures, antidotes), if necessary: At three times the recommended dose for a period of 28 days, a decrease in cholesterol values and episodes of vomiting were observed in cats and diarrhoea was observed in dogs. In the event of an overdose symptomatic

treatment is advised. Withdrawal period(s): Not applicable PHARMACOLOGICAL PROPERTIES: Pharmacotherapeutic group: anti-infective for systemic use; amoxicillin and enzyme inhibitor. ATC vet code: QJ01CR02. Pharmacodynamic properties: Amoxicillin is an aminobenzylpenicillin from the β-lactam penicillin family which prevents the bacterial cell wall formation by interfering with the final step of peptidoglycan synthesis. Clavulanic acid is an irreversible inhibitor of intracellular and extracellular β-lactamases which protects amoxicillin from inactivation by many β-lactamases. Amoxicillin/clavulanate has a wide range of activity which includes β-lactamase producing strains of both Gram-positive and Gram-negative aerobes, facultative anaerobes and obligate anaerobes. Amoxicillin/clavulanic acid breakpoints (NCCLS/2002): Staphylococci: sensitive: MIC < 4/2 µg/ml, resistant: MIC > 8/4 µg/ml. Other organisms: sensitive: MIC < 8/4 µg/ml, resistant: MIC > 32/16 µg/ml. In dog periodontal infections in Europe (isolates of the year 2002 from France, Germany and Belgium) amoxicillin/clavulanic acid combination in a ratio 2/1 showed the following data on sensitivity: Pasteurellaceae: MIC90: 0.4/0.2 µg/ml, Streptococcus spp.: MIC90: 0.4/0.2 µg/ml, Escherichia coli: MIC90: 5.3/2.6 µg/ml. In cat skin infections including wounds and abscesses in Europe (isolates of the year 2002 from France, Germany and Belgium) amoxicillin/clavulanic acid combination in a ratio 2/1 showed the following data on sensitivity: Pasteurellaceae: MIC90: 0.66/0.3 µg/ml, Staphylococcaceae: MIC90: 0.4/0.2 µg/ml, Streptococcaceae: MIC90: 0.4/0.2 µg/ml & Escherichia coli: MIC90: 7.0/3.5 µg/ml. Only 1.5 % of all isolated strains were resistant. Resistance to β-lactam antibiotics is mainly mediated by β-lactamases which hydrolyze antibiotics such as amoxicillin. Susceptibility and resistance patterns can vary with geographical area and bacterial strain, and may change over time. Pharmacokinetic particulars: After oral administration at the recommended dose in dogs and cats, the absorption of amoxicillin and clavulanic acid is fast. In dogs, the maximum plasma concentration of amoxicillin of 8.5 µg/ml is reached in 1.4 h and the maximum plasma concentration of clavulanic acid of 0.9 µg/ml is reached in 0.9h. Half-life is 1 hour in dogs for both substances. In cats, the maximum plasma concentration of amoxicillin of 6.6 µg/ml is reached in 1.8 h and the maximum plasma concentration of clavulanic acid of 3.7 µg/ml is reached in 0.75h. Half-life is 1 to 2 hours in cats for both substances. Elimination is also fast. 12 % of the amoxicillin and 17 % of clavulanic acid is excreted in the urine. The remainder is excreted as inactive metabolites. After repeated oral administration of the recommended dose in dogs and cats, there is no accumulation of amoxicillin or clavulanic acid and the steady state is reached rapidly after first administration. PHARMACEUTICAL PARTICULARS: List of excipients: Brown iron oxide (E172), Crospovidone, Povidone K25, Silicon dioxide, Microcrystalline cellulose, Liver aroma, Yeast aroma, Magnesium stearate & Hypromellose. Incompatibilities: None known. Shelf life: Shelf life of the veterinary medicinal product as packaged for sale: 2 years (50 mg & 62.5 mg) & 3 years (250 mg & 500 mg). Shelf life after first opening the immediate packaging: 16 hours. Special precautions for storage: Do not store above 25°C. Store in the original package. Return any halved tablet to the opened blister-pack and use within 16 hours. Nature and composition of immediate packaging: Aluminium/aluminium blister pack with 10 tablets/blister Cardboard box: Pack sizes of 100, 250 & 500 tablets. Not all pack sizes may be marketed. Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. DATE OF FIRST AUTHORISATION: June 2004 (50 mg, 250 mg & 500 mg), April 2013 (62.5 mg). DATE OF REVISION OF THE TEXT: February 2015. LEGAL CATEGORY: UK: POM-V. IE: POM.

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CLAVASEPTIN® SPC

NAME OF THE VETERINARY MEDICINAL PRODUCT: AURIZON ear drops, suspension. QUALITATIVE AND QUANTITATIVE COMPOSITION: 1 ml of AURIZON contains: Active ingredients: Marbofloxacin 3.0 mg, Clotrimazole 10.0 mg & Dexamethasone acetate 1.0 mg (equivalent to dexamethasone 0.9 mg). Excipients: Propyl galate (E310) 1.0 mg. PHARMACEUTICAL FORM: Ear drops, suspension. Homogenous beige to yellow oily suspension. CLINICAL PARTICULARS: Target species: Dogs. Indications for use, specifying the target species: Treatment of otitis externa of both bacterial and fungal origin respectively due to bacteria sensitive to marbofloxacin, and fungi especially Malassezia pachydermatis sensitive to clotrimazole. The product should be used based on susceptibility testing. Contraindications: Do not administer to dogs suffering from perforation of the tympanic membrane. Do not administer to dogs with known hypersensitivity to any of the ingredients. Do not administer to pregnant or lactating bitches. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: Heavy reliance on a single class of antibiotic may result in the induction of resistance in a bacterial population. It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions which have responded poorly, or are expected to respond poorly, to other classes of antibiotics. Before treating with the product, the integrity of the tympanic membrane must be verified. The external ear canal should be meticulously cleaned and dried before treatment. Special precautions to be taken by the person administering the medicinal products to animals: Wash hands carefully after applying the product. Avoid contact with eyes. If splashed in the eye, rinse with copious amounts of water. Persons with known hypersensitivity to compounds in the product should avoid any contact with the product. Adverse reactions (frequency and seriousness): Usual adverse reactions associated with corticosteroid drugs may be observed (changes in biochemical and haematological parameters, such as increase of alkaline phosphatase, and of aminotransferase, some limited neutrophilia). Prolonged and intensive use of topical corticosteroid preparations is known to trigger local and systemic effects, including suppression of adrenal function, thinning of the epidermis and delayed wound healing. On rare occasions, the use of this product may be associated with deafness, mainly in elderly dogs and mostly of a transient nature. Use during pregnancy, lactation or lay: See “Contraindications”. Interaction with other medicinal products and other forms of interaction: None known. Amounts to be administered and administration route: Shake well before use. Apply ten drops into the ear once daily for 7 to 14 days. After 7 days of treatment, the veterinary surgeon should evaluate the necessity to extend the treatment another week. One drop of the preparation contains 71µg marbofloxacin, 237µg clotrimazole and 23.7µg dexamethasone acetate. After application, the base of the ear may be massaged briefly and gently to allow the preparation to penetrate to the lower part of the ear canal. When the product is intended for use in several dogs, use one cannula per dog. Overdose (symptoms, emergency procedures, antidotes), if necessary: Changes in biochemical and hæmatological parameters (such as increase of alkaline phosphatase, aminotransferase, some limited neutrophilia, eosinopenia, lymphopenia) are observed with three fold the recommended dosage; such changes are not serious and will reverse once the treatment has stopped. Withdrawal period(s): Not applicable. PHARMACOLOGICAL PROPERTIES: Phramacotherapeutic group: corticosteroids and anti-infectives in combination. ATC vet code: QS02CA06. Pharmacodynamic properties: The preparation combines three active ingredients: marbofloxacin, a synthetic bactericidal agent belonging to the fluoroquinolone family that acts by inhibiting DNA gyrase. It exhibits a broad spectrum of activity against Gram-positive bacteria (e.g. Staphylococcus intermedius) and against Gram-negative organisms (Pseudomonas aeruginosa, Escherichia coli and Proteus mirabilis). Clotrimazole, an anti-fungal agent that belongs to the imidazole family and which acts by causing changes in membrane permeability, allowing intracellular compounds to leak from the cell and thus inhibiting cellular molecular synthesis. It exhibits a wide spectrum of activity and is aimed, in particular, at Malassezia pachydermatis. Dexamethasone acetate, a synthetic glucocorticoid exhibiting anti-inflammatory and anti-pruritic activity. Pharmacokinetic particulars: Pharmacokinetics studies in dogs at the therapeutic dosage have shown that: Marbofloxacin plasma concentrations peak at 0.06 µg/ml on the 14th day of treatment. Marbofloxacin bonds weakly to plasma proteins (< 10% in dogs) and is eliminated slowly, mainly in the active form, over 2/3 in urine and over 1/3 in faeces. Clotrimazole absorption is extremely poor (plasma concentration < 0.04 µg/ml). Dexamethasone acetate plasma concentration reaches 1.25 ng/ml on the 14th day of treatment. Dexamethasone resorption is not increased by the inflammatory process induced by otitis. PHARMACEUTICAL PARTICULARS: List of excipients: Propyl gallate (E310), Sorbitan oleate, Silica, colloidal hydrophobic, Triglycerides, medium-chain. Incompatibilities: Not applicable. Shelf life: 2 years. After opening: 2 months. Special precautions for storage:

Do not store above 30°C. Nature and composition of immediate packaging: Low-density polyethylene bottle. Low-density polyethylene nozzle. Threaded polypropylene cap. PVC cannula. Presentations: Box containing 1 x 10 ml bottle and 1 cannula or Box containing 1 x 20 ml bottle and 2 cannulae. Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused product or waste material should be disposed of in accordance with national requirement. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. DATE OF FIRST AUTHORISATION: July 2001. DATE OF REVISION: January 2006.LEGAL CATEGORY: UK: POM-V. IE: POM.

AURIZON® SPC


UK ONLY: NAME OF THE VETERINARY MEDICINAL PRODUCT: MARBOCYL P 5 mg, 20 mg & 80 mg tablets. QUALITATIVE AND QUANTITATIVE COMPOSITION: Active Ingredient: Marbofloxacin 5mg, 20 mg & 80 mg per tablet respectively. PHARMACEUTICAL FORM: Beige brown spotted round tablet. CLINICAL PARTICULARS: Target species: Dogs (5 mg, 20 mg & 80 mg) & Cats (5 mg only). Indications for use, specifying the target species: In dogs: Marbofloxacin is indicated in the treatment of: skin and soft tissue infections (skinfold pyoderma, impetigo, folliculitis, furunculosis and cellulitis), urinary tract infections (UTI) associated or not with prostatitis and respiratory tract infections caused by susceptible strains of organisms. In cats: Marbofloxacin is indicated in the treatment of skin and soft tissue infections (wounds, abscesses, phlegmons) and upper respiratory tract infections caused by susceptible strains of organisms. Contra-indications: Marbofloxacin should not be used in dogs aged less than 12 months, or less than 18 months for exceptionally large breeds of dogs, such as Great Danes, Briard, Bernese, Bouvier and Mastiffs, with a longer growth period. Not recommended for use in cats aged less than 16 weeks. Not suitable for infections resulting from strict anaerobes, yeast or fungi. 20 mg & 80 mg tablets should not be used in cats. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: The fluoroquinolones have been shown to induce erosion of articular cartilage in juvenile dogs and care should be taken to dose accurately especially in young animals. The fluoroquinolones are also known for their potential neurological side effects. Cautious use is recommended in dogs and cats diagnosed as suffering from epilepsy. A low urinary pH could have an inhibitory effect on the activity of marbofloxacin. Fluoroquinolones should be reserved for the treatment of clinical conditions which have responded poorly, or are expected to respond poorly to other classes of antimicrobials. Whenever possible, use of fluoroquinolones should be based on susceptibility testing. Use of the product deviating from the instructions given in the SPC may increase the prevalence of bacteria resistant to the fluoroquinolones and may decrease effectiveness of treatment with other quinolones due to the potential for cross-resistance. Special precautions to be taken by the person administering the veterinary medicinal product to animals: People with known hypersensitivity to fluoroquinolones should avoid using this product. In case of accidental ingestion seek medical attention and show product label and/or package leaflet to the doctor. Wear gloves when handling or dividing tablets. Wash hands after use. Adverse reactions (frequency and seriousness): At the therapeutic recommended dosage, no severe side-effects are to be expected in dogs and cats. In particular, no lesions of the articular joints were encountered in clinical studies at the recommended dose rate. Mild side effects such as vomiting, softening of faeces and modification of thirst or transient increase in activity may occasionally occur. These signs cease spontaneously after treatment and do not necessitate cessation of treatment. Use during pregnancy, lactation or lay: Studies in pregnant rats and rabbits showed no side effects on pregnancy. However no specific studies have been carried out in pregnant cats and dogs. Interaction with other medicinal products and other forms of interaction: Fluoroquinolones are known to interact with orally administered cations (Aluminium, Calcium, Magnesium, Iron). In such cases, the bioavailability may be reduced. Amounts to be administered and administration route: For oral administration. The recommended dose rate is 2 mg/kg/day in a single daily administration. To ensure a correct dosage body weight should be determined as accurately as possible to avoid underdosing. DOGS: in skin and soft tissue infections, treatment duration is at least 5 days. Depending on the course of the disease, it may be extended up to 40 days. In urinary tract infections, treatment duration is at least 10 days. Depending on the course of the disease, it may be extended up to 28 days. In respiratory infections, treatment duration is at least 7 days and depending on the course of the disease, it may be extended up to 21 days. CATS: for skin and soft tissue infections (wounds, abscesses, phlegmons) treatment duration is 3 to 5 days. For upper respiratory infections treatment duration is 5 days. Overdose (symptoms, emergency procedures, antidotes), if necessary: Overdosage may cause acute signs in the form of neurological disorders, which should be treated symptomatically. PHARMACOLOGICAL PROPERTIES: ATC vet code: QJ01MA93. Pharmacodynamic properties: Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group which acts by inhibition of DNA gyrase. It is effective against a wide range of Gram positive bacteria (in particular Staphylococci,Streptococci) and Gram negative bacteria (Escherichia coli, Salmonella typhimurium, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Proteus spp, Klebsiella spp, Shigella spp, Pasteurella spp, Haemophilus spp, Moraxella spp, Pseudomonas spp, Brucella canis) as well as Mycoplasma spp. Marbofloxacin is not active against anaerobes, yeasts or fungi. Pharmacokinetic properties: After oral administration in dogs and cats at the recommended dose of 2 mg/kg, marbofloxacin is readily absorbed and reaches maximal plasma concentrations of 1.5 µg/ml within 2 hours. Its bioavailability is close to 100%. It is weakly bound to plasma proteins (less than 10%), extensively distributed and in most tissues (liver, kidney, skin, lung, bladder, digestive tract) it achieves higher concentrations than in plasma. Marbofloxacin is eliminated slowly (t½ß = 14 h in dogs and 10h in cats) predominantly in the active form in urine (2/3) and faeces (1/3). PHARMACEUTICAL PARTICULARS: List of excipients: Lactose monohydrate, Povidone (K90), Silica, colloidal anhydrous, Crospovidone (Type A), Hydrogenated castor oil, Pig liver powder, Yeast powder, Magnesium stearate & Purified water. Incompatibilities: None known. Shelf life: 3 years. Special precautions for storage: No special precautions for storage. Nature and composition of immediate packaging: Marbofloxacin palatable tablets are packaged in aluminium / aluminium blister packs. 5 mg & 20 mg - Boxes of 100 tablets (10 blister of 10 tablets), 80 mg - Boxes of 72 tablets (12 blisters of 6 tablets). Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. DATE OF FIRST AUTHORISATION: 5 mg: June 2003. 20 mg: June 2003. 80 mg: June 2003. DATE OF REVISION: 5mg: March 2016 20 mg: February 2016. 80 mg: March 2016. LEGAL CATEGORY: POM-V.

REPUBLIC OF IRELAND ONLY: NAME OF THE VETERINARY MEDICINAL PRODUCT: Marbocyl P 5 mg, 20 mg & 80 mg tablets. QUALITATIVE AND QUANTITATIVE COMPOSITION: Each tablet contains: Active Ingredient: Marbofloxacin 5 mg, 20 mg & 80 mg per tablet respectively. PHARMACEUTICAL FORM: Tablet. Brown-beige spotted, circular divisible tablets. CLINICAL PARTICULARS: Target Species: Dogs (5 mg, 20 mg & 80 mg) & Cats (5 mg only). Indications for use, specifying the target species: In dogs: Marbofloxacin tablet is indicated in the treatment of: Skin and soft tissue infections (intertrigo, folliculitis, impetigo, furunculosis, cellulitis) caused by susceptible strains. Lower and upper urinary tract infections (UTI) associated or not with prostatitis or epididymitis caused by susceptible strains. Respiratory tract infections caused by susceptible strains. In cats: Marbofloxacin tablet is indicated in the treatment of skin and soft tissue infections (wounds, abscesses, phlegmons) and upper respiratory tract infections caused by susceptible strains. Contra-indications: Do not use in animals with known hypersensitivity to the active ingredient. Do not use in dogs aged less than 12 months, or less than 18 months for giant breeds of dogs. Not recommended for use in cats aged less than 16 weeks. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: None. Special precautions to be taken by the person administering the veterinary medicinal product to animals: None. Adverse reactions (frequency and seriousness): Hypersensitivity (allergic) reactions may occur in treated animals. At the therapeutic recommended dosage, no severe side-effects are to be expected in dogs and cats. Fluoroquinolones have been shown to induce erosion of articular cartilage in juvenile dogs and care should be taken to dose accurately, especially in young animals. Mild side effects may occasionally occur such as vomiting, softening of faeces, modification of thirst or transient increase in activity. These signs cease spontaneously after treatment and do not necessitate cessation of treatment. Use during pregnancy, lactation or lay: Marbofloxacin may be used in pregnant and lactating queens and bitches. Interaction with other medicinal products and other forms of interaction: Fluoroquinolones are known to interact with orally administered cations (Aluminium, Calcium, Magnesium, Iron). In such cases, the bioavailability may be reduced. Amounts to be administered and administration route: The recommended dose rate is 2 mg/kg/day in a single daily administration. DOGS: in skin and soft tissue infections, treatment duration is at least 5 days. Depending on clinical evolution, it may be extended up to 40 days. In lower urinary tract infections, treatment duration is at least 10 days. In case of associated prostatitis or epididymitis or in case of upper urinary tract infections, treatment may be extended up to 28 days. In respiratory infections, treatment duration is at least 7 days and depending on the course of the disease, it may be extended up to 21 days. CATS: for skin and soft tissue infections (wounds, abscesses, phlegmons) treatment duration is 3 to 5 days. For upper respiratory infections, treatment duration is 5 days. Overdose (symptoms, emergency procedures, antidotes), if necessary: Overdose may cause acute signs in the form of neurological disorders which would have to be treated symptomatically. Withdrawal Period(s): Not applicable. PHARMACOLOGICAL or IMMUNOLOGICAL PROPERTIES: Pharmacotherapeutic group: Antibacterials for systemic use, marbofloxacin. ATC vet code: QJ01MA93. Pharmacodynamic properties: Marbofloxacin is a synthetic, bactericidal antimicrobial, belonging to the fluoroquinolone group which acts by inhibition of DNA gyrase. It is effective against a wide range of Gram positive bacteria (in particular Staphylococci, Streptococci) and Gram negative bacteria (Escherichia coli, Salmonella typhimurium, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Proteus spp, Klebsiella spp, Shigella spp, Pasteurella spp, Haemophilus spp, Moraxella spp, Pseudomonas spp, Brucella canis) as well as Mycoplasma spp. Pharmacokinetic properties: After oral administration in dogs and cats at the recommended dose of 2 mg/kg, marbofloxacin is readily absorbed and reaches maximal plasma concentrations of 1.5 μg/ml within 2 hours. Its bioavailability is close to 100%. It is weakly bound to plasma proteins (less than 10%), extensively distributed and in most tissues (liver, kidney, skin, lung, bladder, digestive tract) it achieves higher concentrations than in plasma. Marbofloxacin is eliminated slowly (t½ß = 14 h in dogs and 10 h in cats) predominantly in the active form in urine (2/3) and faeces (1/3). PHARMACEUTICAL PARTICULARS: List of excipients: Lactose Monohydrate, Povidone, Crospovidone, Liver Powder, Yeast powder, Silica, colloidal anhydrous, Hydrogenated Castor Oil & Magnesium Stearate. Incompatibilities: Not applicable. Shelf-life: Shelf-life of the veterinary medicinal product as packaged for sale: 3 years. Special precautions for storage: This veterinary medicinal product does not require any special storage precautions. Nature and composition of immediate packaging: Marbofloxacin tablets are packaged in aluminium/aluminium thermoshaped blister packs. Carton contains: 10 blisters of 10 tablets (5 mg & 20 mg) & 12 blisters of 6 tablets (80 mg). Special precautions for the disposal of unused veterinary medicinal products or waste materials: Any unused product or waste material should be disposed of in accordance with national requirements. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Ltd., Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. UK. DATE OF THE FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION: April 2009. DATE OF REVISION: February 2010. LEGAL CATEGORY: POM.

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MARBOCYL® P SPC

UK ONLY: NAME OF THE VETERINARY MEDICINAL PRODUCT: MARBOCYL SA 200 mg Powder and solvent for solution for injection. QUALITATIVE AND QUANTITATIVE COMPOSITION: Lyophilisate vial: Active ingredient: Marbofloxacin 200 mg. Antimicrobial preservatives: Disodium edetate 20 mg & Benzalkonium chloride 2mg. PHARMACEUTICAL FORM: Powder and solvent for solution for injection. CLINICAL PARTICULARS: Target species: Dogs & Cats. Indications for use, specifying the target species: In dogs: the treatment of infected wounds and subcutaneous abscesses due to Staphylococcus intermedius, Staphylococcus aureus, Escherichia coli, Pasteurella sp. and Pseudomonas sp. The treatment of lower urinary tract infections due to Escherichia coli and Proteus sp. In cats: the treatment of infected wounds and subcutaneous abscesses due to Pasteurella multocida, Staphylococcus intermedius, Staphylococcus aureus, Staphylococcus sp., Enterobacter sp. and Klebsiella sp. Marbofloxacin is inactive against anaerobic bacteria. Contra-indications: Marbofloxacin should not be used in dogs aged less than 12 months or less than 18 months for exceptionally large breeds of dogs, such as Great Danes or Mastiffs with a longer growth period. Special warnings for each target species: None. Special precautions for use: Special precautions for use in animals: None. Special precautions to be taken by the person administering the veterinary medicinal product to animals: People with known hypersensitivity to fluoroquinolones should avoid using this product. Wash hands after use. Adverse reactions (frequency and seriousness): After subcutaneous administration, no undesirable effect is observed up to 2 times the maximum recommended therapeutic dose in dogs or 3 times the maximum recommended dose for cats. After i.v. administration at 4mg/kg, rare mild and transitory side effects have been reported: ptyalism (excess salivation), nervous disorders: vocalization, excitation, trembling (myoclonia). Use during pregnancy, lactation or lay: Studies carried out with laboratory animals showed no embryotoxic, foetotoxic or teratogenic effects. However, no specific studies have been carried out on pregnant cats or dogs. Interaction with other medicinal products and other forms of interaction: The dosage of theophylline must be reduced when used concurrently. Amounts to be administered and administration route: Reconstitution: Before use, reconstitute the lyophilised powder using the solvent (water for injections) provided for the 200 mg vial. Using aseptic technique withdraw 20 ml from the vial of solvent and add rapidly to the lyophilised powder. When reconstituted in this way, the solution will contain 10 mg marbofloxacin per ml. In dogs, the recommended doses and durations of treatment are: For the treatment of infected wounds and subcutaneous abscesses - a single subcutaneous or intravenous injection, at a dosage of 2mg/kg (1ml/5kg), followed the next day by administration of Marbocyl Tablets daily at a dosage of 2mg/kg for 6 days. For the treatment of lower urinary tract infections - a single subcutaneous or intravenous injection, at a dosage of 2mg/kg (1ml/5kg), followed the next day by administration of Marbocyl Tablets daily at 2mg/kg for at least 10 days and up to 28 days. In cats, the recommended doses and duration of treatment is: For the treatment of infected wounds and subcutaneous abscesses 2 mg/kg/day (0.2ml/kg/day), by subcutaneous or intravenous injection followed by subcutaneous injections for a total of 3 to 5 days. Overdose (symptoms, emergency procedures, antidotes), if necessary: Overdosage may cause acute signs in the form of neurological disorders, hypersalivation or trembling which should be treated symptomatically. Withdrawal period(s): Not Applicable. PHARMACOLOGICAL PROPERTIES: ATC Vet Code: QJ01MA93. Pharmacodynamic properties: Marbofloxacin is a synthetic bactericidal anti-infective, belonging to the fluoroquinolone group. It acts by inhibition of DNA gyrase. It is effective against a wide range of Gram positive bacteria (in particular Staphylococcus Spp.), Gram negative (Escherichia Coli, Salmonella typhimurium, Campylobacter jejunii, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, Morganella morganii, Proteus spp, Shigella spp, Actinobacillus pleuropneumoniae, Bordetella bronchiseptica, Mannheimia haemolytica, Pasteurella multocida, Klebsiella spp, Haemophilus spp, Moraxella spp, Pseudomonas spp, Brucella canis) as well as Mycoplasma. Pharmacokinetic properties: After subcutaneous administration at the recommended dose of 2 mg/kg to dogs and cats, marbofloxacin is rapidly absorbed with a bioavailability close to 100%. After subcutaneous administration of 2 mg/kg in dogs and cats, the maximum plasma concentration achieved is 1.5 μg/ml. IV administration results in a similar pharmacokinetic profile for Area Under the Time Curve (AUC) and elimination (T1/2) values. Marbofloxacin is weakly bound to plasma proteins (< 10% in dogs and cats) and is extensively distributed. In most tissues (skin, muscles, liver, kidney, lungs, bladder, digestive tract), tissue concentrations are higher than in plasma. Marbofloxacin is slowly eliminated with an elimination half life from 10 to14 h in both species, mainly in the active form in urine (2/3), and faeces (1/3). PHARMACEUTICAL PARTICULARS: List of excipients: Disodium edetate

dehydrate, Benzalkonium chloride, Mannitol, Sodium hydroxide & Water for injection Incompatibilities: None. Shelf life: 3 years. The reconstituted solution should be stored below 25°C and protected from light. Any reconstituted product remaining 28 days after preparation should be discarded.Special precautions for storage: Protect both lyophilised powder and reconstituted solutions from light. Do not store above 25°C. Nature and composition of immediate packaging: MARBOCYL SA 200 mg, is packaged in amber Type II glass vials containing 200 mg marbofloxacin in the form of a white freeze dried power. Colourless Type II glass vials of solvent are supplied which contain 20 ml Water for Injections PhEur. Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products: Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal products should be disposed of in accordance with local requirements. MARKETING AUTHORISATION HOLDER: Vetoquinol UK Limited, Vetoquinol House, Great Slade, Buckingham Industrial Park, Buckingham, MK18 1PA. DATE OF FIRST AUTHORISATION: March 1999. DATE OF REVISION OF THE TEXT: August 2007. LEGAL CATEGORY: POM-V.

MARBOCYL® SA 200MG INJECTION SPC


Further information is available on request from:Vetoquinol UK Limited, Vetoquinol House, Great Slade,Buckingham Industrial Park, Buckingham, MK18 1PA.UK: Tel: 01280 814500 Fax: 01280 825460IE: Freephone: 1800 406117 Fax: 1800 406116. Email: [email protected]: www.vetoquinol.co.uk Use medicines responsibly. For further information please visit www.noah.co.uk/responsible


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