Dicural - patient leaflet, side effects, dosage

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• 5.2 Pharmacoki­netic properties

Following an oral dose (a plain tablet) in dogs of 5 mg/kg bodyweight, difloxacin reached its average peak plasma concentration of 1.8 ^g/ml in approximately 3 hours. Approximately 95 % of the oral dose was absorbed. The elimination half-life averaged 9.3 hours.

Long term daily oral treatment over 180 days at 5 mg/kg bodyweight did not influence difloxacin kinetics, neither by accumulation nor by increased drug metabolism.

• 6. PHARMACEUTICAL PARTICULARS

  • 6.1 List of excipients

Sodium starch glycollate Microcrystalline cellulose Magnesium stearate Colloidal silicon dioxide Sodium lauryl sulphate

Lactose

Sodium croscarmellose

Micronised brewer’s yeast

Aromatic liver flavour

• 6.2 Incompati­bilities

  
  

Not applicable.

• 6.3 Shelf-life

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

• 6.4 Special precautions for storage

Do not store above 25°C. Store in a dry place.

• 6.5 Nature and contents of container

PVC/aluminium blisters with 10 tablets per blister. Cardboard boxes of 1, 2 or 10 blisters.

Not all pack sizes may be marketed.

• 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products, if any

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

• 7. MARKETING AUTHORISATION HOLDER

  HORISATION NUMBERS

  
  

Pfizer Limited Ramsgate Road Sandwich

Kent CT13 9NJ United Kingdom

EU/2/97/003/004–015

RENEWAL OF THE AUTHORISATION

10. DATE OF REVISION OF THE TEXT

Detailed information on this veterinary medicinal product is available on the website of the European

Medicines Agency

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Dicural 50 mg/ml solution for injection for cattle and dogs.

• 2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Active substance:

Difloxacin (as hydrochloride)

Excipients:

Benzyl alcohol

For a full list of excipients, see section 6.1

• 3. PHARMACEUTICAL FORM

Solution for injection.

• 4. CLINICAL PARTICULARS

  • 4.1 Target species

Cattle (calves and young cattle)

Dogs.

• 4.2 Indications for use, specifying the target species

In cattle: Dicural 50 mg/ml solution for injection is indicated for the treatment of bovine respiratory disease (shipping fever, calf pneumonia) caused by single or mixed infections with Pasteurella haemolytica , Pasteurella multocida , and/or Mycoplasma spp.

In dogs : Dicural 50 mg/ml solution for injection is indicated for the treatment of:

• Acute uncomplicated urinary tract infections caused by Escherichia coli or Staphylococcus spp
• Superficial pyoderma caused by Staphylococcus intermedius.

• 4.3 Contraindi­cations

Cattle:

None. f(j

Dogs:

As for other quinolones, due to possible adverse effects on the articular cartilage of weight bearing joints difloxacin should not be used during the rapid growth phase. Therefore, do not use in small and medium-sized breeds of dogs up to and including 8 months of age, in large breeds up to 1year of age and in giant breeds up to 18 months of age.

Do not use in epileptic dogs.

• 4.4 Special warnings for each target species

None known.

• 4.5 Special precautions for use
  
  Special precautions for use in animals

  Heavy reliance on a single class of antibiotics may result in the induction of resistance in a bacterial population. It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions that have responded poorly, or are expected to respond poorly, to other classes of antibiotic.

Whenever possible, fluoroquinolones should only be used based on susceptibility testing.

Official and local antimicrobial policies should be taken into account when the product is used.

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 the effectiveness of treatment with other quinolones due to the potential of cross resistance.

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

People with a known hypersensitivity to quinolones should avoid any contact with the product.

• 4.6 Adverse reactions (frequency and seriousness)

Cattle:

In target animal safety studies, subcutaneous administration was generally well tolerated. Transient swelling at the injection site following administration may occur.

Dogs:

In target animal safety studies, subcutaneous administration was generally well tolerated. Pruritis and/or local swellings and occasionally a slight pain reaction on injection have been observed. In general the pruritis disappears within a few minutes and the local swelling within a few days.

• 4.7 Use during pregnancy, lactation or lay

The safety of the veterinary medicinal product has not been established during pregnancy and lactation.

• 4.8 Interaction with other veterinary medicinal products and other forms of interaction

The use of fluoroquinolones in combination with non-steroidal anti-inflammatory drugs (NSAIDs) may cause seizures.

Antagonism may be observed with nitrofurantoin.

• 4.9 Amounts to be administered and administration route

• ♦ vJ

Subcutaneous use

Cattle:

The recommended dose is 2.5mg difloxacin/kg bodyweight/day for 3 days (i.e. 5ml/100 kg bodyweight/day). If there is insufficient improvement after 3 days, the treatment can be continued for another 2 days.

For complicated respiratory disease the dose can be doubled to 5 mg/kg bodyweight/ day.

The volume administered per injection site in cattle should not exceed 7 ml. A new injection site should be used each day

Dogs:

The recommended dose is a single injection of 5.0 mg difloxacin/kg bodyweight Treatment must be continued with Dicural coated tablets (see that SPC)

The volume administered per injection site in dogs should not exceed 5 ml.

• 4.10 Overdose (symptoms, emergency procedures, antidotes)

Cattle:

At very high doses adverse effects on the nervous system (ataxia, unsteadiness, twitching, tremors, convulsions, etc) may occur in cattle. Overdosage may also give rise to oedema and swelling in the knee joints.

Dogs:

The oral administration of difloxacin at up to 5 times the recommended dose rate for 30 days did not result in any adverse reactions.

In another study, dogs treated orally with difloxacin at 10 times the recommended dose for 10 days showed occasionally mild adverse reactions such as orange/yellowing discoloration of the faeces, emesis and hypersalivation.

No specific antidotes for difloxacin (or other quinolones) are known, therefore in case of overdosage symptomatic treatment should be given.

• 4.11 Withdrawal period

Cattle :

Meat and offal: 46 days

Dogs:

Not applicable

• 5. PHARMACOLOGICAL PROPERTIES

  • 5.1 Pharmacody­namic properties

Pharmacotherapeutic group: general anti-infectives for systemic use; antibacterials for systemic use, quinolone antibacterials.

ATC vet code: QJ01MA94

The fluoroquinolones exert their antibacterial effect against both replicating and dormant microorganisms. Difloxacin hydrochloride can be bactericidal in activity and acts primarily through inhibition of bacterial DNA gyrase.

The following organisms were tested and found to be susceptible to difloxacin in vitro :

MPaysctoepulraella spp.

sma spp.

Escherichia coli

Staphylococcus intermedius

The following organism was found to be of intermediate susceptibility:

Staphylococcus spp.

Induction of resistance against quinolones can develop by mutations in the gyrase gene of bacteria and by changes in cell permeability towards quinolones

• 5.2 Pharmacoki­netic properties

Cattle: X.

After subcutaneous administration of difloxacin peak plasma levels of 1.7 pg/ml are achieved at 6 hours post dosing. After subcutaneous administration the bioavailability is 88% and the volume of distribution is 2.5 l/kg.

The parent compound difloxacin is the major component in the faeces and tissues. In the urine, liver, fat and kidneys the metabolites desmethyl-difloxacin and difloxacin N-oxide can be found in small amounts in addition to the major (parent) compound.

The clearance of difloxacin after subcutaneous administration to cattle is 229 ml/h/kg. A half-life time of 7.7 hours has been observed. The majority of difloxacin (i.e. 68 – 82%) is excreted via the faeces. A fraction of difloxacin (i.e. 7 – 18%) is eliminated via the urine.

Dogs:

After subcutaneous administration of difloxacin peak plasma levels of 1.4 –1.9 pg/ml are achieved in 3.1 hours post dosing. After subcutaneous administration the bioavailability is 96%. The volume of distribution is 2.6 l/kg. A half-life time of 5.8 hours has been observed. The majority of difloxacin is excreted via the faeces. A fraction of difloxacin is eliminated by the urine.

• 6. PHARMACEUTICAL PARTICULARS

  6.1 List of excipients

  
  

Ethanol

Benzyl alcohol Propylene glycol Arginine

Water for injections

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

• 6.3 Shelf-life

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

Shelf life after first use of the product: 28 days

• 6.4 Special precautions for storage

Do not store above 25 °C.

Do not freeze.

Keep the container in the outer carton.

• 6.5 Nature and composition of immediate packaging

Dogs:

Cardboard box with one glass vial of 50ml with a rubber stopper and aluminium cap.

Cattle:

Cardboard box with one glass vial of 50ml, 100ml or 250 ml with a rubber stopper and aluminium cap.

Not all pack sizes may be marketed.

• 6.6 Special precautions for the disposal of unused veterinary medicinal product or waste materials derived from the use of such products, if any

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

• 7. MARKETING AUTHORISATION HOLDER

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

• 8. MARKETING AUTHORISATION NUMBERS

• 9. DATE OF RENEWAL OF THE AUTHORISATION

• 10. DATE OF REVISION OF THE TEXT

Detailed information on this veterinary medicinal product is available on the website of the European

Medicines Agency

PROHIBITION OF SALE, SUPPLY AND/OR USE

Not applicable.

ANNEX II

• A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH RELEASE

• B. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION REGARDING SUPPLY AND USE

• C. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION WITH REGARD TO SAFE AND EFFECTIVE USE

D. STATEMENT OF THE MRLs

• A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH RELEASE

Name and address of the manufacturers responsible for batch release:

For all three pharmaceutical forms:

Pfizer Olot, S.L.U.

Ctra. Camprodón, s/n°, Finca La Riba, Vall de Bianya, 17813 Girona

Spain

• B. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHO REGARDING SUPPLY AND USE

  
  

To be supplied only on veterinary prescription.

The holder of this marketing authorisation must inform the European Commission about the marketing plans for the medicinal product authorised by this decision.

• C. CONDITIONS OR RESTRICTIONS OF THE MARKETING AUTHORISATION WITH REGARD TO SAFE AND EFFECTIVE USE

  
  

Not applicable.

• D. STATEMENT OF THE MRLs

which are accepted in accordance with Council Regulation (EEC) No 2377/90 and in accordance with Article 31 (3b) of Council Regulation (EEC) No 2309/93 of 22 July 1993, as amended.

Annex I of Council Regulation (EEC) No 2377/90

Pharmacologically active substance	Marker residue	Animal Species	MRLs	Target tissues	Other provisions
Difloxacin	Difloxacin	Poultry	300 ^g/kg 400 Lig/kg 1900 Lig/kg 600 ^g/kg	Muscle Skin + fat Liver Kidney	Not for use in animals from which eggs are produced for human consumption
Difloxacin	Difloxacin	Bovine	400 Lig/kg 100 Lig/kg 1400 Lig/kg 800 Lig/kg	Muscle Fat Liver Kidney	Not for use in animals from which milk is produced for human consumption

Annex II of Council Regulation (EEC) No 2377/90

Oral solution:

Pharmacologically active substance	Animal Species	Other provisions
Edetic acid	All food-producing species o
Potassium Hydroxide
Propylene glycol
Benzyl alcohol		For use as excipient
Hydrochloric acid		For use as excipient

Solution for injection:

Pharmacologically active substance	Animal Species	Other provisions
Ethanol Propylene glycol Benzyl alcohol Arginine	All food-producing species	For use as excipient

Chickens (broilers and future breeders) and turkeys (young turkeys up to 2 kg body weight).

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• 6. INDICATIONS

Chickens and turkeys – for treatment of chronic respiratory infections caused by sensitive strains of Escherichia coli and Mycoplasma gallisepticum.

Turkeys only – for the treatment of infections caused by Pasteurella multocida.

Dicural oral solution should be used based on susceptibility testing

• 7. METHOD AND ROUTE OF ADMINISTRATION

For oral administration in drinking water.

Read the package leaflet before use.

• 8. WITHDRAWAL PERIOD

Withdrawal periods – Meat and offal (chickens and turkeys): 24 hours.

Not permitted for use in laying birds producing eggs for human consumption.

Dispose of waste material in accordance with local requirements.

• 13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

For animal treatment only- to be su

• 14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN [Not requested on the immediate label]

Keep out of the reach and sight of children.

• 15. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Marketing authorisation holder

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

• 16. MARKETING AUTHORISATION NUMBER(S)

EU/2/97/003/001 – 1 × 250 ml

EU/2/97/003/002 – 1 × 1000 ml

EU/2/97/003/003 – 6 × 1000 ml

• 17. MANUFACTU­RER’S BATCH NUMBER

Lot {number}

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Dicural 50 mg coated tablets for dogs

• 2. STATEMENT OF ACTIVE AND OTHER SUBSTANCES

Difloxacin (as hydrochloride) 50 mg

10 tablets

20 tablets

100 tablets

7. METHOD AND ROUTE OF ADMINISTRATION

Oral use.

Read the packag

pplicable.]

9. SPECIAL WARNINGS, IF NECESSARY

People with known hypersensitivity to quinolones should avoid any contact with the product.

EXP {month/year}

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Dicural 100 mg coated tablets for dogs

• 2. STATEMENT OF ACTIVE AND OTHER SUBSTANCES

Difloxacin (as hydrochloride)

10 tablets

20 tablets

100 tablets

• 7. METHOD AND ROUTE OF ADMINISTRATION

Oral use.

Read the packag

pplicable.]

• 1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Dicural 150 mg coated tablets for dogs

• 2. STATEMENT OF ACTIVE AND OTHER SUBSTANCES

Difloxacin (as hydrochloride)

10 tablets

20 tablets

100 tablets

• 7. METHOD AND ROUTE OF ADMINISTRATION

Oral use.

Read the packag

cable.]

• 9. SPECIAL WARNINGS, IF NECESSARY

People with known hypersensitivity to quinolones should avoid any contact with the product.

EXP {month/year}

EU/2/97/003/013 – 10 tablets

EU/2/97/003/014 – 20 tablets

Withdrawal period: Cattle – meat and offal 46 days

9. SPECIAL WARNING(S), IF NECESSARY

• 13. THE WORDS “FOR ANIMAL TREATMENT ONLY” AND CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE

For animal treatment only – to be supplied only on veterinary prescription..

• 14. THE WORDS “KEEP OUT OF THE REACH AND SIGHT OF CHILDREN”

Keep out of the reach and sight of children. __ 15. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Pfizer Limited Ramsgate Road Sandwich

Kent CT13 9NJ United Kingdom

• 16. MARKETING AUTHORISATION NUMBER(S)

EU/2/97/003/016

• 17. MANUFACTU­RER’S BATCH NUMBER

Lot {number}

PARTICULARS TO APPEAR ON THE IMMEDIATE PACKAGE

Dicural 50 mg/ml, solution for injection for cattle and dogs 50 ml vial label

Withdrawal period: Cattle – meat and offal 46 days

EU/2/97/003/016

Treatment of Bovine respiratory disease (shipping fever, calf pneumonia) caused by single or mixed infections with Pasteurella haemolytica , Pasteurella multocida , and/or Mycoplasma spp.

• 7. METHOD AND ROUTE OF ADMINISTRATION

Subcutaneous use.

Read the package leaflet before use.

[Space shall be provided for the prescribed dose to be indicated on the outer carton]

• 8. ^Withdrawal period

Withdrawal period: Meat and offal 46 days

• 9. SPECIAL WARNING(S), IF NECESSARY

People with a known hypersensitivity to quinolones should avoid any contact with the product.

• 10. EXPIRY DATE

EXP {month/year}

Shelf-life after first use of the product: 28 days

[Recommended, but not required on the immediate label]

EU/2/97/003/017 – 100 ml

EU/2/97/003/018 – 250 ml

17. MANUFACTU­RER’S BATCH NUMBER

Lot {number}

In chickens and turkeys: Dicural oral solution is indicated for treatment of chronic respiratory infections caused by sensitive strains of Escherichia coli and Mycoplasma gallisepticum.

In turkeys: Dicural oral solution is also indicated for the treatment of infections caused by Pasteurella multocida.

Dicural oral solution should only be used based on susceptibility testing

• 5. CONTRAINDI­CATIONS

Since no studies were performed in clinically lame birds, Dicural oral solution should not be used in birds with existing leg-weakness or in birds suffering from osteoporosis.

• 6. ADVERSE REACTIONS

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

  
  

Chickens (broilers and future breeders)

Turkeys (young turkeys up to 2 kg body weight).

• 8. DOSAGE FOR EACH SPECIES, METHOD AND ROUTE OF ADMINISTRATION

Dicural oral solution must be administrated daily via the drinking water in such a concentration that the dose is 10 mg/kg bodyweight. The administration must be continued for 5 days.

For oral administration in drinking water.

Taking into account the content of difloxacin in the oral solution (10%w/v), the following calculation should be made to determine the volume (ml) to be added for each 1000 litres of water:

number of animals in the house X mean weight of individual animal(kg) X 100

total water consumption of the house at the previous day (litres)

• 9. ADVICE ON CORRECT ADMINISTRATION

The screw cap on the 1 litre bottle can be used as measuring device. If filled to the brim the measuring device provides 50 ml. For the 250 ml bottle a separate measuring device is placed on the screw cap. Measuring lines indicate the volume supplied.

The medicated drinking water should be prepared freshly each day.

No other source of drinking water should be available during the medication period.

No additional chlorine, for example from the use of water chlorinators, or hydrogen peroxide should be added to the drinking water used with this product.

At concentrations in the water of 0.03% (= 300 ml in 1000 litres) or greater, palatability for turkeys may be affected.

• 10. WITHDRAWAL PERIODS

Meat and offal (chicken and turkeys): 24 hours.

ed for use in laying birds producing eggs for human consumption.

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the reach and sight of children.

Do not store above 25 °C.

Protect from light.

Do not freeze.

Shelf-life after first opening the container: 1 month.

Do not use after the expiry date stated on the label after EXP

• 12. SPECIAL WARNING(S)

  
  

Do not use in birds in lay and/or within 4 weeks before the onset of the laying period.

Heavy reliance on a single class of antibiotics may result in the induction of resistance in population. It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions that have responded poorly, or are expected to respond poorly, to other classes of antibiotic.

People with known hypersensitivity to quinolones should avoid any contact with the product.

In order to avoid irritation of skin and/or eyes, use gloves and a face-protecting device, when handling this product.

• 13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY

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

xO'

• 14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST REVISED

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Detailed information on this product is available on the website of the European Medicines Agency

plied only on veterinary prescription.

Dicural oral solution is a yellowish clear aqueous solution and is supplied in plastic white bottles with a screw cap containing 250 or 1000 ml oral solution. Not all pack sizes may be marketed.

For any information about this veterinary medicinal product, please contact the local representative of

België/Belgiqu­e/Belgien

Pfizer Animal Health s.a.,

Tél.: +32 (0)2 554 62 11

Luxembourg

Pfizer Animal Health s.a.,

Tél.: + 32 (0)2 554 62 11

Norge

fizer Oy Animal Health

Tlf: +358 (0)9 4300 40

Österreich

Pfizer Corporation Austria Ges.m.b.H

Tel: +43 (0)1 52 11 57 20

Polska

Pfizer Trading Polska Sp. z.o.o.

Tel: +48 22 335 61 00

Portugal

Laboratórios Pfizer, Lda.

Tel: +34 91 4909900

Tel: +351 21 423 55 00

As for other quinolones, due to possible adverse effects on the articular cartilage of weight bearing joints, difloxacin should not be used during the rapid growth phase, that is, do not use in small-and medium breed dogs up to and including 8 months of age, in large breeds up to 1 year of age and in giant breeds up to 18 months of age.

Do not use in epileptic dogs.

• 6. ADVERSE REACTIONS

Adverse reactions were rare in dogs treated with difloxacin. The observed reactions were inappetence, emesis, diarrhoea, and anal irritation. These adverse reactions were self-limiting within one or two days and did not require additional treatment.

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

Dogs

• 8. DOSAGE FOR EACH SPECIES, METHOD AND ROUTE(S) OF ADMINISTRATION

The recommended dose of difloxacin is 5 mg/kg bodyweight per day. Dicural coated tablets should be given once a day for at least 5 days. Superficial pyoderma may require treatment for up to a maximum of 21 days. The tablets should be administered for at least 2 days beyond the cessation of clinical signs.

Therapy should be re-evaluated if no improvement is seen within 5 days, or 10 days in the case of superficial pyoderma.

	Bodyweight (kg)	Dicural 15 mg	Dicural 50 mg	Dicural 100 mg	Dicural 150 mg
Small	0 – 3 4 – 6	1 2
Medium	7 – 10 11 – 20 21 – 30	(3)	1 2 3	(1)	(1)
Large	31 – 40 41 – 60			2 3	(2)

For oral use.

• 9. ADVICE ON CORRECT ADMINISTRATION

• 10. WITHDRAWAL PERIOD

Not applicable.

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the reach and sight of children.

Do not store above 25°C. Store in a dry place.

Do not use after the expiry date stated on the carton after EXP.

• 12. SPECIAL WARNING(S)

People with known hypersensitivity to quinolones should avoid any contact with the product. The use of difloxacin in pregnant or lactating bitches or male stud dogs is not recommended.

Heavy reliance on a single class of antibiotics may result in the induction of resistance in a bacterial population. It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions that have responded poorly, or are expected to respond poorly, to other classes of antibiotic.

• 13. SPECIAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE MATERIALS, IF ANY

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

• 14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST REVISED

Detailed information on this product is available on the website of the European Medicines Agency

• 15. OTHER INFORMATION

For animal treatment only – to be supplied only on veterinary prescription.

Dicural coated tablets consist of a core tablet containing difloxacin hydrochloride and a highly palatable coating. Each strength of the product is available in packs of 10, 20 and 100 tablets. Not all pack sizes may be marketed.

Difloxacin is an aryl-fluoroquinolone with a broad spectrum of antimicrobial activity. Difloxacin can be bactericidal against many Gram-negative micro-organisms and a selection of Gram-positive microorganisms.

♦jC/

The fluoroquinolones exert their antibacterial effects against both replicating and dormant microorganisms. Difloxacin acts primarily through inhibition of bacterial DNA gyrase.

The following organisms were tested and found to be susceptible to difloxacin in vitro :

Escherichia coli

Klebsiella spp.

Pasteurella spp.

Pseudomonas spp.

Staphylococcus intermedius

The following organisms were found to be of intermediate susceptibility:

Proteus spp.

Staphylococcus spp.

Streptococcus canis (beta) Streptococcus spp.

Following an oral dose (a plain tablet) in dogs of 5 mg/kg bodyweight, difloxacin reached its average peak plasma concentration of1.8 ^g/ml in approximately 3 hours. Approximately 95 % of the oral dose was absorbed. The elimination half-life averaged 9.3 hours.

Long term daily oral treatment over 180 days at 5 mg/kg bodyweight did not influence difloxacin kinetics, neither by accumulation nor by increased drug metabolism.

For any information about this veterinary medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgiqu­e/Belgien

Pfizer Animal Health s.a.,

Tél.: +32 (0)2 554 62 11

Luxembourg

Pfizer Animal Health s.a.,

Tél.: + 32 (0)2 554 62 11

Tel: +34 91 4909900

Tel: +351 21 423 55 00

PACKAGE LEAFLET FOR:

Dicural 50 mg/ml solution for injection for cattle and dogs

• 1. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER AND OF THE MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH RELEASE

Marketing authorisation holder:

Pfizer Limited

Ramsgate Road

Sandwich

Kent CT13 9NJ

United Kingdom

Manufacturer for the batch release:

Pfizer Olot, S.L.U.

Ctra. Camprodon, s/n°, Finca La Riba,

Vall de Bianya, 17813 Girona

Spain

• 2. NAME OF THE VETERINARY MEDICINAL PRO

Dicural 50 mg/ml solution for injection for cattle and dogs

• 3. STATEMENT OF THE ACTIVE SUBSTANCE(S) AND OTHER INGREDIENT(S)

Active substance

Difloxacin (as hydrochloride)

Excipients

Benzyl alcohol

Cattle: Treatment of Bov spiratory disease (shipping fever, calf pneumonia) caused by single or mixed infections with Pasteurella haemolytica , Pasteurella multocida , and/or Mycoplasma spp.

Dogs: treatment of:

Acute uncomplicated urinary tract infections caused by Escherichia coli or Staphylococcus spp Superficial pyoderma caused by Staphylococcus intermedius.

Cattle: None.

Dogs: As for other quinolones, due to possible adverse effects on the articular cartilage of weight bearing joints difloxacin should not be used during the rapid growth phase, that is,. do not use in small and medium-sized breeds of dogs up to and including 8 months of age, in large breeds up to 1 year of age and in giant breeds up to 18 months of age.

Do not use in epileptic dogs.

• 6. ADVERSE REACTIONS

Cattle:

In target animal safety studies, subcutaneous administration was generally well tolerated. Transient swelling at the injection site following administration may occur.

Dogs:

In target animal safety studies, subcutaneous administration was generally well tolerated. Pruritis and/or local swellings and occasionally a slight pain reaction on injection have been observed. In general the pruritis disappears within a few minutes and the local swelling within a few days.

If you notice any serious effects or other effects not mentioned in this leaflet, please inform your veterinary surgeon.

• 7. TARGET SPECIES

  
  

Cattle (calves and young cattle)\ Dogs

• 8. DOSAGE FOR EACH SPECIES, METHOD AND ROUTE(S) OF ADMINISTRATION

Subcutaneous use

Cattle:

The recommended dose is 2.5 mg difloxacin/kg bodyweight/day for 3 days (that is, 5ml/100 kg bodyweight/day). If there is insufficient improvement after 3 days, the treatment can be continued for another 2 days. For complicated respiratory disease the dose can be doubled to 5 mg/kg bodyweight / day.

Dogs:

The recommended dose is 5.0 mg difloxacin/kg body weight in a single injection Treatment should be continued with Dicural coated tablets (read the package leaflet of this product)

• 9. ADVICE ON CORRECT ADMINISTRATION

In cattle , the volume administered per injection site should not exceed 7 ml. A new injection site should be used each day.

me administered per injection site should not exceed 5 ml.

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

• 10. WITHDRAWAL PERIOD

Cattle : Meat and offal: 46 days

• 11. SPECIAL STORAGE PRECAUTIONS

Keep out of the reach and sight of children.

Do not store above 25°-C.

Do not freeze.

Keep the container in the outer carton.

Shelf-life after first use of the product: 28 days.

Do not use after the expiry date stated on the vial after EXP.

• 12. SPECIAL WARNING(S)

Heavy reliance on a single class of antibiotics may result in the induction of resistance in a bacterial population. It is prudent to reserve the fluoroquinolones for the treatment of clinical conditions that have responded poorly, or are expected to respond poorly, to other classes of antibiotic.

Dicural 50 mg/ml solution for injection should only be used based on susceptibility testing.

The safety of the veterinary medicinal product has not been established during pregnancy and lactation.

The use of fluoroquinolones in combination with non-steroidal anti-inflammatory drugs (NSAIDs) may cause seizures.

Antagonism may be observed with nitrofurantoin.

People with a known hypersensitivity to quinolones should avoid any contact with the product.

Overdose

Cattle:

At very high doses adverse effects on the nervous system (ataxia, unsteadiness, twitching, tremors, convulsions, etc.) may occur in cattle. Overdosage may also give rise to oedema and swelling in the knee joints.

Dogs:

In dogs the oral administration of difloxacin at up to 5 times the recommended dose rate for 30 days did not result in any adverse reactions.

In another study dogs treated orally with difloxacin at 10 times the recommended dose for 10 days showed occasionally mild adverse reactions such as orange/yellowing discoloration of the faeces, emesis

No specific antidotes for difloxacin (or other quinolones) are known, therefore in case of overdosage symptomatic treatment should be given

IAL PRECAUTIONS FOR THE DISPOSAL OF UNUSED PRODUCT OR WASTE TERIALS, IF ANY

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

• 14. DATE ON WHICH THE PACKAGE LEAFLET WAS LAST REVISED

Detailed information on this product is available on the website of the European Medicines Agency

• 15. OTHER INFORMATION