SUMMARY OF PRODUCT CHARACTERISTICS

1. NAME OF THE VETERINARY MEDICINAL PRODUCT

Advocin 2.5 % Solution for Injection

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

The mg/ml composition of the formulation is as follows:

Active Ingredient	mg/ml
Danofloxacin mesylate	31.73
≡ danofloxacin Also contains:	≡ 25.00
Monothioglycerol	5.00	(anti-oxidant)
Liquefied phenol	3.12	(preservative)

For the full list of all other excipients see section 6.1

3. PHARMACEUTICAL FORM

Solution for injection

4. CLINICAL PARTICULARS

4.1. Target species

Cattle and pigs

4.2. Indications for use, specifying the target species

Cattle

The treatment of respiratory disease caused by Pasteurella haemolytica and P.multocida and the treatment of enteric infections caused by Escherichia coli and Salmonella spp. in cattle.

Pigs

The treatment of respiratory disease caused by P.multocida and A.pleuropneumoniae, and the treatment of enteric infection caused by

E.coli in pigs.

4.3. Contraindications

None.

4.4. Special warnings for each target species

See section 4.9 - Pigs, regarding use in animals weighing less than 2 kg.

4.5. Special precautions for use

i) Special precautions for use in animals

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

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, fluoroquinolones should only be used 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 the effectiveness of treatment with other quinolones due to the potential for cross resistance.

ii) Special precautions to be taken by the person administering the veterinary medicinal product to animals Wash hands after use.

4.6. Adverse reactions (frequency and seriousness)

None.

4.7. Use during pregnancy, lactation or lay

The effects of danofloxacin on reproductive performance and on pregnancy in pigs have not been assessed.

4.8. Interaction with other medicinal products and other forms of interaction

No interactions with other products have been noted.

4.9. Amounts to be administered and administration route

Cattle

Administer by the intramuscular or intravenous routes at a dosage rate of 1.25 mg/kg body weight (1 ml/20 kg body weight). Three treatments should be given at 24 hour intervals. Treatment may be extended by up to 2 additional days for animals not fully recovered after the initial 3 treatments. For the treatment of cattle weighing more than 400 kg, the dose should be divided so that not more than 20 ml are injected at one site.

Pigs

Administer by intramuscular injection at a dosage rate of 1.25 mg/kg body weight (1 ml/20 kg body weight). Three treatments should be given at 24 hour intervals. For the treatment of pigs weighing more than 100 kg, the dose should be divided so that no more than 5 ml are injected at one site.

Seek veterinary advice regarding use of appropriately sized needles and syringes when dosing small animals.

An appropriately graduated syringe must be used to allow accurate administration of the required dose volume. This is particularly important when injecting small volumes, e.g. piglets less than 2 kg body weight. When dosing a large number of animals from a single bottle, the use of an aspirating needle is recommended to avoid excessive broaching of the stopper.

4.10.Overdose (symptoms, emergency procedures, antidotes), if necessary

Cattle

Overdosage by up to 25 times the recommended dose produces only mild signs of intolerance, including head tremors, ataxia and mild depression. No treatment related effects have been seen on gestation, parturition or calf viability.

Pigs

Overdosing of pigs by ten times the recommended dose showed only minor adverse clinical reactions including transient reduction in mobility. Three times the recommended dose given on three consecutive days to neonatal pigs produced no adverse clinical effects.

No antidote is recommended.

4.11.Withdrawal periods

Cattle

Meat: 5 days

Milk: 48 hours

Pigs

Meat: 3 days

5. PHARMACOLOGICAL PROPERTIES

ATCVet code: QJ01MA92

Danofloxacin is a new synthetic fluoroquinolone antimicrobial agent which possesses potent in vitro activity against Mannheimia haemolytica, Pasteurella multocida, Escherichia coli and Salmonella spp., the bacterial pathogens most commonly associated with bovine respiratory and enteric disease.

Danofloxacin also possesses potent antibacterial activity against P.multocida and Actinobacillus pleuropneumoniae, the causative agents of porcine respiratory disease, and E.coli, a causative agent of enteric disease in swine. Danofloxacin is active against pathogens showing resistance to other classes of antimicrobial agents. The in vitro MIC₉₀ for Mycoplasma hyopneumoniaeis reported to be 0.06µg/ml, and for Mycoplasma bovis 0.5 µg/ml.

The antimicrobial activity of danofloxacin is based upon the inhibition of microbial DNA gyrase. The inhibitory effect is on the second step of the enzymatic process, uncoupling the breakage and reunion functions. Danofloxacin, in common with other quinolones, produces a stable complex between the enzyme and DNA. This results in the cessation of DNA replication and transcription, an effect which is the basis of the antimicrobial effect. Pharmacological studies showed that danofloxacin has little effect on the cardiovascular, renal or neurological systems, and, in common with other quinolones, has only mild effects on the gastric system at high dose levels.

In general pharmacological terms, danofloxacin is well tolerated in laboratory animals. Acute toxicity values are high and a limiting No Observed Effect Level of 2.4 mg/kg/day has been established in repeat administration studies in young dogs, the most sensitive test species. The pharmacokinetic properties of danofloxacin, which give high and rapidly achievable levels of danofloxacin in target tissues, show the product to be well suited to the therapy of respiratory and enteric diseases.

Cattle

Peak plasma levels after intramuscular and subcutaneous injection (where authorised) are seen one hour after treatment. High tissue to plasma ratios of up to 4:1 are seen in lung and gastrointestinal tissues.

Pigs

Peak plasma levels after intramuscular injection to pigs are seen one hour after treatment. High tissue to plasma ratios of up to 3:1 for lung and up to 8:1 for gastrointestinal tissues were recorded.

6. PHARMACEUTICAL PARTICULARS

6.1. List of excipients

Lactic Acid

Sodium Hydroxide

Thioglycerol

Phenol (liquefied)

Water for injections

6.2. Major incompatibilities

None known

6.3. Shelf life

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

Shelf-life of the veterinary medicinal product after first opening the immediate packaging: 28 days.

6.4. Special precautions for storage

Do not store above 30°C.

6.5. Nature and composition of immediate packaging

Advocin injectable solution is a clear sterile aqueous solution of danofloxacin mesylate, packaged in 50 ml, 100 ml and 250 ml Type II amber glass round vials with butyl rubber stopper and lacquered onepiece aluminium shell.

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

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

Zoetis UK Limited

1st Floor Birchwood Building

Springfield Drive

Leatherhead

Surrey

KT22 7LP

8. MARKETING AUTHORISATION NUMBER

Vm 42058/4001

9. DATE OF THE FIRST AUTHORISATION

27 November 1995

10. DATE OF REVISION OF THE TEXT

April 2020

Approved: 01 April 2020