SUMMARY OF PRODUCT CHARACTERISTICS

Advocin 2.5 % Solution for Injection

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

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

For the full list of all other excipients see section 6.1

Solution for injection.

Cattle and pigs.

Cattle

The treatment of respiratory disease caused by Pasteurella haemolyticaand P.multocidaand the treatment of enteric infections caused by Escherichia coli and Salmonellaspp. in cattle.

Pigs

The treatment of respiratory disease caused by P.multocidaand A.pleuropneumoniae, and the treatment of enteric infection caused by E.coliin pigs.

None.

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

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.

Wash hands after use.

None.

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

No interactions with other products have been noted.

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.

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.

Cattle

Meat: 5 days

Milk: 48 hours

Pigs

Meat: 3 days

ATCVet code:QJ01MA92

Danofloxacin is a new synthetic fluoroquinolone antimicrobial agent which possesses potent in vitro activity against Mannheimia haemolytica, Pasteurella multocida, Escherichiacoli 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.

Lactic Acid

Sodium Hydroxide

Thioglycerol

Phenol (liquefied)

Water for injections

None known.

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.

Do not store above 30°C.

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 one-piece aluminium shell.

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

Zoetis UK Limited

5th Floor, 6 St. Andrew Street

London

EC4A 3AE

Vm:42058/4001

Date:27 November 1995

Date:April 2014

03 April 2014