Introduction

Pfizer

Company name: Pfizer Limited

Address: Ramsgate Road

Sandwich

Kent CT13 9NJ

Telephone: 0845 300 8034 (Out of hours: 01304 616161)

Fax: 01737 332521

Email: UKVetLine@pfizer.com

Website: www.only4vets.co.uk

Presentation

Advocin 180 solution is a clear sterile aqueous formulation of danofloxacin mesylate that contains 180 mg danofloxacin per ml. The product is ready for immediate administration.

Each ml contains 2.5 mg phenol and 5 mg monothioglycerol as preservative.

Uses

Advocin 180 contains danofloxacin, a fluoroquinolone antimicrobial agent that possesses potent in vitro activity against Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Escherichia coli, the bacterial pathogens most commonly associated with bovine respiratory disease, enteric disease and acute bovine mastitis.

Cattle and calves

Advocin 180 is specifically indicated for the treatment of bovine respiratory disease caused by Mannheimia haemolytica, Pasteurella multocida and Histophilus somni and for the treatment of acute bovine mastitis caused by Escherichia coli sensitive to danofloxacin.

Neonatal calves

Advocin 180 is also indicated for the treatment of enteric infections caused by Escherichia coli sensitive to danofloxacin.

Dosage and administration

6 mg/kg body weight (1 ml/30 kg body weight) as a single injection by the subcutaneous or intravenous route.

If clinical signs of respiratory or enteric disease persist 48 hours after the first injection, an additional dose at 6 mg/kg body weight may be administered. It is recommended to treat animals in the early stages of disease and to evaluate the response to treatment within 48 hours.

For the treatment of acute bovine mastitis, Advocin 180 should be administered at 6 mg/kg body weight (1 ml/30kg body weight) as a single injection by the subcutaneous or intravenous route. The clinical signs should be monitored carefully and supportive therapy should be given as appropriate. If clinical signs of acute bovine mastitis persist 36-48 hours after the first injection, the antibiotic treatment should be reviewed. It is recommended to treat animals in the early stages of disease and to evaluate the response to treatment within 36-48 hours.

For treatment of cattle weighing more than 450 kg, divide the subcutaneous dose so that no more than 15 ml are injected at one site. When dosing a large number of animals from a single vial, the use of an automatic syringe is recommended to avoid excessive broaching of the rubber stopper.

Contra-indications, warnings, etc

Cattle must not be slaughtered for human consumption during treatment. Cattle may be slaughtered for human consumption only after 8 days from the last treatment.

Milk for human consumption must not be taken during treatment. Milk for human consumption may only be taken from 4 days (96 hours) after the last treatment; i.e. at the eighth milking for cows milked twice daily.

For fluoroquinolones as a class, over-dosage at multiples of the recommended dose has been shown to induce erosion of articular cartilage. Care should be taken to dose accurately and Advocin 180 should be used with caution in animals with joint disease or cartilage growth disorders.

Subcutaneous injection of the product induces a moderate inflammatory response in the tissue around the injection site. The resultant lesions may persist for up to 30 days. At doses of three times the therapeutic dose (18 mg/kg bw), erythema of the nasal and ocular mucosae was induced and food intake was reduced.

Studies in laboratory animals have shown adverse effects on reproduction. At high doses in rats (100 to 200 mg/kg/day), increase in foetal delayed ossification and in dilation of the cerebral ventricles were observed. Dams given high doses produced fewer live pups per litter and pup weight and survival were adversely affected. The safety of the product has not been assessed in pregnant cows. The use of the product is not recommended for cows during pregnancy. The safety of the product has not been assessed in breeding bulls.

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

Wash hands after use. In case of contact with the skin, wash off any product immediately with soap and water. If accidental eye exposure occurs, flush the eyes immediately with clean water.

Do not eat, drink or smoke during application.

Store out of the reach of children.

For animal treatment only.

Pharmaceutical precautions

Store in the original packaging.

Do not freeze.

Use the product within 28 days of withdrawal of the first dose from the bottle. Any unused product or waste material should be disposed of in accordance with national requirements.

Legal category

POM-V

Packaging quantities

Multidose glass vials containing 50 ml or 100 ml.

Further information

Advocin 180 is rapidly and extensively absorbed from the site of injection. Bioavailability is around 90%. Danofloxacin is only poorly metabolised and subsequently eliminated via both the renal and hepatic routes. A difference in elimination kinetics is observed between pre-ruminant animals (half-life of 12 hours) and ruminant animals (half-life of 4 hours). Following a single subcutaneous administration at 6 mg/kg body weight, peak plasma and tissue concentrations are achieved within one to two hours after treatment. High drug concentrations in lung, enteric and lymphatic tissues are observed with concentrations in lung and enteric tissues approximately four times greater than in plasma. The dose selected for Advocin 180 was based on the optimisation of the concentration dependent bactericidal activity of danofloxacin against respiratory and enteric pathogens.

The mean milk concentrations of danofloxacin were 4.61 and 0.2 µg/ml at the 8 and 24 hour milking, respectively, following a single subcutaneous injection.

Heavy reliance on a single class of antibiotic may result in the induction of resistance in a bacterial population. Cross-resistance to fluoroquinolones can occur. Use of fluoroquinolones should be based on susceptibility testing and take into account official and local antimicrobial use policies. It is prudent to reserve fluoroquinolones for the treatment of clinical conditions which have responded poorly to other classes of antimicrobials. Efficacy against gram positive strains has not been established.

The antimicrobial activity of danofloxacin is based upon the inhibition of microbial DNA gyrase and topoisomerase IV. The inhibitory effect is on the second step of the enzymatic process, uncoupling the breakage and reunion functions. Danofloxacin produces a stable complex between the enzyme and DNA. This results in the cessation of DNA replication and transcription. The bactericidal effect is also observed on bacteria in the stationary growth phase. Although there is the possibility for cross resistance developing within any class of antimicrobial, because of the specific mode of action of fluoroquinolones cross resistance with other major antibiotics which act on the cell wall or on protein synthesis is unlikely to occur. Danofloxacin is efficacious in the treatment of field cases of acute mastitis with a Gram negative bacterial aetiology.