A180* (Canada)

This page contains information on A180* for veterinary use.
The information provided typically includes the following:
  • A180* Indications
  • Warnings and cautions for A180*
  • Direction and dosage information for A180*

A180*

This treatment applies to the following species:
Manufacturer: Zoetis

danofloxacin mesylate sterile injectable solution

Veterinary Use Only

antibacterial

for cattle

DIN 02261200

Description

A180* Injectable Solution is a sterile solution containing danofloxacin mesylate, a synthetic fluoroquinolone antimicrobial agent. Danofloxacin mesylate is the non-proprietary designation for (1S)-1cyclopropyl-6-fluoro-1,4-dihydro-7-(5-methyl-2,5-diazabicyclo [2.2.1]hept-2-yl)-4-oxo-3-quinolone carboxylic acid monomethanesulfonate. The empirical formula is C19H20FN3O3.CH3SO3H and molecular weight 453.49.

Figure 1. The chemical structure of danofloxacin mesylate

Each mL contains 180 mg of danofloxacin (as danofloxacin mesylate) and 2.5 mg phenol as the preservative.

A180* Indications

For the treatment of bovine respiratory disease associated with Mannheimia haemolytica and Pasteurella multocida.

Efficacy Confirmation: A180 Injectable Solution has been shown in clinical field trials to be effective in the treatment of bovine respiratory disease associated with Mannheimia haemolytica and Pasteurella multocida. Bacterial pathogens isolated in clinical field studies are provided in the Microbiology section.

Dosage and Administration

Administer a subcutaneous dose of 6 mg/kg of body weight (3.3 mL/100 kg). Treatment should be repeated once approximately 48 hours following the first injection. Care should be taken to dose accurately.

Administered dose volume should not exceed 15 mL per injection site.

Table 1. A180 Danofloxacin Mesylate Injectable Solution Dosage Table

Cattle Weight

6 mg/kg given twice 48 hours apart
Dose Volume (mL)

lb

kg

50

22

0.75

100

45

1.5

200

91

3.0

300

136

4.5

400

181

6.0

500

227

7.5

600

272

9.0

700

318

10.5

800

363

12.0

900

408

13.5

1000

454

15.0

Clinical Pharmacology

Danofloxacin distributes extensively throughout the body, as evidenced by a steady state volume of distribution (VDss) exceeding 1L/kg. Danofloxacin concentrations in the lung homogenates markedly exceed those observed in plasma, further suggesting extensive distribution to the indicated site of infection. Danofloxacin is rapidly eliminated from the body (apparent terminal elimination T1/2 ranging from 3 to 6 hours), and therefore negligible accumulation is expected to occur when animals are dosed with a q48h dosing regimen.

Danofloxacin is rapidly absorbed and is highly bioavailable when administered as a subcutaneous injection in the neck. No statistically significant gender difference was observed in peak or total systemic exposure following subcutaneous administration. Linear pharmacokinetics have been demonstrated when danofloxacin is administered by subcutaneous injection at doses up to 10-mg/kg. Pharmacokinetic parameter values associated with a 6-mg/kg dose are provided in Table 2.

Table 2: Danofloxacin pharmacokinetic values (6-mg/kg)

 

 

Steers

Heifers

Mean

%CVe

Mean

%CVe

a AUC0-24

µg x hr/mL

9.4

10

8.8

9

b F

 

92

5

87

3

a Cmax.

µg/mL

1.25

16

1.27

13

a,c Tmax.

h

3.2

42

1.7

31

d CL

L/hr

0.54

12

0.62

9

d VDss

L/kg

2.7

7

2.6

4

a T

hr

4.8

18

4.2

7

a Pharmacokinetic estimates based upon a 6 mg/kg subcutaneous injection administered into the lateral neck region. AUC0-24 = area under the plasma concentration versus time curve from hr zero to hr 24 postdose; Cmax = maximum observed concentration. Tmax = time to Cmax.

b F = extent of drug absorption following subcutaneous administration. Within subject F values were determined as the ratio of AUC0-inf values estimated following a 6-mg/kg dose administered as either a subcutaneous or intravenous injection

c Tmax: statistically significant differences were detected between genders. Given the similarity in Cmax values, these differences are not expected to have any clinical significance.

d CL (clearance) and VDss (steady state volume of distribution) were determined from data obtained after intravenous administration of a 6-mg/kg dose.

e Coefficient of variation %

Microbiology: Danofloxacin exerts its activity by inhibiting the bacterial DNA gyrase enzyme, thereby blocking DNA replication. Inhibition of DNA gyrase is lethal to bacteria and danofloxacin has been shown to be bactericidal. Danofloxacin is active in vitro against gram-negative and gram-positive bacteria.

The Minimum Inhibitory Concentrations (MIC) of danofloxacin were determined for isolates obtained from natural infections in cattle in the United States and Canada, from 1994 to 1997 (Table 3), using the standardized microdilution technique (SENSITITRE/ALAMAR, Accumed International).

Table 3. MIC Values (µg/mL) of Danofloxacin Against Bacterial Isolates from Natural Infections of Cattle

Species

No. Isolates

MIC90*

Mannheimia haemolytica

400

0.06

Pasteurella multocida

318

0.03

Haemophilus somnus**

41

0.06

* The minimum inhibitory concentration for 90% or more of the isolates.

** The clinical significance of these in vitro data has not been demonstrated.

Standardized procedures for in vitro antimicrobial susceptibility testing using broth and disk diffusion techniques are contained in the National Committee for Clinical Laboratory Standards (NCCLS) document: M31-A2: Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals; Approved Standard - Second Edition. The provisional interpretive criteria (breakpoints) listed below have been approved by the NCCLS Subcommittee on Veterinary Antimicrobial Susceptibility Testing (June 2003):

Interpretive Standards (Provisional) for Disk Diffusion and Minimum Inhibitory Concentration (MIC) Susceptibility Testinga

Antimicrobial Agent

Disk Content

Zone Diameter (mm)

MIC (µg/mL)

S

I

R

S

I

R

Danofloxacin (DAN 5)
Bovine (Respiratory Disease)
- Mannheimia haemolytica
- Pasteurella multocida

5 µg

≥ 22

- a

- a

≤ 0.25

- a

- a

a Insufficient data were available to establish breakpoints for the Intermediate (I) and Resistant (R) categories. Zone sizes smaller than 22 mm or MIC values greater than 0.25 mg/mL suggest a decreased susceptibility compared to susceptible (S) strains.

A180* Caution

Quinolone-class drugs should be used with caution in animals with known or suspected central nervous system (CNS) disorders. In such animals, quinolones have, in rare instances, been associated with CNS stimulation, which may lead to convulsive seizures. Quinolone-class drugs have been shown to produce erosions of cartilage of weight-bearing joints and other signs of arthropathy in immature, rapidly growing animals of various species. Care should be taken to dose accurately. The effects of danofloxacin on bovine reproductive performance, pregnancy, and lactation have not been adequately determined.

Safety: Safety studies were conducted in feeder calves using single doses of 10, 20, or 30 mg/kg for six consecutive days and 18, 24, or 60 mg/kg for three consecutive days. No clinical signs of toxicity were observed at doses of 10 and 20 mg/kg when administered for six days nor at doses of 18 and 24 mg/kg when administered for three days. Histologic evidence of fluoroquinolone chondropathy was detected in one of five (1/5) animals in the 18 mg/kg group. Clinical signs of inappetance, transient lameness, ataxia, tremors, nystagmus, and recumbency were observed when a dose of 30 mg/kg had been administered for four consecutive days. Clinical signs of inappetance and recumbency were observed when a dose of 60 mg/kg was administered for three days. Articular cartilage lesions, consistent with fluoroquinolone chondropathy, were also observed after examination of joints from one of six (1/6) and five of six (5/6) animals administered 20 and 30 mg/kg for six days, respectively, and four of four (4/4) animals treated with 60 mg/kg for three days. Swelling at the injection site was noted at each dose level.

Safety was also evaluated in 21-day-old calves. In one group, these immature animals were given injections of 6 mg/kg on study days 0, 2, 3, 5, 6, and 8. A second group of animals received injections of 18 mg/kg for a total of two injections 48 hours apart. The only treatment-related sign was erythema of the sclera and nasal pad in calves that received 18 mg/kg. No changes in clinical pathology parameters were observed. No articular cartilage lesions were observed in the joints at any dosage.

An injection site study conducted in feeder calves demonstrated that the product may induce a reaction in the subcutaneous tissue and the underlying muscle.

Adverse Reactions

A hypersensitivity reaction was noted in two (2) healthy calves treated with A180 Injectable Solution in a laboratory study. No adverse reactions attributable to the treatment were observed during the clinical field trials.

Warnings

Treated animals must not be slaughtered for use as food for at least seven (7) days after the latest treatment with this drug./ Do not use in dairy cattle./ Do not use in veal calves. The withdrawal period has not been established in pre-ruminating calves./Do not use in an extra-label manner in cattle or any other species./

To limit the potential development of antimicrobial resistance:

- Fluoroquinolone drugs such as A180 should not be used indiscriminately.

- A180 should not be used as an arrival treatment for feed-lot cattle.

- A180 should only be used for treating individual cases of bovine respiratory disease after first choice treatments have failed.

- The choice of A180 as the most appropriate treatment should be confirmed by clinical experience supported where possible, by pathogen culture and drug susceptibility testing.

KEEP OUT OF REACH OF CHILDREN

Note: To reduce the possibility of excess trim at the injection site, it is recommended that cattle not be slaughtered for up to 21 days after the latest treatment with this drug.

A180* Caution

Subcutaneous injection can cause a local tissue reaction that may result in trim loss of edible tissue at slaughter.

Storage

Store at or below 30°C. Protect from light and from freezing. The color is yellow to amber. Color does not affect potency.

Presentation: A180 Injectable Solution is supplied in 100 mL amber glass sterile multi-dose vials.

* Registered trade-mark of Pfizer Products Inc.; Pfizer Canada Inc., Licensee

Pfizer Animal Health, Pfizer Canada Inc., Kirkland QC H9J 2M5

8712951

NAC No.: 11983162

ZOETIS CANADA
17,300 TRANS-CANADA HIGHWAY, KIRKLAND, QC, H9J 2M5
Order Desk:   800-663-8888
Technical Services Canada:   800-461-0917
Technical Services USA:   800-366-5288
Website:   www.zoetis.ca
Every effort has been made to ensure the accuracy of the A180* information published above. However, it remains the responsibility of the readers to familiarize themselves with the product information contained on the Canadian product label or package insert.

Copyright © 2014 North American Compendiums. Updated: 2014-04-11

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