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Resflor (Canada)

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

Resflor

This treatment applies to the following species:
Manufacturer: Merck Animal Health

Florfenicol/Flunixin, as flunixin meglumine

DIN 02330997

FOR VETERINARY USE ONLY

Injectable Solution

Sterile Multi-dose Injectable Antibiotic/Non-steroidal Anti-inflammatory Solution

For Subcutaneous Use in Cattle Only.

Description

Resflor is a sterile solution of a synthetic broad-spectrum antibiotic and a non- steroidal anti-inflammatory drug.

Each milliliter of Resflor contains: active ingredients: 300 mg florfenicol; 27.4 mg flunixin meglumine equivalent to 16.5 mg flunixin; non-medicinal ingredients: 250 mg n-methyl-2-pyrrolidone, 10 mg citric acid and polyethylene glycol q.s.; preservative: 150 mg propylene glycol.

Resflor Indications

Resflor is indicated for the treatment of bovine respiratory disease complex (BRD) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni and BRD associated pyrexia.

Dosage and Administration

Resflor should be administered as a single subcutaneous dose of 40 mg/kg florfenicol and 2.2 mg/kg flunixin (2 mL/15 kg BW or 6 mL/100 lbs BW). Do not administer more than 10 mL at each injection site.

The injection should be given only in the neck. Do not puncture the stopper more than 20 times.

Resflor Dosage Guide

Animal Weight

Resflor dosage

2 mL/15 kg body weight (mL)

(kg)

(lbs)

45

100

6.0

90

200

12.0

135

300

18.0

180

400

24.0

225

500

30.0

270

600

36.0

315

700

42.0

360

800

48.0

405

900

54.0

450

1000

60.0

It is recommended to treat animals in the early stages of the disease and to evaluate the response to treatment 72 hours after injection. If clinical signs of respiratory disease persist or increase, or if relapse occurs, treatment should be changed, using another antibiotic, and continued until signs have resolved.

Contraindications

Do not use in animals showing hypersensitivity to flunixin meglumine or florfenicol.

CAUTIONS: Do not exceed the recommended dose. Transient inappetence may occur with the use of this drug. As a class, cyclo-oxygenase inhibitory non-steroidal anti-inflammatory drugs (NSAIDs) may be associated with gastrointestinal and renal toxicity. Use judiciously when renal impairment or gastric ulceration is suspected. Sensitivity to drug-associated adverse effects varies with the individual patient. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular, and/or hepatic dysfunction. Since many NSAIDs may induce gastrointestinal ulceration, concomitant use of Resflor with other anti-inflammatory drugs, such as other NSAIDs and corticosteroids, should be avoided or closely monitored. Repeated Resflor daily dosing has been associated with abomasal erosions in the pre-ruminant calf. The product should be used with caution in this age group. Also see ADVERSE REACTIONS section. The safety of the product has not been tested in calves under 3 weeks of age.

Not for use in cattle of breeding age. The effects of florfenicol on bovine reproductive performance, pregnancy and lactation have not been determined. NSAIDs are known to have potential effects on both parturition and the estrous cycle. There may be a delay in the onset of estrus if flunixin is administered during the prostaglandin phase of the estrous cycle. The effects of flunixin on imminent parturition have not been evaluated in a controlled study. NSAIDs are known to have the potential to delay parturition through a tocolytic effect.

Warnings

Treated cattle must not be slaughtered for use in food for at least 60 days after the latest treatment with this drug. Not for use in lactating and dry dairy cows. This product contains material that can be irritating to skin and eyes. Avoid direct contact with skin, eyes and clothes. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. Consult a physician if irritation persists. In case of accidental injection of this product, consult a physician immediately. KEEP OUT OF REACH OF CHILDREN.

Adverse Reactions

Although all adverse reactions are not reported, the following information is based on voluntary post-approval drug experience reporting. It is generally recognized that this results in significant under-reporting. The adverse reactions listed here reflect reporting and not necessarily causality. Adverse reactions are listed in decreasing order of frequency. All adverse reactions were reported as rare (less than 1/1,000) or very rare events (less than 1/10,000).

Lack of efficacy (rare), death, diarrhea, ataxia, injection site edema, injection site abscess, lethargy, anorexia, dyspnea, lameness (all very rare).

Anaphylaxis, incorrect injection technique and use of the product with other NSAIDs or when administered more than once, have been identified as risk factors for death in animals administered Resflor. Injection into the spinal cord or an artery may result in death. Adverse reactions reporting lack of efficacy are frequently reported in conjunction with other adverse events such as pyrexia, respiratory signs, and death, reflecting the nature and severity of the disease being treated.

Not every adverse event being reported after the use of a pharmaceutical product is due to the administration of the product. Adverse events may be due to underlying disease, medications or vaccinations used concomitantly, comorbidities, improper handling or administration, conditions during use, or off-label use.

Clinical Pharmacology

The pharmacokinetic disposition of florfenicol after subcutaneous injection of RESFLOR to beef cattle is described in Table 1.

Table 1 Mean Pharmacokinetic Parameters of Florfenicol in Male and Female Ruminating Beef Cattle Administered Resflor Subcutaneously at a Florfenicol Dose of 40 mg/kg BW

 

Cmax

(µg/mL)

Tmax

(hr)

AUC0-LOQ

(µg*hr/mL)

AUC0-∞

(µg*hr/mL)

TMIC90

(hr)

T1/2

(hr)

N

28

28

28

28

28

28

Mean

4.31

5.46

132.76

156.04

39.54

53.68

STD ERR

0.21

0.32

3.92

3.94

1.73

3.98

% CV

25.24

31.30

15.64

13.38

23.13

39.19

Cmax: Maximum plasma concentration

Tmax: Time at which Cmax was observed

1/2: Elimination half-life

AUC0-∞: Area Under the Curve

AUC0-LOQ: Area Under the Curve to the limit of quantification

TMIC90: Time at which the value of the MIC90 is obtained

MIC90: The minimum inhibitory concentration for 90% of the isolates

Comparable plasma concentrations of florfenicol were demonstrated in a comparative pharmacokinetic study in cattle administered either Resflor (florfenicol and flunixin meglumine combined formulation) or Nuflor (florfenicol only formulation). Following subcutaneous injection of Resflor (test article) or Nuflor (reference article) at florfenicol nominal concentration of 40 mg/kg BW, the bioequivalence criteria were met for AUC0-LOQ and TMIC90. However, Resflor provided a higher Cmax of florfenicol when compared to Nuflor.

MICROBIOLOGY: Florfenicol is a synthetic, broad-spectrum antibiotic active against many gram-negative and gram-positive bacteria isolated from domestic animals. It acts by binding to the 50S ribosomal subunit and inhibiting bacterial protein synthesis. In vitro studies of florfenicol demonstrate bactericidal activity against commonly isolated pathogens involved in bovine respiratory disease (BRD) including Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. The minimum inhibitory concentrations (MICs) of florfenicol for BRD organisms were determined using US isolates obtained in 2006 from natural infections (Table 2).

Table 2 Florfenicol MIC Values* of Indicated Pathogens Isolated From US Cattle With Naturally-Occurring BRD

Organism

Year of isolation

Isolate Numbers

MIC50**
(µg/mL)

MIC90**
(µg/mL)

MIC range
(µg/mL)

Mannheimia haemolytica

2006

158

1.00

1.00

0.5 to 32

Pasteurella multocida

2006

103

0.50

0.50

≤0.125 to 16

Histophilus somni

2006

85

≤0.125

≤0.125

≤0.125 to 0.25

*The correlation between the in vitro susceptibility data (MIC values) and clinical response has not been determined.

**The minimum inhibitory concentration for 50% and 90% of the isolates.

Table 3 Clinical and Laboratory Standards Institute (CLSI) Recommended Susceptibility Interpretive Criteria and MIC Breakpoints for Florfenicol

Bovine Respiratory Pathogens

Zone Diameter

(mm, 30 µg disk)

MIC Breakpoint

(µg/mL)

S

I

R

S

I

R

Mannheimia haemolytica

Pasteurella multocida

Histophilus somni

≥ 19

15-18

≤ 14

≤ 2

4

≥ 8

S = Susceptible, I = Intermediate, R = Resistant.

Standardized procedures require the use of laboratory control organisms for both standardized disk diffusion assays and standardized dilution assays. The 30 µg florfenicol disk should give the following zone diameters and florfenicol powder should provide the following MIC values for reference strains.

Table 4 Recommended Quality Control Strains for Florfenicol Susceptibility Testing

QC Strains for Florfenicol

ATCC #

NCTC or NCIMB #

Acceptable Zone Diameter
(mm, 30 µg disk)

Acceptable MIC (µg/mL)

Staphylococcus aureus

29213

Not available

not defined

2-8

Staphylococcus aureus

25923

12702

22-29

not defined

Enterococcus faecalis

29212

12697

not defined

2-8

Escherichia coli

25922

12241

22-28

2-8

Pseudomonas aeruginosa

27853

10896

not defined

> 16

Streptococcus pneumoniae

49619

Not available

24-31

1-4

Histophilus somni

700025

Not available

34-44

0.125-0.5

Actinobacillus pleuropneumoniae

27090

Not available

31-40

0.25-1

ANIMAL SAFETY: Safety studies were conducted in ruminating and preruminating cattle using 1X, 3X and 5X the recommended dose for 3X the duration of treatment. Ruminating calves: Decreased food consumption was observed in the 3X and 5X groups. Decreased body weights were observed in the 5X group (secondary to decreased food consumption). Decreased water consumption was observed in the 5X group which was associated with an increased urine specific gravity. As expected, swelling at the site of injection was noted and resolved with time. Pre-ruminating calves: Abomasal erosions were observed in pre-ruminating calves after three times the recommended treatment duration with 1x doses. Abomasal ulcerations were observed after three times the recommended treatment duration with 3 x and 5 x doses. Clinically none of the animals exhibited any signs of illness and continued to grow normally. In a field trial with pre-ruminating calves some animals that received additional treatment with NSAIDs developed ulceration of the stomach.

EFFICACY: The effectiveness of Resflor in the control of pyrexia associated with naturally occurring bovine respiratory disease was confirmed in several well controlled studies conducted in North America and the EU for ruminating and pre-ruminating calves respectively. At 6 hours post-dose Resflor-treated cattle exhibited a more rapid antipyretic response than Nuflor-treated cattle. There was no difference in Day 10 treatment failure rates between animals treated with Resflor and Nuflor.

STORAGE INFORMATION: Store at or below 25 °C. Do not freeze. Use within 28 days of first puncture. The solution is light yellow to straw colored. Color does not affect potency.

How Supplied

Resflor Injection is available in 100, 250 and 500 mL glass sterile multiple dose vials.

Intervet Canada Corp., Kirkland, Qc H9H 4M7

1-866-683-7838

Intervet Canada Corp. is a subsidiary of Merck & Co., Inc.

® Registered trademark of Intervet International B.V. Used under license

Version August 20, 2015

NAC No.: 1208215.5

MERCK ANIMAL HEALTH
Intervet Canada Corp.

16750 ROUTE TRANSCANADIENNE, KIRKLAND, QC, H9H 4M7
Order Desk:   514-428-7013
Toll-Free:   866-683-7838
Fax:   Toll-free 888-498-4444; local 514-428-7014
Website:   www.merck-animal-health.ca
Every effort has been made to ensure the accuracy of the Resflor 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 © 2016 North American Compendiums. Updated: 2016-04-29

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