Nuflor - Performance Data

Feedyard Trial Dashes Conventional Wisdom

Should you use different antibiotics for on-arrival processing and for treatment of bovine respiratory disease? Not necessarily.

To demonstrate this point, consider the results of a recent study comparing the outcomes of three bovine respiratory disease treatment programs.¹ This study involved 750 high-risk calves weighing about 600 pounds on arrival at a Texas feedyard research facility. On arrival, calves were randomly assigned to one of three treatment protocols:

Table 1. Treatment
Treatment Groups
Treatment on Arrival
1^st Pull Therapy 2^nd Pull Therapy 3^rd Pull Therapy
I
Nuflor
40 mg/kg Nuflor
40 mg/kg Naxcel^® Vetisulid^® None
II
None Nuflor
40 mg/kg Nuflor
40 mg/kg Naxcel Vetisulid
III
Nuflor
40 mg/kg Baytril
12.5 mg/kg Naxcel Vetisulid None

Table 2 shows the sickness and mortality rates, and Table 3 shows performance rates among the groups over a 180- to
200-day feeding period.

Table 2. Health Outcomes

Treatment I
Treatment II Treatment III
Number First Pull 137^a 198^b 131^a
Percent First Pull 54.80% 79.84% 52.61%
Number Second Pull 63^a 99^b 58^a
Percent Second Pull 45.99% 50.00% 44.27%
Number Third Pull 1^a 55^b 0^a
Percent Third Pull 1.59% 55.56% 0.00%
Number Mortality 7^a 13^a 13^a
Percent Mortality 2.81% 5.24% 5.22%
Values with different superscripts (a, b) are different @ p<0.0001.

Table 3. Performance Outcomes

Treatment I
Treatment II Treatment III
In Weight 595.37 595.44 591.88
Finish Weight 1359.72 1317.50 1337.34
Gain 764.36 722.06 745.47
Average Daily Gain 3.46 3.33 3.42
Cost of Gain 40.11 39.70 40.28
Dry Consumption 18.67 18.14 18.37
Dry Conversion 5.40 5.44 5.37

These tables make two very important points.

• First, treating high-risk calves on arrival is a valuable practice. Those that didn’t receive Nuflor on arrival had dramatically higher sickness rates and lower performance rates.

In fact, due to the non-collective therapy group’s diminished health and performance, there was a $35 per head advantage in animals that received Nuflor as collective therapy.¹

• Second, Nuflor followed by Nuflor is effective therapy. Many producers are shy of using the same product on arrival and in the hospital. They expect that switching drugs will provide more effective treatment. But this study shows that just the opposite is true with Nuflor. Calves in the Nuflor/Nuflor group responded to treatments at least as well as those that received another first-line treatment.

Its broad spectrum with fast and long-lasting antibacterial action makes Nuflor an effective and therefore cost-effective antibiotic. You can use it with confidence on arrival, for treatment, and for both.

Do not use in female dairy cattle 20 months of age or older as use in lactating dairy cattle may cause milk residues. Not for use in cattle of breeding age. Do not use for calves to be processed for veal. Please see accompanying Product Information summary for important information.

¹ Data on file at Intervet/Schering-Plough Animal Health.
©2003 Schering-Plough Animal Health Corp. All rights reserved. Nuflor is a registered trademark of Schering-Plough Veterinary Corp. Baytril is a registered trademark of Bayer Animal Health.

PRODUCT INFORMATION
F-24823113
NADA #141-063. Approved by FDA.

Injectable Solution 300 mg/mL
For Intramuscular and Subcutaneous Use in Cattle Only.

CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.

DESCRIPTION: NUFLOR Injectable is a solution of the synthetic antibiotic florfenicol. Each milliliter of sterile NUFLOR Injectable Solution contains 300 mg of florfenicol, 250 mg n-methyl-2-pyrrolidone, 150 mg propylene glycol, and polyethylene glycol q.s.

CLINICAL PHARMACOLOGY: The pharmacokinetic disposition of NUFLOR Injectable Solution was evaluated in feeder calves following single intramuscular administration at the recommended dose of 20 mg/kg. NUFLOR Injectable Solution was also administered intravenously to the same cattle in order to calculate the volume of distribution, clearance, and percent bioavailability¹ (Table 1).

TABLE 1. Pharmacokinetic Parameter Values for Florfenicol Following IM Administration of 20 mg/kg Body Weight to Feeder Calves (n=10).

Florfenicol was detectable in the serum of most animals through 60 hours after intramuscular administration with a mean concentration of 0.19 µg/mL. The protein binding of florfenicol was 12.7%, 13.2%, and 18.3% at serum concentrations of 0.5, 3.0, and 16.0 µg/mL, respectively.

MICROBIOLOGY: Florfenicol is a synthetic, broad-spectrum antibiotic active against many gram-negative and gram-positive bacteria isolated from domestic animals. It is primarily bacteriostatic and acts by binding to the 50S ribosomal subunit and inhibiting bacterial protein synthesis. In vitro and in vivo activity has been demonstrated against commonly isolated bacterial pathogens involved in bovine respiratory disease (BRD) including Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus, as well as against commonly isolated bacterial pathogens involved in bovine interdigital phlegmon including Fusobacterium necrophorum and Bacteroides melaninogenicus.

The minimum inhibitory concentrations (MICs) of florfenicol for BRD organisms were determined using isolates obtained from natural infections from 1990 to 1993. The MICs for interdigital phlegmon organisms were determined using isolates obtained from natural infections from 1973 to 1997 (Table 2).

TABLE 2. MIC Values* of Florfenicol Against Bacterial Isolates From Natural Infection of Cattle.

INDICATIONS: NUFLOR Injectable Solution is indicated for treatment of bovine respiratory disease (BRD) associated with Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus, and for the treatment of bovine interdigital phlegmon (foot rot, acute interdigital necrobacillosis, infectious pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus. Also, it is indicated for the control of respiratory disease in cattle at high risk of developing BRD associated with Pasteurella haemolytica, Pasteurella multocida, and Haemophilus somnus.

RESIDUE WARNINGS: Animals intended for human consumption must not be slaughtered within 28 days of the last intramuscular treatment. Animals intended for human consumption must not be slaughtered within 38 days of subcutaneous treatment. Do not use in female dairy cattle 20 months of age or older. Use of florfenicol in this class of cattle may cause milk residues. A withdrawal period has not been established in preruminating calves. Do not use in calves to be processed for veal.

WARNINGS: NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. This product contains materials that can be irritating to skin and eyes. Avoid direct contact with skin, eyes, and clothing. 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. Accidental injection of this product may cause local irritation. Consult a physician immediately. The Material Safety Data Sheet (MSDS) contains more detailed occupational safety information.

For customer service, adverse effects reporting, and/or a copy of the MSDS, call 1-800-211-3573.

CAUTION: Not for use in cattle of breeding age. The effects of florfenicol on bovine reproductive performance, pregnancy, and lactation have not been determined. Intramuscular injection may result in local tissue reaction that persists beyond 28 days. This may result in trim loss of edible tissue at slaughter. Tissue reaction at injection sites other than the neck is likely to be more severe.

ADVERSE EFFECTS: Inappetence, decreased water consumption, or diarrhea may occur transiently following treatment.

TOXICOLOGY: A 10X safety study was conducted in feeder calves. Two intramuscular injections of 200 mg/kg were administered at a 48-hour interval. The calves were monitored for 14 days after the second dose. Marked anorexia, decreased water consumption, decreased body weight, and increased serum enzymes were observed following dose administration. These effects resolved by the end of the study.

A 1X, 3X, and 5X (20, 60, and 100 mg/kg) safety study was conducted in feeder calves for 3X the duration of treatment (6 injections at 48-hour intervals). Slight decrease in feed and water consumption was observed in the 1X dose group. Decreased feed and water consumption, body weight, urine pH, and increased serum enzymes were observed in the 3X and 5X dose groups. Depression, soft stool consistency, and dehydration were also observed in some animals (most frequently at the 3X and 5X dose levels), primarily near the end of dosing.

A 43-day controlled study was conducted in healthy cattle to evaluate effects of NUFLOR Injectable Solution administered at the recommended dose on feed consumption. Although a transient decrease in feed consumption was observed, NUFLOR Injectable Solution administration had no long-term effect on body weight, rate of gain, or feed consumption.

DOSAGE AND ADMINISTRATION: For treatment of bovine respiratory disease (BRD) and bovine interdigital phlegmon (foot rot): NUFLOR Injectable Solution should be administered by intramuscular injection to cattle at a dose rate of 20 mg/kg body weight (3 mL/100 lbs). A second dose should be administered 48 hours later. Alternatively, NUFLOR Injectable Solution can be administered by a single subcutaneous injection to cattle at a dose rate of 40 mg/kg body weight (6mL/100 lbs). Do not administer more than 10 mL at each site. The injection should be given only in the neck.

NOTE: Intramuscular injection may result in local tissue reaction that persists beyond 28 days. This may result in trim loss of edible tissue at slaughter. Tissue reaction at injection sites other than the neck is likely to be more severe.

For control of respiratory disease in cattle at high-risk of developing BRD: NUFLOR Injectable Solution should be administered by a single subcutaneous injection to cattle at a dose rate of 40 mg/kg body weight (6 mL/100 lbs). Do not administer more than 10 mL at each site. The injection should be given only in the neck.

Clinical improvement should be evident in most treated subjects within 24 hours of initiation of treatment. If a positive response is not noted within 72 hours of initiation of treatment, the diagnosis should be reevaluated.

STORAGE CONDITIONS: Store between 2°-30°C (36°-86°F). Refrigeration is not required. The solution is light yellow to straw colored. Color does not affect potency.

HOW SUPPLIED: NUFLOR Injectable Solution is packaged in 100 mL (NDC 0061-1116-04), 250 mL (NDC 0061-1116-05), and 500 mL (NDC 0061-1116-06) glass sterile multiple-dose vials.

REFERENCE: 1. Lobell RD, Varma KJ, et al. Pharmacokinetics of florfenicol following intravenous and intramuscular doses to cattle. J Vet Pharmacol Therap. 1994; 17:253-258.

B-24B23113 Rev. 12/01 US 3025/1