Norfenicol Injectable Solution

Do not inject more than 10 mL per injection site.

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 re-evaluated.

Contraindications

Do not use in animals that have shown hypersensitivity to florfenicol.

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 Safety Data Sheet (SDS) contains more detailed occupational safety information.

To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Norbrook at 1-866-591-5777.

Precautions

Not for use in animals intended for breeding purposes. The effects of florfenicol on bovine reproductive performance, pregnancy, and lactation have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Intramuscular injection may result in local tissue reaction which 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 Reactions

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

Clinical Pharmacology

The pharmacokinetic disposition of florfenicol injectable solution was evaluated in feeder calves following single intramuscular (IM) administration at the recommended dose of 20 mg/kg body weight. Florfenicol injectable solution was also administered intravenously (IV) 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).

* harmonic mean

** mean value

*** following IV administration

C_max Maximum serum concentration

T_max Time at which C_max is observed

T 1/2 Biological half-life

AUC Area under the curve

Vd_ss Volume of distribution at steady state

Cl_t Total body clearance

Florfenicol was detectible 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 acts by binding to the 50S ribosomal subunit and inhibiting bacterial protein synthesis. Florfenicol is generally considered a bacteriostatic drug, but exhibits bactericidal activity against certain bacterial species. In vitro studies demonstrate that florfenicol is active against the bovine respiratory disease (BRD) pathogens Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, and that florfenicol exhibits bactericidal activity against strains of M. haemolytica and H. somni. Clinical studies confirm the efficacy of florfenicol against BRD as well as against commonly isolated bacterial pathogens 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. Florfenicol Minimum Inhibitory Concentration (MIC) Values* of Indicated Pathogens Isolated From Natural Infections of Cattle.

* The correlation between the in vitro susceptibility data and clinical effectiveness is unknown.

** The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.

ANIMAL SAFETY: 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 florfenicol injectable solution administered at the recommended dose on feed consumption. Although a transient decrease in feed consumption was observed, florfenicol injectable solution administration had no long-term effect on body weight, rate of gain, or feed consumption.

STORAGE INFORMATION: Store at or below 77°F (25°C). Refrigeration is not required. Excursions permitted up to 86°F (30°C). Brief exposure to temperature up to 104°F (40°C) may be tolerated provided the mean kinetic temperature does not exceed 77°F (25°C); however, such exposure should be minimized. The solution is light yellow to straw colored. Color does not affect potency.

Use within 28 days of first vial puncture.

How Supplied

Norfenicol Injectable Solution is packaged in 100 mL, 250 mL, and 500 mL 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.

Restricted Drug - California. Use Only as Directed.

Made in the UK.

Manufactured by: Norbrook Laboratories Limited, Newry, BT35 6PU, Co. Down, Northern Ireland.

The Norbrook logos and Norfenicol^® are registered trademarks of Norbrook Laboratories Limited.

162670I02

November 2020

CPN: 1345019.1