Nuflor Injectable Solution 300 mg/mL

Company: Intervet/Merck Animal Health

Product Information

(FLORFENICOL)

Injectable Solution

Sterile

300 mg/mL

Approved by FDA under NADA # 141-063

For intramuscular and subcutaneous use in beef and non-lactating dairy cattle only.

Not for use in female dairy cattle 20 months of age or older or in calves to be processed for veal.

Nuflor Injectable Solution 300 mg/mL Caution

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

Description

NUFLOR Injectable Solution 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 (NMP), 150 mg propylene glycol, and polyethylene glycol qs. The chemical name for florfenicol is 2,2-Dichloro-N-[1-(fluoromethyl)-2-hydroxy-2-[4-(methylsulfonyl)phenyl]ethyl] acetamide.

Nuflor Injectable Solution 300 mg/mL Indications

NUFLOR Injectable Solution is indicated for treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, 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 Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni.

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 (SC) 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.

NOTE: 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.

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.

Recommended Injection Location

Contraindications

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

USER SAFETY 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. Reproductive and developmental toxicities have been reported in laboratory animals following high, repeated exposures to N-methyl-2-pyrrolidone (NMP). Pregnant women should wear gloves and exercise caution or avoid handling this product. The Safety Data Sheet (SDS) contains more detailed occupational safety information.

CONTACT INFORMATION: For customer service, adverse effects reporting and/or a copy of the SDS, call 1-800-211-3573. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae.

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 NUFLOR Injectable Solution was evaluated in feeder calves following single intramuscular (IM) administration at the recommended dose of 20 mg/kg body weight. NUFLOR 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 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 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 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 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.

STORAGE INFORMATION Store between 2°-30°C (36°-86°F). Refrigeration is not required. Protect from light when not in use. Use within 30 days of first puncture. For the 100mL vials, puncture the stopper a maximum of 3 times. For the 250mL and 500mL vials, puncture the stopper a maximum of 17 times.

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.

Copyright© 2022 Merck & Co., Inc., Rahway, NJ, USA and its affiliates.

All rights reserved.

Formulated in Germany.

Rev. 12/22

CPN: 1047137.13