Florfenicol

Cattle (Beef and Non-Lactating Dairy)

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of BRD-associated pyrexia in beef and non lactating dairy cattle.

Resflor GOLD®

Cattle (Beef and Non-Lactating Dairy)

For treatment of bovine interdigital phlegmon (foot rot, acute interdigital necrobacillosis, infectious pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

Nuflor®

Cattle (Beef and Non-Lactating Dairy)

For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis in beef and non-lactating dairy cattle.

For subcutaneous use in beef and non-lactating dairy cattle only. Do not administer more than 15 mL at each site. Not for use in animals intended for breeding purposes. This drug product is not approved for use in female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows. Do not use in calves to be processed for veal. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

NuflorGOLD™

Cattle (Beef and Non-Lactating Dairy)

For control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni.

Nuflor®

Cattle (Beef and Non-Lactating Dairy)

For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Haemophilus somni.

Nuflor®

Beef and non-lactating dairy cattle

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.

Florfeniject™

Beef and non-lactating dairy cattle

For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. For the treatment of bovine interdigital phlegmon (foot rot, acute interdigital necrobacillosis, infectious pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

FLORFENICOL INJECTION

Beef and non-lactating dairy cattle

For treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of BRD-associated pyrexia in beef and non-lactating dairy cattle.

nixiFLOR™

Beef and non-lactating dairy cattle

For the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni.

FLORFENICOL INJECTION

Beef and non-lactating dairy cattle

For treatment of bovine respiratory disease (BRD) and bovine interdigital phlegmon (foot rot).

Loncor® 300

Beef and non-lactating dairy cattle

For control of respiratory disease in cattle at high-risk of developing BRD.

Loncor® 300

Freshwater-reared warmwater finfish

For the control of mortality due to streptococcal septicemia associated with Streptococcus iniae.

PAQFLOR™

Catfish

For the control of mortality due to enteric septicemia of catfish associated with Edwardsiella ictaluri.

Feed containing florfenicol shall not be fed for more than 10 days. Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. A dose-related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for hematopoietic/lymphopoietic tissues to regenerate was not evaluated. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Finfish

For the control of mortality due to columnaris disease associated with Flavobacterium columnare.

Feed containing florfenicol shall not be fed for more than 10 days. Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. For catfish, a dose-related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for hematopoietic/lymphopoietic tissues to regenerate was not evaluated. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Salmonids

For the control of mortality due to coldwater disease associated with Flavobacterium psychrophilum and furunculosis associated with Aeromonas salmonicida.

Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Freshwater-reared salmonids

For the control of mortality due to furunculosis associated with Aeromonas salmonicida. For the control of mortality due to coldwater disease associated with Flavobacterium psychrophilum.

PAQFLOR™

Freshwater-reared finfish

For the control of mortality due to columnaris disease associated with Flavobacterium columnare.

PAQFLOR™

For the control of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Streptococcus suis, and Bordetella bronchiseptica in groups of swine in buildings experiencing an outbreak of SRD.

The safety of florfenicol on swine reproductive performance, pregnancy, and lactation has not been determined. Feed containing florfenicol shall not be fed to pigs for more than 5 days. The expiration date of veterinary feed directives (VFDs) for florfenicol medicated feeds for swine must not exceed 90 days from the date of issuance. VFDs for florfenicol shall not be refilled.

Nuflor®

For the treatment of swine respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis in swine.

Not for use in swine intended for breeding. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

FLORCON

Swine except for nursing piglets and swine of reproductive age intended for breeding

For the treatment of swine respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella Choleraesuis, Streptococcus suis, Bordetella bronchiseptica, and Glaesserella (Haemophilus) parasuis in swine except for nursing piglets and swine of reproductive age intended for breeding.

Nuflor®-S

Florfinasone™ Otic is indicated for the treatment of otitis externa in dogs associated with susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Staphylococcus pseudintermedius).

Florfinasone™ Otic

For the treatment of otitis externa in dogs associated with susceptible strains of bacteria (Staphylococcus pseudintermedius) and yeast (Malassezia pachydermatis).

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

Osurnia™

Indications: Fish Species Indication Florefenicol (mg/kg body weight/day) Florefenicol (grams/ton) Freshwater-reared salmonids For the control of mortality due to furunculosis associated with Aeromonas salmonicida. 10-15 182-2,724 For the control of mortality due to coldwater disease associated with Flavobacterium psychrophilum. Freshwater-reared finfish For the control of mortality due to columnaris disease associated with Flavobacterium columnare. 10-15 182-2,724 Catfish For the control of mortality due to enteric septicemia of catfish associated with Edwardsiella ictaluri. 10-15 182-2,724 Freshwater-reared warmwater finfish For the control of mortality due to streptococcal septicemia associated with Streptococcus iniae. 15 273-2,724 Caution: Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. For catfish, a dose related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for the hematopoietic/lymphopoietic tissues to regenerate was not evaluated. RESIDUE WARNING: Feeds containing PAQFLORTM (florfenicol) must be withdrawn 15 days prior to slaughter. IMPORTANT: This product has been evaluated in salmonid and catfish feeds and should be used in feeds nutritionally similar to these evaluated feeds. Refer to the Freedom of Information Summary for details. Must be thoroughly mixed in feeds or surface-coated (top-coated) onto the feeds before use. Mixing Instructions: For incorporation into feed pellets: For making PAQFLORTM (florfenicol) Type C Medicated Feed: a) PAQFLORTM (florfenicol) is added to other feed ingredients in the mixer prior to extrusion, b) the ingredients are mixed thoroughly to insure homogeneity, c) the mixture is steam pelleted or extruded and pellets are dried, d) medicated feed pellets are mixed/coated with a predetermined amount of fish or vegetable oil, and e) at the completion of mixing, the product is transferred to a storage tank for packaging or transport. For surface-coating (top-coating) onto feed pellets: There are two methods for making PAQFLORTM (florfenicol) Type C Medicated Feed by top-coating. Method 1: a) add a known quantity of fish feed into a mixer, b) weigh out PAQFLORTM (florfenicol), c) mix PAQFLORTM with feed pellets, d) medicated feed pellets are mixed/coated with a predetermined amount of fish or vegetable oil, and e) at the completion of mixing, the product is transferred to a storage tank for packaging or transport. Method 2: a) weigh out fish oil or vegetable oil into a bucket, b) weigh out PAQFLORTM (florfenicol) and mix thoroughly with the oil in the bucket, c) add a known quantity of fish feed into a mixer, d) add the PAQFLORTM (florfenicol) and oil mixture to the feed in the mixer, slowly, while the mixer is running at low speed, e) at the completion of mixing, the product is transferred to a storage tank for packaging or transport. Example of PAQFLORTM (florfenicol) Inclusion Rates for Preparation of Type C Medicated Feed Feeding Rate Florfenicol Concentration in Feed Amount of PAQFLORTM (florfenicol per Ton of Feed) Biomass of Fish Medicated per Ton of Feed per 10-day Treatment Period Grams/ton lbs % Biomass Dose 10 mg/kg Dose 15 mg/kg Dose 10 mg/kg Dose 15 mg/kg lbs 0.5 1,816 2,724 8 12 40,000 1 908 1,362 4 6 20,000 2 454 681 2 3 10,000 3 300 450 1.32 1.98 6,666 5 182 273 0.8 1.2 4,000 Feeding Directions: Feed as the sole ration for 10 consecutive days. PAQFLORTM (florfenicol) medicated feed should only be administered once disease has been appropriately diagnosed. Feeding fish at a percent of biomass and corresponding florfenicol concentration included in the table above will deliver the appropriate florfenicol dose.

PAQFLORTM (Florfenicol)Type A Medicated Article

Fish Species Indication Florfenicol (mg/kg body weight/day) Florfenicol (grams/ton) Caution: Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. For catfish, a dose related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for the hematopoietic/lymphopoietic tissues to regenerate was not evaluated. Freshwater-reared salmonids For the control of mortality due to furunculosis associated with Aeromonas salmonicida. 10 - 15 182-2,724 For the control of mortality due to coldwater disease associated with Flavobacterium psychrophilum. Freshwater-reared finfish For the control of mortality due to columnaris disease associated with Flavobacterium columnare. 10 - 15 182-2,724 Catfish For the control of mortality due to enteric septicemia of catfish associated with Edwardsiella ictaluri. 10 - 15 182-2,724 Freshwater-reared warmwater finfish For the control of mortality due to streptococcal septicemia associated with Streptococcus iniae. 15 273- 2,724

Aquaflor® (Florfenicol)

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.

Nuflor® (FLORFENICOL) Injectable Solution 300 mg/mL

INDICATIONS: Nuflor®-S Injectable Solution is indicated for treatment of swine respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella Choleraesuis, Streptococcus suis, Bordetella bronchiseptica, and Glaesserella (Haemophilus) parasuis in swine except for nursing piglets and swine of reproductive age intended for breeding.

Nuflor®-S (FLORFENICOL) Injectable Solution 300 mg/mL

INDICATION: RESFLOR GOLD® is indicated for treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of BRD-associated pyrexia in beef and non-lactating dairy cattle.

Resflor GOLD®

nixiFLOR™ is indicated for treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of BRD-associated pyrexia in beef and non-lactating dairy cattle.

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

INDICATIONS: FLORCON 2.3% Concentrate Solution is indicated for the treatment of swine respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis in swine.

FLORCON 2.3% Concentrate Solution

SIMPLERA is indicated for the treatment of otitis externa in dogs associated with susceptible strains of yeast (Malassezia pachydermatis) and bacteria (Staphylococcus pseudintermedius).

SIMPLERA™ (florfenicol, terbinafine, mometasone furoate)

OSURNIA is indicated for the treatment of otitis externa in dogs associated with susceptible strains of bacteria (Staphylococcus pseudintermedius) and yeast (Malassezia pachydermatis).

Osurnia® (florfenicol, terbinafine, betamethasone acetate)

For the treatment of swine respiratory disease associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis in swine.

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

Florvio™ 2.3% Concentrate Solution

CLINICAL PHARMACOLOGY: Florfenicol is a bacteriostatic agent whose antimicrobial activity is linked to time above MIC. The pharmacokinetic disposition of FLORCON 2.3% Concentrate Solution was evaluated in swine following oral gavage dosing (15 mg/kg), intravenous (IV) dosing (15 mg/kg), and during a five (5) day course of ad lib itum administration in drinking water (100 ppm) (Table 1). Despite the rapid elimination seen after IV injection or oral gavage dosing, when administered in medicated drinking water, florfenicol concentrations in the serum of most swine were maintained well above 1.0 mcg/mL for the majority of the (5) day dosing interval. These results are consistent with product effectiveness when administered in drinking water concentrations of 100 ppm over a five (5) day dosing period. Although the extent of oral drug absorption (F) tended to be variable (24% to 97% following a single oral gavage dose), florfenicol was rapidly absorbed. Its terminal elimination half-life (T1/2) was also rapid, ranging between two (2) to three (3) hours. The average systemic clearance (CLB) following IV administration was 5.6 mL/kg/min. Since the florfenicol steady state volume of distribution (VDSS) closely approximates that of total body water, peripheral tissue concentrations are expected to be similar to those concentrations observed in serum. Table 1. Pharmacokinetic Parameter Values of Florfenicol following IV or Gavage Dosing Parameter Mean Value (% CV) Vdss a (L/kg) 0.95 (6) CLB a (mL/kg/min) 5.57 (11) T ½ a (hrs) 2.2 (14) Fb (%) 24-97 aparameter estimate based on intravenous data bparameter range based upon a single oral gavage dose

FLORCON 2.3% Concentrate Solution

OSURNIA is a fixed combination of three active substances: florfenicol (antibacterial), terbinafine (antifungal) and betamethasone acetate (steroidal anti-inflammatory). Florfenicol is a bacteriostatic antibiotic which acts by inhibiting protein synthesis. Its spectrum of activity includes Gram-positive and Gram-negative bacteria. Terbinafine is an antifungal which selectively inhibits the early synthesis of ergosterol. Betamethasone acetate is a glucocorticosteroid with anti-inflammatory activity. OSURNIA dissolves in ear wax and is slowly eliminated from the ear mechanically. Ear inflammation can increase the percutaneous absorption of active substances in OSURNIA. In a laboratory study conducted in healthy dogs (see Animal Safety ), low plasma concentrations of florfenicol, terbinafine, and betamethasone acetate were measurable during the first 2-4 days after administration of 1× dose, and during the first 2-7 days after administration of 5× dose. No quantifiable plasma concentrations of any of the three active ingredients were observed in the pre-dose samples of most dogs prior to second and third administrations. Although total and peak exposure in the blood tended to be highly variable between dogs, systemic drug concentrations tended to increase in a less than dose-proportional manner as the administered dose increased from 1× to 5×.

Osurnia® (florfenicol, terbinafine, betamethasone acetate)

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 Cmax Maximum serum concentration Tmax Time at which Cmax is observed T ½ Biological half-life AUC Area under the curve Vdss Volume of distribution at steady state Clt Total body clearance Parameter Median Range Cmax (μg/mL) 3.07* 1.43 - 5.60 Tmax (hr) 3.33 0.75 - 8.00 T ½ (hr) 18.3** 8.30 - 44.0 AUC (μg·min/mL) 4242 3200 - 6250 Bioavailability (%) 78.5 59.3 - 106 Vdss (L/kg)*** 0.77 0.68 - 0.85 Clt (mL/min/kg)*** 3.75 3.17 - 4.31 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.

Norfenicol® (florfenicol)Injectable Solution300mg/mL

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). Parameter Median Range Cmax Maximum serum concentration Tmax Time at which Cmax is observed T ½ Biological half-life AUC Area under the curve Vdss Volume of distribution at steady state Clt Total body clearance Cmax (μg/mL) 3.07harmonic mean 1.43 - 5.60 tmax (hr) 3.33 0.75 - 8.00 T ½ (hr) 18.3mean value 8.30 - 44.0 AUC (μg∙min/mL) 4242 3200 - 6250 Bioavailability (%) 78.5 59.3 - 106 Vdss (L/kg)following IV administration 0.77 0.68 - 0.85 Clt (mL/min/kg) 3.75 3.17 - 4.31 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 flor-fenicol was 12.7%, 13.2%, and 18.3% at serum concentrations of 0.5, 3.0, and 16.0 μg/mL, respectively.

Nuflor® (FLORFENICOL) Injectable Solution 300 mg/mL

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). Parameter Median Range Cmax (µg/mL) 3.07* 1.43 - 5.60 tmax (hr) 3.33 0.75 - 8.00 T ½ (hr) 18.3† 8.30 - 44.0 AUC (µg.min/mL) 4242 3200 - 6250 Bioavailability (%) 78.5 59.3 - 106 Vdss (L/kg)‡ 0.77 0.68 - 0.85 Clt (mL/min/kg)‡ 3.75 3.17 - 4.31 Cmax Maximum serum concentration Tmax Time at which Cmax is observed T ½ Biological half-life AUC Area under the curve Vdss Volume of distribution at steady state Clt Total body clearance *harmonic mean †mean value ‡following IV administration 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.

FDA application 200-760

CLINICAL PHARMACOLOGY The pharmacokinetic disposition of florfenicol was evaluated in feeder calves following single intramuscular (IM) administration at the recommended dose of 20 mg/kg body weight. Florfenicol 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). Parameter Median Range Cmax (μg/mL) 3.07* 1.43 - 5.60 tmax (hr) 3.33 0.75 - 8.00 T ½ (hr) 18.3** 8.30 - 44.0 AUC (μg∙min/mL) 4242 3200 - 6250 Bioavailability (%) 78.5 59.3 - 106 Vdss (L/kg)*** 0.77 0.68 - 0.85 Clt (mL/min/kg)*** 3.75 3.17 - 4.31 ** mean value *** following IV administration Cmax Maximum serum concentration Tmax Time at which Cmax is observed T ½ Biological half-life AUC Area under the curve Vdss Volume of distribution at steady state Clt 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.

FLORFENICOL Injectable Solution 300 mg/mL

The pharmacokinetics (PK) of florfenicol (Table 1) and flunixin (Table 2) after subcutaneous injection of RESFLOR GOLD® is described below: Table 1. Mean (n=28) pharmacokinetic parameters for florfenicol in cattle after a single subcutaneous administration of RESFLOR GOLD (florfenicol dose of 40 mg/kg BW). Mean Florfenicol PK parameters in Cattle PK Parameter AUC0-t (ng*hr/mL) AUC0-inf (ng*hr/mL) Cmax (ng/mL) Tmax (hr) T½ (hr) MRT0-inf (hr) Mean 242527 247577 11151 6.25 28.5 27.3 SD 42741 41391 4194 3.87 9.91 11.6 Table 2. Mean (n=28) pharmacokinetic parameters for flunixin in cattle after a single subcutaneous administration of RESFLOR GOLD (flunixin dose of 2.2 mg/kg BW). Mean Flunixin PK parameters in Cattle PK Parameter AUC0-t AUC0-t = Area under the plasma-concentration-time curve (AUC) from time zero to the last quantifiable concentrations (ng*hr/mL) AUC0-inf AUC0-inf = AUC from time zero to infinity (ng*hr/mL) Cmax Cmax = Maximum plasma concentration (ng/mL) Tmax Tmax = Time at which Cmax was observed (hr) T½ T½ = Terminal elimination half-life (hr) MRT0-inf MRT0-inf = Mean residence time from time zero to infinity (hr) Mean 13370 14448n=27 1913 1.14 9.5 11.4 SDSD = Standard deviation 4964 5116 791 0.97 3.27 4.41

Resflor GOLD®

CLINICAL PHARMACOLOGY: The pharmacokinetic disposition of florfenicol was evaluated in 20 pigs following a single IM injection of Nuflor®-S at the labeled dose of 15 mg/kg BW. The mean ± standard deviation maximum plasma concentration (Cmax) and the time to reach Cmax (Tmax) of florfenicol were 3.42 ± 0.82 μg/mL and 4.70 ± 2.15 hours, respectively. The mean ± standard deviation area under the drug concentration-time curve between times 0 and the last quantifiable concentration (AUC0-LOQ) and the terminal half-life (T1/2) of florfenicol were 70.34 ± 23.78 μg*hours/mL and 11.21 ± 3.73 hours, respectively.

Nuflor®-S (FLORFENICOL) Injectable Solution 300 mg/mL

The pharmacokinetics (PK) of florfenicol (Table 1) and flunixin (Table 2) after subcutaneous injection of florfenicol and flunixin meglumine is described below:

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

Do not use in dogs with known tympanic membrane perforation (see PRECAUTIONS ). SIMPLERA is contraindicated in dogs with known or suspected hypersensitivity to florfenicol, terbinafine hydrochloride, or mometasone furoate.

SIMPLERA™ (florfenicol, terbinafine, mometasone furoate)

Do not use in dogs with known tympanic membrane perforation (see Precautions ). Klentz is contraindicated in dogs with known or suspected hypersensitivity to florfenicol, terbinafine hydrochloride, or mometasone furoate.

Klentz™ (florfenicol, terbinafine, mometasone furoate)

Do not use in dogs with known tympanic perforation (see Precautions ). Do not use in dogs with a hypersensitivity to florfenicol, terbinafine or corticosteroids.

Osurnia® (florfenicol, terbinafine, betamethasone acetate)

CONTRAINDICATIONS: Do not use in animals that have shown hypersensitivity to florfenicol or flunixin.

Resflor GOLD®

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

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

Caution: Feed containing PAQFLORTM (florfenicol) shall not be fed to finfish for more than 10 days. Following administration, fish should be re-evaluated by a licensed veterinarian before initiating a further course of therapy. The expiration date for VFD for PAQFLORTM (florfenicol) must not exceed 6 months from the date of issuance. VFD for PAQFLORTM (florfenicol) shall not be refilled. Sunburn, skin lesions, and skin sloughing have been reported in salmonids treated with florfenicol. Not all adverse drug events are reported to FDA CVM. It is not always possible to reliably estimate the adverse event incidence or to establish a causal relationship to product exposure using this data alone. Before using this drug for the first time, you must inform the appropriate National Pollutant Discharge Elimination System (NPDES) permitting authority of your intentions and of the following information. Acute and chronic water quality benchmarks for the protection of freshwater aquatic life have been derived by FDA for florfenicol following EPA guidance for calculating Tier II water quality criteria for the Great Lakes System (40 CFR 132, App. A). The acute benchmark value (Secondary Maximum Concentration) is 20.6 mg/L (equivalent to one-half of the Secondary Acute Value). The chronic benchmark value (Secondary Continuous Concentration) is 0.23 mg/L (equivalent to the Final Plant Value). The NPDES authority may require an NPDES permit before you can discharge PAQFLORTM. The water quality benchmark concentrations are not discharge limits, but may be used by the NPDES authority to derive such limits for the permit. Additional environmental information on PAQFLORTM and the benchmark values are available in an environmental assessment posted at https://animaldrugsatfda.fda.gov/adafda/app/search/public/document/downloadEA/113

PAQFLORTM (Florfenicol)Type A Medicated Article

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 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. 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 online at www.fda.gov/reportanimalae.

Nuflor®-S (FLORFENICOL) Injectable Solution 300 mg/mL

WARNING: Avoid inhalation, oral exposure, and direct contact with skin or eyes. Operators mixing and handling PAQFLORTM (florfenicol) should use protective clothing, gloves, goggles and NIOSH-approved dust mask. Wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse thoroughly with water. If irritation persists, seek medical attention. Not for human consumption. Keep out of reach of children. The Safety Data Sheet (SDS) contains more detailed occupational safety information. CONTACT INFORMATION: To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Phibro Animal Health Corporation at 888-403-0074 or www.PAHC.com. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae

PAQFLORTM (Florfenicol)Type A Medicated Article

WARNINGS: NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. This product contains material 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. For customer service, adverse effects reporting, and/or a copy of the SDS, contact Parnell at 1-800-887-2763. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

WARNINGS: 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. The Safety Data Sheet (SDS) contains more detailed occupational safety information. NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. CONTACT INFORMATION: To report suspected adverse drug events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS), contact Dechra Veterinary Products at 1-866-933-2472. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/reportanimalae

FLORCON 2.3% Concentrate Solution

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.

FLORFENICOL Injectable Solution 300 mg/mL

A target animal safety study was conducted to evaluate the effects of florfenicol and flunixin meglumine when administered to cattle subcutaneously at 1X, 3X, or 5X the labeled dose for three consecutive days (3X the labeled duration). Decreased feed and water consumption, and decreased body weights (secondary to decreased feed consumption) were observed in the 1X, 3X, and 5X groups. Injection site swellings were noted in the 1X, 3X, and 5X groups. A separate injection site study was conducted in cattle. The study demonstrated that florfenicol and flunixin meglumine, when administered according to the label directions, may induce a transient local reaction in the subcutaneous and underlying muscle tissue.

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

Avoid inhalation, oral exposure, and direct contact with skin or eyes. Operators mixing and handling Aquaflor® (florfenicol) should use protective clothing, gloves, goggles and NIOSH-approved dust mask. Wash thoroughly with soap and water after handling. If accidental eye contact occurs, immediately rinse thoroughly with water. If irritation persists, seek medical attention. Not for human consumption. Keep out of reach of children. The Safety Data Sheet (SDS) contains more detailed occupational safety information. For more information or to report adverse effects, call 1-800-224-5318. For customer service, call 1-800-521-5767. For a copy of SDS sheet, call 1-800-770-8878.

Aquaflor® (Florfenicol)

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 1-866-591-5777.

Norfenicol® (florfenicol)Injectable Solution300mg/mL

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. This product is not approved for use in female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows. A withdrawal period has not been established in pre-ruminating calves. Do not use in calves to be processed for veal.

FLORFENICOL Injectable Solution 300 mg/mL

Human Warnings: Klentz may cause eye injury and irritation (see Precautions, Post-Approval Experience ). If contact with eyes occurs, flush copiously with water for at least 15 minutes. If irritation persists, contact a physician. Humans with known hypersensitivity to any of the active ingredients in Klentz should not handle this product. Not for use in humans. Keep this and all drugs out of the reach of children. Avoid skin contact. In case of accidental ingestion by humans, contact a physician immediately.

Klentz™ (florfenicol, terbinafine, mometasone furoate)

RESIDUE WARNINGS: Animals intended for human consumption must not be slaughtered within 38 days of treatment. This product is not approved for use in female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows. A withdrawal period has not been established in preruminating calves. Do not use in calves to be processed for veal.

Resflor GOLD®

This product has been evaluated in salmonid and catfish feeds and should be used in feeds nutritionally similar to these evaluated feeds. Refer to the Freedom of Information Summary for details. Must be thoroughly mixed in feeds or surface-coated (top-coated) onto the feeds before use.

Aquaflor® (Florfenicol)

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

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

RESIDUE WARNINGS: Swine intended for human consumption must not be slaughtered within 11 days of the last intramuscular treatment.

Nuflor®-S (FLORFENICOL) Injectable Solution 300 mg/mL

CAUTION: Federal (U.S.A.) law restricts this drug to use by or on the order of a licensed veterinarian.

SIMPLERA™ (florfenicol, terbinafine, mometasone furoate)

Feeds containing Aquaflor® (florfenicol) must be withdrawn 15 days prior to slaughter.

Aquaflor® (Florfenicol)

The following adverse reactions were reported during the course of a US field study for treatment of otitis externa in dogs treated with OSURNIA with 1 tube per affected ear(s) and repeated after 7 days: Frequency of Adverse Reaction by Treatment Adverse Reaction OSURNIA (n=190) Placebo (n=94) Elevated Alkaline Phosphatase 15 (7.9%) 3 (3.2%) Vomiting 7 (3.7%) 1 (1.1%) Elevated AST, ALT, ALPAspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP). Two dogs with pre-existing elevations in ALP were reported to have an increase in liver enzymes (ALP, ALT and/or AST) at study exit. Subsequent clinical chemistries returned to pre-treatment levels in one dog, while no follow-up was performed for the second dog. 2 (1.1%) 0 (0.0%) Weight loss (>10% body weight) 1 (0.53%) 0 (0.0%) Hearing Decrease/Loss 1 (0.53%) 1 (1.1%)

Osurnia® (florfenicol, terbinafine, betamethasone acetate)

ADVERSE REACTIONS: Transient inappetence, diarrhea, decreased water consumption, and injection site swelling have been associated with the use of florfenicol in cattle. In addition, anaphylaxis and collapse have been reported post-approval with the use of another formulation of florfenicol in cattle. In cattle, rare instances of anaphylactic-like reactions, some of which have been fatal, have been reported, primarily following intravenous use of flunixin meglumine.

Resflor GOLD®

To report suspected adverse drug events, for technical assistance or to obtain a copy of the SDS, contact Zoetis at 1-888-963-8471. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or www.fda.gov/reportanimalae

Loncor™ 300

ADVERSE REACTIONS: Perianal inflammation, rectal eversion, rectal prolapse and diarrhea may occur transiently following treatment. Decreased feed and water consumption may occur if the labeled dosage regimen is exceeded.

Nuflor®-S (FLORFENICOL) Injectable Solution 300 mg/mL

In a field study conducted in the United States (see Effectiveness ), there were no directly attributable adverse reactions in 146 dogs administered florfenicol, terbinafine, and mometasone furoate otic solution.

Klentz™ (florfenicol, terbinafine, mometasone furoate)

In a field study conducted in the United States (see Effectiveness ), there were no directly attributable adverse reactions in 146 dogs administered CLARO.

CLARO™ Elanco TM (florfenicol, terbinafine, mometasone furoate)

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

FLORFENICOL Injectable Solution 300 mg/mL

ADVERSE REACTION: Perianal inflammation may occur transiently following treatment.

FLORCON 2.3% Concentrate Solution

Cattle (Beef and Non-Lactating Dairy)

Administer by intramuscular injection to cattle at a dose rate of 20 mg/kg body weight. A second dose should be administered 48 hours later. Alternatively, administer by a single subcutaneous injection to cattle at a dose rate of 40 mg/kg body weight. Do not administer more than 10 mL at each site. The injection should be given only in the neck.

Intramuscular, Subcutaneous

Nuflor®

Cattle (Beef and Non-Lactating Dairy)

Administer by a single subcutaneous injection to cattle at a dose rate of 40 mg/kg body weight. Do not administer more than 10 mL at each site. The injection should be given only in the neck.

Intramuscular, Subcutaneous

Nuflor®

Cattle (Beef and Non-Lactating Dairy)

Administer once by subcutaneous injection at a dose rate of 40 mg florfenicol/kg body weight and 2.2 mg flunixin/kg body weight (6 mL/100 lb).

Subcutaneous

Resflor GOLD®

Cattle (Beef and Non-Lactating Dairy)

40 mg/kg body weight (6 mL/100 lb) as a single subcutaneous injection.

Subcutaneous

For subcutaneous use in beef and non-lactating dairy cattle only. Do not administer more than 15 mL at each site. Not for use in animals intended for breeding purposes. This drug product is not approved for use in female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows. Do not use in calves to be processed for veal. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

NuflorGOLD™

Beef and non-lactating dairy cattle

Administer 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, it 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.

Intramuscular, Subcutaneous

Loncor® 300

Beef and non-lactating dairy cattle

Administer by intramuscular injection to cattle at a dose rate of 20 mg/kg body weight (3mL/100 lbs). A second dose should be administered 48 hours later. Alternatively, it 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.

Subcutaneous, Intramuscular

FLORFENICOL INJECTION

Beef and non-lactating dairy cattle

Administer 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.

Intramuscular, Subcutaneous

Loncor® 300

Beef and non-lactating dairy cattle

40 mg florfenicol/kg body weight (BW) and 2.2 mg flunixin/kg BW (equivalent to 2 mL/15 kg BW or 6 mL/100 lbs) once, by subcutaneous injection.

Subcutaneous

nixiFLOR™

Freshwater-reared warmwater finfish

15 mg/kg body weight/day for 10 consecutive days

Oral

PAQFLOR™

Freshwater-reared warmwater finfish

15 mg florfenicol per kg of fish

Oral

Feed containing florfenicol shall not be fed for more than 10 days. Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. For catfish, a dose-related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for hematopoietic/lymphopoietic tissues to regenerate was not evaluated. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Catfish

10 to 15 milligrams (mg) florfenicol per kilogram (kg) of fish

Oral

Feed containing florfenicol shall not be fed for more than 10 days. Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. A dose-related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for hematopoietic/lymphopoietic tissues to regenerate was not evaluated. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Catfish

10-15 mg/kg body weight/day for 10 consecutive days

Oral

PAQFLOR™

Finfish

10 to 15 mg florfenicol per kg of fish

Oral

Feed containing florfenicol shall not be fed for more than 10 days. Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. For catfish, a dose-related decrease in hematopoietic/lymphopoietic tissue may occur. The time required for hematopoietic/lymphopoietic tissues to regenerate was not evaluated. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Salmonids

10 to 15 mg florfenicol per kg of fish

Oral

Following administration, fish should be reevaluated by a licensed veterinarian before initiating a further course of therapy. Not for use in animals intended for breeding purposes. The effects of florfenicol on reproductive performance have not been determined. Toxicity studies in dogs, rats, and mice have associated the use of florfenicol with testicular degeneration and atrophy. Federal law limits this drug to use under the professional supervision of a licensed veterinarian. See Sec. 558.6 of this chapter for additional requirements. The expiration date of veterinary feed directives (VFDs) for florfenicol must not exceed 6 months from the date of issuance. VFDs for florfenicol shall not be refilled.

Aquaflor® Type A Medicated Article

Freshwater-reared salmonids

10-15 mg/kg body weight/day for 10 consecutive days

Oral

PAQFLOR™

Freshwater-reared finfish

10-15 mg/kg body weight/day for 10 consecutive days

Oral

PAQFLOR™

Dilute to 400 mg/gallon of water (100 ppm) and administer as the only source of drinking water for five (5) consecutive days.

Oral

Not for use in swine intended for breeding. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

FLORCON

Administer in drinking water ad libitum at 400 mg per gallon (100 parts per million) for 5 consecutive days.

Oral

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

Nuflor® Concentrate Solution

Feed 182 grams per ton of feed (200 parts per million) continuously as the sole ration for 5 days.

Oral

The safety of florfenicol on swine reproductive performance, pregnancy, and lactation has not been determined. Feed containing florfenicol shall not be fed to pigs for more than 5 days. The expiration date of veterinary feed directives (VFDs) for florfenicol medicated feeds for swine must not exceed 90 days from the date of issuance. VFDs for florfenicol shall not be refilled.

Nuflor®

Swine except for nursing piglets and swine of reproductive age intended for breeding

Administer by intramuscular injection to swine at a dose rate of 15 mg/kg (1 mL/45 lb) body weight. A second dose should be administered 48 hours later.

Intramuscular

Nuflor®-S

Administer one dose (1 dropperette) per affected ear. The duration of effect should last 30 days.

Otic

For otic use in dogs only. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

CLARO™

Administer one dose (1 tube) per affected ear(s) and repeat administration in 7 days.

Otic

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

Osurnia™

Administer one dose (1 dropperette) per affected ear.

Otic

SIMPLERA™

For treatment of bovine respiratory disease (BRD) and bovine interdigital phlegmon (foot rot): FLORFENIJECT 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, FLORFENIJECT 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: FLORFENIJECT 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. FLORFENIJECT Injectable Solution DOSAGE GUIDE ANIMAL WEIGHT (lbs) IM FLORFENIJECT DOSAGE 3.0 mL/100 lb Body Weight (mL) SC FLORFENIJECT DOSAGE 6.0 mL/100 lb Body Weight (mL) 100 3.0 6.0 200 6.0 12.0 300 9.0 18.0 400 12.0 24.0 500 15.0 30.0 600 18.0 36.0 700 21.0 42.0 800 24.0 48.0 900 27.0 54.0 1000 30.0 60.0 Recommended Injection Location 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.

INTRAMUSCULAR, SUBCUTANEOUS

FDA application 200-760

SIMPLERA should be administered by veterinary personnel. Wear eye protection when administering SIMPLERA. (see Human Warnings, PRECAUTIONS, POST-APPROVAL EXPERIENCE ). Splatter may occur if the dog shakes its head following administration. Persons near the dog during administration should also take steps to avoid ocular exposure. Shake before use. Verify the tympanic membrane is intact prior to administration. (see CONTRAINDICATIONS, PRECAUTIONS, POST-APPROVAL EXPERIENCE ). Administer one dose (1 dropperette) per affected ear. 1.Clean and dry the external ear canal before administering the product. 2.Verify the tympanic membrane is intact prior to administration. 3.Remove single dose dropperette from the package. 4.While holding the dropperette in an upright position, remove the cap from the dropperette. 5.Turn the cap over and push the other end of the cap onto the tip of the dropperette. 6.Twist the cap to break the seal and then remove cap from the dropperette. 7.Screw the applicator nozzle onto the dropperette. 8.Insert the tapered tip of the dropperette into the affected external ear canal and squeeze to instill the entire contents (1 mL) into the affected ear. 9.Gently massage the base of the ear to allow distribution of the solution. Restrain the dog to minimize post application head shaking to reduce potential for splatter of product and accidental eye exposure in people and dogs (see POST-APPROVAL EXPERIENCE ). 10.Repeat with other ear as prescribed. 11.The duration of effect should last 30 days. Cleaning the ear after dosing may affect product effectiveness.

AURICULAR (OTIC)

SIMPLERA™ (florfenicol, terbinafine, mometasone furoate)

OSURNIA should be administered by a veterinary professional. Wear eye protection when administering Osurnia (see Human Safety Warnings, Precautions, Post-Approval Experience and Animal Safety). Splatter may occur if the dog shakes its head following administration. Persons near the dog during administration should also take steps to avoid ocular exposure. Clean and dry the external ear canal before administering the initial dose of the product. Verify the tympanic membrane is intact prior to each administration (see Precautions, Contraindications, Animal Safety and Post-Approval Experience). Administer one dose (1 tube) per affected ear(s) and repeat administration in 7 days. Open tube by twisting the soft tip. Insert the flexible tip in the affected external ear canal(s) and squeeze entire tube contents into the external ear canal(s). After application, gently massage the base of the ear to allow the gel to penetrate the lower part of the ear canal. Restrain dog to minimize post-application head shaking to reduce potential for splatter of product, and accidental eye exposure in people and dogs (see Post-Approval Experience and Animal Safety ). Do not clean the ear canal for 45 days after the initial administration to allow contact of the gel with the ear canal. Cleaning the ear may affect product effectiveness (see Effectiveness ). If alternative otic therapies are required, it is recommended to clean the ear(s) before application.

AURICULAR (OTIC)

Osurnia® (florfenicol, terbinafine, betamethasone acetate)

Klentz should be administered by veterinary personnel. Wear eye protection when administering Klentz. (see Human Warnings, Precautions, Post-Approval Experience ). Splatter may occur if the dog shakes its head following administration. Persons near the dog during administration should also take steps to avoid ocular exposure. Shake before use. Verify the tympanic membrane is intact prior to administration. (see Contraindications, Precautions, Post-Approval Experience ). Administer one dose (1 dropperette) per affected ear. 1. Clean and dry the external ear canal before administering the product. 2. Verify the tympanic membrane is intact prior to administration. 3. Remove single dose dropperette from the package. 4. While holding the dropperette in an upright position, twist the cap to open the dropperette. The cap does not come off the dropperette. 5. Insert the tapered tip of the dropperette into the affected external ear canal and squeeze to instill the entire contents (1 mL) into the affected ear. 6. Gently massage the base of the ear to allow distribution of the solution. Restrain the dog to minimize post application head shaking to reduce potential for splatter of product and accidental eye exposure in people and dogs (see Post-Approval Experience ). 7. Repeat with other ear as prescribed. 8. The duration of the effect should last 30 days. Cleaning the ear after dosing may affect product effectiveness.

AURICULAR (OTIC)

Klentz™ (florfenicol, terbinafine, mometasone furoate)

For treatment of bovine respiratory disease (BRD) and bovine interdigital phlegmon (foot rot): Norfenicol® 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, Norfenicol® 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: Norfenicol® 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.

Intramuscular, Subcutaneous

This drug product is not approved for use in female dairy cattle 20 months of age or older, including dry dairy cows. Use in these cattle may cause drug residues in milk and/or in calves born to these cows. A withdrawal period has not been established in preruminating calves

Norfenicol®

DOSAGE AND ADMINISTRATION: For Proportioner: To produce drinking water with a final concentration of 400 mg/gallon (100 ppm): Fill the bottle of FLORCON 2.3% Concentrate Solution with water to the fill line. Add the contents of the bottle to the mixing tank. Mix thoroughly. Confirm that the proportioner is set to deliver 1:128 (0.8%). Turn on the proportioner. Verify that the drinkers are operational. For Bulk Tank: To produce drinking water with a final concentration o f 400 mg/gallon (100 ppm): Add the FLORCON 2.3% Concentrate Solution to the drinking water in the bulk tank. Use one bottle of FLORCON 2.3% Concentrate Solution for every 128 gallons of water. The medicated water should be administered as the only source of drinking water for five (5) consecutive days. Medication should be initiated promptly when swine respiratory disease is diagnosed.

ORAL

FLORCON 2.3% Concentrate Solution

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 adminis-tered 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.

INTRAMUSCULAR, SUBCUTANEOUS

Nuflor® (FLORFENICOL) Injectable Solution 300 mg/mL

DOSAGE AND ADMINISTRATION: Nuflor®-S Injectable Solution should be administered by intramuscular injection to swine at a dose rate of 15 mg/kg (1 mL/45 lb) body weight. A second dose should be administered 48 hours later. The injection should be given only in the neck musculature. If a positive response is not noted within 24 hours after the second injection, the diagnosis should be re-evaluated, and/or an alternative treatment may be considered. Administered dose volume should not exceed 10 mL per injection site. Nuflor®-S DOSAGE GUIDE FOR SWINE ANIMAL WEIGHT (lbs) IM Nuflor®-S DOSAGE (1 mL/ 45 lb Body Weight) (mL) 22 0.5 45 1 90 2 135 3 180 4 225 5 270 6

INTRAMUSCULAR

Nuflor®-S (FLORFENICOL) Injectable Solution 300 mg/mL

DOSAGE AND ADMINISTRATION: RESFLOR GOLD® should be administered once by subcutaneous injection at a dose rate of 40 mg florfenicol/kg body weight and 2.2 mg flunixin/kg body weight (6 mL/100 lb). Do not administer more than 10 mL at each site. The injection should be given only in the neck. Injection sites other than the neck have not been evaluated. For the 500 mL vial, do not puncture the stopper more than 20 times. RESFLOR GOLD® Dosage GuideDo not administer more than 10 mL at each site. ANIMAL WEIGHT (lbs) DOSAGE (mL) 100 6.0 Recommended Injection Location 200 12.0 300 18.0 400 24.0 500 30.0 600 36.0 700 42.0 800 48.0 900 54.0 1000 60.0

SUBCUTANEOUS

Resflor GOLD®

nixiFLOR™ should be administered once by subcutaneous injection at a dose rate of 40 mg florfenicol/kg body weight and 2.2 mg flunixin/kg body weight (6 mL/100 lb). Do not administer more than 10 mL at each site. The injection should be given only in the neck. Injection sites other than the neck have not been evaluated. For the 500 mL vial, do not puncture the stopper more than 20 times. * Do not administer more than 10 mL at each site.

SUBCUTANEOUS

nixiFLOR™(florfenicol and flunixin meglumine)Antimicrobial/Non-Steroidal Anti-Inflammatory Drug

400 mg per gallon of water (100 parts per million (ppm)) provided in the drinking water for 5 consecutive days.

Oral

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

Florvio™ 2.3% Concentrate Solution