pradofloxacin

For the treatment of skin infections (wounds and abscesses) in cats caused by susceptible strains of Pasteurella multocida, Streptococcus canis, Staphylococcus aureus, Staphylococcus felis, and Staphylococcus pseudintermedius.

Do not use in Dogs. Pradofloxacin has been shown to cause bone marrow suppression in dogs. Dogs may be particularly sensitive to this effect, potentially resulting in severe thrombocytopenia and neutropenia. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law prohibits the extralabel use of this drug in food-producing animals.

Veraflox™

For the treatment of BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis in cattle intended for slaughter (beef calves 2 months of age and older, growing beef steers, growing beef heifers, and beef bulls intended for slaughter), and in cattle intended for breeding less than 1 year of age (replacement beef and dairy heifers less than 1 year of age and beef and dairy bulls less than 1 year of age). Not for use in cattle intended for breeding 1 year of age and older (replacement beef and dairy heifers 1 year of age and older, beef and dairy bulls 1 year of age and older, and beef and dairy cows), beef calves less than 2 months of age, dairy calves, and veal calves.

Pradalex™

For the treatment of SRD associated with Bordetella bronchiseptica, Glaesserella (Haemophilus) parasuis, Pasteurella multocida, Streptococcus suis, and Mycoplasma hyopneumoniae in weaned swine intended for slaughter (nursery, growing, and finishing swine, boars intended for slaughter, barrows, gilts intended for slaughter, and sows intended for slaughter). Not for use in swine intended for breeding (boars intended for breeding, replacement gilts, and sows intended for breeding) and in nursing piglets.

Pradalex™

Cattle: Pradalex is indicated for the treatment of BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis in cattle intended for slaughter (beef calves 2 months of age and older, growing beef steers, growing beef heifers, and beef bulls intended for slaughter), and in cattle intended for breeding less than 1 year of age (replacement beef and dairy heifers less than 1 year of age and beef and dairy bulls less than 1 year of age). Not for use in cattle intended for breeding 1 year of age and older (replacement beef and dairy heifers 1 year of age and older, beef and dairy bulls 1 year of age and older, and beef and dairy cows), beef calves less than 2 months of age, dairy calves, and veal calves. Swine: Pradalex is indicated for the treatment of SRD associated with Bordetella bronchiseptica, Glaesserella (Haemophilus) parasuis, Pasteurella multocida, Streptococcus suis, and Mycoplasma hyopneumoniae in weaned swine intended for slaughter (nursery, growing, and finishing swine, boars intended for slaughter, barrows, gilts intended for slaughter, and sows intended for slaughter). Not for use in swine intended for breeding (boars intended for breeding, replacement gilts, and sows intended for breeding) and in nursing piglets.

FDA application 141-550

VERAFLOX is indicated for the treatment of skin infections (wounds and abscesses) in cats caused by susceptible strains of Pasteurella multocida, Streptococcus canis, Staphylococcus aureus, Staphylococcus felis, and Staphylococcus pseudintermedius.

Veraflox™

Mechanism of Action Pradofloxacin is a synthetic fluoroquinolone antibacterial drug. Pradofloxacin acts via inhibition of DNA gyrase and topoisomerase IV enzymes in bacteria to inhibit DNA and RNA synthesis. It is bactericidal with a broad spectrum of activity. As a class, fluoroquinolones are considered concentration dependent antimicrobials. Pradofloxacin induces long post-antibiotic effects (PAE) and extended post-antibiotic sub-MIC effects (PA SME), both in aerobic and anaerobic bacteria. Pharmacokinetics Cattle: The pharmacokinetic parameters of pradofloxacin in Table 4 were determined from two studies following subcutaneous administration of pradofloxacin in 4- to-5-month-old weaned calves weighing 158 to 319 kg. Pradofloxacin exposure (Cmax and AUC) was dose proportional over a 10 to 50 mg/kg dose range with no accumulation when administered once every 4 days over 8 days. Pradofloxacin was excreted in both the urine and the feces, largely unchanged, with the majority of the administered dose being excreted in the first 24 hours post-dosing. Swine: The pharmacokinetic parameters of pradofloxacin in Table 4 were determined following intramuscular administration of pradofloxacin in 18-day-old weaned pigs weighing 5.5 to 7.9 kg. Pradofloxacin exposure (Cmax and AUC) was dose proportional over a 7.5 to 37.5 mg/kg dose range with no accumulation when administered once every 2 days over 4 days. Pradofloxacin was excreted in both the urine and the feces, largely unchanged, with approximately one-third of the administered dose being excreted in the first 24 hours post-dosing. Table 4. Arithmetic mean (± standard deviation) plasma pradofloxacin pharmacokinetic parameters following the first of three administrations of Pradalex (pradofloxacin injection). a Reported as: Median (range) b N=11 due to inability to calculate half-life in 1 animal Cmax = maximum concentration Tmax = time to maximum concentration AUClast = area under the curve from the time of dosing to the time of the last measurable concentration t½ = half-life Pharmacokinetic Parameter Weaned calves (N=12) 10 mg/kg BW SC Weaned pigs (N = 8) 7.5 mg/kg BW IM Cmax (μg/mL) 1.9 ± 0.4 2.5 ± 1.9 Tmax (hours)a 1 (1 to 2) 0.75 (0.5 to 2) AUClast (hr*μg/mL) 10.5 ± 1.2 26.2 ± 3.7 t1/2 (hours) 2.8 ± 0.4b 8.5 ± 2.6

FDA application 141-550

DO NOT USE IN DOGS. Pradofloxacin has been shown to cause bone marrow suppression in dogs. Dogs may be particularly sensitive to this effect, potentially resulting in severe thrombocytopenia and neutropenia. Quinolone-class drugs have been shown to cause arthropathy in immature animals of most species tested, the dog being particularly sensitive to this side effect. Pradofloxacin is contraindicated in cats with a known hypersensitivity to quinolones.

Veraflox™

USER SAFETY WARNINGS Not for use in humans. Keep out of reach of children. Avoid contact with eyes and skin. In case of ocular contact, immediately remove contact lenses and flush eyes with copious amounts of water for 15 minutes. In case of dermal contact, wash skin with soap and water for at least 20 seconds. Consult a physician if irritation persists following ocular or dermal exposures, or in case of accidental ingestion. Individuals with a history of hypersensitivity to quinolones should avoid this product. In humans, there is a risk of user photosensitization within a few hours after excessive exposure to quinolones. If excessive accidental exposure occurs, avoid direct sunlight. Do not eat, drink or smoke while handling this product. To obtain a copy of the Safety Data Sheet, contact Elanco at 1-800-428-4441. ANIMAL SAFETY WARNINGS Not for use in animals intended for breeding because the effects of Pradalex on bovine and swine reproductive performance, pregnancy, and lactation have not been determined. Not for use in pre-ruminating calves or nursing piglets because safety and effectiveness has not been demonstrated. Swelling and inflammation may be seen at the injection site after administration. These local tissue reactions may persist beyond the slaughter withdrawal period and may result in trim loss of edible tissue at slaughter. Quinolones should be used with caution in animals with known or suspected central nervous system (CNS) disorders. In such animals, quinolones have, in rare instances, been associated with CNS stimulation that may lead to convulsive seizures. Quinolones have been shown to produce erosions of cartilage of weightbearing joints and other signs of arthropathy in immature animals of various species. See Target Animal Safety section for additional information.

FDA application 141-550

Cattle intended for human consumption must not be slaughtered within 4 days of treatment. Swine intended for human consumption must not be slaughtered within 2 days of treatment. Not for use in female dairy cattle 1 year of age and older, including dry dairy cows; use in these cattle may cause drug residues in milk and/or in calves born to these cows. Not for use in beef calves less than 2 months of age, dairy calves, and veal calves; a withdrawal period has not been established for this product in pre-ruminating calves.

FDA application 141-550

In a multi-site field study, 282 cats (ages 0.3 to 19 years) were evaluated for safety when given either VERAFLOX at a dose of 7.5 mg/kg (3.4 mg/lb) or placebo (vehicle without active ingredient) at a dose of 0.14 mL/lb (0.3 mL/kg). Each group was treated once daily for 7 consecutive days. Adverse reactions are summarized in Table 1. Table 1: Number of Adverse Reactions Among Cats Treated with Pradofloxacin (N=190) or Vehicle (N=92)* * Some cats may have experienced more than one adverse reaction or more than one occurrence of the same adverse reaction during the study. Adverse Reactions Pradofloxacin Vehicle Diarrhea / loose stools 7 2 Leukocytosis with neutrophilia 4 6 Elevated CPK levels 4 4 Sneezing 4 1 Hematuria 2 2 Hypersalivation 2 1 Pruritus 2 0 Inappetence 1 3 Lethargy 1 2 Cardiac murmur 1 1 Reclusive behavior 1 1 Vomiting 1 1 Bacteriuria 1 0 Lymphadenopathy 1 0 Polydipsia 1 0 Upper respiratory infection 1 0 The Safety Data Sheet (SDS) provides additional occupational safety information.

Veraflox™

Mild to moderate inflammatory changes of the injection site may be seen in cattle and swine treated with Pradalex.

FDA application 141-550

Administer 3.4 mg/lb (7.5 mg/ kg) body weight once daily for 7 consecutive days.

Oral

Do not use in Dogs. Pradofloxacin has been shown to cause bone marrow suppression in dogs. Dogs may be particularly sensitive to this effect, potentially resulting in severe thrombocytopenia and neutropenia. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law prohibits the extralabel use of this drug in food-producing animals.

Veraflox™

Single dose of 10 mg/kg (2.3 mL/100 lb) body weight

Subcutaneous, Intramuscular

Pradalex™

Single dose of 7.5 mg/kg (1.7 mL/100 lb) body weight

Subcutaneous, Intramuscular

Pradalex™

Cattle: Administer once as a subcutaneous injection at a dosage of 10 mg/kg (2.3 mL/100 lb) body weight. Do not inject more than 15 mL per subcutaneous injection site. Table 1. Pradalex Dose Guide for Cattle (2.3 mL/100 lbs) Weight (lb) Dose Volume (mL) 100 2.3 200 4.6 300 6.9 400 9.2 500 11.5 600 13.8 700 16.1 800 18.4 900 20.7 Swine: Administer once as an intramuscular injection in the neck at a dosage of 7.5 mg/kg (1.7 mL/100 lb) body weight. Do not inject more than 5 mL per intramuscular injection site. Table 2. Pradalex Dose Guide for Swine (1.7 mL/100 lbs) Weight (lb) Dose Volume (mL) 15 0.3 30 0.5 50 0.9 100 1.7 150 2.6 200 3.4 250 4.3 Dilution of Pradalex: Pradalex may be diluted with sterile water, sterile saline (0.9%), or 5% dextrose (D5W) prior to injection. The diluted product should be used within 24 hours. Store diluted solution in amber glass bottles between 25-40°C (77-104°F). Table 3. Dilution Guide for Swine* *For 1 mL dose volume from diluted solution **Pradalex can be diluted with sterile water, sterile saline (0.9%), or 5% dextrose (D5W) for injection Swine Weight mL of Pradalex mL of diluent** Number of doses 5 lb 8.5 mL 91.5 mL 100 10 lb 17 mL 83 mL 100 15 lb 25.6 mL 74.4 mL 100 20 lb 34.1 mL 65.9 mL 100 25 lb 42.6 mL 57.4 mL 100 30 lb 51.1 mL 48.9 mL 100 35 lb 59.7 mL 40.3 mL 100 40 lb 68.2 mL 31.8 mL 100 45 lb 76.7 mL 23.3 mL 100 50 lb 85.2 mL 14.8 mL 100 Use bottle within 6 months of first puncture. When administering from the 250 mL bottle, puncture a maximum of 120 times. If more than 120 punctures are anticipated, the use of multi-dosing equipment is recommended. When using a draw-off spike or needle with bore diameter larger than 16-gauge, discard any product remaining in the vial immediately after use.

SUBCUTANEOUS, INTRAMUSCULAR

FDA application 141-550

Shake well before use. To ensure a correct dosage, body weight should be determined as accurately as possible. The dose of VERAFLOX is 7.5 mg/kg (3.4 mg/lb) body weight once daily for 7 consecutive days. Use the syringe provided to ensure accuracy of dosing to the nearest 0.1 mL. Rinse syringe between doses. A sample of the lesion should be obtained for culture and susceptibility testing prior to beginning antibacterial therapy. Once results become available, continue with appropriate therapy. If acceptable response to treatment is not observed, or if no improvement is seen within 3 to 4 days, then the diagnosis should be re-evaluated and appropriate alternative therapy considered.

ORAL

Veraflox™