Tulathromycin

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; for the control of respiratory disease in cattle at high risk of developing BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis; and for the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis.

Do not use in female dairy cattle 20 months of age or older. Do not inject more than 10 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Cattle (Beef and Non-Lactating Dairy)

For the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii.

Do not use in female dairy cattle 20 months of age or older. Do not inject more than 10 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Cattle (Beef and Non-Lactating Dairy)

For the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis.

Do not use in female dairy cattle 20 months of age or older. Do not inject more than 10 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Cattle (Suckling Calves, Dairy Calves, and Veal Calves)

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis.

Do not inject more than 10 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Cattle (Calves)

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis.

Do not inject more than 11.5 mL per injection site. For use in suckling calves, dairy calves, veal calves, and swine. Not for use in ruminating cattle. Not for use in Chickens or Turkeys. Federal (USA) law restricts this drug to useby or on the order of a licensed veterinarian.

Draxxin® 25 Injectable Solution

Beef and Non-Lactating Dairy Cattle

BRD: For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis; and for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. IBK: For the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis. Foot Rot: For the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii.

TULAVEN™ 100

Suckling Calves, Dairy Calves, and Veal Calves

BRD – MACROSYN® 25 Injectable Solution is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis.

MACROSYN® 25

Suckling Calves, Dairy Calves, and Veal Calves

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis.

TULAVEN™ 25

Suckling Calves, Dairy Calves, and Veal Calves

For the treatment of BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis.

Increxxa™

Cattle (beef steers, beef heifers, beef calves 2 months of age and older, beef bulls, dairy bulls, and replacement dairy heifers)

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of pyrexia associated with BRD in beef steers, beef heifers, beef calves 2 months of age and older, beef bulls, dairy bulls, and replacement dairy heifers.

Draxxin® KP

Suckling calves, dairy calves, and veal calves

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis.

Tulissin® 25

Suckling calves, dairy calves, and veal calves

For the treatment of BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis.

RESPIRmycin™

Beef and non-lactating dairy cattle

BRD – For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis; and for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. IBK – For the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis. Foot Rot – For the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii.

RESPIRmycin™

Beef cattle, non-lactating dairy cattle, suckling calves, dairy calves and veal calves

BRD – Tulathromycin Injection is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis; and for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. IBK – Tulathromycin Injection is indicated for the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis. Foot Rot – Tulathromycin Injection is indicated for the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii. Suckling Calves, Dairy Calves, and Veal Calves BRD – Tulathromycin Injection is indicated for the treatment of BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis.

Tulathromycin Injection

MACROSYN® 25 Injectable Solution is indicated for the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis, and Mycoplasma hyopneumoniae; and for the control of SRD associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae in groups of pigs where SRD has been diagnosed.

MACROSYN® 25

For the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, P. multocida, Bordetella bronchiseptica, and H. parasuis and Mycoplasma hyopneumoniae; and for control of SRD associated with Actinobacillus pleuropneumoniae, P. multocida, and M. hyopneumoniae in groups of pigs where SRD has been diagnosed.

Do not inject more than 2.5 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

INDICATIONS Beef and Non-Lactating Dairy Cattle BRD – RESPIRmycin Injectable Solution is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis; and for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. IBK – RESPIRmycin Injectable Solution is indicated for the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis. Foot Rot – RESPIRmycin Injectable Solution is indicated for the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii. Suckling Calves, Dairy Calves, and Veal Calves BRD – RESPIRmycin Injectable Solution is indicated for the treatment of BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis. Swine RESPIRmycin Injectable Solution is indicated for the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis, and Mycoplasma hyopneumoniae; and for the control of SRD associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae in groups of pigs where SRD has been diagnosed.

RESPIRmycin

INDICATIONS Beef and Non-Lactating Dairy Cattle BRD – VACASAN Injectable Solution is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis; and for the control of respiratory disease in cattle at high risk of developing BRD associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. IBK – VACASAN Injectable Solution is indicated for the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis. Foot Rot – VACASAN Injectable Solution is indicated for the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii. Suckling Calves, Dairy Calves, and Veal Calves BRD – VACASAN Injectable Solution is indicated for the treatment of BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis. Swine VACASAN Injectable Solution is indicated for the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis, and Mycoplasma hyopneumoniae; and for the control of SRD associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae in groups of pigs where SRD has been diagnosed.

VACASAN

INDICATIONS Swine RESPIRmycin 25 Injectable Solution is indicated for the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis, and Mycoplasma hyopneumoniae; and for the control of SRD associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, and Mycoplasma hyopneumoniae in groups of pigs where SRD has been diagnosed. Suckling Calves, Dairy Calves, and Veal Calves BRD – RESPIRmycin 25 Injectable Solution is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis.

RESPIRmycin 25

Draxxin® KP is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, and control of pyrexia associated with BRD in beef steers, beef heifers, beef calves 2 months of age and older, beef bulls, dairy bulls, and replacement dairy heifers. Not for use in reproducing animals over one year of age, dairy calves, or veal calves.

Draxxin® KP

At physiological pH, tulathromycin (a weak base) is approximately 50 times more soluble in hydrophilic than lipophilic media. This solubility profile is consistent with the extracellular pathogen activity typically associated with the macrolides.1 Markedly higher tulathromycin concentrations are observed in the lung parenchyma as compared to the plasma, and these elevated concentrations can remain in lung tissue for several days beyond that which can be measured in the plasma. However the clinical relevance of these elevated lung concentrations is undetermined. As a class, macrolides tend to be primarily bacteriostatic, but may be bactericidal against some pathogens.2 When acting as a cidal compound, they tend to exhibit concentration independent killing; the rate of bacterial eradication does not change once serum drug concentrations reach 2 to 3 times the minimum inhibitory concentration (MIC) of the targeted pathogen. Under these conditions, the time that serum concentrations remain above the MIC becomes the major determinant of antimicrobial activity. Macrolides also exhibit a post-antibiotic effect (PAE), the duration of which tends to be both drug and pathogen dependent. In general, by increasing the macrolide concentration and the exposure time, the PAE will increase to some maximal duration. 3 Tulathromycin is eliminated from the body primarily unchanged via biliary excretion. 1 Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. 2 Nightingale, C.J. 1997. Pharmacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443. 3 Andes D, Anon J, Jacobs MR, Craig WA. (2004). Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections. Clin Lab Med., 24:477-502. Swine Following intramuscular (IM) administration to feeder pigs at a dosage of 2.5 mg/kg BW, tulathromycin is nearly completely absorbed, with peak plasma concentrations achieved within ~0.25 hr. The volume of distribution exceeds 15 L/kg, which is consistent with extensive tissue binding. This large distribution volume results in a long terminal elimination half-life (60 to 90 hours) despite a rapid systemic free drug clearance (187 mL/kg/hr). There are no gender differences in swine tulathromycin pharmacokinetics. Comparative Bioavailability Summary Despite slightly lower peak concentrations with tulathromycin injection 25 mg/mL, a single IM dose of 2.5 mg tulathromycin/kg BW of either tulathromycin injection (100 mg/mL) or tulathromycin injection (25 mg/mL) resulted in comparable tulathromycin total systemic exposure. Therefore, tulathromycin injection 25 mg/mL is considered to be therapeutically equivalent to tulathromycin injection 100 mg/mL when administered to swine by IM injection at a dose of 2.5 mg tulathromycin/kg BW. Calves Following subcutaneous (SC) administration into the neck of feeder calves at a dosage of 2.5 mg/kg BW, tulathromycin is nearly completely absorbed, with peak plasma concentrations achieved within ~0.25 hr. The volume of distribution exceeds 11 L/kg4, which is consistent with extensive tissue binding. This large distribution volume results in a long terminal elimination half-life of more than 100 hours, despite a rapid systemic free drug clearance (170 mL/kg/hr). No pharmacokinetic differences are observed in castrated male versus female calves. Comparative Bioavailability Summary Despite lower peak concentrations with tulathromycin injection 25 mg/mL, a single SC dose of 2.5 mg tulathromycin/kg BW of either tulathromycin injection (100 mg/mL) or tulathromycin injection (25 mg/mL) resulted in comparable total systemic tulathromycin exposure. Therefore, tulathromycin injection 25 mg/mL is considered to be therapeutically equivalent to tulathromycin injection 100 mg/mL when administered to calves by SC injection at a dose of 2.5 mg tulathromycin/kg BW. 4 Clearance and volume estimates are based on intersubject comparisons of 2.5 mg/kg BW administered by either subcutaneous or intravenous injection

Tulissin 25®(tulathromycin injection)Injectable Solution

At physiological pH, tulathromycin (a weak base) is approximately 50 times more soluble in hydrophilic than hydrophobic media. This solubility profile is consistent with the extracellular pathogen activity typically associated with the macrolides.1 Markedly higher tulathromycin concentrations are observed in the lungs as compared to the plasma. The extent to which lung concentrations represent free (active) drug was not examined. Therefore, the clinical relevance of these elevated lung concentrations is undetermined. Although the relationship between tulathromycin and the characteristics of its antimicrobial effects has not been characterized, as a class, macrolides tend to be primarily bacteriostatic, but may be bactericidal against some pathogens.2 They also tend to exhibit concentration independent killing; the rate of bacterial eradication does not change once serum drug concentrations reach 2 to 3 times the minimum inhibitory concentration (MIC) of the targeted pathogen. Under these conditions, the time that serum concentrations remain above the MIC becomes the major determinant of antimicrobial activity. Macrolides also exhibit a post-antibiotic effect (PAE), the duration of which tends to be both drug and pathogen dependent. In general, by increasing the macrolide concentration and the exposure time, the PAE will increase to some maximal duration. Of the two variables, concentration and exposure time, drug concentration tends to be the most powerful determinant of the duration of PAE. Tulathromycin is eliminated from the body primarily unchanged via biliary excretion. 1Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. 2Nightingale, C.J. 1997. Pharmacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443. Cattle Following subcutaneous administration into the neck of feeder calves at a dosage of 2.5 mg/kg BW, tulathromycin is rapidly and nearly completely absorbed. Peak plasma concentrations generally occur within 15 minutes after dosing and product relative bioavailability exceeds 90%. Total systemic clearance is approximately 170 mL/hr/kg. Tulathromycin distributes extensively into body tissues, as evidenced by volume of distribution values of approximately 11 L/kg in healthy ruminating calves.3 This extensive volume of distribution is largely responsible for the long elimination half-life of this compound [approximately 2.75 days in the plasma (based on quantifiable terminal plasma drug concentrations) versus 8.75 days for total lung concentrations (based on data from healthy animals)]. Linear pharmacokinetics are observed with subcutaneous doses ranging from 1.27 mg/kg BW to 5.0 mg/kg BW. No pharmacokinetic differences are observed in castrated male versus female calves. 3Clearance and volume estimates are based on intersubject comparisons of 2.5 mg/kg BW administered by either subcutaneous or intravenous injection. Swine Following intramuscular administration to feeder pigs at a dosage of 2.5 mg/kg BW, tulathromycin is completely and rapidly absorbed (Tmax ~0.25 hour). Subsequently, the drug rapidly distributes into body tissues, achieving a volume of distribution exceeding 15 L/kg. The free drug is rapidly cleared from the systemic circulation (CLsystemic = 187 mL/hr/kg). However, it has a long terminal elimination half-life (60 to 90 hours) owing to its extensive volume of distribution. Although pulmonary tulathromycin concentrations are substantially higher than concentrations observed in the plasma, the clinical significance of these findings is undetermined. There are no gender differences in swine tulathromycin pharmacokinetics.

Tulissin 100®(tulathromycin injection)Injectable Solution

Mechanism of Action Ketoprofen is a propionic acid derivate and nonsteroidal anti-inflammatory drug (NSAID) with anti-inflammatory, analgesic and antipyretic effects. Ketoprofen inhibits the activity of the enzymes cyclo-oxygenase I and II, resulting in a decreased formation of precursors of prostaglandins and thromboxanes. Ketoprofen also causes a decrease in the formation of thromboxane A2 synthesis, by thromboxane synthase, thereby inhibiting platelet aggregation. The principal mechanism of action of tulathromycin against bacteria involves direct inhibition of essential protein biosynthesis by selective binding to bacterial 50S ribosomal subunits. Tulathromycin acts by stimulating the dissociation of peptidyl- tRNA from the ribosome during the translocation process. Clinical Pharmacology In a GLP pharmacokinetic study, 60 cattle received one of 3 treatments: 2.5 mg tulathromycin/kg BW, 3 mg ketoprofen/kg BW or a combination of the two active ingredients (2.5 mg tulathromycin and 3 mg of ketoprofen/kg BW) via subcutaneous injection. Blood samples were obtained pre-dose and at 20 min, 40 min, 1, 1.5, 2, 3, 4, 6, 10, 24, 28, 32, 48, 52, 56, 72, 120, 168, 216, 264, 336, and 360 hours after dosing. The samples were analyzed using validated highperformance liquid chromatography-mass spectrometry (LC-MS/MS) methods for tulathromycin and ketoprofen concentrations. The rate of drug exposure was greater for the ketoprofen alone product. The mean [±standard deviation (SD)] maximum plasma concentration (Cmax) and time to Cmax (tmax) was 6451 (±1342) ng/mL and 0.83 (±0.53) hr, respectively for ketoprofen alone compared to a mean (±SD) Cmax and tmax of 2322 (±1505) ng/mL and 4.0 (±2.93) hr, respectively, for ketoprofen in the combination product. However, the extent of drug exposure was slightly greater and terminal half life (t1/2) was longer for ketoprofen in the combination product. The mean (±SD) area under the drug concentration- time curve between times 0 and the last quantifiable concentration (AUC0-t(last)) was 26458 (±3605) ng*hr/mL for ketoprofen in the combination product and 23106 (±3500) for ng*hr/mL for ketoprofen alone. Similarly, the mean t 1/2 was 6.84 (±2.09) hr for ketoprofen in the combination product and 2.86 (±1.09) hr for ketoprofen alone. Although the mean (±SD) Cmax of tulathromycin in the combination group (373 (±105) ng/mL) was less than tulathromycin alone (653 (±261) ng/mL), based on mean (±SD) AUC0-t(last), the combination (13647 (±2577) ng*hr/mL) and tulathromycin alone (14088 (±4408) ng*hr/mL) groups had similar tulathromycin bioavailability. Tulathromycin half life was also similar between the combination (93.3 (±27.9) hr) and tulathromycin alone (98.7 (±23.1) hr) groups.

Draxxin® KP

Swine Following intramuscular (IM) administration to feeder pigs at a dosage of 2.5 mg/kg BW, tulathromycin is nearly completely absorbed, with peak plasma concentrations achieved within ~0.25 hr. The volume of distribution exceeds 15 L/kg, which is consistent with extensive tissue binding. This large distribution volume results in a long terminal elimination half-life (60 to 90 hours) despite a rapid systemic free drug clearance (187 mL/kg/hr). There are no gender differences in swine tulathromycin pharmacokinetics. Comparative Bioavailability Summary Despite slightly lower peak concentrations with tulathromycin injection 25 mg/mL, a single IM dose of 2.5 mg tulathromycin/kg BW of either tulathromycin injection (100 mg/mL) or tulathromycin injection (25 mg/mL) resulted in comparable tulathromycin total systemic exposure. Therefore, tulathromycin injection 25 mg/mL is considered to be therapeutically equivalent to tulathromycin injection 100 mg/mL when administered to swine by IM injection at a dose of 2.5 mg tulathromycin/kg BW. Calves Following subcutaneous (SC) administration into the neck of feeder calves at a dosage of 2.5 mg/kg BW, tulathromycin is nearly completely absorbed, with peak plasma concentrations achieved within ~0.25 hr. The volume of distribution exceeds 11 L/kg4, which is consistent with extensive tissue binding. This large distribution volume results in a long terminal elimination half-life of more than 100 hours, despite a rapid systemic free drug clearance (170 mL/kg/hr). No pharmacokinetic differences are observed in castrated male versus female calves. Comparative Bioavailability Summary Despite lower peak concentrations with tulathromycin 25 mg/mL, a single SC dose of 2.5 mg tulathromycin/kg BW of either tulathromycin injection (100 mg/mL) or tulathromycin injection (25 mg/mL) resulted in comparable total systemic tulathromycin exposure. Therefore, tulathromycin injection 25 mg/mL is considered to be therapeutically equivalent to tulathromycin injection 100 mg/mL when administered to calves by SC injection at a dose of 2.5 mg tulathromycin/kg BW. 4Clearance and volume estimates are based on inter subject comparisons of 2.5 mg/kg BW administered by either subcutaneous or intravenous injection.

VACASAN 25

At physiological pH, tulathromycin (a weak base) is approximately 50 times more soluble in hydrophilic than hydrophobic media. This solubility profile is consistent with the extracellular pathogen activity typically associated with the macrolides. Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. Markedly higher tulathromycin concentrations are observed in the lungs as compared to the plasma. The extent to which lung concentrations represent free (active) drug was not examined. Therefore, the clinical relevance of these elevated lung concentrations is undetermined. Although the relationship between tulathromycin and the characteristics of its antimicrobial effects has not been characterized, as a class, macrolides tend to be primarily bacteriostatic, but may be bactericidal against some pathogens. Nightingale, C.J. 1997. Pharmacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443. They also tend to exhibit concentration independent killing; the rate of bacterial eradication does not change once serum drug concentrations reach 2 to 3 times the minimum inhibitory concentration (MIC) of the targeted pathogen. Under these conditions, the time that serum concentrations remain above the MIC becomes the major determinant of antimicrobial activity. Macrolides also exhibit a post-antibiotic effect (PAE), the duration of which tends to be both drug and pathogen dependent. In general, by increasing the macrolide concentration and the exposure time, the PAE will increase to some maximal duration. Of the two variables, concentration and exposure time, drug concentration tends to be the most powerful determinant of the duration of PAE. Tulathromycin is eliminated from the body primarily unchanged via biliary excretion. 1 Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. 2 Nightingale, C.J. 1997. Pharmacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443.

Draxxin® (tulathromycin injection) Injectable Solution

CLINICAL PHARMACOLOGY At physical pH, tulathromycin (a weak base) is approximately 50 times more soluble in hydrophilic than hydrophobic media. This solubility profile is consistent with the extracellular pathogen activity typically associated with the macrolides.1 Markedly higher tulathromycin concentrations are observed in the lungs as compared to plasma. The extent to which lung concentrations represent free (active) drug was not examined. Therefore, the clinical relevance of these elevated lung concentrations is undetermined. Although the relationship between tulathromycin and the characteristics of its antimicrobial effects has not been characterized, as a class, macrolides tend to be primarily bacteriostatic, but may be bactericidal against some pathogens.2 They also tend to exhibit concentration independent killing; the rate of bacterial eradication does not change once serum drug concentrations reach 2 to 3 times the minimum inhibitory concentration (MIC) of the targeted pathogen. Under these conditions, the tiime that serum concentrations remain above the MIC becomes the major determinant of antimicrobial activity. Macrolides also exhibit a post-antibiotic effect (PAE), the duration of which tends to be both drug and pathogen dependent. In general, by increasing the macrolide concentration and the exposure time, the PAE will increase to some maximal duration. Of the two variables, concentrration and exposure time, drug concentration tends to be the most powerful determinant of the duration of PAE. Tulathromycin is eliminated from the body primarily unchanged via biliary excretion. 1 Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. 2 Nightingale, C.J. 1997. Pharacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443.

RESPIRmycin

Cattle Following subcutaneous administration into the neck of feeder calves at a dosage of 2.5 mg/kg BW, tulathromycin is rapidly and nearly completely absorbed. Peak plasma concentrations generally occur within 15 minutes after dosing and product relative bioavailability exceeds 90%. Total systemic clearance is approximately 170 mL/hr/kg. Tulathromycin distributes extensively into body tissues, as evidenced by volume of distribution values of approximately 11 L/kg in healthy ruminating calves.3 This extensive volume of distribution is largely responsible for the long elimination half-life of this compound [approximately 2.75 days in the plasma (based on quantifiable terminal plasma drug concentrations) versus 8.75 days for total lung concentrations (based on data from healthy animals)]. Linear pharmacokinetics are observed with subcutaneous doses ranging from 1.27 mg/kg BW to 5.0 mg/kg BW. No pharmacokinetic differences are observed in castrated male versus female calves. 3 Clearance and volume estimates are based on intersubject comparisons of 2.5 mg/kg BW administered by either subcutaneous or intravenous injection. Swine Following intramuscular administration to feeder pigs at a dosage of 2.5 mg/kg BW, tulathromycin is completely and rapidly absorbed (Tmax ~0.25 hour). Subsequently, the drug rapidly distributes into body tissues, achieving a volume of distribution exceeding 15 L/kg. The free drug is rapidly cleared from the systemic circulation (CLsystemic = 187 mL/hr/kg). However, it has a long terminal elimination half-life (60 to 90 hours) owing to its extensive volume of distribution. Although pulmonary tulathromycin concentrations are substantially higher than concentrations observed in the plasma, the clinical significance of these findings is undetermined. There are no gender differences in swine tulathromycin pharmacokinetics.

RESPIRmycin

At physiological pH, tulathromycin (a weak base) is approximately 50 times more soluble in hydrophilic than lipophilic media. This solubility profile is consistent with the extracellular pathogen activity typically associated with the macrolides.1 Markedly higher tulathromycin concentrations are observed in the lung parenchyma as compared to the plasma, and these elevated concentrations can remain in lung tissue for several days beyond that which can be measured in the plasma. However the clinical relevance of these elevated lung concentrations is undetermined. As a class, macrolides tend to be primarily bacteriostatic, but may be bactericidal against some pathogens.2 When acting as a cidal compound, they tend to exhibit concentration independent killing; the rate of bacterial eradication does not change once serum drug concentrations reach 2 to 3 times the minimum inhibitory concentration (MIC) of the targeted pathogen. Under these conditions, the time that serum concentrations remain above the MIC becomes the major determinant of antimicrobial activity. Macrolides also exhibit a post-antibiotic effect (PAE), the duration of which tends to be both drug and pathogen dependent. In general, by increasing the macrolide concentration and the exposure time, the PAE will increase to some maximal duration.3 Tulathromycin is eliminated from the body primarily unchanged via biliary excretion. 1 Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. 2 Nightingale, C.J. 1997. Pharmacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443. 3 Andes D, Anon J, Jacobs MR, Craig WA. (2004). Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections. Clin Lab Med., 24:477-502.

Draxxin® 25 (tulathromycin injection) Injectable Solution

CLINICAL PHARMACOLOGY At physical pH, tulathromycin (a weak base) is approximately 50 times more soluble in hydrophilic than hydrophobic media. This solubility profile is consistent with the extracellular pathogen activity typically associated with the macrolides.1 Markedly higher tulathromycin concentrations are observed in the lungs as compared to plasma. The extent to which lung concentrations represent free (active) drug was not examined. Therefore, the clinical relevance of these elevated lung concentrations is undetermined. As a class, macrolides tend to be primarily bacteriostatic, but may be bactericidal against some pathogens.2 When acting as a cidal compound, they tend to exhibit concentration independent killing; the rate of bacterial eradication does not change once serum drug concentrations reach 2 to 3 times the minimum inhibitory concentration (MIC) of the targeted pathogen. Under these conditions, the tiime that serum concentrations remain above the MIC becomes the major determinant of antimicrobial activity. Macrolides also exhibit a post-antibiotic effect (PAE), the duration of which tends to be both drug and pathogen dependent. In general, by increasing the macrolide concentration and the exposure time, the PAE will increase to some maximal duration.3 Tulathromycin is eliminated from the body primarily unchanged via biliary excretion. 1Carbon, C. 1998. Pharmacodynamics of Macrolides, Azalides, and Streptogramins: Effect on Extracellular Pathogens. Clin. Infect. Dis., 27:28-32. 2Nightingale, C.J. 1997. Pharacokinetics and Pharmacodynamics of Newer Macrolides. Pediatr. Infect. Dis. J., 16:438-443. 3Andes D, Anon J, Jacobs MR, Craig, WA. (2004). Application of pharmacokinetics and pharmacodynamics to antimicrobial therapy of respiratory tract infections. Clin Lab Med., 24:477-502.

VACASAN 25

CONTRAINDICATIONS The use of RESPIRmycin 25 Injectable Solution is contraindicated in animals previously found to be hypersensitive to the drug.

RESPIRmycin 25

The use of DRAXXIN KP Injection is contraindicated in animals previously found to be hypersensitive to tulathromycin and ketoprofen.

Draxxin® KP

The use of TULISSIN 100 Injectable Solution is contraindicated in animals previously found to be hypersensitive to the drug.

Tulissin 100®(tulathromycin injection)Injectable Solution

RESIDUE WARNINGS Swine Swine intended for human consumption must not be slaughtered within 5 days from the last treatment. Calves Calves intended for human consumption must not be slaughtered within 22 days from the last treatment with TULISSIN 25 Injectable Solution. This drug is not for use in ruminating cattle. PRECAUTIONS Swine The effects of Tulissin 25 Injectable Solution on porcine reproductive performance, pregnancy, and lactation have not been determined. Intramuscular injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter. Cattle The effects of Tulissin 25 Injectable Solution on bovine reproductive performance, pregnancy, and lactation have not been determined. Subcutaneous injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter

Tulissin 25®(tulathromycin injection)Injectable Solution

PRECAUTIONS Swine The effects of RESPIRmycin 25 Injectable Solution on porcine reproductive performance, pregnancy, and lactation have not been determined. Intramuscular injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter. Cattle The effects of RESPIRmycin 25 Injectable Solution on bovine reproductive performance, pregnancy, and lactation have not been determined. Subcutaneous injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter.

RESPIRmycin 25

WARNINGS FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. NOT FOR USE IN CHICKENS OR TURKEYS. RESIDUE WARNINGS Cattle Cattle intended for human consumption must not be slaughtered within 18 days from the last treatment. This drug 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. Swine Swine intended for human consumption must not be slaughtered within 5 days from the last treatment.

RESPIRmycin

PRECAUTIONS Cattle The effects of RESPIRmycin on bovine reproductive performance, pregnancy, and lactation have not been determined. Subcutaneous injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter. Swine The effects of RESPIRmycin on porcine reproductive performance, pregnancy, and lactation have not been determined. Intramuscular injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter.

RESPIRmycin

PRECAUTIONS Cattle The effects of VACASAN on bovine reproductive performance, pregnancy, and lactation have not been determined. Subcutaneous injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter. Swine The effects of VACASAN on porcine reproductive performance, pregnancy, and lactation have not been determined. Intramuscular injection can cause a transient local tissue reaction that may result in trim loss of edible tissue at slaughter.

VACASAN

Cattle must not be slaughtered for human consumption within 18 days following last treatment with this drug product. Not for use in female dairy cattle 1 year 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 or heifers. 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.

Draxxin® KP

WARNINGS FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. NOT FOR USE IN CHICKENS OR TURKEYS. RESIDUE WARNINGS Swine Swine intended for human consumption must not be slaughtered within 5 days from the last treatment. Calves Calves intended for human consumption must not be slaughtered within 22 days from the last treatment with RESPIRmycin 25 Injectable Solution. This drug is not for use in ruminating cattle.

RESPIRmycin 25

RESIDUE WARNINGS Cattle Cattle intended for human consumption must not be slaughtered within 18 days from the last treatment. This drug 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. Swine Swine intended for human consumption must not be slaughtered within 5 days from the last treatment.

Tulissin 100®(tulathromycin injection)Injectable Solution

Swine Swine intended for human consumption must not be slaughtered within 5 days from the last treatment. Calves Calves intended for human consumption must not be slaughtered within 22 days from the last treatment with DRAXXIN 25 Injectable Solution. This drug is not for use in ruminating cattle.

Draxxin® 25 (tulathromycin injection) Injectable Solution

Cattle Cattle intended for human consumption must not be slaughtered within 18 days from the last treatment. Do not use in female dairy cattle 20 months of age or older. Swine Swine intended for human consumption must not be slaughtered within 5 days from the last treatment.

Draxxin® (tulathromycin injection) Injectable Solution

NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. The Safety Data Sheet (SDS) provides more detailed occupational safety information. To obtain a Safety Data Sheet contact Zoetis Inc. at 1-888-963-8471.

Draxxin® KP

FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. NOT FOR USE IN CHICKENS OR TURKEYS.RESIDUE WARNINGS

Tulieve® (tulathromycin injection)

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

MACROSYNTM (tulathromycin injection)Injectable Solution

Swine In one field study, one out of 40 pigs treated with DRAXXIN Injectable Solution (100 mg/mL) at 2.5 mg/kg BW exhibited mild salivation that resolved in less than four hours. Calves In one BRD field study, two calves treated with DRAXXIN Injectable Solution (100 mg/mL) at 2.5 mg/kg BW exhibited transient hypersalivation. One of these calves also exhibited transient dyspnea, which may have been related to pneumonia. Post Approval Experience The following adverse events are based on post approval adverse drug experience reporting for DRAXXIN Injectable Solution (100 mg/mL). Not all adverse events are reported to the FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. The following adverse events are listed in decreasing order of reporting frequency in cattle: Injection site reactions and anaphylaxis/anaphylactoid reactions. For a complete listing of adverse reactions for DRAXXIN Injectable Solution or DRAXXIN 25 Injectable Solution reported to the CVM see: http://www.fda.gov/AnimalVeterinary.

Draxxin® 25 (tulathromycin injection) Injectable Solution

Swine In one field study, one out of 40 pigs treated with tulathromycin injection (100 mg/mL) at 2.5 mg/kg BW exhibited mild salivation that resolved in less than four hours. Calves In one BRD field study, two calves treated with tulathromycin injection (100 mg/mL) at 2.5 mg/kg BW exhibited transient hypersalivation. One of these calves also exhibited transient dyspnea, which may have been related to pneumonia. Post Approval Experience The following adverse events are based on post approval adverse drug experience reporting for tulathromycin injection (100 mg/mL). Not all adverse events are reported to the FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. The following adverse events are listed in decreasing order of reporting frequency in cattle: Injection site reactions and anaphylaxis/anaphylactoid reactions. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.

Tulissin 25®(tulathromycin injection)Injectable Solution

Cattle In one BRD field study, two calves treated with tulathromycin injection at 2.5 mg/kg BW exhibited transient hypersalivation. One of these calves also exhibited transient dyspnea, which may have been related to pneumonia. Swine In one field study, one out of 40 pigs treated with tulathromycin injection at 2.5 mg/kg BW exhibited mild salivation that resolved in less than four hours. POST APPROVAL EXPERIENCE The following adverse events are based on post approval adverse drug experience reporting. Not all adverse events are reported to the FDA CVM. It is not always possible to reliably estimate the adverse event frequency or establish a causal relationship to product exposure using these data. The following adverse events are listed in decreasing order of reporting frequency in cattle: Injection site reactions and anaphylaxis/anaphylactoid reactions. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or http://www.fda.gov/reportanimalae.

Tulissin 100®(tulathromycin injection)Injectable Solution

ADVERSE REACTIONS Swine In one field study, one out of 40 pigs treated with tulathromycin injection (100 mg/mL)at 2.5 mg/kg BW exhibited mild salivation that resolved in less than four hours. Calves In one BRD field study, two calves treated with tulathromycin injection (100 mg/mL) at 2.5 mg/kg BW exhibited transient hypersalivation. One of these calves also exhibited transient dyspnea, which may have been related to pneumonia.

VACASAN 25

ADVERSE REACTIONS Cattle In one BRD field study, two calves treated with tulathromycin injection at 2.5 mg/kg BW exhibited transient hypersalivation. One of these calves also exhibited transient dyspnea, which may have been related to pneumonia. Swine In one field study, one out of 40 pigs treated with tulathromycin injection at 2.5 mg/kg BW exhibited mild salivation that resolved in less than four hours.

RESPIRmycin

Repeated administration of NSAIDs can result in gastric or renal toxicity. Sensitivity to drug-associated adverse effects varies with the individual patient. Patients at greatest risk for toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with pre-existing gastric ulcers, renal, cardiovascular, and/or hepatic dysfunction.

Draxxin® KP

Cattle (Beef and Non-Lactating Dairy)

Administer 2.5 mg per kilogram (1.1 mL/100 lb) body weight as a single subcutaneous injection in the neck.

Intramuscular, Subcutaneous

Do not use in female dairy cattle 20 months of age or older. Do not inject more than 10 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Cattle (Suckling Calves, Dairy Calves, and Veal Calves)

Administer 2.5 mg per kilogram (1.1 mL/100 lb) body weight as a single subcutaneous injection in the neck.

Intramuscular, Subcutaneous

Do not inject more than 10 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Cattle (Calves)

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW).

Intramuscular, Subcutaneous

Do not inject more than 11.5 mL per injection site. For use in suckling calves, dairy calves, veal calves, and swine. Not for use in ruminating cattle. Not for use in Chickens or Turkeys. Federal (USA) law restricts this drug to useby or on the order of a licensed veterinarian.

Draxxin® 25 Injectable Solution

Beef and Non-Lactating Dairy Cattle

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site.

Subcutaneous, Intramuscular

Increxxa™

Suckling Calves, Dairy Calves, and Veal Calves

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site.

Subcutaneous, Intramuscular

Increxxa™

Cattle (beef steers, beef heifers, beef calves 2 months of age and older, beef bulls, dairy bulls, and replacement dairy heifers)

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg tulathromycin and 3 mg ketoprofen/kg (1.1 mL/100 lb) bodyweight.

Subcutaneous

Draxxin® KP

Suckling calves, dairy calves, and veal calves

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site.

Subcutaneous, Intramuscular

RESPIRmycin™

Beef and non-lactating dairy cattle

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site.

Subcutaneous, Intramuscular

RESPIRmycin™

Beef cattle, non-lactating dairy cattle, suckling calves, dairy calves and veal calves

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site.

Intramuscular, Subcutaneous

Tulathromycin Injection

Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW). Do not inject more than 4 mL per injection site.

Subcutaneous, Intramuscular

Tulissin® 25

Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/ kg (1 mL/22 lb) Body Weight (BW).

Intramuscular, Subcutaneous

Do not inject more than 4 mL per injection site. For use in suckling calves, dairy calves, veal calves, and swine. Not for use in ruminating cattle. Not for use in Chickens or Turkeys. Federal (USA) law restricts this drug to useby or on the order of a licensed veterinarian.

Draxxin® 25 Injectable Solution

Administer 2.5 mg per kilogram (0.25 mL/22 lb) body weight as a single intramuscular injection in the neck.

Intramuscular, Subcutaneous

Do not inject more than 2.5 mL per injection site. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Draxxin®

Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg tulathromycin and 3 mg ketoprofen/kg (1.1 mL/100 lb) bodyweight (BW). Do not inject more than 10 mL per injection site. Use this product within 56 days of the first puncture and puncture a maximum of 20 times. If more than 20 punctures are anticipated, the use of automatic injection equipment or a repeater syringe 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. Table 1. DRAXXIN KP Cattle Dosing Guide Animal Weight (lb) Dose Volume (mL) 150 1.7 200 2.3 250 2.8 300 3.4 350 4.0 400 4.5 500 5.7 600 6.8 700 8.0 800 9.1 900 10.2 1000 11.4

SUBCUTANEOUS

Draxxin® KP

Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) Body Weight (BW). Do not inject more than 4 mL per injection site. Table 1. Increxxa 25 Swine Dosing Guide (25 mg/mL) Animal Weight (Pounds) Dose Volume (mL) 4 0.2 10 0.5 15 0.7 20 0.9 22 1.0 25 1.1 30 1.4 50 2.3 70 3.2 90 4.0 Calves Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) BW. Do not inject more than 11.5 mL per injection site. Table 2. Increxxa 25 Calf Dosing Guide (25 mg/mL) Animal Weight (Pounds) Dose Volume (mL) 50 2.3 75 3.4 100 4.5 150 7.0 200 9.0 250 11.5

INTRAMUSCULAR, SUBCUTANEOUS

Elanco™ Increxxa™ 25 (tulathromycin injection)

DOSAGE AND ADMINISTRATION Cattle Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site. Table 1. RESPIRmycin Cattle Dosing Guide Animal Weight (Pounds) Dose Volume (mL) 100 1.1 200 2.3 300 3.4 400 4.5 500 5.7 600 6.8 700 8.0 800 9.1 900 10.2 1000 11.4

INTRAMUSCULAR, SUBCUTANEOUS

RESPIRmycin

DOSAGE AND ADMINISTRATION Cattle Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site. Table 1. VACASAN Cattle Dosing Guide Animal Weight (Pounds) Dose Volume (mL) 100 1.1 200 2.3 300 3.4 400 4.5 500 5.7 600 6.8 700 8.0 800 9.1 900 10.2 1000 11.4

INTRAMUSCULAR, SUBCUTANEOUS

VACASAN

DOSAGE AND ADMINISTRATION Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW). Do not inject more than 4 mL per injection site. Table 1. RESPIRmycin 25 Swine Dosing Guide (25mg/mL) Animal Weight (Pounds) Dose Volume (mL) 4 0.2 10 0.5 15 0.7 20 0.9 22 1.0 25 1.1 30 1.4 50 2.3 70 3.2 90 4.0

INTRAMUSCULAR, SUBCUTANEOUS

RESPIRmycin 25

Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (0.25 mL/22 lb) BW. Do not inject more than 2.5 mL per injection site. Table 2. RESPIRmycin Swine Dosing Guide Animal Weight (Pounds) Dose Volume (mL) 15 0.2 30 0.3 50 0.6 70 0.8 90 1.0 110 1.3 130 1.5 150 1.7 170 1.9 190 2.2 210 2.4 230 2.6 250 2.8 270 3.1 290 3.3

INTRAMUSCULAR, SUBCUTANEOUS

RESPIRmycin

DOSAGE AND ADMINISTRATION Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW). Do not inject more than 4 mL per injection site. Table 1. VACASAN 25 Swine Dosing Guide (25mg/mL) Animal Weight (Pounds) Dose Volume (mL) 4 0.2 10 0.5 15 0.7 20 0.9 22 1.0 25 1.1 30 1.4 50 2.3 70 3.2 90 4.0

INTRAMUSCULAR, SUBCUTANEOUS

VACASAN 25

Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (0.25 mL/22 lb) BW. Do not inject more than 2.5 mL per injection site. Table 2. VACASAN Swine Dosing Guide Animal Weight (Pounds) Dose Volume (mL) 15 0.2 30 0.3 50 0.6 70 0.8 90 1.0 110 1.3 130 1.5 150 1.7 170 1.9 190 2.2 210 2.4 230 2.6 250 2.8 270 3.1 290 3.3

INTRAMUSCULAR, SUBCUTANEOUS

VACASAN

Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) Body Weight (BW). Do not inject more than 4 mL per injection site. Calves Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW). Do not inject more than 11.5 mL per injection site.

SUBCUTANEOUS, INTRAMUSCULAR

Tulissin 25®(tulathromycin injection)Injectable Solution

Cattle Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1.1 mL/100 lb) body weight (BW). Do not inject more than 10 mL per injection site. Swine Inject intramuscularly as a single dose in the neck at a dosage of 2.5 mg/kg (0.25 mL/22 lb) BW. Do not inject more than 2.5 mL per injection site.

SUBCUTANEOUS, INTRAMUSCULAR

Tulissin 100®(tulathromycin injection)Injectable Solution

Calves Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW). Do not inject more than 11.5 mL per injection site. Table 2. RESPIRmycin 25 Calf Dosing Guide (25mg/mL) Animal Weight (Pounds) Dose Volume (mL) 50 2.3 75 3.4 100 4.5 150 7.0 200 9.0 250 11.5

INTRAMUSCULAR, SUBCUTANEOUS

RESPIRmycin 25

Calves Inject subcutaneously as a single dose in the neck at a dosage of 2.5 mg/kg (1 mL/22 lb) body weight (BW). Do not inject more than 11.5 mL per injection site. Table 2. VACASAN 25 Calf Dosing Guide (25mg/mL) Animal Weight (Pounds) Dose Volume (mL) 50 2.3 75 3.4 100 4.5 150 7.0 200 9.0 250 11.5

INTRAMUSCULAR, SUBCUTANEOUS

VACASAN 25