PRINCIPAL DISPLAY PANEL - 500ml Box

500ml Box
40036996

CONTRAINDICATIONS

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

ADVERSE REACTIONS

Cattle

In one BRD field study, two calves treated with DRAXXIN 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 DRAXXIN at 2.5 mg/kg BW exhibited mild salivation that resolved in less than four hours.

Approved by FDA under NADA # 141-244

zoetis

Distributed by:
Zoetis Inc.
Kalamazoo, MI 49007

Revised: March 2025

CAUTION

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

DESCRIPTION

DRAXXIN Injectable Solution is a ready-to-use sterile parenteral preparation containing tulathromycin, a semi-synthetic macrolide antibiotic of the subclass triamilide. Each mL of DRAXXIN contains 100 mg of tulathromycin as the free base in a 50% propylene glycol vehicle, monothioglycerol (5 mg/mL), with citric and hydrochloric acids added to adjust pH.

DRAXXIN consists of an equilibrated mixture of two isomeric forms of tulathromycin in a 9:1 ratio. Structures of the isomers are shown below.

Figure 1.

The chemical names of the isomers are (2R,3S, 4R,5R,8R,10R,11R,12S,13S,14R)-13-[[2,6-dideoxy-3-C-methyl-3-Ο-methyl-4-C-[(propylamino) methyl]-α-L-ribo-hexopyrano- syl]oxy]-2-ethyl-3,4,10-trihydroxy-3,5,8,10,12,14-hexamethyl-11-[[3,4,6-trideoxy-3-(dimethylamino)-β-D- xylohexopyranosyl]-oxy]-1-oxa-6-azacyclopentadecan-15-one and (2R, 3R,6R, 8R,9R,10S,11S,12R)-11-[[2,6-dideoxy-3-C-methyl- 3-Ο-methyl-4-C-[(propylamino)methyl]-α-L-ribo-hexopyrano- syl]oxy]-2-[(1R,2R)-1,2-dihydroxy-1-methylbutyl]-8-hydroxy-3,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy-3-(dimethylamino)-β-D- xylohexopyranosyl]oxy]-1-oxa-4-azacyclotridecan-13-one, respectively.

INDICATIONS

Beef and Non-Lactating Dairy Cattle

BRD** –**DRAXXIN 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 – DRAXXIN Injectable Solution is indicated for the treatment of infectious bovine keratoconjunctivitis (IBK) associated with Moraxella bovis.

Foot Rot – DRAXXIN 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 – DRAXXIN Injectable Solution is indicated for the treatment of BRD associated with M. haemolytica, P. multocida, H. somni, and M. bovis.

Swine

DRAXXIN 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.

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. DRAXXIN 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

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. DRAXXIN 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

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. 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.

PRECAUTIONS

Cattle

The effects of DRAXXIN 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 DRAXXIN 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.

CLINICAL PHARMACOLOGY

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.

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.

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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.

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.

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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.

MICROBIOLOGY

Cattle

Tulathromycin has demonstrated in vitro activity against Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, four pathogens associated with BRD; against Moraxella bovis associated with IBK; and against Fusobacterium necrophorum and Porphyromonas levii associated with bovine foot rot.

The MICs of tulathromycin against indicated BRD and IBK pathogens were determined using methods recommended by the Clinical and Laboratory Standards Institute (CLSI, M31-A2). The MICs against foot rot pathogens were also determined using methods recommended by the CLSI (M11-A6). All MIC values were determined using the 9:1 isomer ratio of this compound.

BRD - The MICs of tulathromycin were determined for BRD isolates obtained from calves enrolled in therapeutic and at-risk field studies in the U.S. in 1999. In the therapeutic studies, isolates were obtained from pre-treatment nasopharyngeal swabs from all study calves, and from lung swabs or lung tissue of saline-treated calves that died. In the at-risk studies, isolates were obtained from nasopharyngeal swabs of saline-treated non-responders, and from lung swabs or lung tissue of saline-treated calves that died. The results are shown in Table 3.

IBK - The MICs of tulathromycin were determined for Moraxella bovis isolates obtained from calves enrolled in IBK field studies in the U.S. in 2004. Isolates were obtained from pre-treatment conjunctival swabs of calves with clinical signs of IBK enrolled in the DRAXXIN and saline-treated groups. The results are shown in Table 3.

Foot Rot - The MICs of tulathromycin were determined for Fusobacterium necrophorum and Porphyromonas levii obtained from cattle enrolled in foot rot field studies in the U.S. and Canada in 2007. Isolates were obtained from pretreatment interdigital biopsies and swabs of cattle with clinical signs of foot rot enrolled in the DRAXXIN and saline-treated groups. The results are shown in Table 3.

Table 3. Tulathromycin minimum inhibitory concentration (MIC) values* for indicated pathogens isolated from field studies evaluating BRD and IBK in the U.S. and from foot rot field studies in the U.S. and Canada.

Indicated pathogen	Date isolated	No. of isolates	MIC50† (μg/mL)	MIC90† (μg/mL)	MIC range (μg/mL)
The correlation between in vitro susceptibility data and clinical effectiveness is unknown. † The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.
Mannheimia haemolytica	1999	642	2	2	0.5 to 64
Pasteurella multocida	1999	221	0.5	1	0.25 to 64
Histophilus somni	1999	36	4	4	1 to 4
Mycoplasma bovis	1999	43	0.125	1	≤ 0.063 to > 64
Moraxella bovis	2004	55	0.5	0.5	0.25 to 1
Fusobacterium necrophorum	2007	116	2	64	≤ 0.25 to > 128
Porphyromonas levii	2007	103	8	128	≤ 0.25 to > 128

• The correlation between in vitro susceptibility data and clinical effectiveness is unknown.
  **The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.

Swine

In vitro activity of tulathromycin has been demonstrated against Actinobacillus pleuropneumoniae, Pasteurella multocida, Bordetella bronchiseptica, Haemophilus parasuis, and Mycoplasma hyopneumoniae.

The MICs of tulathromycin against indicated SRD pathogens were determined using methods recommended by the Clinical and Laboratory Standards Institute (CLSI, M31-A and M31-A3). MICs for Haemophilus parasuis were determined using Veterinary Fastidious Medium and were incubated up to 48 hours at 35 to 37°C in a CO2-enriched atmosphere. All MIC values were determined using the 9:1 isomer ratio of this compound. Isolates obtained in 2000 and 2002 were from lung samples from saline-treated pigs and non-treated sentinel pigs enrolled in Treatment of SRD field studies in the U.S. and Canada. Isolates obtained in 2007 and 2008 were from lung samples from saline-treated and DRAXXIN-treated pigs enrolled in the Control of SRD field study in the U.S. and Canada. The results are shown in Table 4.

Table 4. Tulathromycin minimum inhibitory concentration (MIC) values* for indicated pathogens isolated from field studies evaluating SRD in the U.S. and Canada.

Indicated pathogen	Date isolated	No. of isolates	MIC50† (μg/mL)	MIC90† (μg/mL)	MIC range (μg/mL)
The correlation between in vitro susceptibility data and clinical effectiveness is unknown. † The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.
Actinobacillus pleuropneumoniae	2000-2002 2007-2008	135 88	16 16	32 16	16 to 32 4 to 32
Haemophilus parasuis	2000-2002	31	1	2	0.25 to > 64
Pasteurella multocida	2000-2002 2007-2008	55 40	1 1	2 2	0.5 to > 64 ≤ 0.03 to 2
Bordetella bronchiseptica	2000-2002	42	4	8	2 to 8

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

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

STORAGE CONDITIONS

Store below 25°C (77°F), with excursions up to 40°C (104°F). Use this product within 45 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 of 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.

HOW SUPPLIED

DRAXXIN Injectable Solution is available in the following package sizes:

50 mL vial
100 mL vial
250 mL vial
500 mL vial