PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

PRINCIPAL DISPLAY PANEL - 500 mL Carton

40028869

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DESCRIPTION SECTION

DESCRIPTION

DRAXXIN KP (tulathromycin and ketoprofen injection) Injectable Solution is a ready to use sterile parenteral preparation containing tulathromycin, a semi- synthetic macrolide antibiotic of the subclass triamilide and ketoprofen a non-steroidal anti-inflammatory drug. ACTIVE INGREDIENTS: Each mL of DRAXXIN KP contains 100 mg of tulathromycin as a free base and 120 mg ketoprofen as a free acid in a 50% propylene glycol vehicle.
INACTIVE INGREDIENTS:
monothioglycerol (5 mg/mL), 2-pyrrolidone (70 mg/mL), citric acid (20 mg/mL) and sodium hydroxide/hydrochloric acid added to adjust pH.

DRAXXIN KP contains an equilibrated mixture of two isomeric forms of tulathromycin in a 9:1 ratio and a racemic mixture of ketoprofen.

The structures of the tulathromycin isomers and ketoprofen are shown below:

Figure 1. Tulathromycin structures


The chemical names of the tulathromycin 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-hexopyranosyl]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- ribohexopyranosyl]oxy]-2-[(1S,2R)-1,2-dihydroxy-1-methylbutyl]-8-hydroxy-3,6,8,10,12-pentamethyl-9-[[3,4,6-trideoxy -3-(dimethylamino)-β-D-xylo- hexopyranosyl]oxy]-1-oxa-4-azacyclotridecan-13-one, respectively.

Figure 2. Ketoprofen Structure


The chemical name of ketoprofen is 2-(3-Benzoylphenyl) propanoic acid.

CLINICAL PHARMACOLOGY SECTION

CLINICAL PHARMACOLOGY

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) nghr/mL for ketoprofen in the combination product and 23106 (±3500) for nghr/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) nghr/mL) and tulathromycin alone (14088 (±4408) nghr/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.

MICROBIOLOGY SECTION

MICROBIOLOGY

Based on data provided for the approval of Draxxin® (tulathromycin injection, NADA 141-244), tulathromycin has demonstrated in vitro activity against Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis, four pathogens associated with BRD.

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VETERINARY INDICATIONS SECTION

INDICATIONS

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.

DOSAGE & ADMINISTRATION SECTION

DOSAGE AND ADMINISTRATION

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

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CONTRAINDICATIONS SECTION

CONTRAINDICATIONS

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

WARNINGS SECTION

USER SAFETY WARNINGS

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.

PRECAUTIONS SECTION

ANIMAL SAFETY WARNINGS and PRECAUTIONS

The effects of DRAXXIN KP on bovine reproductive performance, pregnancy, and lactation have not been determined. Not for use in reproducing animals over one year of age because reproductive safety testing has not been conducted. Administration of tulathromycin and ketoprofen injection may result in injection site swelling that appears the day after treatment and may persist for at least 32 days post-injection. This may result in trim loss of edible tissue at slaughter.

As a class, cyclo-oxygenase inhibitory NSAIDs (Ketoprofen) may be associated with gastrointestinal, hepatic and renal toxicity. Sensitivity to drug- associated adverse effects varies with the individual patient. Patients at greatest risk for renal toxicity are those that are dehydrated, on concomitant diuretic therapy, or those with renal, cardiovascular, and/or hepatic dysfunction. Use judiciously when renal impairment or gastric ulceration is suspected.

Since many NSAIDs possess the potential to induce gastrointestinal ulceration, concomitant use of DRAXXIN KP with other anti-inflammatory drugs, such as other NSAIDs and corticosteroids, should be avoided or closely monitored. Discontinue use if fecal blood is observed.

SAFE HANDLING WARNING SECTION

CAUTION

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

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ADVERSE REACTIONS SECTION

ADVERSE REACTIONS

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.

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HOW SUPPLIED SECTION

HOW SUPPLIED

DRAXXIN KP Injection is available in the following package sizes:
50 mL vial
100 mL vial
250 mL vial
500 mL vial

STORAGE AND HANDLING SECTION

STORAGE CONDITIONS

Store at or below 25°C (77°F), with excursions up to 40°C (104°F). Protect from freezing.

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SPL UNCLASSIFIED SECTION

APPROVED BY FDA under NADA # 141-543

zoetis

Distributed by:
Zoetis Inc.
Kalamazoo, MI 49007

Product of Spain

October 2024

40035963

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