Ketoprofen

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

For the control of pyrexia associated with bovine respiratory disease (BRD)

KETOFEN®

Beef heifers, beef steers, beef calves 2 months of age and older, beef bulls, replacement dairy heifers, and dairy bulls

KetoMed™ (ketoprofen) is indicated for the control of pyrexia associated with Bovine Respiratory Disease (BRD) in beef heifers, beef steers, beef calves 2 months of age and older, beef bulls, replacement dairy heifers, and dairy bulls. Not for use in reproducing animals over one year of age, dairy calves, or veal calves. Not for use in lactating dairy cattle or calves <2 months old.

KetoMed™

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

For the alleviation of inflammation and pain associated with musculoskeletal disorders in the horse.

KetoMed™

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

INDICATION KetoMed(ketoprofen) is recommended for the alleviation of inflammation and pain associated with musculoskeletal disorders in the horse.

KetoMedTM

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

KETOFEN is a non-narcotic, non-steroidal anti-inflammatory agent with analgesic and antipyretic properties. In horses, intravenous dosages of ketoprofen ranging from 0.5 to 1.5 mg/lb resulted in dosage dependent anti-inflammatory effects in the chronic adjuvant carpitis model as depicted in the following graph. n = number of animals MAXIMUM FLEXION (intravenous ketoprofen, mean ± sem, n = 4) sem = standard error of the mean Additional studies using the same model in horses have shown that the effects of ketoprofen are maximal by 12 hours and still measurable at 24 hours after each dosage as depicted in the following graph. n = number of animals MAXIMUM FLEXION (mean ± sem, n = 6) sem = standard error of the mean

KETOFEN®

CONTRAINDICATIONS There are no known contraindications to this drug when used as directed. Intra-arterial injection should be avoided. Do not use in a horse if it has previously shown hypersensitivity to ketoprofen.

KetoMedTM

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

Draxxin® KP

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

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

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

Draxxin® KP

WARNING Do not use in horses intended for human consumption.

KetoMedTM

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

The recommended dosage is 3 mg/kg (1 mL/33.3 kg) or 1.36 mg/lb (1 mL/74 lb) of body weight. Treatment is administered by subcutaneous injection once daily and may be repeated for up to three days if pyrexia persists.

Intravenous

KETOFEN®

Beef heifers, beef steers, beef calves 2 months of age and older, beef bulls, replacement dairy heifers, and dairy bulls

The recommended dosage is 3 mg/kg (1 mL/33.3 kg) or 1.36 mg/lb (1 mL/74 lb) of body weight. Treatment is administered by subcutaneous injection once daily and may be repeated for up to three days if pyrexia persists.

Intravenous

KetoMed™

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

The recommended dosage is 1 mg/lb (1 mL/100 lbs) of body weight once daily. Treatment is administered by intravenous injection and may be repeated for up to five days.

Intravenous

KetoMed™

1.0 milligram per pound of body weight once daily for up to 5 days. For intravenous use.

Intravenous

Do not use in breeding animals. Effects on fertility, pregnancy, or fetal health have not been determined. Do not use in horses intended for human consumption. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

KETOFEN®

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

The recommended dosage is 1 mg/lb (1 mL/100 lbs) of body weight administered intravenously once daily. Treatment may be repeated for up to five days. Onset of activity is within two hours with peak response by 12 hours. Use contents within 4 months of first vial puncture.

INTRAVENOUS, SUBCUTANEOUS

KETOFEN®

DOSAGE AND ADMINISTRATION The recommended dosage is 1 mg/lb (1 mL/100 lbs) of body weight once daily. Treatment is administered by intravenous injection and may be repeated for up to five days. Onset of activity is within two hours with peak response by 12 hours.

INTRAVENOUS

KetoMedTM