gamithromycin

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 in beef and non-lactating dairy cattle.

Zactran®

Cattle (Beef and Non-Lactating Dairy)

For the control of respiratory disease in beef and non-lactating dairy cattle at high risk of developing BRD associated with Mannheimia haemolytica and Pasteurella multocida.

Zactran®

Beef and non-lactating dairy cattle

For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis in beef and non-lactating dairy cattle; and for the control of respiratory disease in beef and non-lactating dairy cattle at high risk of developing BRD associated with Mannheimia haemolytica and Pasteurella multocida.

GAMROZYNE™

INDICATIONS GAMROZYNE is indicated for the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni and Mycoplasma bovis in beef and non-lactating dairy cattle. GAMROZYNE is also indicated for the control of respiratory disease in beef and non-lactating dairy cattle at high risk of developing BRD associated with Mannheimia haemolytica and Pasteurella multocida.

GAMROZYNETM (gamithromycin)

CLINICAL PHARMACOLOGY The macrolide antimicrobials as a class are weak bases and as such concentrate in some cells (such as pulmonary leukocytes). Prolonged exposure of extracellular pulmonary pathogens to macrolides appears to reflect the slow release of drug from its intracellular reservoir to the site of action, the pulmonary epithelial lining fluid (ELF). It is the ELF that is relevant to the successful treatment and control of BRD. Gamithromycin is primarily bacteriostatic at therapeutic concentrations. However, in vitro bactericidal activity has been observed at concentrations of 10 μg/mL (Mueller-Hinton broth) and after exposure to the 6-hour and 24-hour plasma samples derived from cattle dosed at 6 mg gamithromycin/kg BW. Macrolides typically exhibit substantially higher concentrations in the alveolar macrophages and ELF as compared to concentrations observed in plasma. Gamithromycin concentrations in the ELF and ELF cells exceed the concentrations observed in the plasma. Postmortem gamithromycin concentrations in ELF exceed the MIC90 of M. haemolytica, H. somni and P. multocida through at least 72 hours after drug administration. Because M. haemolytica, P. multocida and H. somni are extracellular pathogens, drug concentrations in the ELF are considered to be clinically relevant. The postmortem area under the concentration-time curve (AUC) observed in lysed ELF cells (e. g., alveolar macrophages) are at least 300-times greater than that in the plasma. Although published studies suggest that inflammation can increase the release of drug from macrophages and neutrophils, these high concentrations in the alveolar macrophages should not be considered indicative of the magnitude or duration of response to the pathogens for which this product is indicated. Gamithromycin administered subcutaneously in the neck of cattle at a single dosage of 6 mg/kg BW is rapidly and completely absorbed, with peak concentrations generally occurring within 1 hour after administration. Based upon plasma and lung homogenate data, the terminal half-life (T½) of gamithromycin is approximately 3 days. In vitro plasma protein binding studies show that 26% of the gamithromycin binds to plasma protein, resulting in free drug available for rapid and extensive distribution into body tissues. The free drug is rapidly cleared from the systemic circulation with a clearance rate of 712 mL/hr/kg and a volume of distribution of 25 L/kg. Dose proportionality was established based on AUC over a range of 3 mg/kg BW to 9 mg/kg BW. Biliary excretion of the unchanged drug is the major route of elimination.

GAMROZYNETM (gamithromycin)

CONTRAINDICATIONS As with all drugs, the use of GAMROZYNE is contraindicated in animals previously found to be hypersensitive to this drug.

GAMROZYNETM (gamithromycin)

As with all drugs, the use of ZACTRAN is contraindicated in animals previously found to be hypersensitive to this drug.

ZACTRAN® (gamithromycin)

FOR USE IN CATTLE ONLY. NOT FOR USE IN HUMANS. KEEP THIS AND ALL DRUGS OUT OF REACH OF CHILDREN. NOT FOR USE IN CHICKENS OR TURKEYS. The Safety Data Sheet (SDS) contains more detailed occupational safety information. To report suspected adverse drug events, for technical assistance, or to obtain a copy of the SDS, contact Boehringer Ingelheim Animal Health USA Inc. at 1-888-637-4251. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS, or online at www.fda.gov/reportanimalae.

ZACTRAN® (gamithromycin)

RESIDUE WARNINGS Do not treat cattle within 35 days of slaughter. Because a discard time in milk has not been established, do not use in female dairy cattle 20 months of age or older. A withdrawal period has not been established for this product in pre-ruminating calves. Do not use in calves to be processed for veal.

GAMROZYNETM (gamithromycin)

ADVERSE REACTIONS Transient animal discomfort and mild to moderate injection site swelling may be seen in cattle treated with GAMROZYNE.

GAMROZYNETM (gamithromycin)

Transient animal discomfort and mild to moderate injection site swelling may be seen in cattle treated with ZACTRAN.

ZACTRAN® (gamithromycin)

Cattle (Beef and Non-Lactating Dairy)

6 mg/kg body weight (2 mL per 110 lb BW), administered one time.

Subcutaneous

Zactran®

Beef and non-lactating dairy cattle

Administer 6 mg/kilogram of body weight (2 mL per 110 pounds) one time by subcutaneous injection in the neck.

Subcutaneous

GAMROZYNE™

DOSAGE AND ADMINISTRATION Administer GAMROZYNE one time as a subcutaneous injection in the neck at 6 mg/kg (2 mL/110 lb) body weight (BW). If the total dose exceeds 10 mL, divide the dose so that no more than 10 mL is administered at each injection site. Body Weight (lb) Dose Volume (mL) 110 2 220 4 330 6 440 8 550 10 660 12 770 14 880 16 990 18 1100 20 Animals should be appropriately restrained to achieve the proper route of administration. Use sterile equipment. Inject under the skin in front of the shoulder (see ILLUSTRATION).

SUBCUTANEOUS

GAMROZYNETM (gamithromycin)