Ceftiofur

Dairy cattle (At Dry Off)

For the treatment of subclinical mastitis in dairy cattle at the time of dry off associated with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis.

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

Spectramast™ DC Sterile Suspension

Lactating Dairy Cattle

For use in lactating dairy cattle for (1) the treatment of clinical mastitis associated with coagulase-negative staphylococci, Streptococcus dysgalactiae, and Escherichia coli and (2) the treatment of diagnosed subclinical mastitis associated with coagulase-negative staphylococci and Streptococcus dysgalactiae.

Milk taken from cows during treatment (a maximum of eight daily infusions) and for 72 hours after the last treatment must not be used for human consumption. Following label use for up to eight consecutive days, a 2-day pre-slaughter withdrawal period is required. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal Law prohibits extra-label use of this drug in lactating dairy cattle for disease prevention purposes; at unapproved doses; frequencies, durations, or routes of administration; and in unapproved major food producing species/production classes.

Spectramast® LC Sterile Suspension

Cattle (Beef, Non-Lactating Dairy, Lactating Dairy)

For treatment of Bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni.

EXCENEL® RTU EZ

Cattle (Beef, Non-Lactating Dairy, Lactating Dairy)

For treatment of Acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

EXCENEL® RTU EZ

Cattle (Beef, Non-Lactating Dairy, Lactating Dairy)

For treatment of Acute metritis (0 to 14 days post-partum) associated with bacterial organisms susceptible to ceftiofur.

EXCENEL® RTU EZ

Cattle (excluding veal calves)

For treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni; acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus; and acute metritis (0 to 14 days post-partum) associated with bacteria susceptible to ceftiofur.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Treated cattle must not be slaughtered for 3 days following the last treatment. A withdrawal period has not been established in preruminating calves. Do not use in calves to be processed for veal. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Excenel Sterile Suspension

For treatment of the following bacterial diseases: Bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida and Histophilus somni. Acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus. Acute metritis (0 to 14 days post-partum) associated with bacterial organisms susceptible to ceftiofur.

Cefenil® RTU

For the treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Also indicated for the treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

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

Ceftiofur Sodium Sterile Powder

Treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and Histophilus somni in beef and dairy cattle

Naxcel® Sterile Powder

For treatment of acute bovine interdigital necrobacillosis (foot rot, pododermatitis) associated with Fusobacterium necrophorum and Bacteroides melaninogenicus.

Naxcel® Sterile Powder

For the treatment/control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus (Haemophilus) pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis.

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

Ceftiofur Sodium Sterile Powder

For treatment and control of swine bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Salmonella choleraesuis, and Streptococcus suis.

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Treated swine must not be slaughtered for 4 days following the last treatment.

Excenel Sterile Suspension

Day-Old Chicks

For the control of early mortality, associated with E. coli organisms susceptible to ceftiofur, in day-old chicks.

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

Ceftiofur Sodium Sterile Powder

Chickens (Day Old Chicks)

For control of early mortality associated with Escherichia coli organisms susceptible to ceftiofur in day-old chicks.

Naxcel® Sterile Powder

Day-Old Turkey Poults

For the control of early mortality, associated with E. coli organisms susceptible to ceftiofur, in day-old turkey poults.

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

Ceftiofur Sodium Sterile Powder

Turkeys (Day Old Poults)

For control of early mortality associated with E. coli organisms susceptible to ceftiofur in day-old poults.

Naxcel® Sterile Powder

For the treatment of sheep respiratory disease (sheep pneumonia) associated with Mannheimia haemolytica and Pasteurella multocida.

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

Ceftiofur Sodium Sterile Powder

For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P. multocida.

Naxcel® Sterile Powder

For the treatment of caprine respiratory disease (goat pneumonia) associated with Mannheimia haemolytica and Pasteurella multocida.

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

Ceftiofur Sodium Sterile Powder

For the treatment of canine urinary tract infections associated with Escherichia coli and Proteus mirabilis.

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

Ceftiofur Sodium Sterile Powder

For treatment of respiratory infections in horses associated with Streptococcus zooepidemicus.

Do not use in horses intended for human consumption. Limitations: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Ceftiofur Sodium Sterile Powder

EXCEDE Sterile Suspension is indicated for treatment of bovine respiratory disease (BRD, shipping fever, pneumonia) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef, non-lactating dairy, and lactating dairy cattle. EXCEDE Sterile Suspension is also indicated for the control of respiratory disease in beef and non-lactating dairy cattle which are at high risk of developing BRD associated with M. haemolytica, P. multocida, and H. somni. EXCEDE Sterile Suspension is also indicated for the treatment of bovine foot rot (interdigital necrobacillosis) associated with Fusobacterium necrophorum and Porphyromonas levii in beef, non-lactating dairy, and lactating dairy cattle. EXCEDE Sterile Suspension is also indicated for treatment of acute metritis (0-10 days post-partum) associated with bacterial organisms susceptible to ceftiofur in lactating dairy cattle.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

EXCEDE FOR SWINE Sterile Suspension 100 mg/mL is indicated for the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis; and for the control of SRD associated with Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis, and Streptococcus suis in groups of pigs where SRD has been diagnosed.

EXCEDE® For Swine (Ceftiofur Crystalline Free Acid) Sterile Suspension, 100 mg/mL

SPECTRAMAST® DC Ceftiofur Hydrochloride Sterile Suspension is indicated for the treatment of subclinical mastitis in dairy cattle at the time of dry off associated with Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis. SPECTRAMAST® DC Ceftiofur Hydrochloride Sterile Suspension has been proven effective against Staphylococcus aureus, Streptococcus dysgalactiae, and Streptococcus uberis.

SPECTRAMAST® DC

SPECTRAMAST® LC (ceftiofur intramammary suspension) Sterile Suspension is indicated for use in lactating dairy cattle for (1) the treatment of clinical mastitis associated with coagulase-negative staphylococci, Streptococcus dysgalactiae, and Escherichia coli and (2) the treatment of diagnosed subclinical mastitis associated with coagulase-negative staphylococci and Streptococcus dysgalactiae.

SPECTRAMAST® LC

EXCEDE Sterile Suspension is indicated for the treatment of lower respiratory tract infections in horses caused by susceptible strains of Streptococcus equi ssp. zooepidemicus.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

Ceftiofur administered as either ceftiofur sodium (NAXCEL® Sterile Powder), ceftiofur hydrochloride (EXCENEL® RTU Sterile Suspension) or ceftiofur crystalline free acid (EXCEDE FOR SWINE Sterile Suspension 100 mg/mL) is metabolized rapidly to desfuroylceftiofur, the primary metabolite. Administration of ceftiofur to swine as ceftiofur crystalline free acid (CCFA) at a single IM dosage of 2.27 mg CE/lb (5.0 mg CE/kg) BW provides concentrations of ceftiofur and desfuroylceftiofurrelated metabolites in plasma that are multiples above the MIC90 Minimum inhibitory concentration for 90% of the isolates for the SRD label pathogens Actinobacillus pleuropneumoniae, Pasteurella multocida, Haemophilus parasuis and Streptococcus suis for an extended period of time (see Figure 2 and Tables 1–2). The average plasma concentrations of ceftiofur- and desfuroylceftiofur-related metabolites for CCFA (EXCEDE FOR SWINE Sterile Suspension 100 mg/mL) after IM administration of 2.27 mg CE/lb (5.0 mg CE/kg) BW and those for ceftiofur sodium (NAXCEL Sterile Powder) after IM administration at 1.36 mg CE/lb (3 mg CE/kg) BW for three consecutive days are presented in Figure 2 below. Figure 2. Average plasma concentrations of ceftiofur- and desfuroylceftiofur-related metabolites for CCFA (EXCEDE FOR SWINE Sterile Suspension 100 mg/mL) after IM administration of 2.27 mg CE/lb (5.0 mg CE/kg) BW and those for ceftiofur sodium (NAXCEL Sterile Powder) after IM administration at 1.36 mg CE/lb (3 mg CE/kg) BW for three consecutive days Pharmacokinetic parameters measured after a single IM administration of 2.27 mg CE/lb (5.0 mg CE/kg) BW of EXCEDE FOR SWINE Sterile Suspension 100 mg/mL in the post-auricular region of the neck of swine are presented in the following table (Table 1). Table 1. Pharmacokinetic parameters in swine after a single IM administration of EXCEDE FOR SWINE Sterile Suspension 100 mg/mL at 2.27 mg CE/lb (5.0 mg CE/kg) BW Pharmacokinetic Parameter Mean Value ± Standard Deviation (non-compartmental analyses) Cmax = maximum plasma concentration (in μg CE/mL) tmax = the time after injection when Cmax occurs (in hours) AUC 0-LOQ = the area under the plasma concentration vs. time curve from time of injection to the limit of quantitation of the assay (0.15 μg CE/mL) t1/2 = terminal phase biological half-life (in hours) Cmax (μg/mL) 4.17 ± 0.92 tmax (h) 22.0 ± 12.2 AUC 0-LOQ (μg∙h/mL) 373.0 ± 56.1 t1/2 (h) 49.6 ± 11.8 Table 2. Ceftiofur minimum inhibitory concentration (MIC) valuesThe correlation between in vitro susceptibility data and clinical effectiveness is unknown. of indicated pathogens isolated from SRD treatment and control field studies conducted in the U.S. Indicated Pathogens Year(s) of Isolation Field Study Number of Isolates MIC50 The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively. (μg/mL) MIC90 (μg/mL) MIC Range (μg/mL) Actinobacillus pleuropneumoniae 2000 to 2001 Treatment 5 NA NA ≤0.03 to 0.06 2009 Control 34 0.03 0.06 0.015 to 0.06 Pasteurella multocida 2000 to 2001 Treatment 20 ≤0.03 ≤0.03 ≤0.03No range; all isolates yielded the same value. 2009 Control 67 ≤0.004 ≤0.004 ≤0.004 Streptococcus suis 2000 to 2001 Treatment 30 0.06 0.12 ≤ 0.03 to 0.5 2009 Control 141 0.25 1 0.03 to >2

EXCEDE® For Swine (Ceftiofur Crystalline Free Acid) Sterile Suspension, 100 mg/mL

Ceftiofur is a beta-lactam antibiotic from the cephalosporin class. Beta lactams exert their inhibitory effect by interfering with bacterial cell wall synthesis. This interference is primarily due to its covalent binding to the penicillin-binding proteins, which are essential for synthesis of the bacterial wall. Ceftiofur administered as either ceftiofur sodium (NAXCEL® Sterile Powder) or ceftiofur crystalline free acid (EXCEDE Sterile Suspension) is rapidly metabolized to desfuroylceftiofur, the primary metabolite with antimicrobial activity. Two intramuscular injections of EXCEDE Sterile Suspension at a dose of 6.6 mg/kg body weight in the horse provide concentrations of ceftiofur and desfuroylceftiofur related metabolites in plasma above the therapeutic target of 0.2 µg/mL for the entire 96 hour (4 day) dosing interval and for 6 days after the second injection (or a total of 10 days from the beginning of treatment) (see Figure 2 and Table 3). Figure 2. Average plasma concentration of ceftiofur and desfuroylceftiofur related metabolites in horses following the intramuscular administration of either EXCEDE Sterile Suspension at a dose of 3.0 mg/lb (6.6 mg/kg) administered twice at a 96 hour interval or NAXCEL Sterile Powder at a dose of 1.0 mg/lb (2.2 mg/kg BW) once daily for 10 consecutive days. Table 3. Pharmacokinetic parameters measured after either two intramuscular injections of EXCEDE Sterile Suspension at a dose of 3.0 mg/lb (6.6 mg/kg) BW at a 96 hour interval or NAXCEL Sterile Powder at a dose of 1.0 mg/lb (2.2 mg/kg) BW once daily for 10 consecutive days are summarized in the following table. PK Parameter CCFA-SS at 6.6 mg/kg BW administered twice 96 h apart (Mean ± SD; n=12) Ceftiofur sodium at 2.2 mg/kg BW once daily for 10 days (Mean ± SD; n=11) AUC0-∞ (µg∙h/mL) 157 (19.1) 353 (44.9) t>0.2 (h) 262 (29.0) ND Dose 1 Dose 2 Dose 1 Dose 10 Tmax (h) 21.6 (5.8) 15.6 (6.3) 1.0 2.0 (3.3) Cmax (µg/mL) 0.78 (0.19) 1.0 (0.24) 4.31 ± 0.78 3.99 (1.23)

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

Ceftiofur administered as either ceftiofur sodium (NAXCEL® Sterile Powder), ceftiofur hydrochloride (EXCENEL® RTU Sterile Suspension), or ceftiofur crystalline free acid (EXCEDE Sterile Suspension) is metabolized rapidly to desfuroylceftiofur, the primary metabolite. Subcutaneous administration of ceftiofur crystalline free acid, either in the middle third of the posterior aspect of the ear (middle third of the ear, MOE) of beef and non-lactating dairy cattle, or in the posterior aspect of the ear where it attaches to the head (base of the ear, BOE) of beef, non-lactating dairy, and lactating dairy cattle, provides therapeutic concentrations of ceftiofur and desfuroylceftiofur-related metabolites in plasma above the lowest minimum inhibitory concentration to encompass 90% of the most susceptible isolates (MIC90) for the labeled BRD pathogens, Pasteurella multocida, Mannheimia haemolytica and Histophilus somni, for generally not less than 150 hours after a single administration (See Figure 8).

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

EXCEDE Sterile Suspension is contraindicated in horses with known allergy to ceftiofur or to ß-lactam (penicillins and cephalosporins) group antimicrobials. Due to the extended exposure in horses, based on the drug's pharmacokinetic properties, adverse reactions may require prolonged care.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

As with all drugs, the use of EXCEDE FOR SWINE Sterile Suspension 100 mg/mL is contraindicated in animals previously found to be hypersensitive to the drug.

EXCEDE® For Swine (Ceftiofur Crystalline Free Acid) Sterile Suspension, 100 mg/mL

As with all drugs, the use of SPECTRAMAST® LC Sterile Suspension is contraindicated in animals previously found to be hypersensitive to the drug.

SPECTRAMAST® LC

As with all drugs, the use of NAXCEL Sterile Powder is contraindicated in animals previously found to be hypersensitive to the drug.

Naxcel®

FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and clothing. Sensitization of the skin may be avoided by wearing protective gloves. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention. The material safety data sheet contains more detailed occupational safety information. To obtain a material safety data sheet or to report any adverse event please call 1-888-963-8471. Intra-arterial injection may occur during administration of EXCEDE Sterile Suspension via middle third of the ear injection or base of the ear injection directed towards the opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is likely to result in sudden death of the animal.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth, and clothing. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention. The safety data sheet contains more detailed occupational safety information. To report suspected adverse drug events, for technical assistance or to obtain a copy of the safety data sheet (SDS), contact Norbrook at 1-866-591-5777. 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.

Cefenil® RTU (ceftiofur hydrochloride sterile suspension)

Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and clothing. Sensitization of the skin may be avoided by wearing protective gloves. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention. The Safety Data Sheet contains more detailed occupational safety information. For a copy of the Safety Data Sheet or to report adverse reactions, call Zoetis Inc. at 1-888-963-8471. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or at www.fda.gov/reportanimalae.

SPECTRAMAST® LC

NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and clothing. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention. The safety data sheet contains more detailed occupational safety information. To obtain a safety data sheet (SDS) or to report any adverse event please call 1-888-963-8471. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/AnimalVeterinary/SafetyHealth.

EXCENEL® RTU EZ Ceftiofur Hydrochloride Sterile Suspension

FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and clothing. Sensitization of the skin may be avoided by wearing protective gloves. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention. The material safety data sheet contains more detailed occupational safety information. To report adverse effects in users, to obtain more information or to obtain a material safety data sheet, call 1-888-963-8471.

EXCEDE® For Swine (Ceftiofur Crystalline Free Acid) Sterile Suspension, 100 mg/mL

Human Safety Warnings Not for use in humans. For use in animals only. Keep this and all drugs out of reach of children. Consult a physician in case of accidental human exposure. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposure to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and clothing. Sensitization of the skin may be avoided by wearing protective gloves. Persons with a known sensitivity to penicillin or cephalosporins should avoid exposure to this product. In the case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g. skin rash, hives, difficult breathing) seek medical attention.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

NOT FOR HUMAN USE. KEEP OUT OF REACH OF CHILDREN. Penicillins and cephalosporins can cause allergic reactions in sensitized individuals. Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe allergic reactions in some individuals. Repeated or prolonged exposure may lead to sensitization. Avoid direct contact of the product with the skin, eyes, mouth, and clothing. Persons with a known hypersensitivity to penicillin or cephalosporins should avoid exposure to this product. In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental skin exposure, wash with soap and water. Remove contaminated clothing. If allergic reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention.

Naxcel®

Following label use as either a single-dose or 2-dose regimen, a 13-day pre-slaughter withdrawal period is required after the last treatment. Following label use as either a single-dose or 2-dose regimen, no milk discard period is required for this product. Use of dosages in excess of 3.0 mg CE/lb (6.6 mg CE/kg) BW or administration by unapproved routes (subcutaneous injection in the neck or intramuscular injection) may cause violative residues. A withdrawal period has not been established for this product in preruminating calves. Do not use in calves to be processed for veal.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

Milk taken from cows completing a 30-day dry cow period may be used for food with no milk discard due to ceftiofur residues. Following label use, no pre-slaughter withdrawal period is required for neonatal calves born from treated cows regardless of colostrum consumption. Following intramammary infusion, a 16-day pre-slaughter withdrawal period is required for treated cows. Use of this product in a manner other than indicated under DOSAGE might result in violative residues.

SPECTRAMAST® DC

A maximum of 2 mL of formulation should be injected at each injection site. Injection volumes in excess of 2 mL per injection site may result in violative residues. Following label use as a single treatment, a 14-day pre-slaughter withdrawal period is required. Use of dosages in excess of 5.0 mg ceftiofur equivalents (CE)/kg or administration by an unapproved route may result in illegal residues in edible tissues.

EXCEDE® For Swine (Ceftiofur Crystalline Free Acid) Sterile Suspension, 100 mg/mL

1. Milk taken from cows during treatment (a maximum of eight daily infusions) and for 72 hours after the last treatment must not be used for human consumption. 2. Following label use for up to eight consecutive days, a 2-day pre-slaughter withdrawal period is required. 3. Use of this product in a manner other than indicated under DOSAGE might result in violative residues.

SPECTRAMAST® LC

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal law prohibits extra-label use of this drug in cattle, swine, chickens and turkeys for disease prevention purposes; at unapproved doses, frequencies, durations, or routes of administration; and in unapproved major food producing species/production classes.

Naxcel®

Pre-Approval Experience: A total of 373 horses of various breeds, ranging in age from 4 months to 20 years, were included in the field study safety analysis. Adverse reactions reported in horses treated with EXCEDE and the placebo control are summarized in Table 2. Injection site swelling (edema) was reported in 10 of 278 (3.6%) EXCEDE-treated horses and 1 of 95 (1 %) of the placebo-treated horses. Of the 10 EXCEDE-treated horses with injection site swelling, 8 horses had swellings of 4 cm or less in diameter, one horse had a 10 cm diameter swelling and one horse had injection site reactions to both injections measuring 25 x 12 cm each. The injection site reactions in EXCEDE treated horses resolved over 1 to 20 days. At least one episode of diarrhea, loose, soft, or cowpie stools were observed in 25 of 278 (9%) of the EXCEDE-treated horses and 7 of 95 (7%) of the placebo-treated horses. The duration of episodes in EXCEDE-treated horses ranged from a single observation of loose stool to observations lasting 6 days. All cases were self-limiting and resolved with minimal (a single dose of loperamide) or no treatment. Table 2. Number of Horses with Adverse Reactions During the Field Study with EXCEDE. Adverse Reaction EXCEDE (n=278) Placebo (n=95) Diarrhea/Soft Stool 25 (9%) 7 (7%) Injection Site Swelling 10 (4%) 1 (1%) Post Approval Experience (2019): The following adverse events are based on post-approval adverse drug experience reporting for Excede. Not all adverse events are reported to 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 for horses are listed in decreasing order by system and decreasing order within system classes. Injection site reactions: swelling, pain, inflammation, infection, necrosis, muscle stiffness, fibrosis, injection site stiffness/ reluctance to move, hair change, lameness, granuloma. Systemic: fever, lethargy, edema at locations other than injection site, anorexia. Gastrointestinal: colic, diarrhea. Neurologic: ataxia, muscle tremor, seizure, loss of consciousness. Immune (Allergic reactions): anaphylaxis, urticaria, allergic edema (face, face and neck, lip, or limb edema). In some cases, death has been reported as an outcome of the adverse events listed above. Sudden death (within minutes), or the immediate onset of seizures or collapse, followed by death or euthanasia, have been reported. To report suspected adverse events, for technical assistance or to obtain a copy of the Safety Data Sheet (SDS) contact Zoetis, Inc. at (888) 963-8471. For additional information about adverse drug experience reporting for animal drugs, contact FDA at 1-888-FDA-VETS or online at http://www.fda.gov/reportanimalae.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

Intra-arterial injection may occur during administration of EXCEDE Sterile Suspension via middle third of the ear injection or base of the ear injection directed towards the opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is likely to result in sudden death of the animal. During the conduct of clinical studies, there was a low incidence of acute death (see ANIMAL SAFETY) confirmed to be the result of inadvertent intra-arterial injection. No other adverse systemic effects were noted for either the antibiotic or formulation during any of the clinical and target animal safety studies.

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

An injection site tolerance study demonstrated that EXCEDE FOR SWINE Sterile Suspension 100 mg/mL is well tolerated in pigs. Half of the injection sites at both 3 and 7 days post-injection were scored as "negative" for irritation and the other half were scored as "slight irritation". All gross observations and measurements of injection sites qualified the sites at 10 days post-injection as "negative" for irritation. No adverse effects were observed in multi-location field efficacy studies involving more than 1000 pigs.

EXCEDE® For Swine (Ceftiofur Crystalline Free Acid) Sterile Suspension, 100 mg/mL

The use of ceftiofur may result in some signs of immediate and transient local pain to the animal.

Naxcel®

Dairy cattle (At Dry Off)

Infuse 500 mg per affected quarter at the time of dry off.

Intramammary

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

Spectramast™ DC Sterile Suspension

Lactating Dairy Cattle

Infuse 125 mg per affected quarter. Repeat treatment in 24 hours. Once daily treatment may be repeated for up to 8 consecutive days.

Intramammary

Milk taken from cows during treatment (a maximum of eight daily infusions) and for 72 hours after the last treatment must not be used for human consumption. Following label use for up to eight consecutive days, a 2-day pre-slaughter withdrawal period is required. Federal law restricts this drug to use by or on the order of a licensed veterinarian. Federal Law prohibits extra-label use of this drug in lactating dairy cattle for disease prevention purposes; at unapproved doses; frequencies, durations, or routes of administration; and in unapproved major food producing species/production classes.

Spectramast® LC Sterile Suspension

Cattle (Beef, Non-Lactating Dairy, Lactating Dairy)

Administer by intramuscular or subcutaneous administration at the dosage of 0.5 to 1 mg CE/lb (1.1 to 2.2 mg CE/kg) BW (1 to 2 mL sterile suspension per 100 lb BW). Administer daily at 24 hour intervals for a total of three consecutive days. Additional treatments may be administered on Days 4 and 5 for animals which do not show a satisfactory response (not recovered) after the initial three treatments. Alternatively, for BRD only, administer intramuscularly or subcutaneously 1 mg CE/ lb (2.2 mg CE/kg) BW every other day on Days 1 and 3 (48 hour interval). Selection of dosage level (0.5 to 1 mg CE/lb) and regimen/duration (daily or every other day for BRD only) should be based on an assessment of the severity of disease, pathogen susceptibility and clinical response. Do not inject more than 15 mL per injection site.

Intramuscular, Subcutaneous

EXCENEL® RTU EZ

Cattle (Beef, Non-Lactating Dairy, Lactating Dairy)

Administer by intramuscular or subcutaneous administration 0.5 to 1 mg CE/lb (1.1 to 2.2 mg CE/kg) BW (1 to 2 mL sterile suspension per 100 lb BW). Administer daily at 24-hour intervals for a total of three consecutive days. Additional treatments may be administered on Days 4 and 5 for animals which do not show a satisfactory response (not recovered) after the initial three treatments.

Intramuscular, Subcutaneous

EXCENEL® RTU EZ

Cattle (Beef, Non-Lactating Dairy, Lactating Dairy)

Administer by intramuscular or subcutaneous administration at the dosage of 1 mg CE/lb (2.2 mg CE/kg) BW (2 mL sterile suspension per 100 lb BW). Administer at 24 hour intervals for five consecutive days. Do not inject more than 15 mL per injection site.

Intramuscular, Subcutaneous

EXCENEL® RTU EZ

Cattle (excluding veal calves)

1.1 to 2.2 mg/kg of body weight by intramuscular or subcutaneous injection, at 24-hour intervals for 3 to 5 consecutive days. For bovine respiratory disease, 2.2 mg/kg of body weight may be administered twice at a 48-hour interval. For acute metritis, administer 2.2 mg/kg of body weight daily for 5 consecutive days.

Subcutaneous, Intramuscular

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Treated cattle must not be slaughtered for 3 days following the last treatment. A withdrawal period has not been established in preruminating calves. Do not use in calves to be processed for veal. Federal law restricts this drug to use by or on the order of a licensed veterinarian.

Excenel Sterile Suspension

For bovine respiratory disease and acute bovine interdigital necrobacillosis: administer by intramuscular or subcutaneous administration at the dosage of 0.5 to 1.0 mg ceftiofur equivalents/lb (1.1 to 2.2 mg/kg) BW (1 to 2 mL sterile suspension per 100 lb BW). Administer daily at 24 h intervals for a total of three consecutive days. Additional treatments may be administered on Days 4 and 5 for animals which do not show a satisfactory response (not recovered) after the initial three treatments. In addition, for BRD only, administer intramuscularly or subcutaneously 1.0 mg ceftiofur equivalents/lb (2.2 mg/kg) BW every other day on Days 1 and 3 (48 h interval). Do not inject more than 15 mL per injection site. Selection of dosage level (0.5 to 1.0 mg/lb) and regimen/duration (daily or every other day for BRD only) should be based on an assessment of the severity of disease, pathogen susceptibility and clinical response. For acute post-partum metritis: administer by intramuscular or subcutaneous administration at the dosage of 1.0 mg ceftiofur equivalents/lb (2.2 mg/kg) BW (2 mL sterile suspension per 100 lb BW). Administer at 24 h intervals for five consecutive days. Do not inject more than 15 mL per injection site.

Injection

Cefenil® RTU

Administer by intramuscular or subcutaneous injection at the dosage of 0.5 to 1.0 mg ceftiofur per pound (1.1. to 2.2 mg/kg) of body weight (1-2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of three consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

0.5 to 1.0 mg per pound (1.1 to 2.2 mg/kg) of body weight (1-2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of 3 consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments

Subcutaneous, Intramuscular

Ceftiofur for Injection

0.5 to 1.0 mg/lb body weight by intramuscular or subcutaneous injection for 3 days. Additional treatments may be given on days 4 and 5 for animals which do not show satisfactory response.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

Administer intramuscularly at a dosage of 1.36 to 2.27 mg ceftiofur equivalents (CE)/lb (3 to 5 mg CE/kg) body weight (BW) (1 mL of sterile suspension per 22 to 37 lb BW). Treatment should be repeated at 24 hour intervals for a total of three consecutive days. Do not inject more than 15 mL per injection site.

Intramuscular, Subcutaneous

EXCENEL® RTU EZ

Administer by intramuscular injection at the dosage of 1.36 to 2.27 mg ceftiofur per pound (3.0 to 5.0 mg/kg) of body weight (1 mL of reconstituted sterile solution per 22 to 37 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of three consecutive days.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

Administer intramuscularly at a dosage of 1.36 to 2.27 mg ceftiofur equivalents/lb (3.0 to 5.0 mg/kg) BW (1 mL of sterile suspension per 22 to 37 lb BW). Treatment should be repeated at 24 h intervals for a total of three consecutive days.

Injection

Cefenil® RTU

1.36 to 2.27 mg per pound (3.0 to 5.0 mg/kg) of body weight (1 mL of reconstituted sterile solution per 22 to 37 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of 3 consecutive days.

Subcutaneous, Intramuscular

Ceftiofur for Injection

3 to 5 milligrams per kilogram of body weight by intramuscular injection. Treatment should be repeated at 24-hour intervals for a total of 3 consecutive days.

Subcutaneous, Intramuscular

Federal law restricts this drug to use by or on the order of a licensed veterinarian. Treated swine must not be slaughtered for 4 days following the last treatment.

Excenel Sterile Suspension

3 to 5 mg per kilogram (/kg) body weight by intramuscular injection for 3 consecutive days.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

Day-Old Chicks

Administer by subcutaneous injection in the neck region of day-old chicks at the dosage of 0.08 to 0.20 mg ceftiofur/chick.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

Day-Old Chicks

0.08 to 0.20 mg/chick. One mL of the 50 mg/mL reconstituted solution will treat approximately 250 to 625 day-old chicks.

Subcutaneous, Intramuscular

Ceftiofur for Injection

Chickens (Day Old Chicks)

0.08 to 0.20 mg as a single subcutaneous injection in the neck.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

Day-Old Turkey Poults

0.17 to 0.5 mg/poult. 1 ml of the 50 mg/mL reconstituted solution will treat approximately 100 to 294 day-old turkey poults.

Subcutaneous, Intramuscular

Ceftiofur for Injection

Day-Old Turkey Poults

Administer by subcutaneous injection in the neck region of day-old chicks at the dosage of 0.17 to 0.5 mg ceftiofur/poult.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

Turkeys (Day Old Poults)

0.17 to 0.5 mg as a single subcutaneous injection in the neck.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

Administer by intramuscular injection at the dosage of 0.5 to 1.0 mg ceftiofur per pound (1.1 to 2.2 mg/kg) of body weight (1-2 mL of reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of tree consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

0.5 to 1.0 mg per pound (1.1 to 2.2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of 3 consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments.

Subcutaneous, Intramuscular

Ceftiofur for Injection

0.5 to 1.0 mg/lb body weight by intramuscular injection for 3 days. Additional treatments may be given on days 4 and 5 for animals which do not show satisfactory response.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

Administer to dogs by subcutaneous injection at the dosage of 1.0 mg ceftiofur per pound (2.2 mg/kg) of body weight (0.1 mL reconstituted sterile solution per 5 lbs body weight). Treatment should be repeated at 24-hour intervals for 5-14 days.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

1.0 mg/lb (2.2 mg/kg) body weight by subcutaneous injection. Treatment should be repeated at 24-hour intervals, continued for 48 hours after clinical signs have disappeared, for 5 to 14 days.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

1.0 mg per pound 2.2 mg/kg) of body weight (0.1 mL reconstituted sterile solution per 5 lbs body weight). Treatment should be repeated at 24 hour intervals for 5-14 days.

Subcutaneous, Intramuscular

Ceftiofur for Injection

Administer by intramuscular injection at the dosage of 0.5 to 1.0 mg ceftiofur per pound (1.1. to 2.2 mg/kg) of body weight (1-2 mL reconstituted sterile solution per 100 lbs body weight). Treatment should be repeated at 24-hour intervals for a total of three consecutive days. Additional treatments may be given on days four and five for animals which do not show a satisfactory response (not recovered) after the initial three treatments.

Subcutaneous, Intramuscular

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

Ceftiofur Sodium Sterile Powder

0.5 to 1.0 mg/lb body weight by intramuscular injection for 3 days. Additional treatments may be given on days 4 and 5 for animals which do not show satisfactory response.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

Administer by intramuscular injection at the dosage of 1.0 to 2.0 mg ceftiofur per pound (2.2 to 4.4 mg/kg) of body weight (2-4 mL reconstituted sterile solution per 100 lbs body weight). A maximum of 10 mL may be administered per injection site. Treatment should be repeated at 24-hour intervals, continued for 48 hours after clinical signs have disappeared and should not exceed 10 days.

Subcutaneous, Intramuscular

Do not use in horses intended for human consumption. Limitations: Federal (USA) law restricts this drug to use by or on the order of a licensed veterinarian.

Ceftiofur Sodium Sterile Powder

2.2 to 4.4 mg/kg (1.0 to 2.0 mg/lb) body weight by intramuscular injection. Treatment should be repeated every 24 hours, continued for 48 hours after clinical signs have disappeared, and should not exceed 10 days. A maximum of 10 mL should be administered per injection site.

Intramuscular, Subcutaneous

Naxcel® Sterile Powder

In lactating dairy cattle the injection techniques for subcutaneous (SC) injection in the posterior aspect of the ear where it attaches to the head (base of the ear) can be made by the rostral or ventral injection techniques. In beef and non-lactating dairy cattle the SC injection in the base of the ear can be made by the rostral, ventral or toward the opposite eye injection techniques. Shake well before using. Please read the complete package insert before administering EXCEDE Sterile Suspension subcutaneously in the posterior aspect of the ear where it attaches to the head (base of the ear). The subcutaneous (SC) injection may be made using the toward the opposite eye, rostral, or ventral techniques. Hold the syringe and needle and insert the needle as described below. Deliver the entire contents of the syringe. Do not administer EXCEDE Sterile Suspension in the neck.

INTRAMUSCULAR, SUBCUTANEOUS

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

Shake well before using. Administer two intramuscular injections to horses, 4 days apart, at a dose of 3.0 mg/lb (6.6 mg/kg). A maximum of 20 mL per injection site may be administered. Therapeutic drug concentrations are maintained for 6 days after the second injection (or a total of 10 days from the beginning of treatment) against Streptococcus equi ssp. zooepidemicus. Table 1. Dosing Schedule for EXCEDE Sterile Suspension. Weight (lb) Dose Volume (mL) Weight (lb) Dose Volume (mL) 100 1.5 1100 16.5 200 3.0 1200 18.0 300 4.5 1300 19.5 400 6.0 1400 21.0 500 7.5 1500 22.5 600 9.0 1600 24.0 700 10.5 1700 25.5 800 12.0 1800 27.0 900 13.5 1900 28.5 1000 15.0 2000 30.0

INTRAMUSCULAR, SUBCUTANEOUS

EXCEDE® (Ceftiofur Crystalline Free Acid)Sterile Suspension

DOSAGE Infuse one (1) syringe into each affected quarter. Repeat this treatment in 24 hours. For extended duration therapy, once daily treatment may be repeated for up to 8 consecutive days.

INTRAMAMMARY

SPECTRAMAST® LC

Infuse one (1) syringe into each affected quarter at the time of dry off.

INTRAMAMMARY

SPECTRAMAST® DC

Shake for 90 seconds to ensure complete resuspension before using.

INTRAMUSCULAR, SUBCUTANEOUS

Cefenil® RTU (ceftiofur hydrochloride sterile suspension)

Shake well before using.

INTRAMUSCULAR, SUBCUTANEOUS

EXCENEL® RTU EZ Ceftiofur Hydrochloride Sterile Suspension