Excede Sterile: Product Information (Page 3 of 8)

ANTIBACTERIAL WARNINGS

Use of antibacterial drugs in the absence of a susceptible bacterial infection is unlikely to provide benefit to treated animals and may increase the risk of the development of drug-resistant bacteria.

PRECAUTIONS

Following subcutaneous injection in the middle third of the posterior aspect of the ear, thickening and swelling (characterized by aseptic cellular infiltrate) of the ear may occur. As with other parenteral injections, localized post-injection bacterial infections may result in abscess formation. Attention to hygienic procedures can minimize their occurrence.
Following injection in the posterior aspect of the ear where it attaches to the head (base of the ear), areas of discoloration and signs of inflammation may persist at least 13 days post administration resulting in trim loss of edible tissue at slaughter. Injection of volumes greater than 20 mL, in the middle third of the ear, may result in open draining lesions in a small percentage of cattle.
The effects of ceftiofur on bovine reproductive performance, pregnancy, and lactation have not been determined.

ADVERSE EFFECTS

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.

CLINICAL PHARMACOLOGY

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).

Single Dose Regimen

The pharmacokinetic parameters for the two subcutaneous locations of injection (MOE and BOE) are found in Table 2. Statistical analyses of the data from these two subcutaneous injection sites (MOE and BOE) demonstrate that they are therapeutically equivalent.

Figure 8. Average (n=12/group) plasma concentrations of ceftiofur and desfuroylceftiofur-related metabolites after administration of EXCEDE Sterile Suspension at 3.0 mg CE/lb (6.6 mg CE/kg) BW via subcutaneous injection into one of two different locations of the ear, middle third of the ear (MOE Cattle) and base of the ear (BOE Cattle) in beef cattle as well into the base of the ear (BOE Lactating) in lactating dairy cattle.

Figure 8
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Table 2. Average (n = 12/group) pharmacokinetic parameters for ceftiofur and desfuroylceftiofur metabolites calculated after a single subcutaneous administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW of EXCEDE Sterile Suspension in either the middle third of the ear or the base of the ear.
Pharmacokinetic Parameter Beef — Middle Third of the Ear Mean Value ± Standard Deviation Beef — Base of the Ear Mean Value ± Standard Deviation Dairy Cow — Base of the Ear Mean Value ± Standard Deviation
Cmax (µg CE/mL) = maximum plasma concentration (in µg CE/mL).tmax (h) = the time after injection when Cmax occurs (in hours).AUC 0-LOQ (µg∙h/mL) = 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).t>0.2, model (h) = the time plasma concentrations remain above 0.2 µg CE/mL (in hours), estimated using compartmental pharmacokinetic techniques.t>0.2, nca (h) = the time plasma concentrations remain above 0.2 µg CE/mL (in hours), estimated using noncompartmental pharmacokinetic techniques.t1/2 (h) = terminal phase biological half life (in hours)NE = Not estimated
Cmax (µg CE/mL) 6.90 ± 2.68 6.39 ± 1.79 4.44 ± 1.65
tmax (h) 12.0 ± 6.2 19.8 ± 5.81 19.00 ± 8.02
AUC 0-LOQ (µg∙h/mL) 376 ± 66.1 412 ± 67.3 313 ± 85.5
t>0.2, model (h) 183 ± 40.8 NE NE
t>0.2, nca (h) 246 ± 48.5 218 ± 45.5 205 ± 35.7
t1/2 (h) 62.3 ± 13.5 40.7 ± 11.2 43.92 ± 9.84

Two-Dose Regimen

A two-dose regimen of 6.6 mg CE/kg BW administered 72 hours apart is required for the treatment of acute metritis in lactating cows. The mean plasma concentration vs. time profile for ceftiofur and desfuroylceftiofur-related metabolites for the 2-dose regimen in 12 cows is shown in Figure 9 below. The pharmacokinetic parameters for the 2-dose regimen are provided in Table 3.

Figure 9. LS-Mean DCA Plasma Concentration Time Profile Following Two Subcutaneous Injections of EXCEDE 72 hours apart at a Dose of 3.0 mg CE/lb (6.6 mg CE/kg) BW in 12 lactating cows.

Figure 9
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Table 3. Average (n = 12) Pharmacokinetic Parameters Following Two Subcutaneous Injections of EXCEDE Sterile Suspension at a Dose 3.0 mg CE/lb (6.6 mg CE/kg) BW at a 72 Hour Interval.
PK Parameter Mean ± Standard Deviation
AUC0-LOQ (µg∙h/mL) 651 ± 119
t½ (h) 55.7 ± 4.84
t>0.2 (h) 341 ± 34.0
Tmax (h) 77.1 ± 33.4
Cmax (µg/mL) 5.98 ± 2.51

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