additional techniques for sc injection of excede in beef ... · summary additional techniques for...
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Summary
Additional Techniques for SC Injectionof EXCEDE® in Beef and Dairy Cattle
February 2012
• Two additional techniques were recently approved for SC injection of EXCEDE® Sterile
Suspension at the base of the ear (BOE) of cattle.
# EXCEDE can now be administered SC at the BOE in a rostral direction, toward the
eye on the same side of the head as the ear.
# EXCEDE can also now be administered SC at the BOE in a ventral direction.
• Both additional EXCEDE administration techniques are approved for use in all classes
of cattle.
• Both additional BOE injection techniques are approved for use in lactating dairy cows
and are preferred in these animals relative to the previously approved ‘opposite-eye’
method.
• Research has demonstrated that the rostral and ventral BOE injection techniques are
safe, well-tolerated, and readily accomplished using normal equipment and restraint.
• The rostral and ventral BOE techniques provide injection outcomes similar to those
observed using the previously approved opposite-eye technique.
Pfizer Animal HealthPfizer Inc. Madison, NJ 07940
EXD12002
Two additional
EXCEDE ® injection
techniques provide
more options for
treating beef and
lactating dairy
cattle.XCEDE® Sterile Suspension (ceftiofur
crystalline free acid) is the potent single-
dose treatment for bovine respiratory disease
and foot rot that provides the demonstrated
efficacy of ceftiofur in a convenient extended-
therapy formulation. EXCEDE is intended for
subcutaneous (SC) administration at a dose of 3
mg ceftiofur equivalents (CE) per lb body
weight (BW) (or 1.5 mL EXCEDE/100 lb BW).
An indication for acute post-partum metritis
was recently approved for lactating dairy cows
when a 2-dose regimen of EXCEDE is adminis-
tered 3 days apart.
Previously, EXCEDE was approved for SC
injection of cattle (including lactating dairy
cows) in the posterior aspect of the ear where it
attaches to the head (base of the ear, or
‘BOE’), angled toward the opposite eye. In
addition, EXCEDE could be administered in the
middle third of the posterior aspect of the ear in
beef and non-lactating dairy cattle (not in
lactating dairy cows).
E
2
Research by Pfizer scientists has resulted in
recent FDA approval of two additional BOE
injection techniques for EXCEDE, and more
specific BOE use instructions for lactating
dairy cows. The two additional BOE techniques
are:
• Rostral direction (toward the eye on the
same side of the head);
• Ventral direction (pointing ventrally toward
the base of the ear).
These two additional BOE techniques are
potentially safer and are the preferred methods
for using EXCEDE in lactating dairy cows
relative to the previously approved opposite-
eye technique. The rostral technique (toward
the same eye) is particularly useful for many
dairy cattle operations. However, because head
catches are almost always used for restraint of
beef cattle, the rostral method can be problem-
atic when animals pull backwards against the
vertical bars of the head catch. Thus, the
ventrally directed technique offers a dosing
method espe cially useful for treatment of beef
animals.
Figure 1 summarizes the SC injection options
for use of EXCEDE, depending on the class and
status of cattle being treated. In lactating dairy
cattle, SC injection at the BOE can be made
using the preferred rostral (Figures 2 and 3) or
ventral (Figure 4) injection techniques. For beef
and non-lactating dairy cattle, SC injection can
accomplished using the rostral, ventral, or
opposite-eye (Figure 5) BOE techniques in
addition to the middle-third of the ear option
(Figure 6).
The rostral and ventralinjection techniqueshave been approvedfor lactating dairy cattle as well as beefand non-lactating dairyanimals.
Figure 2 – BOE injections. Injection location for SC administration ofEXCEDE in the posterior aspect of the ear where it attaches tothe head (BOE).
Figure 1 – SC injection technique options foradministration of EXCEDE.
�
�
�
�
B
B
B
M
OE: Rostral
OE: Ventral
OE: Opposite eye
iddle-third of ear
Class of cattle:
�
�
�
BOE: Rostral
BOE: Ventral
BOE: Opposite eye
*
*
Dairy Beef
Non-LactatingLactating
*Preferred technique
Dairy Beef
Non-LactatingLactating
Previously approvedinjection techniques(middle-third of the earor BOE toward theopposite eye) offerother options for beef and non-la ctatingdairy cattle.
3
Figure 3 – Rostral technique (additional). Direction for SC injection ofEXCEDE administered rostrally toward the eye on the same sideof the head into the loose skin in the caudal aspect of the BOE.
Directions:
• Hold the syringe and needle behind the ear to be dosed so the needle and syringe point in the direction of an imaginary line thatwould pass through the head toward the eye on the same side ofthe head (Figures 2 and 3).
• Insert the needle through the loose skin in the posterior aspect ofthe ear where it attaches to the head (BOE) while maintaining theneedle position (Figure 3).
BOE – rostral (toward the same eye) technique
4
Figure 4 – Ventral technique (additional). Location and direction for SCinjection of EXCEDE administered ventrally into the loose skin inthe caudal aspect of the BOE.
Directions:
• Hold the syringe and needle above the ear to be dosed so that the needle and syringe are pointing ventrally toward the base of theear. The needle will be inserted into the loose skin in the posterioraspect of the ear where it attaches to the head (BOE) while pointing ventrally. Care should be taken to not insert the needlethrough the cartilage of the ear (Figure 4).
• Insert the needle through the loose skin in the posterior aspect ofthe ear where it attaches to the head (BOE) while maintaining needle position (Figure 4).
BOE – ventral technique
5
Figure 5 – Toward the opposite eye technique. SC injection of EXCEDE inthe posterior aspect of the ear where it attaches to the head(BOE) (previously approved technique).
Directions:
• Hold the syringe and needle behind the ear to be dosed so the needle and syringe point in the direction of an imaginary line thatwould pass through the head toward the animal’s opposite eye(Figures 2 and 5).
• Insert the needle through the loose skin in the posterior aspect ofthe ear where it attaches to the head (BOE) while maintaining thisangle (Figure 5).
BOE – toward the opposite eye technique
6
Figure 6 – Middle-third of the ear technique. SC injection of EXCEDE in themiddle third of the posterior aspect of the ear (previouslyapproved technique).
Directions:
• Deposit as a single SC injection in the middle third of the posterioraspect of the ear, avoiding all blood vessels (Figure 6).
• Adjust the needle insertion point to avoid any blood vessels, previous implants, ear tags, or ear-tag holes. Do not administerintra-arterially.
• When administered correctly, a subcutaneous bleb of EXCEDE willappear.
• When withdrawing the needle, apply pressure to the needle insertion point, and massage toward the base of the ear.
Middle-third of the ear technique
7
This study demonstrated that BOE administra-
tion of EXCEDE using the additional rostral or
ventral SC injection techniques was safe, well-
tolerated, and readily accomplished in lactating
dairy cows using normal equipment and
restraint. Injection outcomes were similar to
those observed using the previously approved
‘opposite-eye’ technique.
Feedlot heifersA similar field study involving 199 feedlot
heifers (750 lb BW) evaluated injection
procedures and site reactions for BOE injec-
tions of EXCEDE performed using the ventral
technique.2 Healthy cattle were enrolled in the
study at a commercial feedlot and treated with
EXCEDE at the approved dose of 3 mg CE/lb
BW. Ventrally directed BOE injections were
administered by 2 different people using 5/8-
or 1-inch needle lengths. At administration,
animals were scored for restraint, injection
procedure, and post-injection problems. Cattle
were observed for injection site reactions on
days 14 and 28 post-injection.
Study results show that few problems were
observed relative to restraint, re-injection,
leak-back, or excessive bleeding (Table 2). By
day 28, 92.5% of injection sites were scored as
normal using the ventral technique. Needle
length did not affect injection procedures or site
reactions.
This study demonstrated that BOE administra-
tion of EXCEDE using the ventrally directed
SC injection technique was safe, well-tolerated,
and readily accomplished in feedlot cattle using
normal equipment and restraint.
Injection Technique Field StudiesTwo field studies were conducted to gain expe-
rience on the practicality and acceptability of
the additional rostral and ventral BOE injection
techniques in dairy and beef cattle.
Lactating dairy cowsA field study involving 197 lactating dairy
cows compared injection procedures and site
reactions for BOE injections of EXCEDE
directed toward the opposite eye with those
directed either rostrally or ventrally.1 Healthy
lactating cows were enrolled in the study across
2 commercial dairy sites. The rostral and oppo-
site-eye techniques were compared at one site
(4 different treatment administrators, consistent
needle length), while the rostral and ventral
routes were used at the other site (2 different
treatment administrators, 5/8- or 1-inch needle
lengths). All cows received a single SC injec-
tion of EXCEDE at the approved dose of 3 mg
CE/lb BW. At administration, animals were
scored for restraint, injection procedure, and
post-injection problems. Cows were observed
for injection site reactions on days 14 and 28
post-injection.
Results summarized in Table 1 indicate that no
relevant differences were observed in restraint,
re-injection, leak-back, or excessive bleeding
between the 3 techniques. By day 28, 73% of
injection sites were scored as normal using the
rostral technique, compared to 87.8% using the
ventral technique and 64.6% using the oppo-
site-eye technique. Needle length did not affect
injection procedures or site reactions.
Parameter Rostral Ventral Opposite
Number of cows 100 49 48
No added restraint (%) 98.0 89.8 100.0
No re-injection (%) 97.0 87.8 100.0
No leak back (%) 99.0 100.0 100.0
No excessive bleeding (%) 99.0 100.0 100.0
Day 14 normal sites (%) 32.0 46.9 47.9
Day 28 normal sites (%) 73.0 87.8 64.6
Parameter Ventral
Number of heifers 199
No added restraint (%) 95.5
No re-injection (%) 93.5
No leak back (%) 99.0
No excessive bleeding (%) 100.0
Day 14 normal sites (%) 65.3
Day 28 normal sites (%) 92.5
Table 1 – Injection parameters and site outcomes in lactating dairy cows after BOE injection ofEXCEDE using rostral, ventral, or opposite-eyeSC techniques.
Table 2 – Injection parameters andsite outcomes in beefheifers after ventrallydirected BOE injection.
No relevant differences were
observed betweenBOE techniques
(restraint, re-injection,leak-back, bleeding,
site reactions).
Important Safety Information: As with all
drugs, the use of EXCEDE Sterile Suspension is
contraindicated in animals previously found to
be hypersensitive to the drug. Though safe in
cattle when properly administered, inadvertent
intra-arterial injection in the ear is possible and
is fatal. EXCEDE has a pre-slaughter with -
drawal period of 13 days.
ConclusionsEXCEDE can be administered SC at the BOE
of cattle by two additional options, directed
rostrally toward the eye on the same side of the
head, or directed ventrally. Both BOE injection
techniques are approved for use in lactating
dairy cows and are preferred in these animals
relative to the previously approved opposite-
eye method. For beef cattle and non-lactating
dairy animals, the additional rostral and ventral
BOE injection techniques join the previously
approved SC methods (middle-third of the ear
or BOE toward the opposite eye) as options for
administering EXCEDE.
8
9
(Ceftiofur Crystalline Free Acid)Sterile Suspension
ft
CAUTIONdairy cattle. Not for use in calves to be processed for veal.the ear where it attaches to the head (base of the ear) in beef and non-lactating
the posterior middle third of in the to the head (base of the ear) in lactating dairy cattle. For subcutaneous injectionFor subcutaneous injection in the posterior aspect of the ear where it attaches
Federal (USA) law restricts this drug to use by or on the order of a licensed
Sterile Suspensionystalline Freetiofur CrryCef((C
dairy cattle. Not for use in calves to be processed for veal.the ear where it attaches to the head (base of the ear) in beef and non-lactating
posterior aspect ofor in the aspect of the ear to the head (base of the ear) in lactating dairy cattle. For subcutaneous injection
posterior aspect of the ear where it at
Federal (USA) law restricts this drug to use by or on the order of a licensed
Sterile Suspension)idd)e Acci
massage toward the base of the ear.
the ear where it attaches to the head (base of the ear) in beef and non-lactatingposterior aspect of
to the head (base of the ear) in lactating dairy cattle. For subcutaneous injectionttaches
Federal (USA) law restricts this drug to use by or on the order of a licensed
middle third of the posterior aspect of the ear.Figure 2. Subcutaneous administration of EXCEDE Sterile Suspension in the
massage toward the base of the ear.
middle third of the posterior aspect of the ear.Figure 2. Subcutaneous administration of EXCEDE Sterile Suspension in the
Figure 2. Subcutaneous administration of EXCEDE Sterile Suspension in the skin in the caudal aspect of the base of the ear.administered rostrally toward the eye on the same side of the head into the looseFigure 6. Diagram of head showing the direction for the base of ear injections
skin in the caudal aspect of the base of the ear.administered rostrally toward the eye on the same side of the head into the looseFigure 6. Diagram of head showing the direction for the base of ear injections
skin in the caudal aspect of the base of the ear.administered rostrally toward the eye on the same side of the head into the looseFigure 6. Diagram of head showing the direction for the base of ear injections
administered rostrally toward the eye on the same side of the head into the loose
Figure 6. Diagram of head showing the direction for the base of ear injections
DESCRIPTIONveterinarian.
against Gram-
broad a is which ceftiofur, of acid free
EXCEDE Sterile Suspension is a ready-to-use formulation that contains the crystalline
strains. Like other
positive and Gram-negative bacteria including ß-lactamase-producing
inhibition of cell wall synthesis.
cephalosporins, ceftiofur is bactericidal,
Figure 1. Structure of ceftiofur crystalline free acid:cottonseed oil based suspension.
acid equivalent to 200 mg ceftiofur, in a caprylic/capric triglyceride (Miglyo
Each mL of this ready-to-use sterile suspension contains ceftiofur crystalline free
Federal (USA) law restricts this drug to use by or on the order of a licensed
antibiotic cephalosporin spectrum broad
EXCEDE Sterile Suspension is a ready-to-use formulation that contains the crystalline
positive and Gram-negative bacteria including ß-lactamase-producing
, resulting fromin vitrocephalosporins, ceftiofur is bactericidal,
Figure 1. Structure of ceftiofur crystalline free acid:
acid equivalent to 200 mg ceftiofur, in a caprylic/capric triglyceride (Miglyo
Each mL of this ready-to-use sterile suspension contains ceftiofur crystalline free
activeantibiotic
EXCEDE Sterile Suspension is a ready-to-use formulation that contains the crystalline
positive and Gram-negative bacteria including ß-lactamase-producing
, resulting from
and)®lacid equivalent to 200 mg ceftiofur, in a caprylic/capric triglyceride (Miglyo
Each mL of this ready-to-use sterile suspension contains ceftiofur crystalline free
of EXCEDE Sterile Suspension into ear arteries is likely to be fatal.posterior ear and the recommended needle insertion locations. AdministrationFigure 3. Diagram of the approximate locations of the major arteries of the
of EXCEDE Sterile Suspension into ear arteries is likely to be fatal.posterior ear and the recommended needle insertion locations. AdministrationFigure 3. Diagram of the approximate locations of the major arteries of the
of EXCEDE Sterile Suspension into ear arteries is likely to be fatal.posterior ear and the recommended needle insertion locations. AdministrationFigure 3. Diagram of the approximate locations of the major arteries of the
Administration for Base of the Ear: Ventral Technique
inserted into the loose skin in the posterior aspect of the ear where it attaches to
syringe are pointing ventrally toward the base of the ear. The needle will be
Administration for Base of the Ear: Ventral Technique
inserted into the loose skin in the posterior aspect of the ear where it attaches to
syringe are pointing ventrally toward the base of the ear. The needle will be
Administration for Base of the Ear: Ventral Technique
inserted into the loose skin in the posterior aspect of the ear where it attaches to
syringe are pointing ventrally toward the base of the ear. The needle will be
inserted into the loose skin in the posterior aspect of the ear where it attaches to
syringe are pointing ventrally toward the base of the ear. The needle will be
INDICATIONS
thio] methyl]-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene 2-carboxylic acid
7-[[2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetyl]amino]- 3-[[(2-furanylcarbonyl)
Chemical name of ceftiofur crystalline free acid:
cattle.
in Histophilus somniand multocida,(BRD, shipping fever, pneumonia) associated with
EXCEDE Sterile Suspension is indicated for treatment of bovine respiratory disease
thio] methyl]-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-ene 2-carboxylic acid
7-[[2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetyl]amino]- 3-[[(2-furanylcarbonyl)
Chemical name of ceftiofur crystalline free acid:
lactating and dairy, beef, non-lactating
Pasteurella, haemolyticaMannheimia(BRD, shipping fever, pneumonia) associated with
EXCEDE Sterile Suspension is indicated for treatment of bovine respiratory disease
7-[[2-(2-Amino-4-thiazolyl)-2-(methoxyimino)acetyl]amino]- 3-[[(2-furanylcarbonyl)
dairylactating
PasteurellaEXCEDE Sterile Suspension is indicated for treatment of bovine respiratory disease
base of the ear.when Figure 7. Diagram of head showing the direction of base of ear injections
insert the needle through the cartilage of the ear. See Figure 7.
the
attaches to the head (base of the ear) while maintaining needle position. See Figure
base of the ear.loose ventrally into the administered when
Figure 7. Diagram of head showing the direction of base of ear injections
insert the needle through the cartilage of the ear. See Figure 7.
pointing while ear) the of (base head the
attaches to the head (base of the ear) while maintaining needle position. See Figure
theaspect of caudal the skin in loose Figure 7. Diagram of head showing the direction of base of ear injections
insert the needle through the cartilage of the ear. See Figure 7.
notto taken be should Care ventrally. pointing
7.attaches to the head (base of the ear) while maintaining needle position. See Figure
not
7.
cattle.
and P. multocida,, haemolyticaM.with
beef and non-lactating dairy cattle which are at high risk of developing BRD associated
EXCEDE Sterile Suspension is also indicated for the control of respiratory disease in
in beef, non-lactating dairy, and lactating dairy cattle.Porphyromonas leviirot (interdigital necrobacillosis) associated with
also is Suspension Sterile EXCEDE
Treatment of BRD and bovine foot rot
DOSAGE
dairy cattle.
post-partum) associated with bacterial organisms susceptible to ceftiofur in lactating
EXCEDE Sterile Suspension is also indicated for treatment of acute metritis (0-10
where it
Administer as a single subcutaneous injection in the posterior aspect of the ear
100 lb BW).
equivalents (CE)/lb (6.6 mg CE/kg) body weight (BW)
of the ear) to cattle at a dosage of 3.0 mg ceftiofurattaches to the head (base
.H. somnibeef and non-lactating dairy cattle which are at high risk of developing BRD associated
EXCEDE Sterile Suspension is also indicated for the control of respiratory disease in
in beef, non-lactating dairy, and lactating dairy cattle.
Fusobacterium necrophorumrot (interdigital necrobacillosis) associated with
bovine of treatment the for indicated also
Treatment of BRD and bovine foot rot
post-partum) associated with bacterial organisms susceptible to ceftiofur in lactating
EXCEDE Sterile Suspension is also indicated for treatment of acute metritis (0-10
Administer as a single subcutaneous injection in the posterior aspect of the ear
(1.5 mL sterile suspension perequivalents (CE)/lb (6.6 mg CE/kg) body weight (BW)
of the ear) to cattle at a dosage of 3.0 mg ceftiofur
beef and non-lactating dairy cattle which are at high risk of developing BRD associated
EXCEDE Sterile Suspension is also indicated for the control of respiratory disease in
andFusobacterium necrophorumfootbovine
post-partum) associated with bacterial organisms susceptible to ceftiofur in lactating
daysEXCEDE Sterile Suspension is also indicated for treatment of acute metritis (0-10
Administer as a single subcutaneous injection in the posterior aspect of the ear
(1.5 mL sterile suspension per
of the ear) to cattle at a dosage of 3.0 mg ceftiofur
ADMINISTRATION FOR BASE OF THE EAR
be made by the rostral or ventral injection techniques.
in the posterior aspect of the ear where it attaches to the head (base of the ear) can
In lactating dairy cattle the injection techniques for subcutaneous (SC) injection
made by the rostral, ventral or toward the opposite eye injection techniques.
In beef and non-lactating dairy cattle the SC injection in the base of the ear can be
of the ear where it attaches to the head (base of the ear).
EXCEDE administering
well before using.Shake
ADMINISTRATION FOR BASE OF THE EAR
be made by the rostral or ventral injection techniques.
in the posterior aspect of the ear where it attaches to the head (base of the ear) can
In lactating dairy cattle the injection techniques for subcutaneous (SC) injection
made by the rostral, ventral or toward the opposite eye injection techniques.
In beef and non-lactating dairy cattle the SC injection in the base of the ear can be
of the ear where it attaches to the head (base of the ear).
subcutaneously Suspension Sterile EXCEDE
complete the read Please well before using.
in the posterior aspect of the ear where it attaches to the head (base of the ear) can
In lactating dairy cattle the injection techniques for subcutaneous (SC) injection
made by the rostral, ventral or toward the opposite eye injection techniques.
In beef and non-lactating dairy cattle the SC injection in the base of the ear can be
aspectposterior the in
beforeinsert package
CONTRAINDICATIONS
pre
As with all drugs, the use of EXCEDE Sterile Suspension is contraindicated in animals
WARNINGS
viously found to be hypersensitive to the drug.
CONTRAINDICATIONSAs with all drugs, the use of EXCEDE Sterile Suspension is contraindicated in animals
WARNINGS
viously found to be hypersensitive to the drug.
As with all drugs, the use of EXCEDE Sterile Suspension is contraindicated in animals
viously found to be hypersensitive to the drug.
As with all drugs, the use of EXCEDE Sterile Suspension is contraindicated in animals
100 lb BW).
In beef and non-lactating dairy cattle, EXCEDE
adminis
per 100 lb BW).
mg CE/lb (6.6 mg CE/kg) BW3.0 at a dosage of aspect of the ear
subcutaneous single a as tered
Control of BRD
is observed, the diagnosis should be reevaluated.
Most animals will respond to treatment within three to five days. If no improvement
(1.5 mL sterile suspension per 100 lb BW).(6.6 mg CE/kg) BW
(base of the ear) to beef and non-lactating dairy cattle at a dosage of
aspect of the ear or in the posterior aspect of the ear where it attaches to the head
Administer as a subcutaneous injection either in the middle third of the posterior
at “high risk” of devel
effective for the control of respiratory disease in beef and non-lactating dairy cattle
Clinical studies indicate that administration of EXCEDE Sterile Suspension is
oping BRD. One or more of the following factors typically
In beef and non-lactating dairy cattle, EXCEDE Sterile Suspension may also be
(1.5 mL sterile suspensionmg CE/lb (6.6 mg CE/kg) BW
posteriorthe of third middle the in injection subcutaneous
is observed, the diagnosis should be reevaluated.
Most animals will respond to treatment within three to five days. If no improvement
(1.5 mL sterile suspension per 100 lb BW).
3.0 mg CE/lb(base of the ear) to beef and non-lactating dairy cattle at a dosage of
aspect of the ear or in the posterior aspect of the ear where it attaches to the head
Administer as a subcutaneous injection either in the middle third of the posterior
effective for the control of respiratory disease in beef and non-lactating dairy cattle
Clinical studies indicate that administration of EXCEDE Sterile Suspension is
oping BRD. One or more of the following factors typically
Sterile Suspension may also be
(1.5 mL sterile suspension
posterior
Most animals will respond to treatment within three to five days. If no improvement
3.0 mg CE/lb
aspect of the ear or in the posterior aspect of the ear where it attaches to the head
Administer as a subcutaneous injection either in the middle third of the posterior
effective for the control of respiratory disease in beef and non-lactating dairy cattle
Clinical studies indicate that administration of EXCEDE Sterile Suspension is
oping BRD. One or more of the following factors typically
ventral techniques. Hold the syringe and needle and insert the needle as described below.
The subcutaneous (SC) injection may be made using the toward the opposite eye, rostral, or
toward the animal’s opposite eye. See Figures 4 and 5.
the direction of an imaginary line that would pass through the headpoint in
Hold the syringe and needle behind the ear to be dosed so the needle and syringe
Administration for the Base of the Ear: Toward the Opposite Eye Technique
Do not administer EXCEDE Sterile Suspension in the neck.
Deliver the entire contents of the syringe.
attaches to the head (base of the ear) while maintaining this angle. See Figure 4.
posterior aspect of the ear where it attaches to the head (base of the ear).Figure 4. Subcutaneous administration of EXCEDE Sterile Suspension in the
ventral techniques. Hold the syringe and needle and insert the needle as described below.
The subcutaneous (SC) injection may be made using the toward the opposite eye, rostral, or
toward the animal’s opposite eye. See Figures 4 and 5.
the direction of an imaginary line that would pass through the head
Hold the syringe and needle behind the ear to be dosed so the needle and syringe
Administration for the Base of the Ear: Toward the Opposite Eye Technique
Do not administer EXCEDE Sterile Suspension in the neck.
Deliver the entire contents of the syringe.
attaches to the head (base of the ear) while maintaining this angle. See Figure 4.
posterior aspect of the ear where it attaches to the head (base of the ear).Figure 4. Subcutaneous administration of EXCEDE Sterile Suspension in the
ventral techniques. Hold the syringe and needle and insert the needle as described below.
The subcutaneous (SC) injection may be made using the toward the opposite eye, rostral, or
the direction of an imaginary line that would pass through the head
Hold the syringe and needle behind the ear to be dosed so the needle and syringe
Administration for the Base of the Ear: Toward the Opposite Eye Technique
attaches to the head (base of the ear) while maintaining this angle. See Figure 4.
clothing. Sensitization of the skin may be avoided by wearing protective gloves.
to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and
allergic reactions in some
Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe
Penicillins and cephalosporins can cause allergic reactions in sensitized individuals.
exposure to this product.
Persons with a known hypersensitivity to penicillin or cephalosporins should avoid
reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention.
skin exposure, wash with soap and water. Remove contaminated clothing. If allergic
In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental
report any adverse event please call 1-800-366-5288.
information. To obtain a material safety data sheet please call 1-800-733-5500. To
The material safety data sheet contains more detailed occupational safetyposterior aspect of the ear where it attaches to the head (base of the ear).Figure 4. Subcutaneous administration of EXCEDE Sterile Suspension in the
KEEP OUT OF REACH OF CHILDREN.FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE.
clothing. Sensitization of the skin may be avoided by wearing protective gloves.
to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and
individuals. Repeated allergic reactions in some
Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe
Penicillins and cephalosporins can cause allergic reactions in sensitized individuals.
exposure to this product.
Persons with a known hypersensitivity to penicillin or cephalosporins should avoid
reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention.
skin exposure, wash with soap and water. Remove contaminated clothing. If allergic
In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental
report any adverse event please call 1-800-366-5288.
information. To obtain a material safety data sheet please call 1-800-733-5500. To
The material safety data sheet contains more detailed occupational safety
KEEP OUT OF REACH OF CHILDREN.FOR USE IN ANIMALS ONLY. NOT FOR HUMAN USE.
clothing. Sensitization of the skin may be avoided by wearing protective gloves.
to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and
exposure may leador prolonged individuals. Repeated
Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe
Penicillins and cephalosporins can cause allergic reactions in sensitized individuals.
Persons with a known hypersensitivity to penicillin or cephalosporins should avoid
reaction occurs (e.g., skin rash, hives, difficult breathing), seek medical attention.
skin exposure, wash with soap and water. Remove contaminated clothing. If allergic
In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental
report any adverse event please call 1-800-366-5288.
information. To obtain a material safety data sheet please call 1-800-733-5500. To
The material safety data sheet contains more detailed occupational safety
to sensitization. Avoid direct contact of the product with the skin, eyes, mouth and
exposure may lead
Topical exposures to such antimicrobials, including ceftiofur, may elicit mild to severe
Penicillins and cephalosporins can cause allergic reactions in sensitized individuals.
Persons with a known hypersensitivity to penicillin or cephalosporins should avoid
skin exposure, wash with soap and water. Remove contaminated clothing. If allergic
In case of accidental eye exposure, flush with water for 15 minutes. In case of accidental
information. To obtain a material safety data sheet please call 1-800-733-5500. To
The material safety data sheet contains more detailed occupational safety
Cattle are from multiple farm origins,
stops),
transport extended had have cattle
ambient temperature change from origin to arrival of 30° F or more,
cattle have had continued exposure to extremely wet or cold weather conditions,
Treatment of Acute Metritis
procedures (such as castration, dehorning).
cattle have experienced excessive shrink or excessive arrival processing
Table 1. Dosing Schedule for EXCEDE Sterile Suspension.
initial dose.
this dose in the contra-lateral (opposite) ear approximately 72 hours following the
3.0 mg CE/lb (6.6 mg CE/kg) BW (1.5 mL sterile suspension per 100 lb BW). Repeat
it attaches to the head (base of the ear) to lactating dairy cattle at a dosage of
Administer as a subcutaneous injection in the posterior aspect of the ear where
Cattle are from multiple farm origins,
any if few included have may (that times transport
ambient temperature change from origin to arrival of 30° F or more,
cattle have had continued exposure to extremely wet or cold weather conditions,
procedures (such as castration, dehorning).
cattle have experienced excessive shrink or excessive arrival processing
Table 1. Dosing Schedule for EXCEDE Sterile Suspension.
this dose in the contra-lateral (opposite) ear approximately 72 hours following the
3.0 mg CE/lb (6.6 mg CE/kg) BW (1.5 mL sterile suspension per 100 lb BW). Repeat
it attaches to the head (base of the ear) to lactating dairy cattle at a dosage of
Administer as a subcutaneous injection in the posterior aspect of the ear where
restany
cattle have had continued exposure to extremely wet or cold weather conditions,
cattle have experienced excessive shrink or excessive arrival processing
this dose in the contra-lateral (opposite) ear approximately 72 hours following the
3.0 mg CE/lb (6.6 mg CE/kg) BW (1.5 mL sterile suspension per 100 lb BW). Repeat
it attaches to the head (base of the ear) to lactating dairy cattle at a dosage of
Administer as a subcutaneous injection in the posterior aspect of the ear where
RESIDUE WARNINGS
likely to result in sudden death of the animal.
towards the opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is
Suspension via middle third of the ear injection or base of the ear injection directed
Intra-arterial injection may occur during administration of EXCEDE Sterile
RESIDUE WARNINGS
likely to result in sudden death of the animal.
towards the opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is
Suspension via middle third of the ear injection or base of the ear injection directed
Intra-arterial injection may occur during administration of EXCEDE Sterile
pre-slaughter withdrawal period is required after the last treatment.Following label use as either a single-dose or 2-dose regimen, a 13-day
milk discard period is required for this product.single-dose a either as use Following label
administration by unapUse of dosages in excess of 3.0 mg CE/lb (6.6 mg CE/kg) BW or
the neck or intramuscular injection) may cause violative residues.proved routes (subcutaneous injection in
ruminating calves.A withdrawal period has not been established for this product in pre-
Do not use in calves to be processed for veal.
likely to result in sudden death of the animal.
towards the opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is
Suspension via middle third of the ear injection or base of the ear injection directed
Intra-arterial injection may occur during administration of EXCEDE Sterile
pre-slaughter withdrawal period is required after the last treatment.Following label use as either a single-dose or 2-dose regimen, a 13-day
milk discard period is required for this product.noregimen, 2-dose or single-dose
Use of dosages in excess of 3.0 mg CE/lb (6.6 mg CE/kg) BW or
the neck or intramuscular injection) may cause violative residues.proved routes (subcutaneous injection in
A withdrawal period has not been established for this product in pre-
Do not use in calves to be processed for veal.
towards the opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is
Suspension via middle third of the ear injection or base of the ear injection directed
Intra-arterial injection may occur during administration of EXCEDE Sterile
Weight Dose Volume(lb) (mL)
100 1.5
200 3.0
300 4.5
400 6.0
500 7.5
600 9.0
700 10.5
800 12.0
900 13.5
Weight Dose Volume(lb) (mL)
1100 16.5
1200 18.0
1300 19.5
1400 21.0
1500 22.5
1600 24.0
1700 25.5
1800 27.0
1900 28.5
head (base of the ear).Sterile Suspension in Figure 5. Injection location for the subcutaneous administration of EXCEDE
head (base of the ear).ear where it attaches to of the aspect the posterior Sterile Suspension in
Figure 5. Injection location for the subcutaneous administration of EXCEDE
theear where it attaches to Figure 5. Injection location for the subcutaneous administration of EXCEDE
ANTIBACTERIAL WARNINGS
PRECAUTIONS
ment of drug-resistant bacteria.
likely to provide benefit to treated animals and may increase the risk of the develop
Use of antibacterial drugs in the absence of a susceptible bacterial infection is un
minimize their occurrence.
infections may result in
may ear
the ear, thickening and swelling (characterized by aseptic cellular infiltrate) of the
Following subcutaneous injection
open draining lesions in a small percentage of cattle.
Injection of volumes greater than 20 mL, in the middle third of the ear, may result in
least 13 days post administration resulting in trim loss of edible tissue at slaughter.
(base of the ear), areas of discoloration and signs of inflammation may persist at
Following injection in the posterior aspect of the ear where it attaches to the head
ANTIBACTERIAL WARNINGS
PRECAUTIONS
ment of drug-resistant bacteria.
likely to provide benefit to treated animals and may increase the risk of the develop
Use of antibacterial drugs in the absence of a susceptible bacterial infection is un
minimize their occurrence.
abscess formation. Attention to hygienic procedures caninfections may result in
injections, parenteral other with As occur. may
the ear, thickening and swelling (characterized by aseptic cellular infiltrate) of the
in the middle third Following subcutaneous injection
open draining lesions in a small percentage of cattle.
Injection of volumes greater than 20 mL, in the middle third of the ear, may result in
least 13 days post administration resulting in trim loss of edible tissue at slaughter.
(base of the ear), areas of discoloration and signs of inflammation may persist at
Following injection in the posterior aspect of the ear where it attaches to the head
likely to provide benefit to treated animals and may increase the risk of the develop
Use of antibacterial drugs in the absence of a susceptible bacterial infection is un
abscess formation. Attention to hygienic procedures can
bacterialpost-injection localized injections,
the ear, thickening and swelling (characterized by aseptic cellular infiltrate) of the
ofaspect posterior of the in the middle third
open draining lesions in a small percentage of cattle.
Injection of volumes greater than 20 mL, in the middle third of the ear, may result in
least 13 days post administration resulting in trim loss of edible tissue at slaughter.
(base of the ear), areas of discoloration and signs of inflammation may persist at
Following injection in the posterior aspect of the ear where it attaches to the head
-
-
abscess formation. Attention to hygienic procedures can
bacterial
the ear, thickening and swelling (characterized by aseptic cellular infiltrate) of the
of
Injection of volumes greater than 20 mL, in the middle third of the ear, may result in
least 13 days post administration resulting in trim loss of edible tissue at slaughter.
(base of the ear), areas of discoloration and signs of inflammation may persist at
Following injection in the posterior aspect of the ear where it attaches to the head
ADMINISTRATION FOR THE MIDDLE THIRD OF THE EAR
ADMINISTRATION
aspect of the ear, avoiding all blood vessels. See Figures 2 and 3.
subcutaneous single a as Deposit
cattle.
administering EXCEDE Sterile Suspension subcutaneously in the posterior ear of
Please read the complete package insert beforeShake well before using.
tags or ear tag holes. Do not administer intra-arterially.
will appear.
When administered correctly, a subcutaneous bleb of EXCEDE Sterile Suspension
1000 15.0
ADMINISTRATION FOR THE MIDDLE THIRD OF THE EAR
aspect of the ear, avoiding all blood vessels. See Figures 2 and 3.
posteriorthe of third middle the in injection subcutaneous
administering EXCEDE Sterile Suspension subcutaneously in the posterior ear of
Please read the complete package insert before
tags or ear tag holes. Do not administer intra-arterially.
When administered correctly, a subcutaneous bleb of EXCEDE Sterile Suspension
2000 30.0
posterior
administering EXCEDE Sterile Suspension subcutaneously in the posterior ear of
Please read the complete package insert before
When administered correctly, a subcutaneous bleb of EXCEDE Sterile Suspension
Administration for the Base of Ear: Toward the Same Eye Technique or Rostral Direction
toward the eye on the same side of the head. See Figures 5 and 6.
point in the direction of an imaginary line that would pass through the head
to the head (base of the ear) while maintaining the needle position. See Figure 6.
Administration for the Base of Ear: Toward the Same Eye Technique or Rostral Direction
toward the eye on the same side of the head. See Figures 5 and 6.
point in the direction of an imaginary line that would pass through the head
to the head (base of the ear) while maintaining the needle position. See Figure 6.
ctiontion for
Administration for the Base of Ear: Toward the Same Eye Technique or Rostral Direction
toward the eye on the same side of the head. See Figures 5 and 6.
point in the direction of an imaginary line that would pass through the head
to the head (base of the ear) while maintaining the needle position. See Figure 6.
open draining lesions in a small percentage of cattle.
ADVERSE EFFECTS
lactation have not been determined.
The effects of ceftiofur on bovine reproductive performance, pregnancy, and
CLINICAL PHARMACOLOGY
antibiotic or formulation during any of the clinical and target animal safety studies.
intra-arterial injection. No other adverse systemic effects were noted for either the
incidence of acute death (see ANIMAL SAFETY) confirmed to be the result of inadvertent
sudden death of the animal. During the conduct of clinical studies, there was a low
opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is likely to result in
via middle third of the ear injection or base of the ear injection directed towards the
Intra-arterial injection may occur during administration of EXCEDE Sterile Suspension
hydrochloride (EXCENEL
Ceftiofur administered as either ceftiofur sodium (NAXCEL
open draining lesions in a small percentage of cattle.
ADVERSE EFFECTS
lactation have not been determined.
The effects of ceftiofur on bovine reproductive performance, pregnancy, and
CLINICAL PHARMACOLOGY
antibiotic or formulation during any of the clinical and target animal safety studies.
intra-arterial injection. No other adverse systemic effects were noted for either the
incidence of acute death (see ANIMAL SAFETY) confirmed to be the result of inadvertent
sudden death of the animal. During the conduct of clinical studies, there was a low
opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is likely to result in
via middle third of the ear injection or base of the ear injection directed towards the
Intra-arterial injection may occur during administration of EXCEDE Sterile Suspension
RTU Sterile Suspension), or ceftiofur crystalline free acid®hydrochloride (EXCENEL
Ceftiofur administered as either ceftiofur sodium (NAXCEL
open draining lesions in a small percentage of cattle.
The effects of ceftiofur on bovine reproductive performance, pregnancy, and
antibiotic or formulation during any of the clinical and target animal safety studies.
intra-arterial injection. No other adverse systemic effects were noted for either the
incidence of acute death (see ANIMAL SAFETY) confirmed to be the result of inadvertent
sudden death of the animal. During the conduct of clinical studies, there was a low
opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is likely to result in
via middle third of the ear injection or base of the ear injection directed towards the
Intra-arterial injection may occur during administration of EXCEDE Sterile Suspension
RTU Sterile Suspension), or ceftiofur crystalline free acid
Sterile Powder), ceftiofur®Ceftiofur administered as either ceftiofur sodium (NAXCEL
The effects of ceftiofur on bovine reproductive performance, pregnancy, and
intra-arterial injection. No other adverse systemic effects were noted for either the
incidence of acute death (see ANIMAL SAFETY) confirmed to be the result of inadvertent
sudden death of the animal. During the conduct of clinical studies, there was a low
opposite eye. Intra-arterial injection of EXCEDE Sterile Suspension is likely to result in
via middle third of the ear injection or base of the ear injection directed towards the
Intra-arterial injection may occur during administration of EXCEDE Sterile Suspension
RTU Sterile Suspension), or ceftiofur crystalline free acid
Sterile Powder), ceftiofur
10
g g
(EXCEDE Sterile Suspension) is metabolized rapidly to desfuroylceftiofur, the primary
Single Dose Regimen
not less than 150 hours after a single admin
Mannheimia Pasteurella multocida, encompass 90% of the most susceptible isolates (MIC
metabolites in plasma above the lowest minimum inhibitory concentration to
provides therapeutic concentrations
BOE) of beef, non-lactating dairy, and lactating dairy cattle,head (base of the ear,
non-lactating dairy cattle, or in the posterior aspect of the ear where it attaches to the
posterior the of third middle
metabolite. Subcutaneous administration of ceftiofur crystalline free acid, either in the
The pharmacokinetic parameters for the two subcutaneous locations of injection
(EXCEDE Sterile Suspension) is metabolized rapidly to desfuroylceftiofur, the primary
istration (See Figure 8).not less than 150 hours after a single admin
somniHistophilus and haemolyticaMannheimia ) for the labeled BRD pathogens,90encompass 90% of the most susceptible isolates (MIC
metabolites in plasma above the lowest minimum inhibitory concentration to
of ceftiofur and desfuroylceftiofur-relatedprovides therapeutic concentrations
BOE) of beef, non-lactating dairy, and lactating dairy cattle,
non-lactating dairy cattle, or in the posterior aspect of the ear where it attaches to the
ear, the of third (middle ear the of aspect
metabolite. Subcutaneous administration of ceftiofur crystalline free acid, either in the
The pharmacokinetic parameters for the two subcutaneous locations of injection
pathogensTable 4. Ceftiofur minimum inhibitory concentration (MIC) values* of indicated
Indicatedpathogen
Mannheimia haemolyticaPasteurella multocidaHistophilus somniFusobacterium necrophorumPorphyromonas levii
* The correlation between
(EXCEDE Sterile Suspension) is metabolized rapidly to desfuroylceftiofur, the primary
, for generallysomni) for the labeled BRD pathogens,
metabolites in plasma above the lowest minimum inhibitory concentration to
of ceftiofur and desfuroylceftiofur-related
BOE) of beef, non-lactating dairy, and lactating dairy cattle,
non-lactating dairy cattle, or in the posterior aspect of the ear where it attaches to the
andbeef of MOE)
metabolite. Subcutaneous administration of ceftiofur crystalline free acid, either in the
The pharmacokinetic parameters for the two subcutaneous locations of injection
Table 4. Ceftiofur minimum inhibitory concentration (MIC) values* of indicated
Indicated Year of Number ofpathogen isolation isolates
Mannheimia haemolytica 1996 to 1997 75
Pasteurella multocida 1996 to 1997 43
Histophilus somni 1996 to 1997 11
Fusobacterium necrophorum 2006 to 2007 148
Porphyromonas levii 2006 to 2007 141
susceptibility data and clinical effectiveness is unknown.in vitroThe correlation between
Table 4. Ceftiofur minimum inhibitory concentration (MIC) values* of indicated
Number of **50MIC **90MIC MIC range(μg/mL) (μg/mL) (μg/mL)
0.008 0.015 0.001 to 0.015
0.004 0.004 0.001 to 0.015
0.004 0.004 0.002 to 0.015
0.25≤ 0.5 0.25 to >128≤
0.25≤ 2.0 5 to 160.2≤
susceptibility data and clinical effectiveness is unknown.
arterial injection of
injection of EXCEDE Sterile Suspension, the consequences of purposeful intra-
Since intra-arterial injection was confirmed in three animals that died following
Two heifers (body weight
EXCEDE Sterile Suspension were investigated in feeder cattle.
CE/kg) BW bolus dose of mg (6.6
proximately 225 kg) were given a single 3.0 mg CE/lbap
result in death and must be avoided.
minutes of injection. Intra-arterial injection of EXCEDE Sterile Suspension in the ear will
artery. Both heifers collapsed immediately and died within approximately eight
intravenous
Since subcutaneous injection in the ear may potentially result in inadvertent
Three heifers and three steers (body weight range 197-223 kg) were given a single
Sterile EXCEDE of injection intravenous
administration of an injectable product, the consequences of purposeful
injection of EXCEDE Sterile Suspension, the consequences of purposeful intra-
Since intra-arterial injection was confirmed in three animals that died following
EXCEDE Sterile Suspension were investigated in feeder cattle.
proximately 225 kg) were given a single 3.0 mg CE/lb
result in death and must be avoided.
minutes of injection. Intra-arterial injection of EXCEDE Sterile Suspension in the ear will
artery. Both heifers collapsed immediately and died within approximately eight
EXCEDE Sterile Suspension in the middle auricular
Since subcutaneous injection in the ear may potentially result in inadvertent
Three heifers and three steers (body weight range 197-223 kg) were given a single
feeder in investigated were Suspension Sterile
administration of an injectable product, the consequences of purposeful
injection of EXCEDE Sterile Suspension, the consequences of purposeful intra-
Since intra-arterial injection was confirmed in three animals that died following
EXCEDE Sterile Suspension were investigated in feeder cattle.
proximately 225 kg) were given a single 3.0 mg CE/lb
minutes of injection. Intra-arterial injection of EXCEDE Sterile Suspension in the ear will
artery. Both heifers collapsed immediately and died within approximately eight
EXCEDE Sterile Suspension in the middle auricular
Since subcutaneous injection in the ear may potentially result in inadvertent
Three heifers and three steers (body weight range 197-223 kg) were given a single
cattle.feeder
administration of an injectable product, the consequences of purposeful
in lactating dairy cattle.of the ear (BOE Cattle) in beef cattle as well into the base of the ear (BOE Lactating)of two different locations of the ear, middle third of the ear (MOE Cattle) and baseSuspension at 3.0 mg CE/lb (6.6 mg CE/kg) BW via subcutaneous injection into onedesfuroylceftiofur-related metabolites after administration of EXCEDE SterileFigure 8. Average (n=12/group) plasma concentrations of ceftiofur and
equivalent.
subcutaneous injection sites (MOE and BOE) demonstrate that they are therapeutically
(MOE and BOE) are found in Table 2. Statistical analyses of the data from these two
The pharmacokinetic parameters for the two subcutaneous locations of injection
its
met
abol
ites
(μg/
mL)
Conc
entr
atio
n of
cef
tiof
ur a
nd
of the ear (BOE Cattle) in beef cattle as well into the base of the ear (BOE Lactating)of two different locations of the ear, middle third of the ear (MOE Cattle) and baseSuspension at 3.0 mg CE/lb (6.6 mg CE/kg) BW via subcutaneous injection into onedesfuroylceftiofur-related metabolites after administration of EXCEDE SterileFigure 8. Average (n=12/group) plasma concentrations of ceftiofur and
subcutaneous injection sites (MOE and BOE) demonstrate that they are therapeutically
(MOE and BOE) are found in Table 2. Statistical analyses of the data from these two
The pharmacokinetic parameters for the two subcutaneous locations of injection
*
**
The correlation between
respiratory 5. Table
data, the following breakpoints are recommended for BRD pathogens by CLSI.
single administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW and the MIC and susceptibility
Based on pharmacokinetic and clinical effectiveness studies of ceftiofur in cattle after a
The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.
Pathogen
Mannheimia haemolyticaPasteurella multocida
of the ear (BOE Cattle) in beef cattle as well into the base of the ear (BOE Lactating)of two different locations of the ear, middle third of the ear (MOE Cattle) and baseSuspension at 3.0 mg CE/lb (6.6 mg CE/kg) BW via subcutaneous injection into onedesfuroylceftiofur-related metabolites after administration of EXCEDE SterileFigure 8. Average (n=12/group) plasma concentrations of ceftiofur and
subcutaneous injection sites (MOE and BOE) demonstrate that they are therapeutically
(MOE and BOE) are found in Table 2. Statistical analyses of the data from these two
The pharmacokinetic parameters for the two subcutaneous locations of injection
susceptibility data and clinical effectiveness is unknown.in vitroThe correlation between
respiratory criteria* interpretive CLSI-accepted
data, the following breakpoints are recommended for BRD pathogens by CLSI.
single administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW and the MIC and susceptibility
Based on pharmacokinetic and clinical effectiveness studies of ceftiofur in cattle after a
The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.
pathogens.
Pathogen Disk Zone diameterpotency (mm)
S I
Mannheimia haemolyticaPasteurella multocida 30 μg ≥ 21 18 to 20
susceptibility data and clinical effectiveness is unknown.
against cattleceftiofur for criteria*
data, the following breakpoints are recommended for BRD pathogens by CLSI.
single administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW and the MIC and susceptibility
Based on pharmacokinetic and clinical effectiveness studies of ceftiofur in cattle after a
The lowest MIC to encompass 50% and 90% of the most susceptible isolates, respectively.
Zone diameter MIC breakpoint(mm) (μg/mL)
R S I R
18 to 20 ≤ 17 ≤ 2.0 4.0 ≥ 8.0
mg CE/lb (6.6 mg CE/kg) BW bolus dose of EXCEDE 3.0
Three heifers and three steers (body weight range 197-223 kg) were given a single
untoward signs in these or the other cattle. Intravenous injection of EXCEDE Sterile
and one heifer had transient (2 to 5 minutes) increases in heart rate without any other
jugular vein and were monitored for adverse effects following injection.
Safety Studies in Beef CattleSuspension is an unacceptable route of administration.
Middle of the ear injection:
into the
when EXCEDE Sterile Suspension was administered as a single subcutaneous injection
A study was designed and conducted to specifically address tissue tolerance in cattle
material. Additional increases in thickness were observed through Day 14 after injection.
increase in thickness is attributed to the space required for the volume
cattle is well tolerated and characterized by a biphasic thickening of the ear. The initial
EXCEDE Sterile Suspension into the middle third of the posterior aspect of the ear of
(6.6 mg CE/kg) BW. Results from this study indicate that the subcutaneous injection of
posterior aspect of the ear of cattle at the recommended dose of 3.0 mg CE/lb
mg CE/lb (6.6 mg CE/kg) BW bolus dose of EXCEDE
Three heifers and three steers (body weight range 197-223 kg) were given a single
untoward signs in these or the other cattle. Intravenous injection of EXCEDE Sterile
and one heifer had transient (2 to 5 minutes) increases in heart rate without any other
jugular vein and were monitored for adverse effects following injection.
Sterile Suspension in the
Suspension is an unacceptable route of administration.
when EXCEDE Sterile Suspension was administered as a single subcutaneous injection
A study was designed and conducted to specifically address tissue tolerance in cattle
material. Additional increases in thickness were observed through Day 14 after injection.
increase in thickness is attributed to the space required for the volume
cattle is well tolerated and characterized by a biphasic thickening of the ear. The initial
EXCEDE Sterile Suspension into the middle third of the posterior aspect of the ear of
(6.6 mg CE/kg) BW. Results from this study indicate that the subcutaneous injection of
posterior aspect of the ear of cattle at the recommended dose of 3.0 mg CE/lb
Three heifers and three steers (body weight range 197-223 kg) were given a single
untoward signs in these or the other cattle. Intravenous injection of EXCEDE Sterile
and one heifer had transient (2 to 5 minutes) increases in heart rate without any other
One steerjugular vein and were monitored for adverse effects following injection.
Sterile Suspension in the
when EXCEDE Sterile Suspension was administered as a single subcutaneous injection
A study was designed and conducted to specifically address tissue tolerance in cattle
material. Additional increases in thickness were observed through Day 14 after injection.
of injected
cattle is well tolerated and characterized by a biphasic thickening of the ear. The initial
EXCEDE Sterile Suspension into the middle third of the posterior aspect of the ear of
(6.6 mg CE/kg) BW. Results from this study indicate that the subcutaneous injection of
posterior aspect of the ear of cattle at the recommended dose of 3.0 mg CE/lb
administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW of EXCEDE Sterile Suspension inand desfuroylceftiofur metabolites calculated after a single subcutaneousTable 2. Average (n = 12/group) pharmacokinetic parameters for ceftiofur
its
met
abol
ites
(μg/
mL)
Conc
entr
atio
n of
cef
tiof
ur a
nd
administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW of EXCEDE Sterile Suspension inand desfuroylceftiofur metabolites calculated after a single subcutaneousTable 2. Average (n = 12/group) pharmacokinetic parameters for ceftiofur
Day
Histophilus somni
S – Susceptible
I – Intermediate
EFFECTIVENESS
have not been established.
used to determine antimicrobial susceptibility. Interpretive criteria for bovine foot rot pathogens
* These interpretive criteria are only intended for use when CLSI M31-A2 performance standards are
R – Resistant
days. The 3.0 mg CE/lb (6.6 mg CE/kg) BW EXCEDE Sterile Suspension dose significantly (p
evaluated clinically
subcutaneously in the middle third of the pos
bacterial component of BRD under field conditions. All treatments were administered
single doses of 2.0 and 3.0 mg CE/lb (4.4 or 6.6 mg CE/kg) BW for the treatment of the
A field dose confirmation study for the treatment of BRD evaluated the effectiveness of
administration of 3.0 mg CE/lb (6.6 mg CE/kg) BW of EXCEDE Sterile Suspension inand desfuroylceftiofur metabolites calculated after a single subcutaneousTable 2. Average (n = 12/group) pharmacokinetic parameters for ceftiofur
Histophilus somni
S – Susceptible
I – Intermediate
EFFECTIVENESS
have not been established.
used to determine antimicrobial susceptibility. Interpretive criteria for bovine foot rot pathogens
* These interpretive criteria are only intended for use when CLSI M31-A2 performance standards are
R – Resistant
days. The 3.0 mg CE/lb (6.6 mg CE/kg) BW EXCEDE Sterile Suspension dose significantly (p
and 28 and 14 4, to 2 Days on evaluated
terior aspect of the ear. Cattle weresubcutaneously in the middle third of the pos
bacterial component of BRD under field conditions. All treatments were administered
single doses of 2.0 and 3.0 mg CE/lb (4.4 or 6.6 mg CE/kg) BW for the treatment of the
A field dose confirmation study for the treatment of BRD evaluated the effectiveness of
used to determine antimicrobial susceptibility. Interpretive criteria for bovine foot rot pathogens
* These interpretive criteria are only intended for use when CLSI M31-A2 performance standards are
days. The 3.0 mg CE/lb (6.6 mg CE/kg) BW EXCEDE Sterile Suspension dose significantly (p
studyother all on were observed and
terior aspect of the ear. Cattle were
bacterial component of BRD under field conditions. All treatments were administered
single doses of 2.0 and 3.0 mg CE/lb (4.4 or 6.6 mg CE/kg) BW for the treatment of the
A field dose confirmation study for the treatment of BRD evaluated the effectiveness of
portions of the carcass around the base of the ear.
CFR 301.2). No signs of irritation were observed on the edibleinedible tissues in the US (9
cattle. The discoloration was markedly reduced in size by the end of the study. Ears are
areas of discoloration and some foci of hemorrhage were observed in ears of injected
injected ear in a drooping position for 7 days post injection. At necropsy, subcutaneous
After Day 14, post injection ear thickness
Sterile EXCEDE
The local tolerance of the ear of cattle to a single subcutaneous injection of
well tolerated and was acceptable under feedlot conditions.
administration of EXCEDE Sterile Suspension in the posterior aspect of the ear was
immediately animals treated the of
Leak back and/or bleeding from the injection site was observed in a small fraction
from this trial due to ear irritation although swelling was noted at some injection sites.
study. None of the 1927 animals treated with EXCEDE Sterile Suspension were removed
also was Suspension
EXCEDE
A study evaluated the 56-day feedlot performance of beef steers administered
Sterile Suspension alone, EXCEDE Sterile Suspension with a growth
portions of the carcass around the base of the ear.
CFR 301.2). No signs of irritation were observed on the edible
cattle. The discoloration was markedly reduced in size by the end of the study. Ears are
areas of discoloration and some foci of hemorrhage were observed in ears of injected
injected ear in a drooping position for 7 days post injection. At necropsy, subcutaneous
decreased in all animals. One animal carried anAfter Day 14, post injection ear thickness
The local tolerance of the ear of cattle to a single subcutaneous injection of
well tolerated and was acceptable under feedlot conditions.
administration of EXCEDE Sterile Suspension in the posterior aspect of the ear was
concluded was It administration. after immediately
Leak back and/or bleeding from the injection site was observed in a small fraction
from this trial due to ear irritation although swelling was noted at some injection sites.
study. None of the 1927 animals treated with EXCEDE Sterile Suspension were removed
effectivenessmulti-location large a in evaluated also
A study evaluated the 56-day feedlot performance of beef steers administered
Sterile Suspension alone, EXCEDE Sterile Suspension with a growth
CFR 301.2). No signs of irritation were observed on the edible
cattle. The discoloration was markedly reduced in size by the end of the study. Ears are
areas of discoloration and some foci of hemorrhage were observed in ears of injected
injected ear in a drooping position for 7 days post injection. At necropsy, subcutaneous
decreased in all animals. One animal carried an
The local tolerance of the ear of cattle to a single subcutaneous injection of
administration of EXCEDE Sterile Suspension in the posterior aspect of the ear was
thatconcluded
Leak back and/or bleeding from the injection site was observed in a small fraction
from this trial due to ear irritation although swelling was noted at some injection sites.
study. None of the 1927 animals treated with EXCEDE Sterile Suspension were removed
effectiveness
A study evaluated the 56-day feedlot performance of beef steers administered
Sterile Suspension alone, EXCEDE Sterile Suspension with a growth
either the middle third of the ear or the base of the ear.Pharmacokinetic Beef - Middle
Parameter Third of the EarMean Value ±
Deviation
(μg CE/mL)maxC 6.90 ± 2.68
(h)maxt
0-LOQAUC 376 ± 66.1
(h)>0.2, modelt 183 ± 40.8
(h)>0.2, ncat 246 ± 48.5
(h)1/2t 62.3 ± 13.5
(μg CE/mL)C maximum plasma concentration (in μg CE/mL).
either the middle third of the ear or the base of the ear.Beef - Middle Beef - Base of
Third of the Ear the Ear Base of the EarMean Value ± Mean Value ± Mean Value ±
Standard StandardDeviation Deviation
6.90 ± 2.68 6.39 ± 1.79
12.0 ± 6.2 19.8 ± 5.81
376 ± 66.1 412 ± 67.3
183 ± 40.8 NE
246 ± 48.5 218 ± 45.5
62.3 ± 13.5 40.7 ± 11.2
maximum plasma concentration (in μg CE/mL).
0.05) increased Day 14 treatment success rate, defined as ≤
days. The 3.0 mg CE/lb (6.6 mg CE/kg) BW EXCEDE Sterile Suspension dose significantly (p
ancillary any
and had no or mild depression on that day.
Suspension administered subcutaneously in the middle third of the poste
following arrival processing. Administration of a
Effectiveness evaluation was based on the
Suspension Sterile
at high risk for BRD were assigned to one of four arrival treatments, including EXCEDE
addition to standard processing on arrival at feedlots, cattle (
BRD in feedlot cattle was evaluated in a nine-location field effectiveness study. In
The effectiveness of a single dose of EXCEDE Sterile Suspension for the control of
controls.
cattle feedlot
of the ear at arrival processing significantly reduced the incidence of BRD in high-risk
Base of the ear administration (beef and non-lactating dairy cattle) and middle third of
Dairy Cow -Base of the EarMean Value ±
StandardDeviation
4.44 ± 1.65
19.00 ± 8.02
313 ± 85.5
NE
205 ± 35.7
43.92 ± 9.84
0.05) increased Day 14 treatment success rate, defined as
days. The 3.0 mg CE/lb (6.6 mg CE/kg) BW EXCEDE Sterile Suspension dose significantly (p
of temperature rectal a had and treatment ancillary
and had no or mild depression on that day.
Suspension administered subcutaneously in the middle third of the poste
following arrival processing. Administration of a
incidence of clinical BRD within 28 daysEffectiveness evaluation was based on the
mg CE/kg) 6.6 or (4.4 CE/lb mg 3.0 or 2.0 at Suspension
at high risk for BRD were assigned to one of four arrival treatments, including EXCEDE
addition to standard processing on arrival at feedlots, cattle (
BRD in feedlot cattle was evaluated in a nine-location field effectiveness study. In
The effectiveness of a single dose of EXCEDE Sterile Suspension for the control of
processing arrival after period 28-day the in cattle
of the ear at arrival processing significantly reduced the incidence of BRD in high-risk
Base of the ear administration (beef and non-lactating dairy cattle) and middle third of
0.05) increased Day 14 treatment success rate, defined as
days. The 3.0 mg CE/lb (6.6 mg CE/kg) BW EXCEDE Sterile Suspension dose significantly (p
respiration normal 104°F, <of
animals that did not require
index,
Suspension administered subcutaneously in the middle third of the poste
single dose of EXCEDE Sterile
incidence of clinical BRD within 28 days
negative control.or BWmg CE/kg)
at high risk for BRD were assigned to one of four arrival treatments, including EXCEDE
3911) considered to ben=addition to standard processing on arrival at feedlots, cattle (
BRD in feedlot cattle was evaluated in a nine-location field effectiveness study. In
The effectiveness of a single dose of EXCEDE Sterile Suspension for the control of
negativeto compared processing
of the ear at arrival processing significantly reduced the incidence of BRD in high-risk
rior aspect
Base of the ear administration (beef and non-lactating dairy cattle) and middle third of
EXCEDE
implants was well tolerated by cattle and did not
Suspension in the posterior aspect of the ear
bred steers. The administration of EXCEDE Sterile207 Angus and Angus cross-
promoting implant growth implant, promoting
Sterile Suspension alone, EXCEDE Sterile Suspension with a growth
the boundaries of the middle third of the ear in some within
administered after EXCEDE Sterile Suspension may need to be adjusted slightly
performance. Based upon the results of this study, the location of
Base of the ear injection:
Suspension Sterile EXCEDE of ear
to ear the of tolerance local The
2926 beef cattle. Normal restraint was adequate for adminis
Suspension for 99.8% of cattle. No post injection problems (exces
leak back) were observed in 99.8% of cattle. On Days 28 and 56 post-injec
and 98.9% of the cattle had “normal” (no observed swelling) ears.
In a residue study, 72 beef cattle were injected in the
implants was well tolerated by cattle and did not
with or without growth promotingSuspension in the posterior aspect of the ear
bred steers. The administration of EXCEDE Sterile
product, in or neither alone, promoting implant
Sterile Suspension alone, EXCEDE Sterile Suspension with a growth
the boundaries of the middle third of the ear in some
administered after EXCEDE Sterile Suspension may need to be adjusted slightly
performance. Based upon the results of this study, the location of
affect feedlot cattleadversely
animals.
was Suspension
base the at injection subcutaneoussingle a
2926 beef cattle. Normal restraint was adequate for adminis
field multi-location a in evaluated
Suspension for 99.8% of cattle. No post injection problems (exces
tration of EXCEDE Sterile
leak back) were observed in 99.8% of cattle. On Days 28 and 56 post-injec
sive bleeding or
and 98.9% of the cattle had “normal” (no observed swelling) ears.
tion,
base of the ear with EXCEDEIn a residue study, 72 beef cattle were injected in the
with or without growth promoting
bred steers. The administration of EXCEDE Sterile
a total ofproduct, in
Sterile Suspension alone, EXCEDE Sterile Suspension with a growth
administered after EXCEDE Sterile Suspension may need to be adjusted slightly
implantsperformance. Based upon the results of this study, the location of
affect feedlot cattle
theof base
instudy field
tration of EXCEDE Sterile
sive bleeding or
97.8%tion,
base of the ear with EXCEDE
gTwo-Dose Regimen
the 2-dose regimen are provided in Table 3.
shown is cows regimen in 12
ceftiofur for profile time vs.
for the treatment of acute metritis in lactating cows. The mean plasma concentration
A two-dose regimen of 6.6 mg CE/kg BW administered 72 hours apart is required
(μg CE/mL)maxC =
(h)maxt
maximum plasma concentration (in μg CE/mL).
=
0-LOQAUC
the time after injection when C
(h)model>0.2,t
to the limit of quantitation of the assay (0.15 μg CE/mL).
=
(h)>0.2, nca t
estimated using compartmental pharmacokinetic techniques.
the time plasma concentrations remain above 0.2 μ
=
(h)1/2t
estimated using noncompartmental pharmacokinetic techniques.
the time plasma concentrations remain above 0.2 μg CE/mL (in hours),
=
NE
terminal phase biological half life (in hours)
= Not estimated
the 2-dose regimen are provided in Table 3.
pharmacokinetic The below. 9 Figure in shown
metabolites desfuroylceftiofur-related and
for the treatment of acute metritis in lactating cows. The mean plasma concentration
A two-dose regimen of 6.6 mg CE/kg BW administered 72 hours apart is required
maximum plasma concentration (in μg CE/mL).
occurs (in hours).maxthe time after injection when C
to the limit of quantitation of the assay (0.15 μg CE/mL).
estimated using compartmental pharmacokinetic techniques.
the time plasma concentrations remain above 0.2 μ
estimated using noncompartmental pharmacokinetic techniques.
the time plasma concentrations remain above 0.2 μg CE/mL (in hours),
terminal phase biological half life (in hours)
Not estimated
forparameters pharmacokinetic
2-dosethe for metabolites
for the treatment of acute metritis in lactating cows. The mean plasma concentration
A two-dose regimen of 6.6 mg CE/kg BW administered 72 hours apart is required
pharmacokiear
administration (lactating dairy cattle) were compared to the middle third of thethe ear
therapeutically equivalent.
EXCEDE-treated cattle (58.4%) compared to vehicle-treated control cattle (13.2%).
There analysis.
swelling and lameness scores. A total of 169 beef and dairy cattle were included in the
post-treatment
or an equivalent volume of a vehicle control. Cattle were clinically evaluated 7 days
injection in the base of the ear as a single dose of 3.0 mg CE/lb (6.6 mg
were enrolled and treated with EXCEDE Sterile Suspension, administered by subcutaneous
evaluated in a six-location field effectiveness study. Cattle diagnosed with bovine foot rot
effectiveness of EXCEDE Sterile Suspension for the The
either a two-dose regimen of EXCEDE (6.6 mg CE/BW) or an equivalent volume of vehicle
discharge and a rectal temperature of ≥
evaluated in a 15-location field effectiveness study. A total of 1023 cows with a fetid vaginal
The effectiveness of EXCEDE Sterile Suspension for the treatment of acute metritis was
estimated using compartmental pharmacokinetic techniques.
g CE/mL (in hours),
estimated using noncompartmental pharmacokinetic techniques.
the time plasma concentrations remain above 0.2 μg CE/mL (in hours),
pharmacoki
administration (lactating dairy cattle) were compared to the middle third of the
therapeutically equivalent.
non-lactating and beef for data netic
EXCEDE-treated cattle (58.4%) compared to vehicle-treated control cattle (13.2%).
significant difference statistically a was There
swelling and lameness scores. A total of 169 beef and dairy cattle were included in the
based was which success, treatment for post-treatment
or an equivalent volume of a vehicle control. Cattle were clinically evaluated 7 days
injection in the base of the ear as a single dose of 3.0 mg CE/lb (6.6 mg
were enrolled and treated with EXCEDE Sterile Suspension, administered by subcutaneous
evaluated in a six-location field effectiveness study. Cattle diagnosed with bovine foot rot
effectiveness of EXCEDE Sterile Suspension for the
either a two-dose regimen of EXCEDE (6.6 mg CE/BW) or an equivalent volume of vehicle
°F were enrolled in the study and treated with 103 discharge and a rectal temperature of ≥
evaluated in a 15-location field effectiveness study. A total of 1023 cows with a fetid vaginal
The effectiveness of EXCEDE Sterile Suspension for the treatment of acute metritis was
administration (lactating dairy cattle) were compared to the middle third of the
Base of the ear administration (beef and non-lactating dairy cattle) and middle third of
beto found were and cattle dairy non-lactating
EXCEDE-treated cattle (58.4%) compared to vehicle-treated control cattle (13.2%).
forsuccess treatment in 0.0054) = (p
swelling and lameness scores. A total of 169 beef and dairy cattle were included in the
lesion,in decreases defined on based
or an equivalent volume of a vehicle control. Cattle were clinically evaluated 7 days
BWE/kg) Cinjection in the base of the ear as a single dose of 3.0 mg CE/lb (6.6 mg
were enrolled and treated with EXCEDE Sterile Suspension, administered by subcutaneous
evaluated in a six-location field effectiveness study. Cattle diagnosed with bovine foot rot
foot rot wastreatment of bovine effectiveness of EXCEDE Sterile Suspension for the
either a two-dose regimen of EXCEDE (6.6 mg CE/BW) or an equivalent volume of vehicle
°F were enrolled in the study and treated with
evaluated in a 15-location field effectiveness study. A total of 1023 cows with a fetid vaginal
The effectiveness of EXCEDE Sterile Suspension for the treatment of acute metritis was
inflammation (hemorrhage, conges
the animals showed ear drooping. At necropsy, signs ofanimals. None of 72
site swelling during the study; swelling resolved prior to euthanasia in 23 of
trimming procedures similar to slaughterhouse practices. All animals had injection
swelling and drooping, and evaluated grossly at necropsy, using skin
were observed daily from treatment to necropsy (4, 7, 10, or 13 days post-injection) for
Sterile Suspension at a dose rate of 3.0 mg CE/lb (6.6 mg CE/kg) BW
In a residue study, 72 beef cattle were injected in the
post-injection, gross lesions were found in the
material were seen in the area around the injection site and on the carcass. At 13 days
in all 18 animals, and in the exposed carcass tissue in 11 of 18 animals.
Injection site scores were normal for 65.3% and 92.5% of cattle on Days 14 and 28,
injection technique. Normal restraint was adequate for 95.5% of animals in the study.
Suspension at a dose of 6.6 mg CE/kg BW at the base of the ear using the ventral
study in 200 beef cattle. Each animal received a single injection of EXCEDE Sterile
The ventral base of the ear injection technique was evaluated in a conditions of use
inflammation (hemorrhage, conges
the animals showed ear drooping. At necropsy, signs of
site swelling during the study; swelling resolved prior to euthanasia in 23 of
trimming procedures similar to slaughterhouse practices. All animals had injection
swelling and drooping, and evaluated grossly at necropsy, using skin
were observed daily from treatment to necropsy (4, 7, 10, or 13 days post-injection) for
. Injection sitesSterile Suspension at a dose rate of 3.0 mg CE/lb (6.6 mg CE/kg) BW
base of the ear with EXCEDEIn a residue study, 72 beef cattle were injected in the
post-injection, gross lesions were found in the
material were seen in the area around the injection site and on the carcass. At 13 days
and firmness of tissue) and presence of drugtion,
in all 18 animals, and in the exposed carcass tissue in 11 of 18 animals.
inedible portions of the base of the ear
Injection site scores were normal for 65.3% and 92.5% of cattle on Days 14 and 28,
injection technique. Normal restraint was adequate for 95.5% of animals in the study.
Suspension at a dose of 6.6 mg CE/kg BW at the base of the ear using the ventral
study in 200 beef cattle. Each animal received a single injection of EXCEDE Sterile
The ventral base of the ear injection technique was evaluated in a conditions of use
the animals showed ear drooping. At necropsy, signs of
site swelling during the study; swelling resolved prior to euthanasia in 23 of
trimming procedures similar to slaughterhouse practices. All animals had injection
ning andswelling and drooping, and evaluated grossly at necropsy, using skin
were observed daily from treatment to necropsy (4, 7, 10, or 13 days post-injection) for
. Injection sites
base of the ear with EXCEDE
material were seen in the area around the injection site and on the carcass. At 13 days
and firmness of tissue) and presence of drug
inedible portions of the base of the ear
Injection site scores were normal for 65.3% and 92.5% of cattle on Days 14 and 28,
injection technique. Normal restraint was adequate for 95.5% of animals in the study.
Suspension at a dose of 6.6 mg CE/kg BW at the base of the ear using the ventral
study in 200 beef cattle. Each animal received a single injection of EXCEDE Sterile
The ventral base of the ear injection technique was evaluated in a conditions of use
(6.6 mg CE/kg) BW in 12 lactating cows.Subcutaneous Injections of EXCEDE 72 hours apart at a Dose of 3.0 mg CE/lbFigure 9. LS-Mean DCA Plasma Concentration Time Profile Following Two
the 2-dose regimen are provided in Table 3.
its
met
abol
ites
(μg/
mL)
Conc
entr
atio
n of
cef
tiof
ur a
nd
(6.6 mg CE/kg) BW in 12 lactating cows.Subcutaneous Injections of EXCEDE 72 hours apart at a Dose of 3.0 mg CE/lbFigure 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/lbFigure 9. LS-Mean DCA Plasma Concentration Time Profile Following Two
Systemic Safety StudiesANIMAL SAFETY
determined the probable cause of death to be intra-arterial injection.
cow died 15 to 20 minutes after the second administration of EXCEDE. Necropsy findings
in EXCEDE-treated cows (362/493, 74.3%) than in vehicle-treated cows (271/489, 55.3%). One
observation period were classified as a cure. The cure rate was significantly higher (p < 0.0001)
temperature < 103 °F, and that did not require alternate (“escape”) therapy during the
and vaginal discharge score were recorded. Cows with a non-fetid discharge, and a rectal
post-treatment, each cow remaining in the study was examined and rectal temperature
control, administered approximately 72 hours apart at the base of opposite ears. At 14
either a two-dose regimen of EXCEDE (6.6 mg CE/BW) or an equivalent volume of vehicle
tolerance study conducted with ceftiofur sodium in normal feeder calves indicated
to evaluate the systemic safety of EXCEDE Sterile
desfuroylceftiofur. Therefore, studies
Suspension), ceftiofur sodium and ceftiofur hydrochloride are rapidly metabolized to
After parenteral administration, ceftiofur crystalline free acid (as EXCEDE Sterile
Systemic Safety StudiesANIMAL SAFETY
determined the probable cause of death to be intra-arterial injection.
cow died 15 to 20 minutes after the second administration of EXCEDE. Necropsy findings
in EXCEDE-treated cows (362/493, 74.3%) than in vehicle-treated cows (271/489, 55.3%). One
observation period were classified as a cure. The cure rate was significantly higher (p < 0.0001)
temperature < 103 °F, and that did not require alternate (“escape”) therapy during the
and vaginal discharge score were recorded. Cows with a non-fetid discharge, and a rectal
post-treatment, each cow remaining in the study was examined and rectal temperature
control, administered approximately 72 hours apart at the base of opposite ears. At 14
either a two-dose regimen of EXCEDE (6.6 mg CE/BW) or an equivalent volume of vehicle
tolerance study conducted with ceftiofur sodium in normal feeder calves indicated
Suspension. Results from a five-dayto evaluate the systemic safety of EXCEDE Sterile
conducted with ceftiofur sodium are adequatedesfuroylceftiofur. Therefore, studies
Suspension), ceftiofur sodium and ceftiofur hydrochloride are rapidly metabolized to
After parenteral administration, ceftiofur crystalline free acid (as EXCEDE Sterile
determined the probable cause of death to be intra-arterial injection.
cow died 15 to 20 minutes after the second administration of EXCEDE. Necropsy findings
in EXCEDE-treated cows (362/493, 74.3%) than in vehicle-treated cows (271/489, 55.3%). One
observation period were classified as a cure. The cure rate was significantly higher (p < 0.0001)
14_day temperature < 103 °F, and that did not require alternate (“escape”) therapy during the
and vaginal discharge score were recorded. Cows with a non-fetid discharge, and a rectal
post-treatment, each cow remaining in the study was examined and rectal temperature
days control, administered approximately 72 hours apart at the base of opposite ears. At 14
either a two-dose regimen of EXCEDE (6.6 mg CE/BW) or an equivalent volume of vehicle
tolerance study conducted with ceftiofur sodium in normal feeder calves indicated
Suspension. Results from a five-day
conducted with ceftiofur sodium are adequate
Suspension), ceftiofur sodium and ceftiofur hydrochloride are rapidly metabolized to
After parenteral administration, ceftiofur crystalline free acid (as EXCEDE Sterile
Safety Studies in Lactating Dairy Cattlesize comparable to other study animals by Day 14.
unusually an animal had respectively. One
The local tolerance of the ear to a single subcutaneous injec
of cattle using nor
cattle. Successful injection in the base of the ear was achieved in 97.4%adult dairy
Sterile Suspension was evaluated in a multi-location field study in 114ear of EXCEDE
bleeding was observed fol
facilities and restraint equipment. No leak back or excessivemal
as normal with no injection site swelling.
Suspension in the base of the ear, 95.6% and 100% of ears, respectively, were observed
ranging from 15 to 30 mL. On Days 28 and 56 following injection of EXCEDE Sterile
lowing injection for 99.1% of cattle, with injection volumes
days after injection. At necropsy, all six cows showed evidence of injection site10
the injection site at all observation times after treatment. Cows were slaughtered
drooping ears at any time after treatment but all animals had
of BW CE/kg) mg (6.6 CE/lb mg 3.0
In a residue study, six dairy cows were injected in the base of the ear at a dose rate of
Safety Studies in Lactating Dairy Cattlesize comparable to other study animals by Day 14.
reduced which large swelling on Day 7 unusually
The local tolerance of the ear to a single subcutaneous injec
cattle. Successful injection in the base of the ear was achieved in 97.4%
Sterile Suspension was evaluated in a multi-location field study in 114
tion at the base of the
facilities and restraint equipment. No leak back or excessive
as normal with no injection site swelling.
Suspension in the base of the ear, 95.6% and 100% of ears, respectively, were observed
ranging from 15 to 30 mL. On Days 28 and 56 following injection of EXCEDE Sterile
lowing injection for 99.1% of cattle, with injection volumes
days after injection. At necropsy, all six cows showed evidence of injection site
the injection site at all observation times after treatment. Cows were slaughtered
signs of swelling atdrooping ears at any time after treatment but all animals had
animals No Suspension. Sterile EXCEDE of
In a residue study, six dairy cows were injected in the base of the ear at a dose rate of
ato reduced
cattle. Successful injection in the base of the ear was achieved in 97.4%
Sterile Suspension was evaluated in a multi-location field study in 114
tion at the base of the
facilities and restraint equipment. No leak back or excessive
Suspension in the base of the ear, 95.6% and 100% of ears, respectively, were observed
ranging from 15 to 30 mL. On Days 28 and 56 following injection of EXCEDE Sterile
lowing injection for 99.1% of cattle, with injection volumes
days after injection. At necropsy, all six cows showed evidence of injection site
the injection site at all observation times after treatment. Cows were slaughtered
signs of swelling at
exhibitedanimals
In a residue study, six dairy cows were injected in the base of the ear at a dose rate of
at a 72 Hour Interval.of EXCEDE Sterile Injections
Table 3. Average (n = 12) Pharmacokinetic Parameters Following Two Subcutaneous
PK Parameter
0-LOQAUC
(h)½t
(h)0.2t>
(h)maxT
Conc
entr
atio
n of
cef
tiof
ur a
nd
mg CE/lb (6.6 a Dose 3.0 Suspension at of EXCEDE Sterile Table 3. Average (n = 12) Pharmacokinetic Parameters Following Two Subcutaneous
Mean ± Standard Deviation
55.7 ± 4.84
341 ± 34.0
77.1 ± 33.4
imately 8 times the approved dose of EXCEDE Sterile
that ceftiofur was well tolerated at 25 mg CE/lb/day for five con
tolerance study conducted with ceftiofur sodium in normal feeder calves indicated
CE/kg) BW. Ceftiofur administered parenterally had no adverse systemic effects.
In a 15-day safety/toxicity study, five steer and five heifer calves per group were admin
is
calves. Local tissue tolerance to
that ceftiofur has a wide margin of safety when injected intramuscularly into feeder
mg CE/lb/day (6.6 mg CE/kg) BW. There were no adverse systemic effects, indicating3.0
thus, evaluating up to 3.3 times the approved dose of EXCEDE Sterile Suspension of
tered ceftiofur sodium intramuscularly at 0 (vehicle control), 1, 3, 5
the posterior ear of cattle was evaluated in a separate study
The systemic safety of ceftiofur concentrations
two routes of administration are therapeutically equivalent.
Based upon the results of this relative bioavailability study, it was determined that the
two the of
administration at the base of the ear was established via a pharmacokinetic comparison
BWmg CE/kg) mg CE/lb (6.6 Table 3. Average (n = 12) Pharmacokinetic Parameters Following Two Subcutaneous
Mean ± Standard Deviation
imately 8 times the approved dose of EXCEDE Sterile
that ceftiofur was well tolerated at 25 mg CE/lb/day for five con
tolerance study conducted with ceftiofur sodium in normal feeder calves indicated
CE/kg) BW. Ceftiofur administered parenterally had no adverse systemic effects.
In a 15-day safety/toxicity study, five steer and five heifer calves per group were admin
calves. Local tissue tolerance to
that ceftiofur has a wide margin of safety when injected intramuscularly into feeder
mg CE/lb/day (6.6 mg CE/kg) BW. There were no adverse systemic effects, indicating
thus, evaluating up to 3.3 times the approved dose of EXCEDE Sterile Suspension of
tered ceftiofur sodium intramuscularly at 0 (vehicle control), 1, 3, 5
the posterior ear of cattle was evaluated in a separate study
subcutaneous injection of EXCEDE Sterile Suspension in
The systemic safety of ceftiofur concentrations
two routes of administration are therapeutically equivalent.
Based upon the results of this relative bioavailability study, it was determined that the
ear the of (base administration of routes
administration at the base of the ear was established via a pharmacokinetic comparison
imately 8 times the approved dose of EXCEDE Sterile
secutive days, approx-that ceftiofur was well tolerated at 25 mg CE/lb/day for five con
tolerance study conducted with ceftiofur sodium in normal feeder calves indicated
CE/kg) BW. Ceftiofur administered parenterally had no adverse systemic effects.
mg3.0 mg CE/lb (6.6 Suspension
In a 15-day safety/toxicity study, five steer and five heifer calves per group were admin-
that ceftiofur has a wide margin of safety when injected intramuscularly into feeder
mg CE/lb/day (6.6 mg CE/kg) BW. There were no adverse systemic effects, indicating
thus, evaluating up to 3.3 times the approved dose of EXCEDE Sterile Suspension of
or 10 mg CE/lb/daytered ceftiofur sodium intramuscularly at 0 (vehicle control), 1, 3, 5
.the posterior ear of cattle was evaluated in a separate study
subcutaneous injection of EXCEDE Sterile Suspension in
The systemic safety of ceftiofur concentrations
two routes of administration are therapeutically equivalent.
Based upon the results of this relative bioavailability study, it was determined that the
of the ear).middle third versus ear
administration at the base of the ear was established via a pharmacokinetic comparison
ing from productresult
inflammation (discoloration of fat
days after injection. At necropsy, all six cows showed evidence of injection site10
of tissue dor
tissue/fascia) and four of six cows had discoloration
.sectioned surface
discoloration, tan nodules and a
sal and posterior to the ear canal on the carcass. In addition to
at 2 or 3, 11, and 54±3 days after the second injection, respectively.
injections administered. Injection site scores were normal in 50.3%, 73.2%, and 96.4%
above. study described effectiveness
Injection site safety for base of the ear administration was evaluated in the metritis
TISSUE AND MILK RESIDUE DEPLETION
(rostral), 87.8% (ventral), and 64.6% (opposite eye) of cattle on Day 28, respectively.
(rostral), 46.9% (ventral), and 47.9% (opposite eye) of cattle on Day 14, and 73%
(opposite eye) of animals in the study. Injection site scores were normal for 32%
cattle. Normal restraint was adequate for 89.8% (ventral), 98% (rostral), and 100%
eye technique opposite toward the
The ventral and rostral base of the ear injection techniques were compared with the
days after injection. At necropsy, all six cows showed evidence of injection site
tissue/fascia) and four of six cows had discoloration
milky white fluid exudate were also present at the
sal and posterior to the ear canal on the carcass. In addition to
at 2 or 3, 11, and 54±3 days after the second injection, respectively.
injections administered. Injection site scores were normal in 50.3%, 73.2%, and 96.4%
adequate for ≥ was restraint Normal above.
Injection site safety for base of the ear administration was evaluated in the metritis
TISSUE AND MILK RESIDUE DEPLETION
(rostral), 87.8% (ventral), and 64.6% (opposite eye) of cattle on Day 28, respectively.
(rostral), 46.9% (ventral), and 47.9% (opposite eye) of cattle on Day 14, and 73%
(opposite eye) of animals in the study. Injection site scores were normal for 32%
cattle. Normal restraint was adequate for 89.8% (ventral), 98% (rostral), and 100%
lactating dairy197 study in of use in a conditions eye technique
The ventral and rostral base of the ear injection techniques were compared with the
days after injection. At necropsy, all six cows showed evidence of injection site
tissue/fascia) and four of six cows had discoloration
milky white fluid exudate were also present at the
sal and posterior to the ear canal on the carcass. In addition to
injections administered. Injection site scores were normal in 50.3%, 73.2%, and 96.4%
of97.8% adequate for ≥
Injection site safety for base of the ear administration was evaluated in the metritis
(rostral), 87.8% (ventral), and 64.6% (opposite eye) of cattle on Day 28, respectively.
(rostral), 46.9% (ventral), and 47.9% (opposite eye) of cattle on Day 14, and 73%
(opposite eye) of animals in the study. Injection site scores were normal for 32%
cattle. Normal restraint was adequate for 89.8% (ventral), 98% (rostral), and 100%
lactating dairy
The ventral and rostral base of the ear injection techniques were compared with the
(h)maxT
(μg/mL)maxC
MICROBIOLOGY
with bovine foot rot.
Fusobacterium necrophorumagainst and BRD,
Histophilus somni, and Pasteurella multocida,Ceftiofur has demonstrated
foot rot isolates, respectively.
and Laboratory Standards Institute (CLSI) M7-A3 and M11-A6 standards for BRD and
diagnosed with foot rot. Susceptibility testing was conducted according to the Clinical
cattle enrolled in a field study conducted in the United States and Canada that were
the United States that were diagnosed with BRD. Foot rot isolates were obtained from
4. BRD isolates were obtained from cattle enrolled in a field study conducted inTable
A summary of the susceptibility of BRD and foot rot pathogens is presented in
77.1 ± 33.4
5.98 ± 2.51
Porphyromonas leviiand Fusobacterium necrophorum three major pathogens associated withHistophilus somni,
Mannheimia haemolytica, activity against in vitroCeftiofur has demonstrated
foot rot isolates, respectively.
and Laboratory Standards Institute (CLSI) M7-A3 and M11-A6 standards for BRD and
diagnosed with foot rot. Susceptibility testing was conducted according to the Clinical
cattle enrolled in a field study conducted in the United States and Canada that were
the United States that were diagnosed with BRD. Foot rot isolates were obtained from
4. BRD isolates were obtained from cattle enrolled in a field study conducted in
A summary of the susceptibility of BRD and foot rot pathogens is presented in
two routes of administration are therapeutically equivalent.
Investigation of Intra-Arterial and Intravenous Injectionfollowing five daily doses of NAXCEL Sterile Powder in beef cattle.
after two doses of EXCEDE were statistically no higher than (AUC)
interval at 6.6 mg/kg BW. The peak concentration (C
were compared pharmacokinetically with EXCEDE administered 2 times at a 72 hour
projected daily doses of NAXCEL Sterile Powder (ceftiofur sodium) at 2.2 mg/kg BW
To support systemic target animal safety for the 2-dose metritis regimen, five
of the two major auricular (ear) arteries.
resulted from inadvertent intra-arterial injection of this oil-based suspension into one
the time of injection. The exact cause was confirmed in three animals. These deaths
following injection of EXCEDE Sterile Suspension.
In approximately 6000 animals enrolled in the BRD clinical studies, nine animals died
in direct administration of the oil-based formula
the brain resulting in embolism and death.
associatedPorphyromonas levii three major pathogens associated with
Mannheimia haemolytica,
and Laboratory Standards Institute (CLSI) M7-A3 and M11-A6 standards for BRD and
diagnosed with foot rot. Susceptibility testing was conducted according to the Clinical
cattle enrolled in a field study conducted in the United States and Canada that were
the United States that were diagnosed with BRD. Foot rot isolates were obtained from
4. BRD isolates were obtained from cattle enrolled in a field study conducted in
A summary of the susceptibility of BRD and foot rot pathogens is presented in
two routes of administration are therapeutically equivalent.
Investigation of Intra-Arterial and Intravenous Injectionfollowing five daily doses of NAXCEL Sterile Powder in beef cattle.
after two doses of EXCEDE were statistically no higher than
interval at 6.6 mg/kg BW. The peak concentration (C
were compared pharmacokinetically with EXCEDE administered 2 times at a 72 hour
projected daily doses of NAXCEL Sterile Powder (ceftiofur sodium) at 2.2 mg/kg BW
To support systemic target animal safety for the 2-dose metritis regimen, five
of the two major auricular (ear) arteries.
resulted from inadvertent intra-arterial injection of this oil-based suspension into one
the time of injection. The exact cause was confirmed in three animals. These deaths
All deaths were within 30 minutes offollowing injection of EXCEDE Sterile Suspension.
In approximately 6000 animals enrolled in the BRD clinical studies, nine animals died
in direct administration of the oil-based formula
Intra-arterial injection at this location resulted
the brain resulting in embolism and death.
tion
two routes of administration are therapeutically equivalent.
Investigation of Intra-Arterial and Intravenous Injectionfollowing five daily doses of NAXCEL Sterile Powder in beef cattle.
the exposureafter two doses of EXCEDE were statistically no higher than
) and the extent of exposuremaxinterval at 6.6 mg/kg BW. The peak concentration (C
were compared pharmacokinetically with EXCEDE administered 2 times at a 72 hour
projected daily doses of NAXCEL Sterile Powder (ceftiofur sodium) at 2.2 mg/kg BW
To support systemic target animal safety for the 2-dose metritis regimen, five
resulted from inadvertent intra-arterial injection of this oil-based suspension into one
the time of injection. The exact cause was confirmed in three animals. These deaths
All deaths were within 30 minutes of
In approximately 6000 animals enrolled in the BRD clinical studies, nine animals died
Intra-arterial injection at this location resulted
into the arterial blood supply oftion
TISSUE AND MILK RESIDUE DEPLETION
kidney, 2.0 ppm in liver, 1.0 ppm in muscle and 0.1 ppm in milk.
for ceftiofur residues in milk. The tolerances for ceftiofur residues are 0.4 ppm in
residues in cattle kidney, liver and muscle. A separate study established the tolerance
A radiolabeled residue metabolism study established tolerances for ceftiofur
13
days after dosing. These data collectively support a13kidney, liver and muscle by
in tissues were less than the tolerances for ceftiofur residues in tissues such as the
cows received a single injection of
A pivotal tissue residue decline study was conducted in dairy cattle. In this study,
-day pre-slaughter withdrawal period.
collectively support that no milk discard period is required for this product.
residues in milk were less than tolerances at all time points after treatment. These data
study, cows received a single injection of
study decline milk residue pivotal A
TISSUE AND MILK RESIDUE DEPLETION
kidney, 2.0 ppm in liver, 1.0 ppm in muscle and 0.1 ppm in milk.
for ceftiofur residues in milk. The tolerances for ceftiofur residues are 0.4 ppm in
residues in cattle kidney, liver and muscle. A separate study established the tolerance
A radiolabeled residue metabolism study established tolerances for ceftiofur
days after dosing. These data collectively support a
in tissues were less than the tolerances for ceftiofur residues in tissues such as the
. Ceftiofur 3.0 mg CE/lb (6.6 mg CE/kg) BWcows received a single injection of
A pivotal tissue residue decline study was conducted in dairy cattle. In this study,
day pre-slaughter withdrawal period.
collectively support that no milk discard period is required for this product.
residues in milk were less than tolerances at all time points after treatment. These data
3.0 mg CE/lb (6.6 mg CE/kg) BWstudy, cows received a single injection of
cattle. dairy conducted in lactating was study
for ceftiofur residues in milk. The tolerances for ceftiofur residues are 0.4 ppm in
residues in cattle kidney, liver and muscle. A separate study established the tolerance
A radiolabeled residue metabolism study established tolerances for ceftiofur
days after dosing. These data collectively support a
in tissues were less than the tolerances for ceftiofur residues in tissues such as the
residues. Ceftiofur
A pivotal tissue residue decline study was conducted in dairy cattle. In this study,
collectively support that no milk discard period is required for this product.
residues in milk were less than tolerances at all time points after treatment. These data
. Ceftiofur3.0 mg CE/lb (6.6 mg CE/kg) BW
thisIn cattle.
11
Two-Dose Residue Decline Studies
last dose.
collectively continue to support a 13-day pre-slaughter withdrawal period after the
residues ceftiofur
between injections. Ceftiofur residues in tissues were less than the tolerances for
cows received two injections of 3.0 mg CE/lb (6.6 mg CE/kg) BW with a 72 hour interval
A pivotal tissue residue decline study was conducted in dairy cattle. In this study,
STORAGE CONDITIONS
milk discard period is required for this product.
interval between injections. Milk residue decline data from this study supports that no
study, cows received two injections of 3.0 mg CE/lb (6.6 mg CE/kg) BW with a 72 hour
A pivotal milk residue decline study was conducted in lactating dairy cattle. In this
Two-Dose Residue Decline Studies
collectively continue to support a 13-day pre-slaughter withdrawal period after the
the after days 13 by kidney the in residues
between injections. Ceftiofur residues in tissues were less than the tolerances for
cows received two injections of 3.0 mg CE/lb (6.6 mg CE/kg) BW with a 72 hour interval
A pivotal tissue residue decline study was conducted in dairy cattle. In this study,
STORAGE CONDITIONS
milk discard period is required for this product.
interval between injections. Milk residue decline data from this study supports that no
study, cows received two injections of 3.0 mg CE/lb (6.6 mg CE/kg) BW with a 72 hour
A pivotal milk residue decline study was conducted in lactating dairy cattle. In this
collectively continue to support a 13-day pre-slaughter withdrawal period after the
dataThese dose. second
between injections. Ceftiofur residues in tissues were less than the tolerances for
cows received two injections of 3.0 mg CE/lb (6.6 mg CE/kg) BW with a 72 hour interval
A pivotal tissue residue decline study was conducted in dairy cattle. In this study,
interval between injections. Milk residue decline data from this study supports that no
study, cows received two injections of 3.0 mg CE/lb (6.6 mg CE/kg) BW with a 72 hour
A pivotal milk residue decline study was conducted in lactating dairy cattle. In this
STORAGE CONDITIONS
using.
Store at controlled room temperature 20° to 25°C (68° to 77°F). Shake well before
HOW SUPPLIED
Contents should be used within 12 weeks after the first dose is removed.
250 mL vial
100 mL vial
EXCEDE Sterile Suspension is available in the following package sizes:
www.EXCEDE.com or call 1-866-387-2287
NADA #141-209, Approved by FDA
Pharmacia & Upjohn CompanyDistributed by
Division of Pfizer Inc, NY, NY 10017
STORAGE CONDITIONSStore at controlled room temperature 20° to 25°C (68° to 77°F). Shake well before
Contents should be used within 12 weeks after the first dose is removed.
EXCEDE Sterile Suspension is available in the following package sizes:
www.EXCEDE.com or call 1-866-387-2287
NADA #141-209, Approved by FDA
Pharmacia & Upjohn CompanyDivision of Pfizer Inc, NY, NY 10017
Store at controlled room temperature 20° to 25°C (68° to 77°F). Shake well before
Contents should be used within 12 weeks after the first dose is removed.
EXCEDE Sterile Suspension is available in the following package sizes:
Revised: December 2011
www.EXCEDE.com or call 1-866-387-2287
Revised: December 2011
www.EXCEDE.com or call 1-866-387-2287