:
RESFLOR GOLD®
Rx
Intervet/Schering-Plough Animal Health
PRODUCT INFORMATION
NADA 141-299, Approved by FDA.
(Florfenicol and Flunixin Meglumine)
Antimicrobial/Non-Steroidal Anti-Inflammatory Drug
For subcutaneous use in beef and
non-lactating dairy cattle only.
Not for use in female dairy cattle 20
months of age or older or in calves to be processed for veal.
CAUTION: Federal law restricts this
drug to use by or on the order of a licensed veterinarian.
DESCRIPTION: RESFLOR GOLD® is an injectable solution of the synthetic
antibiotic florfenicol and the non-steroidal anti-inflammatory drug
(NSAID) flunixin. Each milliliter of sterile RESFLOR GOLD® contains 300 mg florfenicol, 16.5 mg
flunixin as flunixin meglumine, 300 mg 2-pyrrolidone, 35 mg malic acid,
and triacetin qs.
INDICATIONS: RESFLOR GOLD® is indicated for treatment of bovine
respiratory disease (BRD) associated with Mannheimia
haemolytica, Pasteurella multocida, Histophilus
somni, and Mycoplasma bovis, and control
of BRD-associated pyrexia in beef and non-lactating dairy cattle.
DOSAGE AND ADMINISTRATION: RESFLOR
GOLD® should be administered once by
subcutaneous injection at a dose rate of 40 mg florfenicol/kg body
weight and 2.2 mg flunixin/kg body weight (6 mL/100 lb). Do not
administer more than 10 mL at each site. The injection should be given
only in the neck. Injection sites other than the neck have not been
evaluated. For the 500mL vial, do not puncture the stopper more than 10
times. RESFLOR GOLD® Dosage Guide*
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ANIMAL WEIGHT (lbs)
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DOSAGE (mL)
|
100
|
6.0
|
200
|
12.0
|
300
|
18.0
|
400
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24.0
|
500
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30.0
|
600
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36.0
|
700
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42.0
|
800
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48.0
|
900
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54.0
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1000
|
60.0 |
CONTRAINDICATIONS: Do not use in
animals that have shown hypersensitivity to florfenicol or flunixin.
WARNINGS: NOT FOR
HUMAN USE. KEEP OUT OF REACH OF CHILDREN. This product contains
material that can be irritating to skin and eyes. Avoid direct contact
with skin, eyes, and clothing. In case of accidental eye exposure, flush
with water for 15 minutes. In case of accidental skin exposure, wash
with soap and water. Remove contaminated clothing. Consult a physician
if irritation persists. Accidental injection of this product may cause
local irritation. Consult a physician immediately. The Material Safety
Data Sheet (MSDS) contains more detailed occupational safety
information.
For customer service or to obtain a copy of the MSDS,
call 1-800-211-3573. For technical assistance or to report suspected
adverse reactions, call 1-800-219-9286.
PRECAUTIONS: As a class,
cyclo-oxygenase inhibitory NSAIDs may be associated with
gastrointestinal, renal, and hepatic toxicity. Sensitivity to
drug-associated adverse events varies with the individual patient.
Patients at greatest risk for adverse events are those that are
dehydrated, on diuretic therapy, or those with existing renal,
cardiovascular, and/or hepatic dysfunction. Concurrent administration of
potentially nephrotoxic drugs should be carefully monitored. NSAIDs may
inhibit the prostaglandins that maintain normal homeostatic function.
Such anti-prostaglandin effects may result in clinically significant
disease in patients with underlying or pre-existing disease that have
not been previously diagnosed. Since many NSAIDs possess the potential
to produce gastrointestinal ulceration, concomitant use of RESFLOR GOLD® with other anti-inflammatory drugs, such as
NSAIDs or corticosteroids, should be avoided or closely monitored.
Flunixin is a cyclo-oxygenase inhibitory NSAID, and as
with others in this class, adverse effects may occur with its use. The
most frequently reported adverse effects have been gastrointestinal
signs. Events involving suspected renal, hematologic, neurologic,
dermatologic, and hepatic effects have also been reported for other
drugs in this class.
Not for use in animals intended for breeding purposes.
The effects of florfenicol on bovine reproductive performance,
pregnancy, and lactation have not been determined. Toxicity studies in
dogs, rats, and mice have associated the use of florfenicol with
testicular degeneration and atrophy. NSAIDs are known to have potential
effects on both parturition and the estrous cycle. There may be a delay
in the onset of estrus if flunixin is administered during the
prostaglandin phase of the estrous cycle. The effects of flunixin on
imminent parturition have not been evaluated in a controlled study.
NSAIDs are known to have the potential to delay parturition through a
tocolytic effect.
RESFLOR GOLD®, when
administered as directed, may induce a transient reaction at the site of
injection and underlying tissues that may result in trim loss of edible
tissue at slaughter.
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RESIDUE WARNINGS: Animals intended
for human consumption must not be slaughtered within 38 days of
treatment. Do not use in female dairy cattle 20 months of age or older.
Use of florfenicol in this class of cattle may cause milk residues. A
withdrawal period has not been established in pre-ruminating calves. Do
not use in calves to be processed for veal.
|
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ADVERSE REACTIONS: Transient
inappetence, diarrhea, decreased water consumption, and injection site
swelling have been associated with the use of florfenicol in cattle. In
addition, anaphylaxis and collapse have been reported post-approval with
the use of another formulation of florfenicol in cattle. In cattle,
rare instances of anaphylactic-like reactions, some of which have been
fatal, have been reported, primarily following intravenous use of
flunixin meglumine.
CLINICAL PHARMACOLOGY:
The pharmacokinetics (PK) of florfenicol (Table 1)
and flunixin (Table 2) after subcutaneous injection of RESFLOR GOLD® is described below:
Table 1. Mean (n=28) pharmacokinetic
parameters for florfenicol in cattle after a single subcutaneous
administration of RESFLOR GOLD (florfenicol dose of 40 mg/kg BW).
Mean Florfenicol PK parameters in Cattle
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PK Parameter
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AUC 0-t1 (ng*hr/mL)
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AUC0-inf 2 (ng*hr/mL)
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Cmax3 (ng/mL)
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Tmax4 (hr)
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T1/25 (hr)
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MRT0-inf 6 (hr)
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Mean
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242527
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247577
|
11151
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6.25
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28.5
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27.3
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SD7
|
42741
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41391
|
4194
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3.87
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9.91
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11.6
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Table 2. Mean (n=28) pharmacokinetic
parameters for flunixin in cattle after a single subcutaneous
administration of resfLor goLd (flunixin dose of 2.2 mg/kg BW).
Mean Florfenicol PK parameters in Cattle
|
PK Parameter
|
AUC 0-t1 (ng*hr/mL)
|
AUC0-inf 2 (ng*hr/mL)
|
Cmax3 (ng/mL)
|
Tmax4 (hr)
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T1/25 (hr)
|
MRT0-inf 6 (hr)
|
Mean
|
13370
|
14448**
|
1913
|
1.14
|
9.5**
|
11.4
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SD7
|
4964
|
5116
|
791
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0.97
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3.27
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4.41
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1 AUC0-t = Area under the plasma-concentration-time
curve (AUC) from time zero to the last quantifiable concentrations
2 AUC0-inf = AUC from time zero to infinity
3 Cmax
= Maximum plasma concentration
4 Tmax
= Time at which Cmax was observed
5 T1/2
= Terminal elimination half-life
6 MRT0-inf = Mean residence time from time zero to
infinity
7 SD = Standard deviation
** n=27
MICROBIOLOGY: Florfenicol is a
synthetic, broad-spectrum antibiotic active against many Gram-negative
and Gram-positive bacteria isolated from domestic animals. It acts by
binding to the 50S ribosomal subunit and inhibiting bacterial protein
synthesis. Florfenicol is generally considered a bacteriostatic drug,
but exhibits bactericidal activity against certain bacterial species. In vitro studies demonstrate that florfenicol is
active against the BRD pathogens M. haemolytica, P.
multocida, and H. somni, and that
florfenicol exhibits bactericidal activity against strains of M. haemolytica and H. somni.
The minimum inhibitory concentrations (MICs) of
florfenicol were determined for BRD isolates obtained from calves
enrolled in BRD field studies in the U.S. in 2006 using methods
recommended by the Clinical and Laboratory Standards Institute (M31-A2).
Isolates were obtained from pre-treatment nasal swabs from all calves
enrolled at all four sites, post-treatment nasal swabs from treatment
failures in the RESFLOR GOLD and saline control treatment groups at
three sites, and lung tissue from one calf that died in the saline
control treatment group. The results are shown in Table 3.
Table 3. Florfenicol MIC values* of
indicated pathogens isolated from cattle with naturally-occurring BRD
Indicated pathogens
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Year of isolation
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Number of isolates
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MIC50** (µg/mL)
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MIC90** (µg/mL)
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MIC range (µg/mL)
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Mannheimia haemolytica
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2006
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183
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1.0
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1.0
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0.5 to 32
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Pasteurella multocida
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2006
|
139
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0.5
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0.5
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≤ 0.125 to 16
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Histophilus somni
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2006
|
84
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≤ 0.125
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≤ 0.125
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≤ 0.125 to 0.25
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* The correlation between in vitro
susceptibility data and clinical effectiveness is unknown.
** The lowest MIC to encompass 50% and 90% of the most
susceptible isolates, respectively.
EFFECTIVENESS: In a multi-site field
study, calves with naturally-occurring BRD were treated with RESFLOR
GOLD®, Nuflor Gold® (NADA 141-265), or saline. A treatment
success was defined as a calf with normal respiration to mild
respiratory distress, normal attitude to mildly depressed, and a rectal
temperature < 104.0 °F on Day 11. The treatment success rate for BRD
for the RESFLOR GOLD® treatment group
(68.4%) was statistically significantly greater (p = 0.0255) compared to
the saline control treatment group (42.9%). RESFLOR GOLD® was non-inferior to Nuflor Gold® for the treatment of BRD, with a one-sided
95% lower confidence bound for the difference between the two treatments
equal to -13.2%.
In the same study, the change in rectal temperature from
pre-treatment to six hours post-treatment was evaluated to determine
the effectiveness of RESFLOR GOLD® for
the control of BRD-associated pyrexia. The proportion of calves whose
rectal temperatures decreased by ≥ 2.0 °F from pre-treatment to six
hours post-treatment was statistically significantly greater (p =
0.0019) in the RESFLOR GOLD® treatment
group compared to the saline control treatment group. The mean decrease
in rectal temperature from pre-treatment to six hours post-treatment was
statistically significantly greater in the RESFLOR GOLD® treatment group compared to the Nuflor Gold® and saline control treatment groups (p =
0.0031 and 0.0002, respectively).
The effectiveness of RESFLOR GOLD for the treatment of
BRD associated with Mycoplasma bovis was
demonstrated by examining the M. bovis data
from cattle enrolled in the BRD treatment study described above. There
were numerically more treatment successes (6 of 8 calves, 75%) than
treatment failures (2 of 8 calves, 25%) in RESFLOR GOLD-treated calves
that cultured positive for M. bovis
pre-treatment.
ANIMAL SAFETY: A target animal
safety study was conducted to evaluate the effects of RESFLOR GOLD® when administered to cattle subcutaneously
at 1X, 3X, or 5X the labeled dose for three consecutive days (3X the
labeled duration). Decreased feed and water consumption, and decreased
body weights (secondary to decreased feed consumption) were observed in
the 1X, 3X, and 5X groups. Injection site swellings were noted in the
1X, 3X, and 5X groups.
A separate injection site study was conducted in cattle.
The study demonstrated that RESFLOR GOLD®,
when administered according to the label directions, may induce a
transient local reaction in the subcutaneous and underlying muscle
tissue.
STORAGE INFORMATION: Do not store
above 30°C (86°F). Use within 28 days of first use.
HOW SUPPLIED: RESFLOR GOLD® is available in 100, 250, and 500 mL
sterile, multiple-dose, glass vials.
Made in Germany
Intervet Inc. Roseland, NJ 07068
©2009, Intervet Inc. All rights reserved.
May 2009
100ml Multiple Dose Vial
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US 3448_1 R/US 3448_1 V
5/09 US 1448_1
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250ml Multiple Dose Vial
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5/09 US 1401_1
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500ml Multiple Dose Vial
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5/09 US 1399_1
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NAC No.: 10472981
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