Zeniquin Tabs (Marbofloxacin) 50mg Zeniquin (marbofloxacin) tablets are indicated for the treatment of infections associated with bacteria susceptible to marbofloxacin, including bacterial skin and soft tissue infections in dogs and cats and urinary tract infections (cystitis) in dogs. For oral use in dogs and cats only. Federal law prohibits the extra-label use of this drug in food-producing animals. Manufacturer: Zoetis MWI SKU: 032887 Manf Code: 10000310 RX: Yes Human Label: No
Zeniquin®
Zoetis
(marbofloxacin)
Tablets
For oral use in dogs and cats only
CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.
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Federal law prohibits the extra label use of this drug in food-producing animals.
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DESCRIPTION: Marbofloxacin is a
synthetic broad-spectrum antibacterial agent from the fluoroquinolone
class of chemotherapeutic agents. Marbofloxacin is the non-proprietary
designation
for 9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[3,2,1-ij][4,1,2]
benzoxadiazine-6-carboxylic acid. The empirical formula is C17H19FN4O4
and the molecular weight is 362.36. The compound is soluble in water;
however, solubility decreases in alkaline conditions. The
N-octanol/water partition coefficient (Kow) is 0.835 measured at pH 7
and 25°C.
Figure 1: Chemical structure of marbofloxacin
CLINICAL PHARMACOLOGY: Marbofloxacin
is rapidly and almost completely absorbed from the gastrointestinal
tract following oral administration to fasted animals. Divalent cations
are generally known to diminish the absorption of fluoroquinolones. The
effects of concomitant feeding on the absorption of marbofloxacin have
not been determined. (See Drug Interactions.) In the dog, approximately 40% of an oral dose of marbofloxacin is excreted unchanged in the urine1.
Excretion in the feces, also as unchanged drug, is the other major
route of elimination in dogs. Ten to 15% of marbofloxacin is metabolized
by the liver in dogs.
In vitro plasma protein binding
of marbofloxacin in dogs was 9.1% and in cats was 7.3%. In the cat,
approximately 70% of an oral dose is excreted in the urine as
marbofloxacin and metabolites with approximately 85% of the excreted
material as unchanged drug. Pharmacokinetic parameters related to
intravenous dosing were estimated in a study of 6 healthy adult beagle
dogs, and are summarized in Table 1. The absolute bioavailability
following dosing of oral tablets to the same animals was 94%.
Marbofloxacin plasma concentrations were determined over
time in healthy adult beagle dogs (6 dogs per dosage group) following
single oral doses of 1.25 mg/lb or 2.5 mg/lb. Absorption of orally
administered marbofloxacin increases proportionally over the dose range
of 1.25 to 2.5 mg/lb. Marbofloxacin plasma concentrations were
determined over time in 7 healthy adult male cats following a single
oral dose of 2.5 mg/lb. Plasma pharmacokinetic parameters following oral
dosing of dogs and cats are summarized in Figures 2 and 3 and in
Table 2. Based on the terminal elimination half-life and the dosing
interval, steady-state levels are reached after the third dose and are
expected to be approximately 25% greater in dogs and 35% greater in cats
than those achieved after a single dose. Marbofloxacin is widely
distributed in canine tissues. Tissue concentrations of marbofloxacin
were determined in healthy male beagle dogs (4 dogs per time period) at
2, 18 and 24 hours after a single oral dose (1.25 or 2.5 mg/lb) and are
summarized in Tables 3a and 3b.
Table 1: Mean pharmacokinetic
parameters following intravenous administration of marbofloxacin to 6
adult beagle dogs at a dosage of 2.5 mg/lb.
Parameter
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Estimate ± SD*
n=6
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Total body clearance, (mL/h•kg)
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94 ± 8
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Volume of distribution at steady state, VSS, (L/kg)
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1.19 ± 0.08
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AUC0-inf (µg•h/mL)
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59 ± 5
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Terminal plasma elimination half-life, t1/2(h)
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9.5 ± 0.7
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* SD = standard deviation
Table 2: Mean pharmacokinetic
parameters following oral administration of marbofloxacin tablets to
adult beagle dogs at a nominal dosage of 1.25 mg/lb or 2.5 mg/lb and to
cats at 2.5 mg/lb.†
Parameter
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Dog
Estimate ± SD*
(1.25 mg/lb)
n=6
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Dog
Estimate ± SD*
(2.5 mg/lb)
n=6
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Cat
Estimate ± SD*
(2.5 mg/lb)
n=7
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Time of maximum concentration, Tmax (h)
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1.5 ± 0.3
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1.8 ± 0.3
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1.2 ± 0.6
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Maximum concentration, Cmax, (µg/mL)
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2.0 ± 0.2
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4.2 ± 0.5
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4.8 ± 0.7
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AUC0-inf (µg•h/mL)
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31.2 ± 1.6
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64 ± 8
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70 ± 6
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Terminal plasma elimination half-life, t1/2(h)
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10.7 ± 1.6
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10.9 ± 0.6
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12.7 ± 1.1
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† mean actual dosages administered to dogs were 1.22
mg/lb and 2.56 mg/lb, respectively, and the mean actual dosage
administered to cats was 2.82 mg/lb.
* SD = standard deviation
Figure 2: Mean plasma
concentrations (µg/mL) following single oral administration of
marbofloxacin to adult beagle dogs at dosages of 1.25 mg/lb or 2.5
mg/lb.
* See Table 4 in Microbiology section for MIC data.
Figure 3: Mean plasma concentrations (µg/mL) following single oral administration of marbofloxacin to adult cats at a dosage of 2.5 mg/lb.
* See Table 5 in Microbiology section for MIC data.
Table 3a: Tissue distribution
following a single oral administration of marbofloxacin tablets to adult
beagle dogs at a dosage of 1.25 mg/lb*.
Tissue
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Marbofloxacin Concentrations (µg/g ± SD)
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2 hours
(n=4)
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18 hours
(n=4)
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24 hours
(n=4)
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bladder
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4.8 ± 1.1
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2.6 ± 1.5
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1.11 ± 0.19
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bone marrow
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3.1 ± 0.5
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1.5 ± 1.5
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0.7 ± 0.2
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feces
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15 ± 9
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48 ± 40
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26 ± 11
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jejunum
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3.6 ± 0.5
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1.3 ± 1.0
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0.7 ± 0.3
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kidney
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7.1 ± 1.7
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1.4 ± 0.5
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0.9 ± 0.3
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lung
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3.0 ± 0.5
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0.8 ± 0.2
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0.57 ± 0.19
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lymph node
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5.5 ± 1.1
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1.3 ± 0.3
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1.0 ± 0.3
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muscle
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4.1 ± 0.3
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1.0 ± 0.3
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0.7 ± 0.2
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prostate
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5.6 ± 1.4
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1.8 ± 0.6
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1.1 ± 0.4
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skin
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1.9 ± 0.6
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0.41 ± 0.13
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0.32 ± 0.08
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* SD = standard deviation
Table 3b: Tissue distribution
following a single oral administration of marbofloxacin tablets to adult
beagle dogs at a dosage of 2.5 mg/lb.
Tissue
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Marbofloxacin Concentrations (µg/g ± SD*)
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2 hours
(n=4)
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18 hours
(n=4)
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24 hours
(n=4)
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bladder
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12 ± 4
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6 ± 7
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1.8 ± 0.4
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bone marrow
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4.6 ± 1.5
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1.28 ± 0.13
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0.9 ± 0.3
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feces
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18 ± 3
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52 ± 17
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47 ± 28
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jejunum
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7.8 ± 1.1
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2.0 ± 0.3
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1.1 ± 0.3
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kidney
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12.7 ± 1.7
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2.7 ± 0.3
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1.6 ± 0.2
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lung
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5.48 ± 0.17
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1.45 ± 0.19
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1.0 ± 0.2
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lymph node
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8.3 ± 0.7
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2.3 ± 0.5
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2.03 ± 0.06
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muscle
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7.5 ± 0.5
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1.8 ± 0.3
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1.20 ± 0.12
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prostate
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11 ± 3
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2.7 ± 1.0
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2.0 ± 0.5
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skin
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3.20 ± 0.33
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0.705 ± 0.013
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0.46 ± 0.09
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* SD = standard deviation
Microbiology: The primary action of
fluoroquinolones is to inhibit the bacterial enzyme, DNA gyrase. In
susceptible organisms, fluoroquinolones are rapidly bactericidal at
relatively low concentrations. Marbofloxacin is bactericidal against a
broad range of gram-negative and gram-positive organisms. The minimum
inhibitory concentrations (MICs) of pathogens isolated in clinical field
studies performed in the United States were determined using National
Committee for Clinical Laboratory Standards (NCCLS) standards, and are
shown in Tables 4 and 5.
Table 4: MIC Values* (µg/mL) of
marbofloxacin against pathogens isolated from skin, soft tissue and
urinary tract infections in dogs enrolled in clinical studies conducted
during 1994-1996.
Organism
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No. of Isolates
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MIC50
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MIC90
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MIC Range
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Staphylococcus intermedius
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135
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0.25
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0.25
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0.125-2
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Escherichia coli
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61
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0.03
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0.06
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0.015-2
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Proteus mirabilis
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35
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0.06
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0.125
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0.03-0.25
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Beta-hemolytic Streptococcus, (not Group A or Group B)
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25
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1
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2
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0.5-16
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Streptococcus, Group D enterococcus
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16
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1
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4
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0.008-4
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Pasteurella multocida
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13
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0.015
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0.06
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≤0.008-0.5
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Staphylococcus aureus
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12
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0.25
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0.25
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0.25-0.5
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Enterococcus faecalis
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11
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2
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2
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1-4
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Klebsiella pneumoniae
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11
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0.06
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0.06
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0.01-0.06
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Pseudomonas spp.
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9
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**
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**
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0.06-1
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Pseudomonas aeruginosa
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7
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**
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**
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0.25-1
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* The correlation between in vitro susceptibility data (MIC) and clinical response has not been determined.
** MIC50 and MIC90 not calculated due to insufficient number of isolates.
Table 5: MIC Values* (µg/mL) of
marbofloxacin against pathogens isolated from skin and soft tissue
infections in cats enrolled in clinical studies conducted in 1995 and
1998.
Organism
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No. of Isolates
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MIC50
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MIC90
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MIC Range
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Pasteurella multocida
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135
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0.03
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0.06
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≤0.008-0.25
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Beta-hemolytic Streptococcus
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22
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1
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1
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0.06-1
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Staphylococcus aureus
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21
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0.25
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0.5
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0.125-1
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Corynebacterium spp.
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14
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0.5
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1
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0.25-2
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Staphylococcus intermedius
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11
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0.25
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0.5
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0.03-0.5
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Enterococcus faecalis
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10
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2.0
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2.0
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1.0-2.0
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Escherichia coli
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10
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0.03
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0.03
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0.015-0.03
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Bacillus spp.
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10
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0.25
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0.25
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0.125-0.25
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* The correlation between in vitro susceptibility data (MIC) and clinical response has not been determined.
INDICATIONS AND USAGE: Zeniquin
(marbofloxacin) tablets are indicated for the treatment of infections in
dogs and cats associated with bacteria susceptible to marbofloxacin.
CONTRAINDICATIONS: Marbofloxacin and
other quinolones have been shown to cause arthropathy in immature
animals of most species tested, the dog being particularly sensitive to
this side effect. Marbofloxacin is contraindicated in immature dogs
during the rapid growth phase (small and medium breeds up to 8 months of
age, large breeds up to 12 months of age and giant breeds up to 18
months of age). Marbofloxacin is contraindicated in cats under 12 months
of age. Marbofloxacin is contraindicated in dogs and cats known to be
hypersensitive to quinolones.
WARNING: For use in animals only. Keep out of reach of children. Avoid
contact with eyes. In case of contact, immediately flush eyes with
copious amounts of water for 15 minutes. In case of dermal contact, wash
skin with soap and water. Consult a physician if irritation persists
following ocular or dermal exposure. Individuals with a history of
hypersensitivity to fluoroquinolones should avoid this product. In
humans, there is a risk of user photosensitization within a few hours
after excessive exposure to quinolones. If excessive accidental exposure
occurs, avoid direct sunlight.
PRECAUTIONS: Quinolones should be
used with caution in animals with known or suspected central nervous
system (CNS) disorders. In such animals, quinolones have, in rare
instances, been associated with CNS stimulation which may lead to
convulsive seizures. Quinolones have been shown to produce erosions of
cartilage of weight-bearing joints and other signs of arthropathy in
immature animals of various species. The use of fluoroquinolones in cats
has been reported to adversely affect the retina. Such products should
be used with caution in cats. The safety of marbofloxacin in animals
used for breeding purposes, pregnant, or lactating has not been
demonstrated.
ADVERSE REACTIONS: The following
clinical signs were reported during the course of clinical field studies
in dogs receiving marbofloxacin at dosages up to 2.5 mg/lb daily:
decreased or loss of appetite (5.4%), decreased activity (4.4%), and
vomiting (2.9%). The following signs were reported in less than 1% of
cases in dogs: increased thirst, soft stool/diarrhea, behavioral
changes, shivering/shaking/tremors, and ataxia. One dog which had a
seizure the day before study enrollment experienced a seizure while on
marbofloxacin therapy.
The following clinical signs were reported during
clinical field studies in cats receiving 1.25 mg/lb/day: diarrhea (2.1%)
and soft stool (1.4%). Vomiting was reported in less than 1% of cases
in cats.
DOSAGE AND ADMINISTRATION: The
recommended dosage for oral administration to dogs and cats is 1.25 mg
marbofloxacin per lb of body weight once daily, but the dosage may be
safely increased to 2.5 mg/lb.
For the treatment of skin and soft tissue infections,
Zeniquin tablets should be given for 2-3 days beyond the cessation of
clinical signs for a maximum of 30 days. For the treatment of urinary
tract infections, Zeniquin tablets should be administered for at least
10 days. If no improvement is noted within 5 days, the diagnosis should
be re-evaluated and a different course of therapy considered.
Drug Interactions: Compounds (e.g.,
sucralfate, antacids, and mineral supplements) containing divalent and
trivalent cations (e.g., iron, aluminum, calcium, magnesium, and zinc)
can interfere with the absorption of quinolones which may result in a
decrease in product bioavailability. Therefore, the concomitant oral
administration of quinolones with foods, supplements, or other
preparations containing these compounds should be avoided