Zeniquin Tabs (Marbofloxacin) 25mg
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: 032885
Manf Code: 10000308
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.
Federal law prohibits the extra label use of this drug in food-producing animals.
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
Estimate � SD*
n=6
Total body clearance, (mL/h�kg)
94 � 8
Volume of distribution at steady state, VSS, (L/kg)
1.19 � 0.08
AUC0-inf (�g�h/mL)
59 � 5
Terminal plasma elimination half-life, t1/2(h)
9.5 � 0.7
* 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
Dog
Estimate � SD*
(1.25 mg/lb)
n=6
Dog
Estimate � SD*
(2.5 mg/lb)
n=6
Cat
Estimate � SD*
(2.5 mg/lb)
n=7
Time of maximum concentration, Tmax (h)
1.5 � 0.3
1.8 � 0.3
1.2 � 0.6
Maximum concentration, Cmax, (�g/mL)
2.0 � 0.2
4.2 � 0.5
4.8 � 0.7
AUC0-inf (�g�h/mL)
31.2 � 1.6
64 � 8
70 � 6
Terminal plasma elimination half-life, t1/2(h)
10.7 � 1.6
10.9 � 0.6
12.7 � 1.1
� 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 (�g/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 (�g/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
Marbofloxacin Concentrations (�g/g � SD)
2 hours
(n=4)
18 hours
(n=4)
24 hours
(n=4)
bladder
4.8 � 1.1
2.6 � 1.5
1.11 � 0.19
bone marrow
3.1 � 0.5
1.5 � 1.5
0.7 � 0.2
feces
15 � 9
48 � 40
26 � 11
jejunum
3.6 � 0.5
1.3 � 1.0
0.7 � 0.3
kidney
7.1 � 1.7
1.4 � 0.5
0.9 � 0.3
lung
3.0 � 0.5
0.8 � 0.2
0.57 � 0.19
lymph node
5.5 � 1.1
1.3 � 0.3
1.0 � 0.3
muscle
4.1 � 0.3
1.0 � 0.3
0.7 � 0.2
prostate
5.6 � 1.4
1.8 � 0.6
1.1 � 0.4
skin
1.9 � 0.6
0.41 � 0.13
0.32 � 0.08
* 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
Marbofloxacin Concentrations (�g/g � SD*)
2 hours
(n=4)
18 hours
(n=4)
24 hours
(n=4)
bladder
12 � 4
6 � 7
1.8 � 0.4
bone marrow
4.6 � 1.5
1.28 � 0.13
0.9 � 0.3
feces
18 � 3
52 � 17
47 � 28
jejunum
7.8 � 1.1
2.0 � 0.3
1.1 � 0.3
kidney
12.7 � 1.7
2.7 � 0.3
1.6 � 0.2
lung
5.48 � 0.17
1.45 � 0.19
1.0 � 0.2
lymph node
8.3 � 0.7
2.3 � 0.5
2.03 � 0.06
muscle
7.5 � 0.5
1.8 � 0.3
1.20 � 0.12
prostate
11 � 3
2.7 � 1.0
2.0 � 0.5
skin
3.20 � 0.33
0.705 � 0.013
0.46 � 0.09
* 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* (�g/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
No. of Isolates
MIC50
MIC90
MIC Range
Staphylococcus intermedius
135
0.25
0.25
0.125-2
Escherichia coli
61
0.03
0.06
0.015-2
Proteus mirabilis
35
0.06
0.125
0.03-0.25
Beta-hemolytic Streptococcus, (not Group A or Group B)
25
1
2
0.5-16
Streptococcus, Group D enterococcus
16
1
4
0.008-4
Pasteurella multocida
13
0.015
0.06
≤0.008-0.5
Staphylococcus aureus
12
0.25
0.25
0.25-0.5
Enterococcus faecalis
11
2
2
1-4
Klebsiella pneumoniae
11
0.06
0.06
0.01-0.06
Pseudomonas spp.
9
**
**
0.06-1
Pseudomonas aeruginosa
7
**
**
0.25-1
* 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* (�g/mL) of marbofloxacin against pathogens isolated from skin and soft tissue infections in cats enrolled in clinical studies conducted in 1995 and 1998.
Organism
No. of Isolates
MIC50
MIC90
MIC Range
Pasteurella multocida
135
0.03
0.06
≤0.008-0.25
Beta-hemolytic Streptococcus
22
1
1
0.06-1
Staphylococcus aureus
21
0.25
0.5
0.125-1
Corynebacterium spp.
14
0.5
1
0.25-2
Staphylococcus intermedius
11
0.25
0.5
0.03-0.5
Enterococcus faecalis
10
2.0
2.0
1.0-2.0
Escherichia coli
10
0.03
0.03
0.015-0.03
Bacillus spp.
10
0.25
0.25
0.125-0.25
* 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
