Cefpodoxime Proxetil Tablets For Oral Use In Dogs Only
CAUTION: Federal law restricts this drug to use by or on the order of a licensed veterinarian.
DESCRIPTION Cefpodoxime proxetil is an orally administered, extended spectrum, semi- synthetic cephalosporin antibiotic. The chemical name is: (+/-)-1-Hy- droxyethyl(+)-(6R,7R)-7-[2-(2-amino-4-thiazolyl)glyoxylamido]-3-methoxy methyl)-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate, 72
-(Z)-
(0-methyloxime), isopropyl carbonate (ester) [87239-81-4]. Cefpodoxime Proxetil Chemical Structure:
ADVERSE REACTIONS A total of 216 dogs of various breeds and ages ranging from 2 months to 15 years were included in the field study safety analysis. The following table shows the number of dogs displaying each clinical observation.
Table 3. Abnormal Health Findings in the U.S. Field Study1 Clinical
Cefpodoxime Increased water
drinking Decreased
appetite
2 1 0
1 Active
Observation Proxetil (n=118) Control (n=98) Vomiting Diarrhea
4 1 2
1 1Dogs may have experienced more than one of the observations during
the study. To report a suspected adverse reaction call 1-866-683-0660.
To request a Material Safety Data Sheet (MSDS) for Cefpodoxime Proxetil Tablets, call 1-866-683-0660.
Cefpodoxime proxetil is a prodrug; its active metabolite is cefpodoxime. All doses of Cefpodoxime Proxetil Tablets are expressed in terms of the active cefpodoxime moiety. Cefpodoxime Proxetil Tablets is available as: 100 mg Tablet, each yellow, elliptical, scored tablet contains cefpodoxime proxetil equivalent to 100 mg of cefpodoxime. 200 mg Tablet, each orange, oblong, tablet contains cefpodoxime proxetil equivalent to 200 mg of cefpodoxime.
INDICATION Cefpodoxime Proxetil Tablets are indicated for the treatment of skin infections (wounds and abscesses) in dogs caused by susceptible strains of Staphylococcus intermedius, Staphylococcus aureus, Streptococcus
canis (group G, ß hemolytic), Escherichia coli, Pasteurella multocida, and Proteus mirabilis.
1
DOSAGE AND ADMINISTRATION Dose range: The dose range of Cefpodoxime Proxetil Tablets is 5-10 mg/kg (2.3-4.5 mg/lb) body weight, administered orally, once a day. The dose may be given with or without food. The determination of dosage for any particular patient must take into consideration such factors as the severity and nature of the infection, the susceptibility of the causative organisms, and the integrity of the patient’s host-defense mechanisms. Obtain a sample of the pathogenic organism for culture and sensitivity testing prior to beginning antimicrobial therapy. Once results become available, continue with appropriate therapy. Duration: Cefpodoxime Proxetil Tablets should be administered once daily for 5-7 days or for 2-3 days beyond the cessation of clinical signs, up to a maximum of 28 days. Treatment of acute infections should not be continued for more than 3-4 days if no response to therapy is seen. Dosing Charts: For daily oral administration of Cefpodoxime Proxetil Tablets at 5 mg/kg (Table 1) and 10 mg/kg (Table 2).
Table 1. Dose Table for Cefpodoxime Proxetil Tablets at 5 mg/kg Total Daily Dosage
Weight of Dog (lbs) Daily Dose
No. of 100 mg tablets No. of 200 mg tablets
Daily Dose
No. of 100 mg tablets No. of 200 mg tablets
22 44 66 88 132 0.5 1 1.5
1 1 1 Weight of Dog (kgs)
10 20 30 40 60 0.5 1 1.5
1 1 1
Table 2. Dose Table for Cefpodoxime Proxetil Tablets at 10 mg/kg Total Daily Dosage
Weight of Dog (lbs) Daily Dose
No. of 100 mg tablets 0.5 1 No. of 200 mg tablets
Daily Dose
11 22 44 66 88 132 1
1 1 2 3 Weight of Dog (kgs)
No. of 100 mg tablets 0.5 1 No. of 200 mg tablets
5 10 20 30 40 60 1
1 1 2 3
CONTRAINDICATIONS Cefpodoxime proxetil is contraindicated in dogs with known allergy to
cefpodoxime or to the ß-lactam (penicillins and cephalosporins) group of antibiotics.
WARNINGS Not for human use. Keep this and all drugs out of reach of children. Antimicrobial drugs, including penicillins and cephalosporins, can cause allergic reactions in sensitized individuals. To minimize the possibility of allergic reactions, those handling such antimicrobials, including cefpodoxime, are advised to avoid direct contact of the product with the skin and mucous membranes.
PRECAUTIONS The safety of cefpodoxime proxetil in dogs used for breeding, pregnant dogs, or lactating bitches has not been demonstrated. As with other cephalosporins, cefpodoxime proxetil may occasionally induce a positive direct Coombs’ test.
0.1
0 48 12 1620 24 28 32 36 Time (hr)
Cefpodoxime is distributed in the body with an apparent volume
of distribution of 151 ± 27 mL/kg. Like other ß-lactam antibiotics, cefpodoxime is eliminated from the body primarily in the urine, with an apparent elimination half-life of approximately 5-6 hours after oral administration. This is similar to the 4.7 hour apparent elimination half-life observed after intravenous dosing. Following intravenous
administration of 10 mg/kg, the average total body clearance (ClB) was 22.7 ± 4.19 mL/hr/kg.
Table 4. Summary of Pharmacokinetic Parameters Obtained after a Single Oral Dose of 10 mg Cefpodoxime/kg BW, Administered as a Tablet
PK Parameter
AUC0-∞ AUC0-LOQ
Unit Tablet (SD)
mcg·hr/mL 145 (77.6) mcg·hr/mL 142 (77.5)
elimination half-life (t½,z) Time of maximum
Maximum concentration (Cmax) mcg/mL 16.4 (11.8) Terminal plasma
hr
concentration (tmax) Mean residence time (MRT0-∞)
hr hr 5.61 (1.15) 2.21 (0.542) 9.21 (1.97)
Microbiology: Like other ß-lactam antibiotics, cefpodoxime exerts its inhibitory effect by interfering with bacterial cell wall synthesis. This
interference is primarily due to its covalently binding to the penicillin- binding proteins (PBPs) (i.e. transpeptidase and/or carboxypeptidase), which are essential for synthesis of the bacterial cell wall. Therefore, cefpodoxime is bactericidal. Cefpodoxime is stable in the presence of
many common ß-lactamase enzymes. As a result, many organisms resistant to other ß-lactam antibiotics (penicillins and some cephalosporins) due to the production of ß-lactamases may be susceptible to cefpodoxime.
Cefpodoxime has a broad spectrum of clinically useful antibacterial activity that includes staphylococci, streptococci, and Gram-negative species (including Pasteurella, Escherichia, and Proteus). The compound is not active against most obligate anaerobes, Pseudomonas spp., or enterococci. The minimum inhibitory concentrations (MICs) for cefpodoxime against Gram-positive and Gram-negative pathogens isolated from canine skin infections (wounds and abscesses) in a 2002 U. S. field study are presented in Table 5. All MICs were determined in accordance with the National Committee for Clinical Laboratory Standards (NCCLS). Appropriate quality control (QC) ranges for in vitro susceptibility testing are presented in Table 6.
b These ranges are for quality control strains used to monitor accuracy of minimum inhibitory concentrations (MICs) of fastidious organisms. When
susceptibility testing is performed for Streptococcus canis (group G, ß hemolytic), Streptococcus pneumoniae ATCC 49619 should be included as a QC strain in the presence of 5% lysed sheep blood (KB disk diffusion method) or 2.5% lysed horse blood (broth micro-dilution method).
EFFECTIVENESS The clinical effectiveness of cefpodoxime proxetil was established in a multi-location (23 site) field study.
In this study, In this study, 216 dogs with infected
wounds or abscesses were treated with either cefpodoxime proxetil (n=118) once daily at 5 mg/kg (2.3 mg/lb) body weight or with a active control antibiotic (n=98) administered twice daily for 5-7 days.
cefpodoxime proxetil was considered noninferior to the active control (88.7% versus 88.4% respectfully) in the treatment of canine skin infections (wounds and abscesses) caused by susceptible strains of Staphylococcus
intermedius, Staphylococcus aureus, Streptococcus canis (group G, ß hemolytic), Escherichia coli, Pasteurella multocida, and Proteus mirabilis.
ANIMAL SAFETY In target animal safety studies, cefpodoxime was well tolerated at exaggerated daily oral doses of 100 mg/kg/day (10 times the maximum label dose) for 13 weeks in adult dogs and for 28 days in puppies (18- 23 days of age). Therefore, once daily administration of cefpodoxime oral tablets at the maximum labeled dose of 10 mg/kg for up to 28 days was shown to be safe in adult dogs and puppies.
Blood dyscrasia including neutropenias, may be seen following high doses of cephalosporins. Cephalosporin administration should be discontinued in such cases.
STORAGE INFORMATION Store at controlled room temperature, 68-77ºF (20-25ºC). Replace cap securely after each opening.
HOW SUPPLIED Cefpodoxime Proxetil Tablets are available in the following strengths (cefpodoxime equivalent), colors, and sizes:
100 mg (yellow, scored, elliptical, debossed with PV on one side, and 17 on the other side) Bottles of 100……………………………………............…NDC 26637-331-10
200 mg (orange, oblong, debossed with PV on one side, 18 on the other side) Bottles of 100……………………………………............…NDC 26637-332-10
ANADA #200-543, Approved by FDA
Manufactured for: Putney, Inc. Portland, ME 04101 USA 1-866-683-0660
Made in Austria May 2012
CLINICAL PHARMACOLOGY Pharmacokinetics/Pharmacodynamics: Cefpodoxime proxetil is a prodrug that is absorbed from and de-esterified in the gastrointestinal tract to its active metabolite, cefpodoxime. Following oral administration to fasting Beagles, oral bioavailability was 63.1 ± 5.3%.
Figure 1. Canine Plasma Concentration of Cefpodoxime After a Single Oral Dose of 10 mg/kg Cefpodoxime Proxetil Tablets
100 10
Table 5. Cefpodoxime Minimum Inhibitory Concentration Values (mcg/mL) from a 2002 Field Study Evaluating Skin Infections (wounds and abscesses) of Canines in the United States.
Organism* # of Isolates MIC50 MIC90 Staphylococcus
intermedius Streptococcus
118
canis (group G, ß hemolytic)
aureus
multocida Proteus mirabilis Staphylococcus
Escherichia coli Pasteurella
33
41 32
14 19
Range 0.12 0.50 0.12->32.0 ≤0.03 ≤0.03 ≤0.03†
0.25 0.50 0.12->32.0 ≤0.03 ≤0.03 ≤0.03-0.12
≤0.03 0.06 ≤0.03-0.06 2.0
2.0 0.12-2.0 †No Range, all isolates yielded the same value.
*Veterinary specific interpretive criteria have not been established for the above listed canine pathogens by the NCCLS at this time.
Table 6. Acceptable Quality Control Ranges for Cefpodoxime QC ATCC
KB Disk strain Drug Escherichia coli
25922 Staphylococcus
aureus 25923 Staphylococcus
pneumoniae 49619
aureus 29213 Streptococcus
10 mcg 28-34 mmb Zone
concentration diameter 10 mcg 23-28 mma
10 mcg 19-25 mma 1-8 mcg/mLa
0.03-0.12 mcg/mLb
a These ranges are for quality control strains used to monitor accuracy of
minimum inhibitory concentrations (MICs) of non-fastidious organisms using cation-adjusted Mueller-Hinton agar or broth medium. The dilution range should encompass the QC ranges of these strains in the broth micro-dilution method.
Broth
Diffusion Method Micro-dilution Method
MIC 0.25-1 mcg/mLa
Conc . (mcg/mL)
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