Cefpodoxime proxetil: what the FDA reviewed for dog products
4 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Cefpodoxime proxetil, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Canine; Dog; Dogs.
Products
- Cefpodoxime Proxetil Tablets (NADA/ANADA 200-543)
- Cefpodoxime Proxetil Tablets (NADA/ANADA 200-815)
- Simplicef® (NADA/ANADA 141-232)
Cefpodoxime Proxetil Tablets NADA 200-543, Original approval, December 14, 2012; sponsor Dechra Veterinary Products LLC; species: Dogs; foi_id 1230; FDA PDF
Indication
treatment of skin infections (wounds and abscesses) in dogs caused by susceptible Staphylococcus intermedius, Staphylococcus aureus, Streptococcus canis (group G, beta hemolytic), Escherichia coli, Pasteurella multocida and Proteus mirabilis
Dose regimen
5-10 mg/kg (2.3-4.5 mg/lb), Oral, once a day, 5-7 days or 2-3 days beyond cessation of clinical signs, up to a maximum of 28 days; stop after 3-4 days if no response in acute infections
5-10 mg/kg (2.3-4.5 mg/lb) body weight once a day for 5-7 days or 2-3 days beyond the cessation of clinical signs, up to a maximum of 28 days.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 146.65 (test) and 150.85 (reference) (mg/mL)*hr, geometric means AUCt-last (unit as printed) | single oral 100 mg tablet, 40 fasted male beagles, 4-period replicate crossover | The estimated geometric means for the test and reference AUCt-last are 146.65 and 150.85 (mg/mL)*hr, respectively. |
| auc | bioequivalence bounds 90.73%, 104.17% | average bioequivalence, 90% confidence bounds, acceptance 80.0-125.0% | The calculated bioequivalence bounds for AUC (90.73%, 104.17%) fall within the acceptance bounds of 80.0% to 125.0%. |
| cmax | geometric mean ratio test/reference 0.9704 | reference-scaled bioequivalence (CDER progesterone guidance) because within-subject SD of reference >= 0.294 | For CMAX, the geometric mean ratio of the test to reference product (0.9704) is between 0.80 and 1.25 |
| tmax | 3.45 hours (arithmetic mean; SD 3.420; range 1.5-16.0) test | single oral 100 mg, fasted, n=40; columns = mean, SD, minimum, maximum | Test 3.45 3.420 1.5 16.0 |
| tmax | 2.86 hours (arithmetic mean; SD 1.932; range 1.5-16.0) reference | single oral 100 mg, fasted, n=40; columns = mean, SD, minimum, maximum | Reference 2.86 1.932 1.5 16.0 |
Effectiveness
Blood-level bioequivalence study (not a clinical field study): randomized 4-period, 2-treatment, 2-sequence replicate crossover of generic 100 mg tablet vs SIMPLICEF 100 mg tablet in fasted beagles, 7-day washout; n = 40; primary endpoint: AUC (average BE, 80-125%) and CMAX (reference-scaled BE); each test animal >= 2 mg/mL for at least 8 hours (T2-8); result: Bioequivalence concluded; 200 mg strength biowaived on dissolution (>85% dissolved in <15 minutes in all media)
A randomized, four-way crossover, single dose, replicate design bioequivalence study to evaluate the relative bioavailability of a test tablet formulation of cefpodoxime proxetil (100 mg) compared to an equivalent dose of a commercially available reference drug product SIMPLICEF (cefpodoxime proxetil) Tablets (100 mg, Pfizer, Inc.) in 40 fasted, healthy beagle dogs.
Extraction notes: Generic (ANADA) approval; 'CVM did not require effectiveness studies for this approval' and 'CVM did not require target animal safety studies for this approval'. The summary reports no adverse-event data for the bioequivalence study. Concentration units are printed as mg/mL in the extracted text (likely μg/mL lost in PDF extraction); quoted as printed.
Simplicef® NADA 141-232, Supplemental approval, December 16, 2014; sponsor Zoetis Inc.; species: Dog; foi_id 772; FDA PDF
Indication
treatment of skin infections (wounds and abscesses) in dogs caused by susceptible Staphylococcus pseudintermedius, Staphylococcus aureus, Streptococcus canis (group G, beta hemolytic), Escherichia coli, Pasteurella multocida and Proteus mirabilis
Dose regimen
5-10 mg/kg (2.3-4.5 mg/lb), Oral (chewable tablet), once a day, 5 to 7 days, or 2 to 3 days beyond cessation of clinical signs, up to a maximum of 28 days
The dose range of SIMPLICEF (cefpodoxime proxetil) Chewable tablets is 5-10 mg/kg (2.3-4.5 mg/lb) body weight, administered orally, once a day for 5 to 7 days, or for 2 to 3 days beyond the cessation of clinical signs, up to a maximum of 28 days.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| cmax | 44.5 μg/mL (tablet) and 44.3 μg/mL (chewable), least squares means | fed female Beagles (n=30), single oral 100 mg cefpodoxime, 3-period crossover | The following least squares mean PK values were determined for SIMPLICEF tablets and the chewable tablet, respectively: Cmax, 44.5 and 44.3 μg/mL; and AUC0-t(last), 336 and 328 μg•h/mL. |
| auc | 336 μg•h/mL (tablet) and 328 μg•h/mL (chewable), AUC0-t(last) least squares means | fed female Beagles (n=30), single oral 100 mg | The following least squares mean PK values were determined for SIMPLICEF tablets and the chewable tablet, respectively: Cmax, 44.5 and 44.3 μg/mL; and AUC0-t(last), 336 and 328 μg•h/mL. |
| auc | ratio of LS means chewable/tablet 101% (CI 98.8% - 104%) | fed bioequivalence study, n=30; 90% confidence limits; bioequivalent | AUC0-t(last), Chewable tablet/tablet 101% 98.8% - 104% Yes |
| cmax | ratio of LS means chewable/tablet 99.5% (CI 91.5% - 108%) | fed bioequivalence study, n=30; 90% confidence limits; bioequivalent | Cmax Chewable tablet/tablet 99.5% 91.5% - 108% Yes |
| auc | ratio of LS means tablet/chewable 103% (CI 94.1 – 112%) | fasted bioequivalence study, 30 Beagles (15 male, 15 female), single oral 100 mg; 90% confidence limits, standard BE limits | AUC0-t(last), Tablet/Chewable tablet 103% 94.1 – 112% Yes |
| cmax | geometric mean ratio chewable/tablet 1.11; upper confidence bound -0.08; within-animal SD 0.444 (CV 0.47) | fasted bioequivalence study, n=30; scaled (reference-scaled) bioequivalence, upper 95% confidence bound | Cmax 1.11 -0.08 0.444 0.47 Yes |
Effectiveness
Bioequivalence (not a clinical field study): fed comparative PK study of SIMPLICEF film-coated tablet vs chewable tablet, three-sequence, three-period, two-treatment crossover, single oral 100 mg dose (plus a second fasted crossover study in 30 Beagles and comparative dissolution); n = 30 (fed study); 30 (fasted study); primary endpoint: AUC0-t(last) and Cmax 90% CI within 80-125% (scaled BE for Cmax in fasted study); result: SIMPLICEF tablets and SIMPLICEF Chewable tablets bioequivalent in fed and fasted dogs; all strengths >85% dissolved in 15 minutes
Description of Test Animals: Thirty (30) healthy, female Beagles, over 9 months of age and weighing 8.2 to 12.8 kg, were used in the study.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| profuse vomiting with pruritus/urticaria (possible drug reaction), fed BE study | one dog | One dog that vomited profusely and became pruritic with urticaria was removed from the study prior to Period 3 due to a possible drug reaction. The dog recovered. |
Extraction notes: Supplemental approval (2014) adding a flavored chewable tablet; effectiveness demonstrated via bioequivalence to the original tablet and TAS not required ('CVM did not require target animal safety studies for this supplemental approval'). Indication quote taken from Agency Conclusions because the General Information indication text is broken by a PDF line split ('Fo r the treatment'). Fasted study animals: 'Thirty (30) healthy Beagles (15 male and 15 female), aged 9 months to 5 years and weighing 8.2 to 15.8 kg'.
Cefpodoxime Proxetil Tablets NADA 200-815, Original approval, July 08, 2025; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 17208; FDA PDF
Indication
Treatment of skin infections (wounds and abscesses) in dogs caused by susceptible strains of Staphylococcus pseudintermedius, S. aureus, Streptococcus canis (group G, beta hemolytic), Escherichia coli, Pasteurella multocida and Proteus mirabilis.
Dose regimen
5-10 mg/kg (2.3-4.5 mg/lb) body weight, Oral, once a day, once daily for 5-7 days or for 2-3 days beyond cessation of clinical signs, up to a maximum of 28 days; acute infections should not be continued beyond 3-4 days if no response (General Information J, continues across a page break)
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.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | generic 110.79 vs RLNAD 116.77 (μg/mL)*hour (geometric means); ratio 0.95; CI 0.88-1.02 | single 100 mg tablet, oral, fasted beagle dogs, n=40, 4-period crossover; Table II.1 row order: Parameter, sWR, Generic Mean, RLNAD Mean, Ratio, 95% Upper Bound, 90% CI for the Ratio; sWR 0.2135 | AUC (μg/mL)*hour 0.2135 110.79† 116.77† 0.95 NE (0.88, 1.02) |
| cmax | generic 10.61 vs RLNAD 11.24 μg/mL (geometric means); ratio 0.95 | single 100 mg tablet, oral, fasted beagle dogs, n=40; same Table II.1 column order; sWR 0.3273 so RSABE used; 95% upper bound -0.0524 | CMAX (μg/mL) 0.3273 10.61† 11.24† 0.95 -0.0524 NE |
| tmax | generic 2.65 (SD 0.70) vs RLNAD 3.25 (SD 3.39) hours (arithmetic means) | single 100 mg tablet, oral, fasted beagle dogs, n=40; Table II.1 flattened row | TMAX (hours) (SD)‡ NE 2.65 (0.70)‡ 3.25 (3.39)‡ NE NE NE |
Effectiveness
Bioequivalence study (not a clinical effectiveness study): randomized, masked, four-period, two-sequence, single-dose crossover blood-level study of generic 100 mg vs RLNAD SIMPLICEF 100 mg cefpodoxime proxetil tablets in fasted intact male beagle dogs, 7-day washout (Study CEFC-KC2-9723); n = 40; primary endpoint: CMAX and AUC (mixed reference-scaled average bioequivalence approach); TMAX summarized; result: Bioequivalence demonstrated for AUC (average BE; 90% CI within 0.80-1.25) and CMAX (RSABE criteria met); biowaiver granted for the 200 mg strength based on comparative dissolution (>85% in 15 minutes)
The in vivo blood-level study was conducted in 40 healthy, fasted dogs.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| serious adverse events related to administration (bioequivalence study) | There were no serious adverse events related to administration of the generic product or RLNAD reported during the study. |
Extraction notes: Generic ANADA (RLNAD SIMPLICEF, NADA 141-232, Zoetis). No target animal safety or clinical effectiveness studies; effectiveness field holds the pivotal blood-level bioequivalence study. Table II.1 was flattened by PDF extraction; column order given in PK conditions. Duration text of dose regimen spans a page break and is paraphrased in duration_or_conditions.
Simplicef® NADA 141-232, Original approval, July 22, 2004; sponsor Zoetis Inc.; species: Canine; foi_id 771; FDA PDF
Indication
treatment of skin infections (wounds and abscesses) in dogs caused by susceptible Staphylococcus intermedius, Staphylococcus aureus, Streptococcus canis (group G, beta hemolytic), Escherichia coli, Pasteurella multocida and Proteus mirabilis
Dose regimen
5-10 mg/kg (2.3-4.5 mg/lb), Oral, once a day, 5 to 7 days, or 2 to 3 days beyond cessation of clinical signs, up to a maximum of 28 days
The dose range of SIMPLICEF (cefpodoxime proxetil) tablets is 5-10 mg/kg (2.3-4.5 mg/lb) body weight, administered orally, once a day for 5 to 7 days, or for 2 to 3 days beyond the cessation of clinical signs, up to a maximum of 28 days.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 145 (SD 77.6) mcg•hr/mL tablet; 148 (SD 43.1) suspension (AUC0-∞) | single oral 10 mg cefpodoxime/kg, Beagles n=12, 2-way crossover, fasted; columns = suspension (SD), suspension dose-normalized (SD), tablet (SD), tablet dose-normalized (SD) | AUC0-∞ mcg•hr/mL 148 (43.1) 164 (54) 145 (77.6) 161 (72) |
| cmax | 16.4 (SD 11.8) mcg/mL tablet; 17.8 (SD 5.5) suspension | single oral 10 mg/kg, Beagles n=12, crossover; same column order | Cmax mcg/mL 17.8 (5.5) 20.1 (6.20) 16.4 (11.8) 17.8 (11.4) |
| half-life | 5.61 (SD 1.15) hr tablet; 6 (SD 3.01) hr suspension | single oral 10 mg/kg, Beagles n=12; terminal elimination half-life | t1/2,z hr 6 (3.01) - 5.61 (1.15) - |
| tmax | 2.21 (SD 0.542) hr tablet; 2 (SD 0.564) hr suspension | single oral 10 mg/kg, Beagles n=12 | tmax hr 2 (0.564) - 2.21 (0.542) - |
| half-life | 4.67 (± 0.680) hr | single IV 10 mg/kg cefpodoxime sodium, 12 Beagles (Study 7926-2002-0095) | The average values for the terminal elimination half-life was 4.67 (± 0.680) hr, and the average AUC0-∞ was 454 (± 83.1) hr•mcg/mL. |
| clearance | CLtotal 0.023 L/hr/kg (%CV 18); VDss 0.134 (15) L/kg | single IV 10 mg/kg, 12 Beagles | The values (mean, %CV) for VDss, VDλ and CLtotal = 0.134 (15) L/kg, 0.151 (18) L/kg, and 0.023 L/hr/kg (18), respectively. |
| bioavailability | F 0.63 (dose-corrected, tablet) | Royer study 7256-90-084, 6 male Beagles, 100 mg oral tablet vs IV, 3-way crossover; row columns = AUC0-last (%CV), AUC0-last/dose, AUC0-inf/dose, Cmax, Cmax/dose, Tmax, F | tab 259.32 (20) 34.14 (15) 34.71 30.00 (23) 3.96 (20) 2.67 (26) 0.63 (9) |
| half-life | 4.8±0.3 hour | Royer study, plasma terminal elimination half-life; Vdss ~0.11 L/kg, clearance ~0.018 L/hr/kg | The terminal elimination half-life of PNU-76253 in plasma was 4.8±0.3 hour. |
Target-animal safety
dose multiples 0X, 2.5X, 10X; duration 13 consecutive weeks (91 days), once daily; animals 24 (12 male and 12 female).
Description of Test Animals: 12 male and 12 female Beagle dogs 10-14 months old. 3 Control and Treatment Groups: The 24 animals were allocated into 4 replicates of 6 dogs each (3 males and 3 females).
| Finding | Quote |
|---|---|
| Design: 0, 25, 100 mg/kg bulk cefpodoxime in capsules once daily for 13 weeks (0x, 2.5x, 10x of 10 mg/kg) | Dosage amount, frequency, and duration: 0, 25, 100 mg/kg bulk cefpodoxime was administered once daily for 13 consecutive weeks (91 days). |
| No clinical effect except white material (unabsorbed drug) in feces at 100 mg/kg | No observable effect except for white material noted in the feces of the 100 mg/kg group which was considered to be unabsorbed drug. |
| Platelets statistically decreased at 100 and 25 mg/kg/day but means within normal range | The dose group of 100 mg/kg/day was significantly decreased in platelets (PLT) as compared to the control group at weeks 8 and 12 (all p < 0.01) and the dose group of 25 mg/kg/day was also decreased in platelets at weeks 4, 8, and 12 (p < 0.1). However, all treated group means were in the normal range. |
| ALT increases at 100 and 25 mg/kg/day, means within normal range | There were significant increases for the 100 mg/kg/day group at weeks 4 and 8 and for the 25 mg/kg/day group at week 8 as compared to the control group (all p < 0.05). However, all treated group means were in the normal range. |
| Conclusion: differences not toxicologically significant | The statistically significant differences were not considered to be toxicologically significant and not to have clinical relevance because they were sporadic, were not dose-dependent and were within the range of background changes noted in the laboratory where the study was conducted. |
| Puppy tolerance study (3-week-old Beagles, 100 mg/kg for 28 days): no treatment-related effects | No treatment related effects were observed, except for unabsorbed drug in the feces, when PNU-76252 (bulk cefpodoxime) was given to Beagle puppies orally for 28 consecutive days, at a dose of 100 mg/kg. |
| PK-bridged margin of safety for the tablet = 5.9 (suspension 7.0) | Margin of safety tablet = Safety study margin * corrected F bulk drug/F tablet = (100 mg/kg/10 mg/kg)* (0.308/0.52) = 5.9 |
Effectiveness
Multi-center U.S. field study (23 investigators, Jan-Jul 2002), active-controlled non-inferiority: cefpodoxime 5 mg/kg once daily for 5-7 days (tablets or suspension) vs amoxicillin/clavulanic acid 13.75 mg/kg twice daily for 5-7 days in dogs with infected wounds/abscesses; 216 enrolled (118 cefpodoxime, 98 control), 192 evaluable; one-sided 90% CI lower limit > -15%; n = 106 cefpodoxime / 86 amoxicillin-clavulanate (evaluable); primary endpoint: Clinical cure rate at final exam (no purulent exudate, inflammation not worse, no further antimicrobial needed, lesion healed/healing, no relapse); secondary: veterinarian cure rate; result: Clinical cure 94/106 (88.7%) cefpodoxime vs 76/86 (88.4%) control, difference 0.3%, 90% CI (-7.3%, 8.4%), non-inferior; veterinarian cure 101/106 (95.3%) vs 79/86 (91.9%)
Clinical Cure 94/106 88.7% 76/86 88.4% 0.3% (4.6) (-7.3%, 8.4%) Veterinarian Cure 101/106 95.3% 79/86 91.9% 3.4% (3.5) (-2.5%, 10.2%)
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting | 2/118 | 4/98 | Clinical Observation cefpodoxime (n=118) amoxicillin/clavulanic acid (n=98) Vomiting 2 4 Diarrhea 1 1 Increased water drinking 0 2 Decreased appetite 1 1 |
| Diarrhea | 1/118 | 1/98 | Clinical Observation cefpodoxime (n=118) amoxicillin/clavulanic acid (n=98) Vomiting 2 4 Diarrhea 1 1 Increased water drinking 0 2 Decreased appetite 1 1 |
| Increased water drinking | 0/118 | 2/98 | Clinical Observation cefpodoxime (n=118) amoxicillin/clavulanic acid (n=98) Vomiting 2 4 Diarrhea 1 1 Increased water drinking 0 2 Decreased appetite 1 1 |
| Decreased appetite | 1/118 | 1/98 | Clinical Observation cefpodoxime (n=118) amoxicillin/clavulanic acid (n=98) Vomiting 2 4 Diarrhea 1 1 Increased water drinking 0 2 Decreased appetite 1 1 |
Extraction notes: Original 2004 NADA. Effectiveness quote is the flattened Table 3 row pair (columns: #Cure/Total, %, for cefpodoxime then amoxicillin/clavulanic acid, difference (SE), 90% CI); enrollment quote as extracted: 'I cefpodoxime 5 mg/kg SID for 5-7 days 118 (106) II amoxicillin/clavulanic acid 13.75 mg/kg BID for 5-7 days 98 (86) total 216 (192)'. Field study used VANTIN tablets, bridged to SIMPLICEF by dissolution. Adverse-reaction quote is the flattened Table 5 (columns cefpodoxime n=118, amoxicillin/clavulanic acid n=98). TAS pivotal study (1985, Sankyo, GLP) used bulk drug in capsules, hence the PK bridge; margins of safety computed as 5.9 (tablet) and 7.0 (suspension). Dose-characterization wound-model study (50 dogs, 5 and 10 mg/kg vs placebo, p <= 0.001) not extracted into fields.
Reproduce: foi_structured_search(query="Cefpodoxime proxetil") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).