Amoxicillin Trihydrate, Clavulanate Potassium: what the FDA reviewed for dog products
9 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Amoxicillin Trihydrate, Clavulanate Potassium, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dog and cats; Dogs; Dogs (canine periodontal claim; label also covers cats); Dogs (canine soft tissue claim; labeling combined with cats); Dogs and cats.
Products
- Amoxicillin and Clavulanate Potassium Tablets (NADA/ANADA 200-702)
- Amoxicillin and Clavulanate Potassium for Oral Suspension (NADA/ANADA 200-709)
- CLAVAMOX® CHEWABLE Tablets CLAVAMOX® tablets (NADA/ANADA 055-099)
- Clavacillin® (NADA/ANADA 200-592)
- Clavacillin® (NADA/ANADA 200-604)
- Clavamox® Drops (NADA/ANADA 055-101)
Amoxicillin and Clavulanate Potassium Tablets NADA 200-702, Original approval, April 23, 2021; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs and cats; foi_id 10753; FDA PDF
Indication
Dogs: skin and soft tissue infections (wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma) due to susceptible Staphylococcus aureus, Staphylococcus spp., Streptococcus spp. and E. coli; periodontal infections. (Cats: skin/soft tissue and urinary tract infections.)
Dose regimen
6.25 mg/lb body weight, Oral, Twice a day
Dogs: The recommended dosage is 6.25 mg/lb of body weight twice a day.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 25982.3 ng/mL*hour | Amoxicillin, generic 125 mg tablet, geometric mean; 40 fasted female dogs, 4-period crossover (Table II.3 columns: generic, RLNAD, ratio, lower 90% CI, upper 90% CI) | AUC (ng/mL)*hour 25982.3 27140.1 0.96 0.91 1.0 |
| auc | 27140.1 ng/mL*hour | Amoxicillin, RLNAD CLAVAMOX® 125 mg tablet, geometric mean; fasted dogs | AUC (ng/mL)*hour 25982.3 27140.1 0.96 0.91 1.0 |
| cmax | 8689.8 ng/mL | Amoxicillin, generic 125 mg tablet, geometric mean; fasted dogs | CMAX (ng/mL) 8689.8 8999.5 0.97 0.92 1.01 |
| cmax | 8999.5 ng/mL | Amoxicillin, RLNAD CLAVAMOX® 125 mg tablet, geometric mean; fasted dogs | CMAX (ng/mL) 8689.8 8999.5 0.97 0.92 1.01 |
| tmax | 1.3 hr (SD 0.3) | Amoxicillin, generic 125 mg tablet, arithmetic mean; fasted dogs (RLNAD 1.4) | TMAX (hr) (SD) 1.3 (0.3)‡ 1.4 (0.4)‡ NE NE NE |
| other | AUC generic:RLNAD point estimate 0.97; upper confidence bound -0.11 | Clavulanic acid, reference-scaled average bioequivalence (Table II.4 columns: generic mean, RLNAD mean, point estimate, 95% upper confidence bound); means not estimated | AUC (ng/mL)*hour NE NE 0.97 -0.11 |
| other | CMAX generic:RLNAD point estimate 0.99; upper confidence bound -0.12 | Clavulanic acid, reference-scaled average bioequivalence; fasted dogs | CMAX (ng/mL) NE NE 0.99 -0.12 |
| tmax | 1.3 hr (SD 0.3) | Clavulanic acid, generic 125 mg tablet, arithmetic mean; fasted dogs (RLNAD 1.4) | TMAX (hr) (SD) 1.3 (0.3)‡ 1.4 (0.4)‡ NE NE |
Effectiveness
Blood-level bioequivalence study in dogs (17.0566.001), labelled as such: randomized, masked, four-period, two-sequence, single-dose crossover of generic 125 mg tablets vs RLNAD 125 mg CLAVAMOX® in fasted female dogs, 14-day washout; n = 40; primary endpoint: CMAX and AUC (90% CI within 0.80-1.25 for amoxicillin; RSABE for clavulanic acid); result: Bioequivalent: amoxicillin AUC ratio 0.96 (0.91-1.0), CMAX 0.97 (0.92-1.01); clavulanic acid point estimates 0.97 and 0.99 with 95% upper bounds < 0
Study Animals: 40 female dogs between 13 months and 3 years of age.
Extraction notes: Generic ANADA (Cronus, 2021). No effectiveness or target animal safety studies required; effectiveness field records the dog bioequivalence study. Adverse reactions: no serious adverse events reported. Cat bioequivalence study (30 cats) and dissolution biowaiver not extracted.
Amoxicillin and Clavulanate Potassium for Oral Suspension NADA 200-709, Original approval, August 18, 2021; sponsor Cronus Pharma Specialities India Private Ltd.; species: Dogs and cats; foi_id 11187; FDA PDF
Indication
Dogs: skin and soft tissue infections (wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma) due to susceptible Staphylococcus aureus, Staphylococcus spp., Streptococcus spp. and E. coli; periodontal infections. (Cats: skin/soft tissue and urinary tract infections.)
Dose regimen
6.25 mg/lb (1 mL/10 lb) body weight, Oral, Twice a day, Skin/soft tissue and periodontal infections 5-7 days or 48 hours after symptoms subside; deep pyoderma may require 21 days; maximum 30 days
Dogs: The recommended dosage is 6.25 mg/lb (1 mL/10 lb) of body weight twice a day.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 23834.817 ng/mL*hour | Amoxicillin, generic suspension 6.25 mg/lb, geometric mean; 40 fasted female dogs, 4-period crossover (Table II.1 columns: generic, RLNAD, ratio, lower 90% CI, upper 90% CI) | AUC (ng/mL)*hour 23834.817† 21506.937† 1.108 1.011 1.215 |
| auc | 21506.937 ng/mL*hour | Amoxicillin, RLNAD CLAVAMOX® suspension, geometric mean; fasted dogs | AUC (ng/mL)*hour 23834.817† 21506.937† 1.108 1.011 1.215 |
| cmax | 9196.796 ng/mL | Amoxicillin, generic suspension, geometric mean; fasted dogs | CMAX (ng/mL) 9196.796† 8796.990† 1.045 0.995 1.099 |
| cmax | 8796.990 ng/mL | Amoxicillin, RLNAD CLAVAMOX® suspension, geometric mean; fasted dogs | CMAX (ng/mL) 9196.796† 8796.990† 1.045 0.995 1.099 |
| tmax | 1.166 hours (SD 0.343) | Amoxicillin, generic suspension, arithmetic mean; fasted dogs (RLNAD 1.219) | TMAX (hours) (SD‡) 1.166 (0.343)‡ 1.219 (0.380)‡ NE NE NE |
| auc | 6972.384 ng/mL*hour | Clavulanate, generic suspension, geometric mean; fasted dogs (Table II.2; RLNAD 6787.996) | AUC (ng/mL)*hour 6972.384† 6787.996† 1.027 0.958 1.102 |
| cmax | 5007.901 ng/mL | Clavulanate, generic suspension, geometric mean; fasted dogs (RLNAD 4792.935) | CMAX (ng/mL) 5007.901† 4792.935† 1.045 0.972 1.123 |
| tmax | 0.772 hours (SD 0.331) | Clavulanate, generic suspension, arithmetic mean; fasted dogs (RLNAD 0.839) | TMAX (hours) (SD‡) 0.772 (0.331)‡ 0.839 (0.354)‡ NE NE NE |
Effectiveness
Blood-level bioequivalence study in dogs (17.0566.006), labelled as such: randomized, masked, four-period, two-sequence, two-treatment, single-dose crossover of generic suspension vs RLNAD CLAVAMOX® at 6.25 mg/lb in fasted female dogs; n = 40; primary endpoint: CMAX and AUC (90% CI of geometric mean ratio within 0.80-1.25; average bioequivalence for both analytes); result: Bioequivalent: amoxicillin AUC ratio 1.108 (1.011-1.215), CMAX 1.045 (0.995-1.099); clavulanate AUC 1.027 (0.958-1.102), CMAX 1.045 (0.972-1.123)
Study Animals: 40 female dogs between 16 months and 3 years of age
Extraction notes: Generic ANADA (Cronus, 2021). No effectiveness or target animal safety studies required; effectiveness field records the dog bioequivalence study. Adverse reactions: no serious adverse events reported. Cat bioequivalence study (30 cats) not extracted.
CLAVAMOX® CHEWABLE Tablets CLAVAMOX® tablets NADA 055-099, Supplemental approval, December 16, 1985; sponsor Zoetis Inc.; species: Dogs (canine soft tissue claim; labeling combined with cats); foi_id 2629; FDA PDF
Indication
Canine skin and soft tissue infections (wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma) due to susceptible Staphylococcus aureus, Staphylococcus spp., Streptococcus spp. and E. coli
Dose regimen
6.25 mg per pound body weight, Oral (film-coated tablet), Twice a day, Skin and soft tissue infections 5 to 7 days or 48 hours after signs subside; deep pyoderma may require 21 days; maximum 30 days
The recommended dosage is 6.25 mg per pound of body weight administered twice a day.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| cmax | 6.03 mcg/ml | Amoxicillin serum peak after CLAVAMOX oral dosing (amoxicillin 5 mg/lb); crossover in 12 dogs (6 of each sex); AMOXI-TABS 6.41 | The peak height was 6.41 for AMOXI-TABS® and 6.03 for CLAVAMOX®. |
| tmax | 1.67 hours | Amoxicillin time to peak after CLAVAMOX oral dosing, 12 dogs (AMOXI-TABS 1.46) | The time to peak was 1.46 for AMOXI-TABS® and 1.67 for CLAVAMOX®. |
| auc | 15.56 mcg/ml X hrs | Amoxicillin AUC after CLAVAMOX oral dosing, 12 dogs (AMOXI-TABS 18.09) | The area under the curve (mcg/ml X hrs.) was 18.09 for AMOXI-TABS® versus 15.56 for CLAVAMOX®. |
Target-animal safety
dose multiples 0.5X, 1.1X, 2.2X, 5.5X; duration 180 days (6X the recommended duration); animals 52.
A chronic 6 month toxicity study was conducted with amoxicillin/clavulanic acid in 52 beagle dogs (26 male and 26 female) by Dr. Breckenridge at BioResearch Laboratories, Montreal, Canada.
| Finding | Quote |
|---|---|
| Daily dose levels 0, 15, 30, 60, 150 mg/kg = approx. 0.5X-5.5X for 180 days | These dosage levels are approximately 0.5X, 1.1X, 2.2X and 5.5X for a period of 180 days (6X the recommended duration). |
| Minor reversible hepatic and renal histological changes at the high dose | These histological studies revealed minor hepatic and renal changes in the form of cytoplasmic glycogen diminuation or disappearance and tubuler vacuolization via the high dose group which regressed during the 30 day post-treatment regression period. |
| Corroborative 60-day target species study (16 dogs, 1X/3X/5X): safe and non-toxic at 5X | Based on the results obtained in this 60 day study, CLAVAMOX® tablets appear to be safe and non-toxic at a 5X dosage. No differences were observed between the 3 treatment groups and the control. |
Effectiveness
Multicenter blinded randomized field study (22 investigators, 14 states) of CLAVAMOX vs AMOXI-TABS in canine soft tissue infections (wounds/abscesses/cellulitis); 211 cases submitted, 127 bacteriologically evaluable; n = 79 CLAVAMOX, 48 AMOXI-TABS; primary endpoint: Investigator-assessed clinical cure/improvement and bacteriological elimination; result: Cure 86% (68/79) CLAVAMOX vs 75% (36/48) AMOXI-TABS; cure/improvement 95% vs 83%; bacteriological elimination 92% (108/117 isolates) vs 82% (56/68)
Of the 79 dogs treated with CLAVAMOX Tablets, 68 or 86% were evaluated by the investigator as cured compared to 36 of 48 or 75% cured with AMOXI-TABS.
Extraction notes: 1985 supplement adding the canine soft tissue claim; summary repeats the 1984 skin-infection field study, bioequivalency study and safety sections (section parser found no sections; extracted from raw text). The sentence 'Salivation and emesis were observed in the high dose group' is split by a page header in this file and is omitted from findings. No adverse reaction data reported.
CLAVAMOX® CHEWABLE Tablets CLAVAMOX® tablets NADA 055-099, Supplemental approval, December 23, 1997; sponsor Zoetis Inc.; species: Dogs (canine periodontal claim; label also covers cats); foi_id 1952; FDA PDF
Indication
Periodontal infections in dogs due to susceptible aerobic and anaerobic bacteria (added claim)
Dose regimen
6.25 mg (5.0 mg amoxicillin trihydrate/1.25 mg clavulanate potassium)/lb body weight, Oral, Twice a day, Periodontal and skin/soft tissue infections 5-7 days or 48 hours after symptoms subside; deep pyoderma up to 21 days; maximum 30 days
The recommended dosage is 6.25 mg (5.0 mg amoxicillin trihydrate/1.25 mg clavulanate potassium)/lb of body weight twice a day.
Target-animal safety
dose multiples 1X; duration 7 to 10 days (clinical studies at label dose).
Studies AU-G 5000-94 and AU-G 5001-94 demonstrated the safety of Clavamox® for use in clinical cases of canine periodontal infections associated with aerobic and anaerobic infections.
| Finding | Quote |
|---|---|
| No adverse effects in Clavamox-treated dogs in the periodontal clinical studies | No adverse effects were noted in any of the dogs treated with Clavamox® Tabs. |
Effectiveness
Placebo-controlled clinical study (AU-G 5000-94, Univ. of Pennsylvania) in dogs with early gingivitis/periodontal disease: 18 Clavamox vs 18 placebo, 6.25 mg/lb BID for 7-10 days; supported by positive-control study AU-G 5001-94 (42 Clavamox vs 50 Antirobe clindamycin, 6 board-certified dental investigators); n = 18 treated, 18 placebo; primary endpoint: Change in sum of periodontal pocket depths of 6 upper teeth and gingival index pre- vs post-treatment; result: Reduction in summed pocket depth favored Clavamox (2.08 mm) over placebo (0.42 mm), p < 0.05; no clinical failures in either group; 73/77 isolates (94.8%) susceptible. In AU-G 5001-94, Clavamox (1.24 mm) vs Antirobe (0.44 mm) not significantly different (p=0.15)
b. Treated: 18 dogs treated with Clavamox® Tablets. c. Controls: 18 dogs received a placebo.
Extraction notes: Supplemental approval adding the canine periodontal claim. Effectiveness numbers in 'result' are from the text (the sentence containing 2.08 mm is split by an extraction artifact 'Th e overall effect'). TAS is clinical safety at the label dose only; original margin-of-safety studies are in the 1984 FOI summary. No adverse effects reported, so adverse_reactions left empty.
Clavamox® Drops NADA 055-101, Supplemental approval, December 23, 1997; sponsor Zoetis Inc.; species: Dogs (canine periodontal claim; label also covers cats); foi_id 1953; FDA PDF
Indication
Periodontal infections in dogs due to susceptible aerobic and anaerobic bacteria (added claim)
Dose regimen
6.25 mg (5.0 mg amoxicillin trihydrate/1.25 mg clavulanate potassium)/lb body weight (1 mL/10 lb), Oral, Twice a day, Periodontal and skin/soft tissue infections 5-7 days or 48 hours after symptoms subside; deep pyoderma up to 21 days; maximum 30 days
The recommended dosage is 6.25 mg (5.0 mg amoxicillin trihydrate/1.25 mg clavulanate potassium)/lb (1 mL/10 lb) of body weight twice a day.
Effectiveness
No new studies; claim supported by the Clavamox® Tabs periodontal studies (NADA 55-099): placebo-controlled study in 36 dogs and Antirobe-controlled study (42 vs 50 dogs), bridged to Drops by previously demonstrated bioequivalence of Drops to Tabs; n = 36; primary endpoint: Sum of periodontal pocket depths; result: Summed periodontal pocket depths decreased vs placebo; both Clavamox and Antirobe improved periodontal health; no adverse effects
The first study utilized 36 dogs with early signs of gingivitis and periodontal disease, half of which were treated with Clavamox® Tabs and the other half with a placebo.
Extraction notes: Supplemental approval adding the canine periodontal claim to Clavamox Drops; no new studies (effectiveness references the Clavamox Tabs studies in the NADA 55-099 FOI summary; safety references the original Tabs approval). No PK or TAS content.
CLAVAMOX® CHEWABLE Tablets CLAVAMOX® tablets NADA 055-099, Supplemental approval, May 23, 2017; sponsor Zoetis Inc.; species: Dog and cats; foi_id 1462; FDA PDF
Indication
Dogs: skin and soft tissue infections (wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma) due to susceptible Staphylococcus aureus, Staphylococcus spp., Streptococcus spp. and E. coli; periodontal infections. (Cats: skin/soft tissue and urinary tract infections.)
Dose regimen
6.25 mg/lb body weight, Oral, Twice a day, Dosage unchanged from prior approvals of NADA 055-099
Dogs: The recommended dosage is 6.25 mg/lb of body weight twice a day.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 17.69 hr*μg/mL | Amoxicillin AUClast, film-coated CLAVAMOX® 125 mg tablet (reference), geometric LS mean; fasted Beagles, 3-period crossover (Table 2a row columns: AUClast Ref, AUClast Test, Cmax Ref, Cmax Test, Tmax Ref, Tmax Test, Thalf Ref, Thalf Test) | Mean 17.69* 17.68* 5.78* 5.94* 1.48** 1.44** 1.26** 1.24** |
| cmax | 5.78 μg/mL | Amoxicillin Cmax, film-coated CLAVAMOX® 125 mg (reference), geometric LS mean (chewable test 5.94) | Mean 17.69* 17.68* 5.78* 5.94* 1.48** 1.44** 1.26** 1.24** |
| tmax | 1.48 hr | Amoxicillin Tmax, film-coated CLAVAMOX® (reference), arithmetic LS mean (chewable 1.44) | Mean 17.69* 17.68* 5.78* 5.94* 1.48** 1.44** 1.26** 1.24** |
| half-life | 1.26 hr | Amoxicillin terminal half-life, film-coated CLAVAMOX® (reference), arithmetic LS mean (chewable 1.24) | Mean 17.69* 17.68* 5.78* 5.94* 1.48** 1.44** 1.26** 1.24** |
| auc | 4.56 hr*μg/mL | Clavulanic acid AUClast, film-coated CLAVAMOX® 125 mg (reference), geometric LS mean (Table 2c row, same column order; chewable 4.75) | Mean 4.56* 4.75* 3.09* 3.15* 0.93** 1.03** 0.58** 0.59** |
| cmax | 3.09 μg/mL | Clavulanic acid Cmax, film-coated CLAVAMOX® (reference), geometric LS mean (chewable 3.15) | Mean 4.56* 4.75* 3.09* 3.15* 0.93** 1.03** 0.58** 0.59** |
| tmax | 0.93 hr | Clavulanic acid Tmax, film-coated CLAVAMOX® (reference), arithmetic LS mean (chewable 1.03) | Mean 4.56* 4.75* 3.09* 3.15* 0.93** 1.03** 0.58** 0.59** |
| half-life | 0.58 hr | Clavulanic acid terminal half-life, film-coated CLAVAMOX® (reference), arithmetic LS mean (chewable 0.59) | Mean 4.56* 4.75* 3.09* 3.15* 0.93** 1.03** 0.58** 0.59** |
Effectiveness
Bioequivalence study (A461N-US-14-474), labelled as such: two-treatment, three-period crossover of CLAVAMOX® CHEWABLE vs film-coated CLAVAMOX® 125 mg tablet in fasted Beagles; plus a non-randomized, unmasked multi-center palatability field study (A163C-US-13-170) in 112 client-owned dogs; n = 27; primary endpoint: AUClast and Cmax geometric mean ratio 90% CI within 0.80-1.25; result: Bioequivalent: amoxicillin AUClast GMR 1.00 (0.93-1.07), Cmax 1.03 (0.95-1.11); clavulanic acid AUClast GMR 1.04 (0.90-1.21), Cmax 1.02 (0.87-1.20). Palatability: 1293 of 1567 doses (82.51%) freely accepted within five minutes
Description of Test Animals: Twenty-seven (27) healthy, male and female Beagles, over 6 months of age and weighing 7.2 to 13.2 kg, were used in the study.
Extraction notes: Supplement adds a flavored chewable tablet; effectiveness and safety bridged to film-coated tablets by bioequivalence (no new TAS study). Indication quote retains the extraction artifact 'non-β-lactamase- producing'. PK rows are flattened table rows; column order described in conditions. Cat relative bioavailability studies (two 24-cat studies; amoxicillin failed unscaled BE in one, RSABE passed in the other) not extracted. No adverse reactions reported in the summary.
Clavacillin® NADA 200-604, Original approval, October 20, 2021; sponsor Dechra Veterinary Products LLC; species: Dogs and cats; foi_id 11403; FDA PDF
Indication
Dogs: skin and soft tissue infections (wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma) due to susceptible Staphylococcus aureus, Staphylococcus spp., Streptococcus spp. and E. coli; periodontal infections. (Cats: skin/soft tissue and urinary tract infections.)
Dose regimen
6.25 mg/lb (1 mL/10 lb) body weight, Oral, Twice a day, Skin/soft tissue and periodontal infections 5-7 days or 48 hours after symptoms subside; deep pyoderma may require 21 days; maximum 30 days
Dogs: The recommended dosage is 6.25 mg/lb (1 mL/10 lb) of body weight twice a day.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 22.57 µg/mL*hour | Amoxicillin, generic suspension 0.1 mL/lb, geometric mean; 30 fasted male dogs, 2-period crossover (Table II.1 columns: generic, RLNAD, ratio, lower 94.4% CI, upper 94.4% CI) | AUC (µg/mL)*hour 22.57† 22.85† 0.99 0.94 1.04 |
| auc | 22.85 µg/mL*hour | Amoxicillin, RLNAD Clavamox® Drops, geometric mean; fasted dogs | AUC (µg/mL)*hour 22.57† 22.85† 0.99 0.94 1.04 |
| cmax | 8.13 µg/mL | Amoxicillin, generic suspension, geometric mean; fasted dogs | CMAX (µg/mL) 8.13† 8.31† 0.98 0.92 1.04 |
| cmax | 8.31 µg/mL | Amoxicillin, RLNAD Clavamox® Drops, geometric mean; fasted dogs | CMAX (µg/mL) 8.13† 8.31† 0.98 0.92 1.04 |
| tmax | 1.12 hours (SD 0.26) | Amoxicillin, generic suspension, arithmetic mean; fasted dogs (RLNAD 1.19) | TMAX (hours) (SD‡) 1.12 (0.26)‡ 1.19 (0.35)‡ NE NE NE |
| auc | 6.27 µg/mL*hour | Clavulanic acid, generic suspension, geometric mean; fasted dogs (Table II.2; RLNAD 6.47) | AUC (µg/mL)*hour 6.27† 6.47† 0.97 0.87 1.08 |
| cmax | 4.07 µg/mL | Clavulanic acid, generic suspension, geometric mean; fasted dogs (RLNAD 4.21) | CMAX (µg/mL) 4.07† 4.21† 0.97 0.85 1.10 |
| tmax | 0.80 hours (SD 0.26) | Clavulanic acid, generic suspension, arithmetic mean; fasted dogs (RLNAD 0.85) | TMAX (hours) (SD‡) 0.80 (0.26)‡ 0.85 (0.39)‡ NE NE NE |
Effectiveness
Blood-level bioequivalence study in dogs (D19001), labelled as such: randomized two-period, two-treatment, two-sequence crossover with a two-stage sample-size adaptive sequential design; generic suspension vs Clavamox® Drops at 0.1 mL per lb in fasted male dogs; n = 30; primary endpoint: CMAX and AUC (94.4% CI of geometric mean ratio within 0.80-1.25 at Stage 1); result: Bioequivalent: amoxicillin AUC ratio 0.99 (0.94-1.04), CMAX 0.98 (0.92-1.04); clavulanic acid AUC 0.97 (0.87-1.08), CMAX 0.97 (0.85-1.10)
Study Animals: 30 male dogs between 12.8 – 13.6 months of age and weighing 7.2 to 10.8 kg.
Extraction notes: Generic ANADA (Dechra, 2021; catalogue name Clavacillin®). No effectiveness or target animal safety studies required; effectiveness field records the dog bioequivalence study. PK values from flattened tables (column order in conditions). Adverse reactions: no serious adverse events reported. Cat bioequivalence study (40 cats) not extracted.
Clavacillin® NADA 200-592, Original approval, September 08, 2016; sponsor Dechra Veterinary Products LLC; species: Dogs and cats; foi_id 1263; FDA PDF
Indication
Dogs: skin and soft tissue infections (wounds, abscesses, cellulitis, superficial/juvenile and deep pyoderma) due to susceptible Staphylococcus aureus, Staphylococcus spp., Streptococcus spp. and E. coli; periodontal infections. (Cats: skin/soft tissue and urinary tract infections.)
Dose regimen
6.25 mg/lb body weight, Oral, Twice a day, Skin/soft tissue and periodontal infections 5-7 days or 48 hours after symptoms subside; deep pyoderma may require 21 days; maximum 30 days
Dogs: The recommended dosage is 6.25 mg/lb of body weight twice a day.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 18.26 µg/mL*hour | Amoxicillin, generic 125 mg tablet, geometric mean; 40 fasted intact male beagles, 4-period crossover (Table 1 columns: generic, RLNAD, lower bound, upper bound) | AUC (µg/mL) *hour 18.26* 18.82* 88% 106% |
| auc | 18.82 µg/mL*hour | Amoxicillin, RLNAD CLAVAMOX 125 mg tablet, geometric mean; fasted dogs | AUC (µg/mL) *hour 18.26* 18.82* 88% 106% |
| cmax | 6.31 µg/mL | Amoxicillin, generic 125 mg tablet, geometric mean; fasted dogs | CMAX (µg/mL) 6.31* 6.51* 87% 107% |
| cmax | 6.51 µg/mL | Amoxicillin, RLNAD CLAVAMOX 125 mg tablet, geometric mean; fasted dogs | CMAX (µg/mL) 6.31* 6.51* 87% 107% |
| tmax | 1.47 hour | Amoxicillin, generic 125 mg tablet, arithmetic mean; fasted dogs (RLNAD 1.48) | TMAX (hour) 1.47† 1.48† NA NA |
| other | AUC generic/RLNAD geometric mean ratio 0.92; upper bound -0.034 | Clavulanic acid, reference-scaled average bioequivalence (Table 2 columns: generic mean, RLNAD mean, generic/RLNAD ratio, 95% upper bound) | AUC (µg /mL) *hour NA NA 0.92* -0.034 |
| other | CMAX generic/RLNAD geometric mean ratio 0.92; upper bound -0.037 | Clavulanic acid, reference-scaled average bioequivalence; fasted dogs | CMAX (µg /mL) NA NA 0.92* -0.037 |
| tmax | 1.01 hour | Clavulanic acid, generic 125 mg tablet, arithmetic mean; fasted dogs (RLNAD 1.03) | TMAX (hour) 1.01† 1.03† NA NA |
Effectiveness
Blood-level bioequivalence study in dogs (S12865), labelled as such: randomized two-sequence, four-period replicate crossover of generic 125 mg tablets vs CLAVAMOX 125 mg in fasted intact male beagles, 7-day washout; n = 40; primary endpoint: AUC and CMAX (90% CI within 80-125% for amoxicillin; RSABE for clavulanic acid); result: Bioequivalent: amoxicillin AUC bounds 88-106%, CMAX 87-107%; clavulanic acid ratios 0.92 with 95% upper bounds below 0
The study was conducted as a two-sequence, four-period, crossover design using 40 dogs with a 7-day washout between periods.
Extraction notes: Generic ANADA (Putney, 2016; catalogue name Clavacillin®). CVM did not require effectiveness or target animal safety studies; effectiveness field records the dog bioequivalence study. Indication quote retains the extraction artifact 'non-β-lactamase- producing'. Cat bioequivalence study (30 cats, 62.5 mg) and dissolution biowaiver not extracted. No adverse reactions reported in the summary.
CLAVAMOX® CHEWABLE Tablets CLAVAMOX® tablets NADA 055-099, Original approval, September 28, 1984; sponsor Zoetis Inc.; species: Dogs; foi_id 2625; FDA PDF
Indication
Skin infections (superficial/juvenile and deep pyoderma) of dogs due to susceptible beta-lactamase producing and non-producing Staphylococcus aureus and Staphylococcus spp.
Dose regimen
6.25 mg per pound body weight (5 mg amoxicillin + 1.25 mg clavulanic acid per pound), Oral (film-coated tablet), Twice a day, 10-14 days or 48 hours after symptoms subside; re-evaluate if no response after 7 days; maximum 30 days
The recommended dosage is 6.25 mg per pound of body weight administered twice a day. This results in a therapeutic dosage of 5 mg of amoxicillin and 1.25 mg of clavulanic acid per pound of body weight per dose.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| cmax | 6.03 mcg/ml | Amoxicillin serum peak after SYNULOX oral dosing (amoxicillin 5 mg/lb); crossover in 12 dogs (6 of each sex); AMOXI-TABS comparator 6.41 | The peak height was 6.41 for AMOXI -TABS® and 6.03 for SYNULOX™. |
| tmax | 1.67 hours | Amoxicillin time to peak after SYNULOX oral dosing, 12 dogs (AMOXI-TABS 1.46) | The time to peak was 1.46 for AMOXI-TABS® and 1.67 for SYNULOX™. |
| auc | 15.56 mcg/ml X hrs | Amoxicillin AUC after SYNULOX oral dosing, 12 dogs (AMOXI-TABS 18.09); no statistically significant differences | The area under the curve (mcg/ml X hrs.) was 18.09 for AMOXI -TABS® versus 15.56 for SYNULOX™. |
Target-animal safety
dose multiples 0.5X, 1.1X, 2.2X, 5.5X; duration 180 days (6X the recommended duration) plus 30-day regression in high-dose and control subsets; animals 52.
A chronic 6 month toxicity study was conducted with amoxicillin/clavulanic acid in 52 beagle dogs (26 male and 26 female) by Dr. Breckenridge at BioResearch Laboratories, Montreal, Canada.
| Finding | Quote |
|---|---|
| Daily dose levels 0, 15, 30, 60, 150 mg/kg = approx. 0.5X-5.5X for 180 days | These dosage levels are approximately 0.5X, 1.1X, 2.2X and 5.5X for a period of 180 days (6X the recommended duration). |
| Salivation and emesis in the high-dose group | Salivation and emesis were observed in the high dose group. |
| Minor reversible hepatic and renal histological changes at the high dose | These histological studies revealed minor hepatic and renal changes in the form of cytoplasmic glycogen diminuation or disappearance and tubuler vacuolization via the high dose group which regressed during the 30 day post-treatment regression period. |
| Corroborative 60-day target species study (16 dogs, 1X/3X/5X): safe and non-toxic at 5X | Based on the results obtained in this 60 day study, SYNULOX™ tablets appear to be safe and non-toxic at a 5X dosage. No differences were observed between the 3 treatment groups and the control. |
| No histological evidence of testicular/ovarian toxicity at 5X for 60 days | No histological evidence of toxicity was noted at the 5X dosage after 60 days of treatment. |
Effectiveness
Multicenter blinded randomized field study (16 investigators, 9 states) of SYNULOX (amoxicillin 5 mg/lb + clavulanic acid 1.25 mg/lb BID) vs AMOXI-TABS (amoxicillin 5 mg/lb BID) in canine skin infections; 296 cases enrolled, 113 evaluable; n = 74 SYNULOX, 39 amoxicillin (113 evaluable); primary endpoint: Overall clinical response (cure / improvement / failure) and bacteriological elimination; result: Cure rate 61% SYNULOX vs 41% amoxicillin (cure/improvement 74% vs 56%); deep pyoderma cure 48% vs 0%; bacteriological elimination 80% (66/83) vs 74% (37/50)
Of the 113 acceptable cases, 74 involved treatment with SYNULOX™ and 39 with amoxicillin. The SYNULOX™ cases demonstrated a 61% "cure" rate while a 41% "cure" rate was observed in the amoxicillin cases.
Extraction notes: 1984 original approval under the SYNULOX name (Beecham); catalogue lists NADA 055-099 as CLAVAMOX. Section parser found only agency_conclusions; extracted from raw text. PK is a 1984 amoxicillin serum bioequivalency study vs AMOXI-TABS (no clavulanate PK). Pivotal TAS is the 6-month chronic study; corroborative 60-day study used 0, 125, 375, 625 mg per 20 lb dog BID (1X/3X/5X) in 16 dogs. Field study reported no adverse reaction table. Extensive laboratory-animal toxicology not extracted.
Reproduce: foi_structured_search(query="Amoxicillin Trihydrate, Clavulanate Potassium") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).