Cephalexin: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Cephalexin, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Rilexine® (NADA/ANADA 141-326)
Rilexine® NADA 141-326, Original approval, June 16, 2012; sponsor Virbac AH, Inc.; species: Dogs; foi_id 883; FDA PDF
Indication
Treatment of secondary superficial bacterial pyoderma in dogs caused by susceptible strains of Staphylococcus pseudintermedius.
Dose regimen
22 mg/kg (10 mg/lb) body weight, Oral (chewable tablets), Twice daily, 28 days
The recommended dose of RILEXINE (cephalexin) tablets is 22 mg/kg (10 mg/lb) of body weight twice daily for 28 days.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| bioavailability | 90% absolute bioavailability | oral administration, dogs | RILEXINE is readily and nearly completely absorbed following oral administration (90% absolute bioavailability). |
| protein binding | 9 to 13% | canine plasma, concentrations of 0.5 to 100 μg/mL | Binding to canine plasma proteins is low, ranging from 9 to 13% for concentrations of 0.5 to 100 μg/mL. |
| auc | 105.36 ± 17.31 mg.h/L (AUCINF_obs, fasted) | single 22 mg/kg oral dose of RILEXINE Chewable Tablets, beagle dogs, N=12, protein corrected; Table 1 row lists FASTED then FED mean ± SD | AUCINF_obs (mg.h/L) 105.36 ± 17.31 108.35 ± 25.85 |
| auc | 108.35 ± 25.85 mg.h/L (AUCINF_obs, fed) | single 22 mg/kg oral dose of RILEXINE Chewable Tablets, beagle dogs, N=12, protein corrected; Table 1 row lists FASTED then FED mean ± SD | AUCINF_obs (mg.h/L) 105.36 ± 17.31 108.35 ± 25.85 |
| cmax | 21.66 ± 2.74 mg/L (fasted) | single 22 mg/kg oral dose of RILEXINE Chewable Tablets, beagle dogs, N=12, protein corrected; Table 1 row lists FASTED then FED mean ± SD | Cmax (mg/L) 21.66 ± 2.74 16.99 ± 2.71 |
| cmax | 16.99 ± 2.71 mg/L (fed) | single 22 mg/kg oral dose of RILEXINE Chewable Tablets, beagle dogs, N=12, protein corrected; Table 1 row lists FASTED then FED mean ± SD | Cmax (mg/L) 21.66 ± 2.74 16.99 ± 2.71 |
| half-life | 7.33 ± 4.3 h (fasted); 8.79 ± 6.44 h (fed) | single 22 mg/kg oral dose of RILEXINE Chewable Tablets, beagle dogs, N=12, protein corrected; Table 1 row lists FASTED then FED mean ± SD | T1/2 (h) 7.33 ± 4.3 8.79 ± 6.44 |
| tmax | 1.42 ± 0.42 h (fasted); 1.17 ± 0.25 h (fed) | single 22 mg/kg oral dose of RILEXINE Chewable Tablets, beagle dogs, N=12, protein corrected; Table 1 row lists FASTED then FED mean ± SD | Tmax (h) 1.42 ± 0.42 1.17 ± 0.25 |
Target-animal safety
dose multiples 1X, 3X, 5X; duration 12 weeks (three times a day at 1X, 3X, 5X of 22 mg/kg; plus a 22 mg/kg twice-a-day group and placebo control); animals Forty Beagles (20 M and 20 F), four/sex/group.
The objective of the study was to evaluate the safety of RILEXINE Chewable Tablets when administered orally, three times a day, to young, healthy Beagles at 1, 3, and 5 times the proposed target dose (22 mg/kg) for 12 weeks and twice a day at the 1X dose (22 mg/kg) for 12 weeks. b. Test Animals: Forty healthy Beagles (20 M and 20 F), 12 weeks of age at the first treatment (weighing 3.4 to 5.9 kg at randomization), were randomly assigned to the control group or the RILEXINE treatment groups (four/sex/group).
| Finding | Quote |
|---|---|
| All dogs survived to study termination. | Results: All dogs survived to termination of the study. |
| Most common clinical findings across dose groups: epiphora, salivation, vomiting, diarrhea (mild, sporadic). | The most common clinical findings included epiphora, salivation, vomiting, and diarrhea among all the dose groups. |
| Statistically significant dose-dependent ALT increases (110 mg/kg TID and 22 mg/kg BID groups); minimal and within historical control ranges. | There were statistically significant increases in alanine aminotransferase (ALT) (pooled overall results) in the 110 mg/kg three times a day group (P = 0.0246) and in the 22 mg/kg twice a day group (P = 0.0359) that increased in a dose-dependent pattern. These changes were minimal and the values remained within expected historical control ranges. |
| Statistically significant decreases in total protein (110 mg/kg TID) and/or globulin (22, 66, 110 mg/kg TID) vs controls; mild, not clinically relevant. | There were statistically significant decreases in total protein in the 110 mg/kg three times a day group (P = 0.0053), and/or globulin in the 22 (P = 0.0003), 66 (P = 0.0027), and 110 mg/kg (P = 0.0002) three times a day groups compared to the controls. |
| Statistically significant prothrombin time prolongation in the 22 mg/kg TID group, within reference ranges, not clinically relevant. | Coagulation: A statistically significant (P = 0.0222) prolongation in prothrombin time (PT) was observed in the 22 mg/kg three times a day group (pooled results). |
| Macroscopic and microscopic lesions rare and incidental / typical for age and breed. | Gross Pathology and Histopathology: Macroscopic lesions were rare, and were considered incidental findings. |
| Conclusion: 1X, 3X and 5X TID and 1X BID for 12 weeks were well tolerated. | Conclusions: The daily oral administration of cephalexin tablets to young Beagles, three times a day at 1, 3, and 5 times the proposed dose (22 mg/kg), and twice a day at the proposed dose (22 mg/kg) for 12 weeks was well tolerated. |
Effectiveness
Two-group, parallel, multicenter, placebo-controlled, blinded, randomized field study in dogs with naturally occurring secondary superficial bacterial pyoderma; 2:1 randomization to RILEXINE 22 mg/kg (10 mg/lb) orally twice daily for 28 days vs placebo; 211 dogs enrolled (145 RILEXINE, 66 placebo), 131 evaluable for effectiveness; 17 US sites, Oct 2008-Jun 2010.; n = 91 RILEXINE and 40 placebo (effectiveness population); primary endpoint: Treatment success = no lesions to culture at end of treatment (Day 29) and one week later (Day 36) (PCS of 0 for papules, pustules, folliculitis); result: Success 64/91 (70.3%) RILEXINE vs 5/40 (12.5%) placebo, p=0.0009.
N 91 40 Success 64 (70.3%) 5 (12.5%) 0.0009 Failures 27 35 *Absence of lesions at the end of the study At the end of the study, 70% of the dogs in the RILEXINE treatment group were considered a success, whereas 13% of dogs in the placebo treatment group were considered a success (p=0.0009).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Number of dogs with adverse reactions (any) | 50/145 (34%) | 22/66 (33%) | ADVERSE REACTION Rilexine n=145 Placebo n=66 Number of dogs with adverse reactions* 50 (34%) 22 (33%) Vomiting 29 9 Diarrhea 19 6 Anorexia 13 2 Lethargy 9 3 Pruritus 5 0 Dermatitis 4 3 Skin Lesions 5 1 Otitis Externa 4 2 |
| Vomiting | 29/145 | 9/66 | ADVERSE REACTION Rilexine n=145 Placebo n=66 Number of dogs with adverse reactions* 50 (34%) 22 (33%) Vomiting 29 9 Diarrhea 19 6 Anorexia 13 2 Lethargy 9 3 Pruritus 5 0 Dermatitis 4 3 Skin Lesions 5 1 Otitis Externa 4 2 |
| Diarrhea | 19/145 | 6/66 | ADVERSE REACTION Rilexine n=145 Placebo n=66 Number of dogs with adverse reactions* 50 (34%) 22 (33%) Vomiting 29 9 Diarrhea 19 6 Anorexia 13 2 Lethargy 9 3 Pruritus 5 0 Dermatitis 4 3 Skin Lesions 5 1 Otitis Externa 4 2 |
| Anorexia | 13/145 | 2/66 | ADVERSE REACTION Rilexine n=145 Placebo n=66 Number of dogs with adverse reactions* 50 (34%) 22 (33%) Vomiting 29 9 Diarrhea 19 6 Anorexia 13 2 Lethargy 9 3 Pruritus 5 0 Dermatitis 4 3 Skin Lesions 5 1 Otitis Externa 4 2 |
| Lethargy | 9/145 | 3/66 | ADVERSE REACTION Rilexine n=145 Placebo n=66 Number of dogs with adverse reactions* 50 (34%) 22 (33%) Vomiting 29 9 Diarrhea 19 6 Anorexia 13 2 Lethargy 9 3 Pruritus 5 0 Dermatitis 4 3 Skin Lesions 5 1 Otitis Externa 4 2 |
| Pruritus | 5/145 | 0/66 | ADVERSE REACTION Rilexine n=145 Placebo n=66 Number of dogs with adverse reactions* 50 (34%) 22 (33%) Vomiting 29 9 Diarrhea 19 6 Anorexia 13 2 Lethargy 9 3 Pruritus 5 0 Dermatitis 4 3 Skin Lesions 5 1 Otitis Externa 4 2 |
Extraction notes: PK Table 1 and adverse-reaction Table 4 were flattened by PDF extraction; PK rows are quoted as extracted with FASTED value first, FED value second; Table 4 rows are 'term Rilexine-count Placebo-count' with n=145 and n=66 in the header. Additional PK (not captured): AUClast 97.33 ± 13.18 (fasted) / 95.19 ± 11.84 (fed) mg.h/L; PK/PD target T>MIC (MIC90 2 μg/mL assumed) met in all 12 dogs after first dose fed and fasted. Duration of dosing supported by a European field study of a non-palatable formulation (15 mg/kg BID vs amoxicillin/clavulanate; 22/24 vs 21/29 lesion-free, p>0.05). TAS study: geometric mean trough cephalexin at Week 12 was 11.2 mcg/mL (110 mg/kg TID), 8.7 (66 mg/kg TID), 2.6 (22 mg/kg TID); 0.7-1.3 mcg/mL for 22 mg/kg BID. Of 211 enrolled, 80 excluded from effectiveness evaluation (mostly negative culture). MIC data: pre-treatment S. pseudintermedius MIC50 1, MIC90 2 μg/mL. Five-year exclusivity.
Reproduce: foi_structured_search(query="Cephalexin") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).