Clomipramine Hydrochloride: what the FDA reviewed for dog products
4 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Clomipramine Hydrochloride, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- CLOMICALM® (NADA/ANADA 141-120)
- Clomipramine Hydrochloride Tablets (NADA/ANADA 200-635)
- Clomipramine Hydrochloride Tablets (NADA/ANADA 200-825)
CLOMICALM® NADA 141-120, Original approval, December 10, 1998; sponsor Virbac AH, Inc.; species: Dogs; foi_id 646; FDA PDF
Indication
Part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age.
Dose regimen
2 to 4 mg/kg/day (0.9 - 1.8 mg/lb/day), Oral, single daily dose or divided twice daily, May be given with a small amount of food to reduce vomiting; dose may be reduced or discontinued once the desired effect is achieved and behavior modification instituted; tapering recommended.
The recommended daily dose of Clomicalm Tablets is 2 to 4 mg/kg/day (0.9 - 1.8 mg/lb/day). It can be administered as a single daily dose or divided twice daily based on patient response and/or tolerance of side effects.
Target-animal safety
dose multiples 1X (4 mg/kg/day), 3X (12 mg/kg/day), 5X (20 mg/kg/day); duration 6 months daily oral dosing, tapered over the last 6 days; animals 24M, 24F Beagles in 4 groups of 12.
Animals: Forty-eight (24M, 24F) Beagle dogs, 5 months of age, were randomly assigned to 4 groups of 12 dogs each.
| Finding | Quote |
|---|---|
| All animals survived; vomiting occurred in all groups including controls but more frequently at 12 and 20 mg/kg/day. | All animals survived to the scheduled necropsy. Vomiting was seen in all groups including controls, but occurred more frequently in dogs receiving 12 and 20 mg/kg/day during the study. |
| Decreased activity in one 4 mg/kg/day dog and four 20 mg/kg/day dogs during weeks 1-13. | One dog from the 4 mg/kg/day group and 4 dogs from the 20 mg/kg/day group showed decreased activity levels during weeks 1-13. |
| No test article-related changes in hematology, biochemistry, macroscopic, organ weight or microscopic findings. | There were no test article-related alterations in the hematology or biochemistry parameters evaluated or the macroscopic, organ weights or microscopic observations at necropsy. |
| Corroborative 12-month Corgi study (12.5, 50, 100 mg/kg/day): five high-dose (100 mg/kg/day) dogs died between weeks 8 and 21. | Five dogs from the high dose group died between weeks 8 and 21. Death was preceded by a period of weight loss and the clinical signs seen included convulsions, lethargy and pupil dilation. |
| Corgi study: testicular hypoplasia at doses of 50 mg/kg/day and above (12.5X maximum dose). | Testicular hypoplasia was associated with doses ≥ 50 mg/kg/day (12.5X the recommended maximum dose). |
| Cardiac telemetry study: 20 mg/kg (5X) once daily for 7 days produced reproducible bradycardia and sporadic SA block, AV block and ventricular extrasystole in 3 of 8 dogs. | At 20 mg/kg (5X the maximum recommended dose), Clomicalm Tablets induced reproducible bradycardia. Sino-atrial block, atrio-ventricular block and ventricular extrasystole were also observed sporadically in 3 of 8 dogs when dosed with Clomicalm Tablets. |
Effectiveness
Clinical trial (study B): multi-centered, double-blinded, placebo-controlled; clomipramine 2-4 mg/kg once daily or divided twice daily vs placebo for 56 days, all dogs receiving behavior modification; veterinary evaluations Days 28 and 56 plus daily owner diary tabulated weekly.; n = 181 enrolled; 176 safety; 159 efficacy; primary endpoint: Number of dogs improved in the four entry signs of separation anxiety (salivation, destruction, urination, defecation) compared with the initial visit; result: Once and twice daily regimens did not differ and were combined; percentage improved was higher for clomipramine than placebo each week (e.g. 47% vs 29% week 1, p=0.020; 75% vs 56% week 4, p=0.014); combined regression slope -0.074 vs -0.036 for placebo (p ≤ 0.0220).
Animals: One hundred eighty-one (181) client-owned dogs exhibiting at least one of the following signs of separation anxiety (salivation, destruction, urination, defecation) were enrolled in this study. A total of 176 of these dogs were included in the safety analysis. A total of 159 dogs were included in the efficacy analysis.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting | 20 (17%) | 7 (12%) | Vomiting 20 (17%) 7 (12%) |
| Lethargy | 20 (17%) | 5 (9%) | Lethargy 20 (17%) 5 (9%) |
| Diarrhea | 10 (9%) | 2 (3%) | Diarrhea 10 (9%) 2 (3%) |
| Polydipsia | 6 (5%) | 0 | Polydipsia 6 (5%) 0 |
| Decreased Appetite | 3 (3%) | 3 (5%) | Decreased Appetite 3 (3%) 3 (5%) |
| Dry Mouth | 1 (0.9%) | 1 (2%) | Dry Mouth 1 (0.9%) 1 (2%) |
Extraction notes: Original NADA (1998). The summary has no separate species field; 'Dogs' is taken from the indication. No pharmacokinetic data. Effectiveness uses the pivotal clinical trial (study B); the earlier dose-establishment study A (115 enrolled, 89 efficacy; high dose 1.0-2.0 mg/kg BID vs low dose 0.5-<1.0 mg/kg BID vs placebo, 84 days) is not separately recorded. Result percentages come from Table 3/Table 4 (flattened by PDF extraction). Adverse reactions are Table 5 of study B (clomipramine N = 118, placebo N = 58; columns: treated, placebo). Target animal safety uses the pivotal six-month Beagle study at 4, 12 and 20 mg/kg/day; the summary states 20 mg/kg/day is 5X the daily use rate and the 1X/3X labels are relative to the 4 mg/kg/day maximum label dose. Corgi and telemetry studies are recorded as additional findings.
CLOMICALM® NADA 141-120, Supplemental approval, November 22, 2006; sponsor Virbac AH, Inc.; species: Dogs; foi_id 647; FDA PDF
Indication
Part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age.
Dose regimen
2 to 4 mg/kg/day (0.9 - 1.8 mg/lb/day), Oral, single daily dose or divided twice daily, Scored tablets in 5, 20, 40 and 80 mg strengths.
The recommended daily dose of CLOMICALM Tablets is 2 to 4 mg/kg/day (0.9 - 1.8 mg/lb/day). It can be administered as a single daily dose or divided twice daily based on patient response and/or tolerance of side effects.
Extraction notes: Supplemental NADA (2006) adding a 5 mg tablet size. No new effectiveness or target animal safety studies were required; the summary refers to the original approval FOI summary of December 10, 1998 (foi 646).
Clomipramine Hydrochloride Tablets NADA 200-825, Original approval, October 21, 2025; sponsor Felix Pharmaceuticals Pvt. Ltd.; species: Dogs; foi_id 17687; FDA PDF
Indication
As part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age
Dose regimen
2 to 4 mg/kg/day (0.9 - 1.8 mg/lb/day), Oral (tablets); may be given with a small amount of food to reduce vomiting, Single daily dose or divided twice daily, Once desired effect is achieved the dose may be reduced or discontinued; tapering recommended
The recommended daily dose of Clomipramine Hydrochloride Tablets is 2 to 4 mg/kg/day (0.9 – 1.8 mg/lb/day) (see dosing table below). It can be administered as a single daily dose or divided twice daily based on patient response and/or tolerance of the side effects.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 614.3 (ng/mL)*hour (geometric mean) | Generic clomipramine HCl, single 40 mg oral dose (two 20 mg tablets), fed, 30 dogs, 2-period crossover | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
| auc | 566.5 (ng/mL)*hour (geometric mean) | Clomicalm 20 mg tablets (RLNAD), single 40 mg oral dose, fed, 30 dogs | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
| cmax | 156.4 ng/mL (geometric mean) | Generic, single 40 mg oral dose, fed, 30 dogs | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
| cmax | 153.6 ng/mL (geometric mean) | Clomicalm (RLNAD), single 40 mg oral dose, fed, 30 dogs | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
| tmax | 1.5 hours (arithmetic mean, SD 0.84) | Generic, fed, 30 dogs | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
| tmax | 1.4 hours (arithmetic mean, SD 0.51) | Clomicalm (RLNAD), fed, 30 dogs | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
| other | Geometric mean ratio generic:RLNAD 1.08 for AUC (CI 1.0-1.17) and 1.02 for CMAX (CI 0.90-1.16) | Average bioequivalence; 90% confidence intervals; acceptance limits 0.80-1.25 | AUC (ng/mL)*hour 614.3† 566.5† 1.08 1.0 1.17 CMAX (ng/mL) 156.4† 153.6† 1.02 0.90 1.16 TMAX (hours) (SD)‡ 1.5 (0.84)‡ 1.4 (0.51)‡ NE NE NE |
Effectiveness
ANADA blood-level bioequivalence study only: GLP, randomized, masked, two-period, two-sequence, two-treatment, single-dose crossover (7-day washout) of generic 20 mg vs Clomicalm 20 mg tablets (40 mg dose) in fed dogs; biowaiver for 5, 40 and 80 mg strengths by dissolution; no clinical effectiveness or safety study; n = 30; primary endpoint: 90% CI of geometric mean ratios (generic:RLNAD) for CMAX and AUC within 0.80-1.25; result: Bioequivalent: ratio 1.08 (AUC; 90% CI 1.0-1.17) and 1.02 (CMAX; 90% CI 0.90-1.16)
The laboratory study was conducted as a randomized, masked two-period, two- sequence, two-treatment, single-dose crossover design using 30 dogs with a 7-day washout between periods.
Extraction notes: Generic (ANADA) summary: no effectiveness or target animal safety studies are required or reported; safety/effectiveness rely on the RLNAD Clomicalm (NADA 141-120). Only the in vivo bioequivalence study is summarized (Table II.1 values quoted; the study dosed 40 mg as two 20 mg tablets). No serious adverse events were reported; adverse_reactions left empty. The effectiveness quote contains the PDF line-break artifact 'two- sequence' verbatim.
Clomipramine Hydrochloride Tablets NADA 200-635, Original approval, October 29, 2019; sponsor Mizner Bioscience LLC; species: Dogs; foi_id 7832; FDA PDF
Indication
Part of a comprehensive behavioral management program to treat separation anxiety in dogs greater than 6 months of age
Dose regimen
2 to 4 mg/kg/day (0.9 – 1.8 mg/lb/day), oral, single daily dose or divided twice daily, May be given with a small amount of food to reduce vomiting; may be reduced or discontinued once desired effect achieved and behavior modification instituted
The recommended daily dose of Clomipramine Hydrochloride Tablets is 2 to 4 mg/kg/day (0.9 – 1.8 mg/lb/day) (see dosing table below). It can be administered as a single daily dose or divided twice daily based on patient response and/or tolerance of the side effects.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| auc | 55855 min*ng/mL (geometric mean, generic test product) | Generic 20 mg tablet; single-dose two-period crossover, 28 fed healthy female Beagles (27 evaluable); RLNAD 55315; ratio 1.01 (90% CI 90-113%) | AUC (min*ng/mL) 55855† 55315† 1.01 90 113 |
| cmax | 217 ng/mL (geometric mean, generic test product) | Generic 20 mg tablet; single-dose crossover, fed Beagles; RLNAD 224; ratio 0.97 (90% CI 82-114%) | CMAX (ng/mL) 217† 224† 0.97 82 114 |
| tmax | 89.26 min (arithmetic mean, generic test product) | Generic 20 mg tablet; single-dose crossover, fed Beagles; RLNAD 91.11 min | TMAX (min) 89.26‡ 91.11‡ NE NE NE |
Effectiveness
ANADA bioequivalence study in lieu of clinical effectiveness: randomized, two-period, two-sequence, single-dose crossover of generic 20 mg clomipramine tablet vs RLNAD CLOMICALM 20 mg tablet in fed healthy female Beagle dogs, 21-day washout; biowaiver granted for 5, 40 and 80 mg strengths based on dissolution; n = 28; primary endpoint: 90% confidence interval of generic/RLNAD ratio for AUC and CMAX within 80.00%-125.00%; result: Bioequivalence demonstrated: AUC ratio 1.01 (90-113%), CMAX ratio 0.97 (82-114%)
The in vivo blood- level study was conducted in 28 healthy, fed dogs; however, one animal was removed from the study because of a dosing failure. Bioequivalence was demonstrated between the 20 mg RLNAD clomipramine hydrochloride tablet and the 20 mg generic clomipramine hydrochloride tablet by demonstrating that the confidence limits for the difference between the pivotal parameters CMAX and AUC are contained within the equivalence limits of 80.00% and 125.00%.
Extraction notes: Generic (ANADA) summary: contains only the bioequivalence study; no target animal safety section, no clinical effectiveness study and no adverse-reaction table. The effectiveness block records the pivotal bioequivalence study, clearly labeled as such. PK values are the generic (test) product's BE-study means.
Reproduce: foi_structured_search(query="Clomipramine Hydrochloride") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).