Imepitoin: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Imepitoin, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Pexion™ (NADA/ANADA 141-509)
Pexion™ NADA 141-509, Original approval, December 04, 2018; sponsor Boehringer lngelheim Animal Health USA, Inc.; species: Dogs; foi_id 5907; FDA PDF
Indication
Treatment of noise aversion in dogs
Dose regimen
30 mg/kg (13.6 mg/lb), oral (tablet), twice daily, approximately 12 hours apart, Initiate 2 days prior to the day of the expected noise event and continue through the noise event
PexionTM should be administered orally at a dose of 13.6 mg/lb (30 mg/kg) of body weight twice daily, approximately 12 hours apart using a suitable combination of whole and half tablets. Initiate therapy starting 2 days prior to the day of the expected noise event, and continuing through the noise event.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| tmax | approximately 2 hours | 30 mg/kg oral, fed/fasted crossover, 12 Beagles | Following an oral dose of 30 mg/kg body weight, maximum concentrations of imepitoin were achieved at approximately 2 hours. |
| half-life | approximately 1.5 to 2 hours | 30 mg/kg oral, fed/fasted crossover, 12 Beagles | Imepitoin was eliminated with a half-life from approximately 1.5 to 2 hours. |
| other | fasted dogs approximately 20% greater systemic exposure (AUC) than fed dogs | 30 mg/kg oral, fed vs fasted crossover | A prandial effect was noted wherein fasted dogs had approximately 20% greater systemic exposure than dogs that were fed prior to dosing. |
| cmax | 17168 ng/ml (geometric mean, fasted) | 30 mg/kg oral, 12 Beagles, 2x2 fed/fasted crossover, days 0-5; flattened Table III.3 row order: Tmax (hr), t1/2 (hr), Cmax (ng/ml, geometric mean), AUCinf (hr*ng/ml, geometric mean), Vz (ml/kg), Cl (ml/hr/kg) | Fasted 2.17 1.47 17168 90310 663 320 |
| auc | 90310 hr*ng/ml (AUCinf geometric mean, fasted) | 30 mg/kg oral, 12 Beagles, 2x2 fed/fasted crossover, days 0-5; flattened Table III.3 row order: Tmax (hr), t1/2 (hr), Cmax (ng/ml, geometric mean), AUCinf (hr*ng/ml, geometric mean), Vz (ml/kg), Cl (ml/hr/kg) | Fasted 2.17 1.47 17168 90310 663 320 |
| clearance | 320 ml/hr/kg (fasted) | 30 mg/kg oral, 12 Beagles, 2x2 fed/fasted crossover, days 0-5; flattened Table III.3 row order: Tmax (hr), t1/2 (hr), Cmax (ng/ml, geometric mean), AUCinf (hr*ng/ml, geometric mean), Vz (ml/kg), Cl (ml/hr/kg) | Fasted 2.17 1.47 17168 90310 663 320 |
| cmax | 14892 ng/ml (geometric mean, fed) | 30 mg/kg oral, 12 Beagles, 2x2 fed/fasted crossover, days 0-5; flattened Table III.3 row order: Tmax (hr), t1/2 (hr), Cmax (ng/ml, geometric mean), AUCinf (hr*ng/ml, geometric mean), Vz (ml/kg), Cl (ml/hr/kg) | Fed 2.02 1.95 14892 69238 1129 417 |
| auc | 69238 hr*ng/ml (AUCinf geometric mean, fed) | 30 mg/kg oral, 12 Beagles, 2x2 fed/fasted crossover, days 0-5; flattened Table III.3 row order: Tmax (hr), t1/2 (hr), Cmax (ng/ml, geometric mean), AUCinf (hr*ng/ml, geometric mean), Vz (ml/kg), Cl (ml/hr/kg) | Fed 2.02 1.95 14892 69238 1129 417 |
| half-life | 1.0 to 3.6 hours (range at Week 4); 1.1 to 5.3 hours (Week 24) | 6-month TAS study, 30/90/150 mg/kg twice daily, fasted; systemic accumulation noted | The elimination of half-life values for imepitoin ranged from 1.0 to 3.6 hours at Week 4, and from 1.1 to 5.3 hours at Week 24 (mean values ranged from 1.6 to 2.3 hours at Week 4, and from 1.7 to 2.8 hours at Week 24). |
Target-animal safety
dose multiples 1X (30 mg/kg twice daily), 3X (90 mg/kg twice daily), 5X (150 mg/kg twice daily); duration 6 months (26 consecutive weeks), twice daily oral, fasted, masked GLP; animals 32 (8 per group).
Study Animals: 32 healthy Beagle dogs, approximately 5.5 months of age and 4.9 to 7.3 kg body weight, 8 dogs per group (4 males and 4 females) Treatment Groups and Drug Administration: Imepitoin was administered as an oral tablet twice-daily at approximately 12-hour intervals for 6 months (26 consecutive weeks).
| Finding | Quote |
|---|---|
| Sedation signs (decreased activity, relaxed nictitating membranes) in all groups, dose-dependent; eyelid closure and ataxia only at 5X | Signs of sedation: Decreased activity and relaxed nictitating membranes were seen in all groups and increased in frequency as the dose increased. Eyelid closure and ataxia were seen in 5X dogs only. |
| Vomiting and salivation in all groups, most frequent at 5X | Vomiting and salivation were seen in all groups and had the greatest frequency in the 5X group. |
| Dose-dependent serum creatinine elevation at 3X and 5X; cholesterol elevation in all treated groups | Clinical Chemistry: All dogs in the 3X and 5X groups had dose-dependent elevations in serum creatinine. Dose-dependent elevations in cholesterol occurred in all treated groups. |
| Reduced weight gain and food consumption at 5X in growing dogs | The final body weight, mean cumulative body weight gain, and food consumption were less for dogs in the 5X group when compared to the other groups after 6 months of treatment, suggesting that doses of 5X may delay weight gain in growing animals. |
| No treatment-related ophthalmologic or ECG changes | There were no treatment-related changes in ophthalmologic examinations and ECGs for any of the treated groups compared to the control group. |
| Systemic accumulation of imepitoin during the study | The plasma drug levels observed indicate that systemic accumulation of imepitoin occurred during the study. |
Effectiveness
Multi-site (Germany, Netherlands) randomized 1:1, masked, vehicle-controlled GCP field study (study 2015385) using New Year's Eve fireworks as the noise event; 251 randomized, 238 treated (114 imepitoin, 124 vehicle); 30 mg/kg twice daily from 2 days before through the event; n = 193 evaluable (89 imepitoin, 104 control); primary endpoint: Co-primary: owner-rated overall treatment effect vs previous untreated years (excellent/good/some/no/worse) and sum of 16 Lincoln Sound Sensitivity Scale behavior scores at four fixed time points; result: Good/excellent effect 59/89 imepitoin vs 26/104 control (odds ratio 5.048, 95% CI 2.64-9.66, p=0.0001); behavior-score treatment difference -6.8 (95% CI -10.1 to -3.5), p=0.0004
One hundred and ninety-three (193) animals (89 treated and 104 control) were evaluated for effectiveness. For the first co-primary variable of owner assessed overall treatment effect, the proportion of dogs with good or excellent treatment effect was higher in dogs treated with imepitoin (59/89 dogs) than in those administered control product (26/104 dogs).
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Ataxia | 39 (34.2%) | 4 (3.2%) | Ataxia 39 (34.2) 4 (3.2) |
| Increased appetite | 21 (18.4%) | 1 (0.8%) | Increased appetite 21 (18.4) 1 (0.8) |
| Lethargy | 13 (11.4%) | 3 (2.4%) | Lethargy 13 (11.4) 3 (2.4) |
| Emesis | 9 (7.9%) | 2 (1.6%) | Emesis 9 (7.9) 2 (1.6) |
| Hyperactivity | 7 (6.1%) | 1 (0.8%) | Hyperactivity 7 (6.1) 1 (0.8) |
| Aggression | 3 (2.6%) | 0 | Aggression 3 (2.6) 0 |
Extraction notes: Adverse reaction denominators (Table II.2): imepitoin n=114, vehicle n=124; 46.5% vs 12.1% of dogs had at least one reaction; ataxia led to discontinuation in 6 dogs. Fed/fasted PK values come from flattened Table III.3 rows (geometric means; column order given in conditions). The trademark renders as 'PexionTM' in the extracted text.
Reproduce: foi_structured_search(query="Imepitoin") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).