Fuzapladib sodium: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Fuzapladib sodium, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- PANOQUELL®-CA1 (NADA/ANADA 141-567)
PANOQUELL®-CA1 NADA 141-567, Original approval, November 14, 2022; sponsor Ishihara Sangyo Kaisha, Ltd.; species: Dogs; foi_id 13134; FDA PDF
Indication
Management of clinical signs associated with acute onset of pancreatitis in dogs (conditional approval).
Dose regimen
0.4 mg/kg (0.1 mL/kg of reconstituted solution), Intravenous bolus injection over 15 seconds to 1 minute, Once daily, Three consecutive days; lyophilized powder reconstituted with supplied diluent to a 4 mg/mL solution
The reconstituted product is administered at a dosage of 0.4 mg (0.1 mL) per kg of body weight once daily for three consecutive days by intravenous bolus injection over 15 seconds to 1 minute.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | C0 3.55 ± 1.17 µg/mL | Toxicokinetics in 9-day margin-of-safety study; 0.4 mg/kg IV once daily, after ninth dose; mean ± SD; back-extrapolated concentration at time zero | C0 (µg/mL) 3.55 ± 1.17 |
| auc | AUCss 19.2 ± 12.7 hour*µg/mL | 0.4 mg/kg IV once daily for nine days; AUC over dosing interval at steady state; mean ± SD | AUCss (hour*µg/mL) 19.2 ± 12.7 |
| half-life | 7.32 ± 4.08 hour | Terminal elimination half-life; 0.4 mg/kg IV once daily for nine days; mean ± SD | T1/2 (hour) 7.32 ± 4.08 |
| other | Vss 0.216 ± 0.070 L/kg | Volume of distribution at steady state; 0.4 mg/kg IV once daily for nine days | Vss (L/kg) 0.216 ± 0.070 |
| clearance | Clss 0.026 ± 0.009 L/h/kg | Clearance at steady state; 0.4 mg/kg IV once daily for nine days | Clss (L/h/kg) 0.026 ± 0.009 |
| other | Mean accumulation ratio 1.37, 1.36, 1.35 | 0.4, 1.2 and 2 mg/kg IV once daily for nine days (1X, 3X, 5X groups) | Minimal accumulation was observed with a mean accumulation ratio of 1.37, 1.36, and 1.35, for the 0.4, 1.2, and 2 mg/kg dose groups, respectively. |
| other | Exposure greater than dose-proportional between 0.4 and 2 mg/kg | After first and ninth IV dose | The extent of plasma exposure (AUC) was greater than dose-proportional between 0.4 and 2 mg/kg after the first dose and ninth dose. |
Target-animal safety
dose multiples 0X, 1X, 3X, 5X; duration Once daily IV for nine consecutive days; animals 32.
Study Animals: The study included 32 intact Beagle dogs (16 males and 16 females), aged approximately 6.5 - 7.5 months old, with a bodyweight range of 5.8 - 8.7 kg at the start of dosing.
| Finding | Quote |
|---|---|
| Hypertension (>=160 mmHg) only in fuzapladib-treated dogs: 1 dog 1X, 1 dog 3X, 4 dogs 5X | Hypertension, with values ranging from 163 - 194 mmHg, occurred in one dog in the 1X group, one dog in the 3X group, and four dogs in the 5X group. |
| Mild thrombocytopenia in two 1X, one 3X and one 5X dog (one day each) | Mild thrombocytopenia (between 121 - 169 x 103/L; reference range: 171- 361 x 103/L) was observed in two 1X dogs, one 3X dog, and one 5X dog during the treatment phase of the study on one day each. |
| Injection-site swelling more frequent and severe in 5X group | The frequency and severity of swelling increased in the 5X group compared to the other groups. |
| Injection-site histopathology (dermal fibroplasia, inflammation, subcutaneous hemorrhage) in all treated groups, not in controls | The following microscopic observations were noted in dogs in the 1X, 3X, and 5X groups: dermal fibroplasia and subcutaneous inflammation, dermal inflammation, and subcutaneous hemorrhage at the cephalic vein injection sites. |
| No systemic toxicity; acceptable margin of safety at 0, 0.4, 1.2 and 2 mg/kg for nine days | The administration of PANOQUELL®-CA1 as an IV injection once daily for nine days at doses of 0, 0.4, 1.2, and 2 mg/kg fuzapladib sodium did not produce systemic toxicity and had an acceptable margin of safety. |
Effectiveness
Pilot, randomized, blinded, vehicle-controlled, dose-ranging multi-site field study in client-owned dogs with acute onset of pancreatitis (Study AH0027); 61 dogs enrolled (31 fuzapladib, 30 vehicle), 36 evaluable; supports reasonable expectation of effectiveness (conditional approval); n = 17 fuzapladib sodium, 19 vehicle control (evaluable); primary endpoint: Change in group mean total Modified Canine Activity Index (MCAI) score from Day 0 to Day 3; result: Mean change in MCAI score -7.7 (fuzapladib) vs -5.7 (vehicle); statistically significant reduction vs control (p = 0.0193)
Group Fuzapladib sodium Vehicle Control Number of Dogs 17 19 Mean Change in MCAI Scorea -7.7 -5.7 Standard Deviation 2.54 3.79 Median Change in MCAI Score -7.0 -6.0
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Anorexia | 5 (16.1%) | 2 (6.7%) | Anorexia 5 (16.1%) 2 (6.7%) |
| Digestive tract disorders | 5 (16.1%) | 3 (10.0%) | Digestive tract disorders 5 (16.1%) 3 (10.0%) |
| Respiratory tract disorders | 4 (12.9%) | 3 (10.0%) | Respiratory tract disorders 4 (12.9%) 3 (10.0%) |
| Hepatopathy, jaundice | 4 (12.9%) | 2 (6.7%) | Hepatopathy, jaundice 4 (12.9%) 2 (6.7%) |
| Cardiac arrest | 2 (6.5%) | 0 | Cardiac arrest 2 (6.5%) 0 |
| Anaphylaxis | 1 (3.2%) | 0 | Anaphylaxis 1 (3.2%) 0 |
Extraction notes: Conditional approval (reasonable expectation of effectiveness). PK values are toxicokinetic parameters from the 9-day margin-of-safety study (Table III.2, 0.4 mg/kg group after nine doses), quoted as flattened table rows. Adverse reaction rows are from Table II.3 of the pilot field study; column order is fuzapladib sodium (n = 31) then vehicle control (n = 30). Five of 61 enrolled dogs died during the study (4 fuzapladib, 1 vehicle); foreign post-approval reports include facial/tongue swelling, collapse and seizure within 24 hours of administration. Dose selection also supported by a laboratory pancreatitis model (Study AH0019).
Reproduce: foi_structured_search(query="Fuzapladib sodium") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).