Crofelemer: what the FDA reviewed for dog products
1 Freedom of Information summary from the FDA Center for Veterinary Medicine for products containing Crofelemer, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- CANALEVIA®-CA1 (NADA/ANADA 141-552)
CANALEVIA®-CA1 NADA 141-552, Original approval, December 21, 2021; sponsor Jaguar Animal Health; species: Dogs; foi_id 11727; FDA PDF
Indication
Treatment of chemotherapy-induced diarrhea in dogs (conditional approval).
Dose regimen
1 tablet twice daily for 3 days (dogs weighing 140 pounds or less); 2 tablets twice daily for 3 days (dogs over 140 pounds), Oral, twice daily, 3 days; each delayed-release tablet contains 125 mg crofelemer; tablets must not be broken, crushed or chewed (one additional dose may be given if chewed); with or without food.
Administer 1 tablet orally twice daily for 3 days for dogs weighing ≤ 140 pounds. Administer 2 tablets orally twice daily for 3 days for dogs weighing > 140 pounds.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| other | no quantifiable plasma concentrations before 6 hours post-dose on Day 0 | 30-day study WIL-288006, enteric-coated SP-303 tablets in gelatin capsules, 50/175/600 mg/kg once daily; HPLC LLOQ 100 ng/mL | On Day 0, there were no quantifiable plasma concentrations before 6 hours in any of the groups. |
| other | less than dose-proportional increase in exposure at 175 and 600 mg/kg | 30-day study WIL-288006, once daily oral dosing; systemic exposure attributed to possible disruption of intestinal permeability at high doses | There was a less than dose proportional increase in drug exposure for the 175 and 600 mg/kg groups. |
| other | accumulation index on Day 29 of 2.3, 1.9 and 1.5 for the 50, 175 and 600 mg/kg groups | 30-day study WIL-288006, once daily oral dosing | The accumulation index on Day 29 for the 50, 175, and 600 mg/kg groups was 2.3, 1.9, and 1.5 respectively. |
Target-animal safety
dose multiples 27.2 mg/kg BID, 54.3 mg/kg BID, 162.9 mg/kg BID; duration Twice daily for 9 days (necropsy Day 10); animals 16 males, 16 females (Beagles, about four months old).
Study Animals: Thirty-two healthy Beagle dogs (16 males, 16 females), aged approximately four months old on Study Day 0, weighing 4 to 6.8 kg, determined as healthy based on physical examination and clinical pathology.
| Finding | Quote |
|---|---|
| Dose-dependent red discolored, watery and mucoid feces and vomiting, increased at 162.9 mg/kg; five high-dose dogs vomited tablets. | The findings of red discolored feces, watery feces, mucoid feces, and vomiting were dose dependent and were increased in Group 4 (162.9 mg/kg dose). Five dogs in Group 4 had vomiting with tablets present in the vomitus. |
| Decreased hematocrit at study end in three dogs (one 27.2 mg/kg male, two 162.9 mg/kg females). | Three dogs had a decreased hematocrit (reference range 37.2-52%) at study end compared to pre-study |
| No clinically significant effects on body weight, physical examination, food consumption, ophthalmoscopy, ECG or necropsy. | There were no clinically significant effects on body weight, physical examination findings, food consumption, ophthalmoscopic examination findings, electrocardiogram (ECG), or necropsy findings for any of the groups during the study. |
| Conclusion: no systemic toxicity at 0, 27.2, 54.3 and 162.9 mg/kg twice daily for nine days. | CANALEVIA™ -CA1 administered orally twice a day for nine days at doses of 0, 27.2, 54.3, and 162.9 mg/kg did not produce systemic toxicity. |
| 9-month study (WIL-288022, non-commercial formulation, 50/175/600 mg/kg/day): microcytic hypochromic anemia with thrombocytosis at 600 mg/kg/day. | The results of the hematology indicate a drug effect in the 600 mg/kg/day group only, consisting of microcytic, hypochromic anemia with mild regeneration (inadequate) and thrombocytosis. |
| 9-month study: dose-dependent gross gastrointestinal irritation and discoloration and lymph node discoloration in all crofelemer groups. | Gross lesions including localized irritation of the gastrointestinal tract (reddened areas, erosion, and red streaks) and discoloration of the gastrointestinal tract (dark red areas and gray areas) and lymph nodes (red, gray, and green) were observed in all groups administered crofelemer. |
Effectiveness
Pilot study CANA-001a supporting reasonable expectation of effectiveness (conditional approval): randomized, masked, vehicle-controlled, multicenter field study in shelter-housed and client-owned dogs with acute diarrhea (fecal score 4-5); crofelemer 1.9-12.9 mg/kg (non-commercial enteric-coated beads) or vehicle orally every 12 hours for three days; fecal scores every four hours.; n = 24 evaluable (12 crofelemer, 12 vehicle control); primary endpoint: Resolution of diarrhea (fecal score of 1 or 2, maintained) during the three-day treatment; Fisher's exact test; result: Resolution in 9/12 (75%) crofelemer dogs vs 3/12 (25%) vehicle dogs (P = 0.04; 95% CI 42.8-94.5 vs 5.5-57.2); results extrapolated to chemotherapy-induced diarrhea.
The remaining 24 dogs consisted of 12 dogs who received crofelemer and 12 dogs who received vehicle control. The overall proportion of cases achieving resolution (success) are 75% and 25% for the crofelemer group and the vehicle control group, respectively.
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting (field study CANA-003, acute diarrhea) | 11 (8.2%) | 1 (1.5%) | Vomiting 11 (8.2%) 1 (1.5%) |
| Decreased blood glucose (field study CANA-003) | 10 (7.5%) | 3 (4.5%) | Decreased blood glucose1 10 (7.5%) 3 (4.5%) |
| Urinary system abnormality (field study CANA-003) | 10 (7.5%) | 2 (3%) | Urinary system abnormality2 10 (7.5%) 2 (3%) |
| Upper respiratory signs (field study CANA-003) | 7 (5.2%) | 0 (0%) | Upper respiratory signs3 7 (5.2%) 0 (0%) |
| Decreased serum calcium (field study CANA-003) | 5 (3.7%) | 0 (0%) | Decreased serum calcium4 5 (3.7%) 0 (0%) |
| Appetite decreased (pilot study CANA-001a) | 7 (24%) | 9 (28%) | Appetite decreased 7 (24%) 9 (28%) |
Extraction notes: Conditional approval (2021) under application 141-552 (summary header reads 'Conditional Approval Application'). Effectiveness is a reasonable-expectation pilot study in acute (not chemotherapy-induced) diarrhea with a non-commercial formulation; 37 of 61 enrolled dogs (29 crofelemer, 32 vehicle) were excluded from the effectiveness analysis. Target animal safety uses the 9-day margin of safety study 2530-001 with the commercial formulation; the summary gives doses in mg/kg without label multiples (dose_multiples lists the doses as stated). Toxicokinetics in that study were not evaluated; PK entries come from the 30-day study WIL-288006 (non-commercial enteric-coated tablets) and are qualitative statements plus accumulation indices, not standard parameters. Adverse reaction rows 1-5 are Table III.6 of field study CANA-003 (crofelemer N = 134, placebo N = 66; footnote digits '1'-'4' are attached to the terms in the extracted text); row 6 is Table II.3 of the pilot study (crofelemer N = 29, vehicle N = 32). The cardiovascular study (4 dogs, single doses 60/200/600 mg/kg) showed no cardiovascular effects; pilot studies CANA-001b (48 dogs) and CANA-002 (8 dogs with chemotherapy-induced diarrhea, uncontrolled) are described in the summary but not recorded as rows.
Reproduce: foi_structured_search(query="Crofelemer") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).