Ilunocitinib: what the FDA reviewed for dog products
2 Freedom of Information summaries from the FDA Center for Veterinary Medicine for products containing Ilunocitinib, as typed records: every value below is followed by the verbatim passage it was taken from. Species as stated by each summary: Dogs.
Products
- Zenrelia™ (NADA/ANADA 141-585)
Zenrelia™ NADA 141-585, Original approval, September 19, 2024; sponsor Elanco US Inc.; species: Dogs; foi_id 15865; FDA PDF
Indication
Control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age.
Dose regimen
0.6 to 0.8 mg/kg (0.27 to 0.36 mg/lb), Oral (tablet), Once daily, With or without food; Zenrelia should be discontinued at least 28 days to 3 months prior to vaccination and not given for at least 28 days after any vaccination
The dose of ZenreliaTM (ilunocitinib tablets) is 0.27 to 0.36 mg ilunocitinib/lb (0.6 to 0.8 mg ilunocitinib/kg) body weight, administered orally, once daily, with or without food.
Pharmacokinetics
| Parameter | Value | Conditions | Quote |
|---|---|---|---|
| bioavailability | 80% fed, 60% fasted (AUClast-based) | Single oral or IV dose of 0.8 mg/kg; geometric means | Following a single oral or intravenous administration of ilunocitinib at 0.8 mg/kg, the oral bioavailability based on area under the curve from the time of dosing to the last quantifiable plasma concentration (AUClast) was 80% in the fed state and 60% in the fasted state. |
| clearance | 399 mL/h/kg | Systemic clearance after IV administration of 0.8 mg/kg | The systemic clearance following intravenous administration was 399 mL/h/kg with a terminal half-life of 3.6 h. |
| half-life | 3.6 h | Terminal half-life after IV administration of 0.8 mg/kg | The systemic clearance following intravenous administration was 399 mL/h/kg with a terminal half-life of 3.6 h. |
| other | Volume of distribution 1390 mL/kg | IV administration; n=8 | The volume of distribution was 1390 mL/kg (n=8). |
| other | Food effect: Cmax 120% and AUClast 45% higher fed vs fasted | Single oral dose 0.8 mg/kg; n=16 | The maximum plasma concentration (Cmax) and AUClast were 120% and 45% higher, respectively, in the fed state as compared to the fasted state (n=16). |
| cmax | 310 ng/mL (CV 20.6%) | 0.8 mg/kg (1X) group, Day 182 of 6-month margin-of-safety study, fed; geometric mean | Cmax (ng/mL) 310 (20.6%) |
| auc | AUClast 1360 h*ng/mL (CV 25.1%) | 0.8 mg/kg group, Day 182, fed; geometric mean; AUCinf 1370 h*ng/mL | AUClast (h*ng/mL) 1360 (25.1%) |
| half-life | 3.29 h (CV 11.9%) | 0.8 mg/kg group, Day 182 (steady state), fed; Tmax median 2 h (range 1-2); minimal accumulation (ratios 1.1-1.6) | t½ (h) 3.29 (11.9%) |
Target-animal safety
dose multiples 0X, 1X, 2X, 3X, 5X; duration 182 consecutive days (6 months), once daily oral tablet in the fed state, 11-12-month-old Beagles (0.8 mg/kg/day = 1X); animals Forty (20 female, 20 male).
Study Animals: Forty beagle dogs (20 female and 20 male), approximately 11-12 months of age, weighing between 5.5 to 12.4 kg, and determined as healthy based on physical examination and clinical pathology were included in the study.
| Finding | Quote |
|---|---|
| Dose-dependent interdigital furunculosis (cysts), swollen/scabbing paws, paw skin thickening | Zenrelia™-related clinical observations included a dose-dependent increase in the frequency and severity of interdigital furunculosis (cysts), with or without discharge on one or more paws, swollen and/or scabbing paws, and paw skin thickening and/or discoloration. |
| Decreased HCT, HGB and RBC without reticulocyte response; decreased MCH, MCHC and eosinophils | Zenrelia™-related clinical pathology findings included decreases in HCT, HGB, and RBC counts without a corresponding increase in absolute reticulocyte count, and decreases in MCH, MCHC, and eosinophil counts. |
| Decreased prostate gland weights in 5X males; papillomas and localized demodicosis | Pathology: Zenrelia™-related pathology changes included decreased prostate gland weights in the 5X group males. |
| Pilot 6-month gavage study (non-final formulation): three dogs at 3X/4.5X euthanized with necrotizing hemorrhagic pneumonia | Results: One dog in the 4.5X group and two dogs in the 3X group were prematurely euthanized (Days 52, 57, and 134, respectively) due to an acute onset of lethargy, labored breathing, fever, tremors, and pale gums, starting within four hours of dosing via oral gavage. |
| Vaccine response study at 3X: two of eight treated dogs euthanized (intussusception with C. canis infection; adenoviral hepatitis/pancreatitis) | Results: Two dogs in the Zenrelia™ group developed serious adverse reactions and were euthanized on Days 52 and 54, prior to evaluation of post-vaccine titers on Day 88. |
| Inadequate rabies titer in 4 of 6 remaining treated dogs on Day 88; vaccination during treatment deemed unsafe | Four of the remaining six dogs receiving Zenrelia™ failed to achieve an adequate immune response on Day 88 to the RV vaccination. |
Effectiveness
Masked, randomized, placebo-controlled, multi-site field study for control of atopic dermatitis (Study ELA1900313; 25 sites); 268 dogs enrolled (181 Zenrelia, 87 placebo) dosed 0.6-0.8 mg/kg once daily for up to 112 days; GCP; n = 172 Zenrelia, 77 placebo (success analysis population); primary endpoint: Treatment success on Day 28: at least 50% reduction from baseline in owner-assessed PVAS pruritus score or in investigator-assessed CADESI-4 skin lesion score; result: Success 141/172 (estimated proportion 0.83, 95% CI 0.74-0.89) vs 25/77 placebo (0.31, 95% CI 0.17-0.50); p<0.001
ZenreliaTM (N=172) 141 0.83 (0.74, 0.89) Placebo (N=77) 25 0.31† (0.17, 0.50)
Adverse reactions
| Term | Treated | Control | Quote |
|---|---|---|---|
| Vomiting or nausea | 40 (22.1%) | 14 (16.1%) | Vomiting or nausea 40 (22.1%) 14 (16.1%) |
| Diarrhea | 36 (19.9%) | 9 (10.3%) | Diarrhea 36 (19.9%) 9 (10.3%) |
| Lethargy | 22 (12.2%) | 9 (10.3%) | Lethargy 22 (12.2%) 9 (10.3%) |
| Otitis externa | 19 (10.5%) | 20 (23%) | Otitis externa 19 (10.5%) 20 (23%) |
| Dermal growth (e.g., cyst, papilloma) | 16 (8.8%) | 4 (4.6%) | Dermal growth (e.g., cyst, papilloma) 16 (8.8%) 4 (4.6%) |
| Urinary tract infection | 10 (5.5%) | 2 (2.3%) | Urinary tract infection 10 (5.5%) 2 (2.3%) |
Extraction notes: PK: first five entries are from the Dosage Characterization pharmacology paragraph (geometric means; single 0.8 mg/kg oral/IV dose); last three are steady-state values from Table III.2 of the 6-month margin-of-safety study, quoted as flattened rows (t½ row uses the '½' glyph). n_animals for the safety study is spelled 'Forty' in the design quote (8 per group per Table III.1). Adverse reactions are from Table II.9 of the atopic dermatitis field study (Zenrelia N=181 vs placebo N=87, through Day 112). A second pivotal field study for pruritus associated with allergic dermatitis (ELA1900107; 206 Zenrelia, 100 placebo) showed Day 7 success 0.25 vs 0.08 (p=0.006). Field study noted increased susceptibility to neoplasia and infection; the original approval carried a boxed warning about vaccine-induced disease (later revised, see FOI 17467).
Zenrelia™ NADA 141-585, Supplemental approval, September 19, 2025; sponsor Elanco US Inc.; species: Dogs; foi_id 17467; FDA PDF
Indication
Control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age.
Dose regimen
0.6 to 0.8 mg/kg (0.27 to 0.36 mg/lb), Oral (tablet), Once daily, With or without food; dose unchanged by this supplement
The dose of Zenrelia™ (ilunocitinib tablets) is 0.27 to 0.36 mg ilunocitinib/lb (0.6 to 0.8 mg ilunocitinib/kg) body weight, administered orally, once daily, with or without food.
Target-animal safety
dose multiples 3X; duration Re-evaluation of liver tissue from the original vaccine response study (Study ELAVV200035; 2.4 mg/kg/day for 89 days); no new dosing.
Using the PCR method, formalin -fixed paraffin embe dded liver tissues were tested from the two dogs euthanized during the vaccine response study ; none of the liver tissues from the other dogs were tested.
| Finding | Quote |
|---|---|
| Nested PCR and sequencing detected canine adenovirus type 1 (not vaccine CAV-2) in liver tissue of the dog with fatal adenoviral hepatitis/pancreatitis | The CAV -1 PCR results were confirmed by nucleic acid sequencing to align with the reference genome of CAV-1 (National Center for Biotechnology Information (NCBI) Reference Sequence: AC_000003. 1) but not CAV-2 (NCBI Reference Sequence: AC_000020.1) . |
| Fatal hepatitis/pancreatitis likely a natural adenoviral infection rather than vaccine induced; risk of fatal vaccine-induced disease removed from labeling | The totality of evidence support s removal of the risk of fatal vaccine -induced disease from modified live virus vaccines from the labeling. |
Extraction notes: Category II supplemental approval revising the boxed warning and Animal Safety Warnings; no new effectiveness or PK studies (refers to the original approval FOI dated September 19, 2024). The target_animal_safety entry records only the post-hoc PCR re-evaluation of archived liver tissue from the 3X vaccine response study; quotes reproduce the extracted text's spacing artifacts (e.g. 'formalin -fixed', 'support s').
Reproduce: foi_structured_search(query="Ilunocitinib") and foi_summary_get(foi_id=...) in dog-geroscience-mcp; dataset foi-summaries-dog (config structured).