Zenrelia™ (ilunocitinib tablets): An Innovative, Once Daily Canine Treatment That Targets Itch

Pruritus is a frequent presenting complaint in small animal primary care practice. Allergic dermatitis, a common cause of pruritus,has been the most common cause for canine pet insurance claims for over a decade.¹ This is inflammation in the skin caused by any allergen and may include hypersensitivity to fleas, cutaneous adverse food reactions, and atopic dermatitis. Atopic dermatitis is a reaction to environmental allergens and can affect up to 15% of dogs.²

Pruritus negatively impacts the quality of life of both pets and their family. Because of the numerous potential underlying causes and the complications of secondary infections, these cases can be frustrating for both the veterinary team and clients. Determining the underlying cause, while controlling symptoms and treating secondary infections, can take multiple visits, which requires an investment of both time and finances.

Controlling pruritus is an essential part of the treatment plan, which is often multi-modal. Finding an effective, safe medication to control itch is essential to maximize patient comfort. Compliance is improved when medications work quickly and are cost-effective, especially those needed for long-term use.

Introducing an Option for Canine Pruritus Control

Zenrelia^TM (ilunocitinib tablets) is a once daily oral medication for the treatment of pruritus associated with allergic dermatitis and contr of atopic dermatitis in dogs over 12 months of age. It breaks the itch-scratch cycle by interrupting inflammatory cytokine signaling pathways through the inhibition of Janus kinase (JAK) enzymes.³

In a double-blind, placebo-controlled, randomized, multi-site field study of 268 dogs with atopic dermatitis, owner-reported pruritus was measured using the Pruritus Visual Analog Scale (PVAS) and skin lesions were measured by veterinarians using the Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). Patients receiving Zenrelia had significant improvement in PVAS and CADESI-4 scores at day 28 compared to placebo.³

Zenrelia has a boxed warning which veterinarians should read and understand prior to using the product. It’s well-tolerated at label dosages, and its safety for long-term administration at label dose has been demonstrated across multiple studies. The most common adverse effects reported in clinical field trials include vomiting, diarrhea, and lethargy. Laboratory abnormalities identified in the clinical field studies included thrombocytopenia, leukopenia, neutropenia, lymphopenia, eosinopenia, monocytopenia, and decreased RBC count.^3,4

Zenrelia has not been studied with concurrent use of corticosteroids, cyclosporine, or other immunosuppressant medications, or in pregnant or nursing dogs.³ Due to JAK inhibitors having the potential to cause immunosuppression, Zenrelia is not recommended in dogs with concurrent severe infection.

How Does Zenrelia Compare to Oclacitinib?

A multi-site, randomized, controlled, blinded, head-to-head study was performed to compare the efficacy of Zenrelia to oclacitinib in 338 atopic dogs. Zenrelia was administered once daily, and oclacitinib was administered twice daily for 14 days then reduced to once daily administration, per label dosing instructions for each drug.⁴

Similar reductions in itch were noted between treatment groups over the first 2 weeks (days 1-14). Zenrelia was as effective as oclacitinib at the primary study endpoint, day 28, based upon improvement in both PVAS and CADESI-4 scores. The rate of adverse events reported were similar between groups. In an optional continuation phase through day 112, Zenrelia showed promising results for pruritus reduction and the potential for clinical remission.⁴

Because Zenrelia does not require a loading dose and is administered once daily, Zenrelia may help improve owner compliance and can be cost effective* for pet owners. Additionally, when oclacitinib dosing is decreased from twice-daily to once-daily dosing, a transient increase in pruritus has been reported, called rebound pruritus.⁵ Because Zenrelia is dosed once daily from the start, it avoids rebound itch.

Understanding Zenrelia’s Boxed Warning

The Zenrelia label contains a boxed warning that states: “Based on the results of the vaccine response study, dogs receiving Zenrelia are at risk of fatal vaccine-induced disease from modified live virus vaccines and inadequate immune response to any vaccine. Discontinue Zenrelia for 28 days to 3 months prior to vaccination and withhold Zenrelia for at least 28 days after vaccination.”³

It is important to note that this warning is based on a single study of post-vaccine antibody titers that included 8, 10-month-old beagles with concurrent illness (Coccidia) receiving the drug at 3 times the label dose.³ Additional studies are needed to investigate serologic response to vaccination in healthy adult patients receiving the label dose of Zenrelia.

Because Zenrelia does not require a loading dose and is administered once daily, Zenrelia may help improve owner compliance and can be cost effective* for pet owners.

Tales of Zen

Remi

Remi was evaluated by her veterinarian following a longstanding history of dermatitis, which started when she was approximately a year or two old. Clinical signs included persistent pruritus and excessive licking of the abdominal area, resulting in raw and irritated skin. Previous therapies failed to deliver adequate control of her symptoms.

According to her veterinarian, Remi is “an example of one of the most frustrating cases” he manages, as available treatment options had consistently failed to resolve her condition. He ultimately prescribed once daily Zenrelia.

During a follow-up evaluation 8 weeks later, Remi’s owner reported that Remi’s itch was effectively under control. Remi’s owner expressed peace of mind in having finally identified an effective treatment, ending the ongoing search for alternatives.

Missy

Missy began showing clinical signs of frequent itching and gnawing, particularly around her tail and leg. Suspecting the symptoms were allergy-related, she was evaluated by her veterinarian, who prescribed once daily Zenrelia.

During a follow-up exam 2 months later, Missy’s veterinarian reported that her condition had fully resolved, confirming remission. On evaluation, there was no evidence of active inflammation or skin redness. Her itch level was rated at 0—consistent with that of a healthy dog—and her skin score was also 0. According to her veterinarian, Missy is a “rousing success” on Zenrelia.

INDICATIONS

Zenrelia is indicated for control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age.

IMPORTANT SAFETY INFORMATION

Read the entire package insert before using this drug, including the Boxed Warning. For full prescribing information call 1-888-545-5973 or visit http://www.elancolabels.com/us/zenrelia

WARNING: VACCINE-INDUCED DISEASE AND INADEQUATE IMMUNE RESPONSE TO VACCINES.

Based on results of the vaccine response study, dogs receiving Zenrelia are at risk of fatal vaccine-induced disease from modified live virus vaccines and inadequate immune response to any vaccine. Discontinue Zenrelia for at least 28 days to 3 months prior to vaccination and withhold Zenrelia for at least 28 days after vaccination. Dogs should be up to date on vaccinations prior to starting Zenrelia. Do not use in dogs less than 12 months old or dogs with a serious infection. Monitor dogs for infections because Zenrelia may increase susceptibility to opportunistic infections. Neoplastic conditions (benign and malignant) were observed during clinical studies. Consider the risks and benefits of treatment in dogs with a history of recurrence of these conditions. The most common adverse reactions were vomiting, diarrhea and lethargy. Zenrelia has not been evaluated in breeding, pregnant, or lactating dogs and concurrent use with glucocorticoids, cyclosporine, or other systemic immunosuppressive agents has not been tested.

For full prescribing information see package insert.

REFERENCES

1. Davis K. Skin allergies, gastrointestinal disease among most common conditions that prompt veterinary visits nationwide. April 24, 2024. Accessed November 16, 2024. https://news.nationwide.com/ most-common-conditions-that-prompt-veterinary-visits-2024/
2. Collins B. Atopic dermatitis (atopy). Cornell University College of Veterinary Medicine. Accessed November 16, 2024. https:// www.vet.cornell.edu/departments-centers-and-institutes/ riney-canine-health-center/canine-health-information/ atopic-dermatitis-atopy
3. Zenrelia. Package Insert.
4. Forster S, Boegel A, Despa S, Trout C, King S. Comparative efficacy and safety of ilunocitinib and oclacitinib for the control of pruritus and associated skin lesions in dogs with atopic dermatitis. Vet Dermatol. 2025;36(2):165 176. doi: 10.1111/vde.13319
5. Olivry T, Lokianskiene V, Blanco A, et al. A randomised controlled trial testing the rebound-preventing benefit of four days of prednisolone during the induction of oclacitinib therapy in dogs with atopic dermatitis. Vet Dermatol. 2023;34(2):99-106. doi:10.1111/vde.13134

*At label dose the average price for a monthly supply of Zenrelia is less than Apoquel. Cost may vary depending on a dog’s weight. [2024 Zoetis Petcare Products Veterinary Price List vs. 2025 Elanco Zenrelia Veterinary List Price]

Zenrelia, Elanco, and the diagonal bar logo are trademarks of Elanco or its affiliates. PM-US-24-2203.