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  5. Dear Veterinarian Letter regarding important safety information associated with the use of Zenrelia (ilunocitinib tablets) for controlling pruritus associated with allergic dermatitis and atopic dermatitis in dogs
  1. Product Safety Information

Dear Veterinarian Letter regarding important safety information associated with the use of Zenrelia (ilunocitinib tablets) for controlling pruritus associated with allergic dermatitis and atopic dermatitis in dogs

Dear Veterinarian,

We want to inform you of a new product the U.S. Food and Drug Administration (FDA) recently approved as well as important safety information, especially regarding vaccination and infections, associated with its use. Zenrelia (ilunocitinib tablets) is a new animal drug used to control pruritus associated with allergic dermatitis and to control atopic dermatitis in dogs at least 12 months of age. 

Zenrelia is an immunosuppressant that is administered orally, once daily, with or without food. The active ingredient, ilunocitinib, is a non-selective Janus kinase (JAK) inhibitor, which inhibits the function of a variety of pruritogenic, pro-inflammatory, and allergy-related cytokines that are dependent on JAK enzymes. Ilunocitinib is not a corticosteroid or an antihistamine. 

In two field studies in client-owned dogs, Zenrelia was shown to be effective at reducing pruritus and skin lesions in dogs with allergic dermatitis or atopy. Before using Zenrelia, read the entire package insert, including the boxed warning describing the risk of vaccine-induced disease and inadequate immune response to vaccines.  

Vaccination Safety Concerns

Based on data from a vaccine response study, the FDA concluded that it is not safe to administer vaccines in dogs that are concurrently receiving Zenrelia. In the study, dogs receiving 2.4 mg/kg/day of Zenrelia (3X the maximum exposure dose) experienced drug-induced immunosuppression, which resulted in fatal vaccine-induced adenoviral hepatitis and pancreatitis in one dog; infectious enteritis that potentially contributed to a fatal intussusception in one dog; and an inadequate immune response to canine distemper and rabies vaccinations in one (of six) and four (of six) dogs, respectively. In addition to the animal safety concerns, the failure of treated dogs to mount an adequate immune response to the killed rabies vaccine raises a public health concern, given the serious zoonotic risk of rabies. These animal and public health concerns can be mitigated by withholding Zenrelia for at least 28 days to 3 months before vaccination and for at least 28 days afterward and by making sure a dog is up to date on vaccinations before starting treatment. 

The 28-day to 3-month time period to discontinue Zenrelia before vaccination is based on data from the vaccine response study that showed evidence of recovery from drug-induced immunosuppression 27 to 83 days after stopping Zenrelia. A 3-month washout period for immunosuppressants before vaccination is supported by veterinary and human vaccination guidelines (2024 World Small Animal Veterinary Association and 2023 Centers for Disease Control and Prevention vaccination guidelines1, 2). The 28-day time period to withhold Zenrelia after vaccination is based on published and unpublished data on the duration of viral shedding after administration of a modified live virus vaccine. The timing of vaccine administration relative to Zenrelia use should be assessed on a case-by-case basis, with additional consideration given when rabies vaccination is involved.

Risk of Infection

Zenrelia-induced immunosuppression may increase the risk of opportunistic infections, including demodicosis, interdigital furunculosis, coccidiosis, and pneumonia, and may also exacerbate subclinical or uncomplicated infections. New neoplastic conditions (benign and malignant) were observed in dogs treated with Zenrelia during clinical studies. You should consider the risks and benefits of treatment before starting Zenrelia in a dog with a history of recurrent serious infections or recurrent demodicosis or neoplasia. You should also monitor the dog for the development of infections while on the drug. 

Labeling Information

The following are summaries of important information from the drug’s labeling:

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.

ANIMAL SAFETY WARNINGS: Due to the risk of fatal vaccine-induced disease from modified live virus vaccines and inadequate immune response to any vaccine, including rabies vaccines, do not administer vaccines to a dog receiving Zenrelia. 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 monitored for the development of infections because Zenrelia may increase susceptibility to opportunistic infections, including demodicosis, interdigital furunculosis, coccidiosis, and pneumonia, and exacerbation of subclinical or uncomplicated infections. Zenrelia is not for use in dogs with serious infections.

Zenrelia may cause a progressive or persistently decreased hematocrit, hemoglobin, and/or red blood cell count without a corresponding increase in absolute reticulocyte count.

New neoplastic conditions (benign and malignant) were observed in dogs treated with Zenrelia during clinical studies.

PRECAUTIONS: Dogs should be up to date on vaccinations prior to starting Zenrelia. The safe use of Zenrelia has not been evaluated in breeding, pregnant, or lactating dogs. Decreased prostate gland weights in intact male dogs were observed in a laboratory safety study. The safe use of Zenrelia has not been evaluated in combination with glucocorticoids, cyclosporine, or other systemic immunosuppressive agents.

Freedom of Information Summary

The Freedom of Information summary, which provides a detailed summary of the effectiveness and safety studies conducted for Zenrelia, is available at Animal Drugs @ FDA.

Report Adverse Events

If one of your patients has a side effect to Zenrelia, please work with the dog owner to report the problem to Elanco US Inc at 1-888-545-5973. Elanco is required to submit reports of all adverse events associated with Zenrelia to the FDA. If you prefer to report the side effect directly to the FDA, see How to Report Animal Drug and Device Side Effects and Product Problems. Regardless of if you report the problem to Elanco or the FDA, please include information regarding the dog’s vaccination history and the timing of any recent vaccinations. The form for reporting adverse drug events (FORM FDA 1932A) does not specifically ask for vaccination information, but this is important to include due to Zenrelia’s potential vaccination safety concerns. Please also include if the dog developed any clinical infections or neoplasia after starting Zenrelia. 

The FDA’s Center for Veterinary Medicine (CVM) is committed to promoting and protecting animal health by ensuring safe and effective drugs are available for animals. For more information, please contact CVM’s Education & Outreach Staff at AskCVM@fda.hhs.gov.

Sincerely,

FDA’s Center for Veterinary Medicine

1 Squires, RA, Crawford, C, Marcondes, M, Whitley, N. 2024 guidelines for the vaccination of dogs and cats – complied by the Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA). J Small Anim Pract. 2024 May;65(5):277-316.

2 Centers for Disease Control and Prevention. Altered immunocompetence general best practice guidelines for immunization. Updated Aug 1, 2023. Available at: https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.html. Accessed Sept 9, 2024.

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