Zenrelia is a JAK inhibitor approved by the FDA in September of 2024 for control of pruritus associated with allergic dermatitis and control of atopic dermatitis in dogs at least 12 months of age. It is an oral tablet, dosed once daily at 0.6-0.8 mg/kg.

Zenrelia is rapidly absorbed after oral administration and begins to work after the first dose, with visible improvements in itch from Day 1.¹

The dose of Zenrelia has been optimized to provide relief from allergies with simple, continuous, once daily dosing from the start. It has a relatively short half-life within the bloodstream and does not accumulate in the body, meaning that if dosing is stopped the drug is cleared from the dog’s body within about 24 hours. This facilitates starting and stopping treatment as needed to control allergic itch and inflammation or while performing a diagnostic trial.

Yes. Dogs with food allergies were included in the allergic dermatitis clinical field trial conducted for FDA approval. Allergic dermatitis is an umbrella term that encompasses many different pruritic skin conditions in dogs, including canine atopic dermatitis (AD), ectoparasite hypersensitivity (flea allergy dermatitis, sarcoptic mange), food allergy dermatitis, and contact dermatitis. Dogs included in the clinical field trial could have one or more of these conditions.

Yes. Zenrelia can be used to control symptoms during a food trial and stopped toward the end of the food trial to see if symptoms return. Zenrelia is rapidly absorbed after administration, has a relatively short half-life in the blood, and does not accumulate; meaning it begins working after the first dose and is cleared from the dog’s body within about 24 hours after stopping treatment. This facilitates starting and stopping treatment as needed to control symptoms while doing a food trial or other diagnostic trial in dogs with allergies.

Zenrelia is supplied as a scored tablet in four different strengths, allowing for accurate dosing of dogs as small as 6.6 lbs. Dogs should be dosed once daily according to the label dosing chart. Zenrelia is available in both 90-count bottles and 30-count blister packs. Note that the blister packs are supplied for convenient, 30-count dispensing; the tablets do not require storage within a blister for stability. The product label also includes 10-count blister packs, but these are not being marketed currently.

Zenrelia is labeled for use in dogs as small as 6.6 lbs., which was the weight of the smallest dog in the pivotal studies conducted to achieve FDA approval.

Zenrelia does not contain pork, beef, soy, lactose or dairy.

Zenrelia tablets are not flavored.²

Zenrelia can be administered with or without food. Although there is increased bioavailability if dosed with food, efficacy was demonstrated in clinical field trials in which dogs were dosed both with and without food.

Since one intended indication for Zenrelia is atopic dermatitis which is a chronic condition, there is no limit on duration of use.

There are no specific requirements on the Zenrelia label for bloodwork prior to starting treatment. Establishing a baseline prior to starting a dog on any chronic medication could be considered best practice and would be done at the discretion of the veterinarian.

Zenrelia is rapidly absorbed, with maximum blood concentration reached in 1-2 hours after administration, so if a dog vomits after that time it is likely unnecessary to give Zenrelia again until the next day. In the clinical field studies, Zenrelia was re-dosed if a dog vomited within 20 minutes of receiving Zenrelia.³

Zenrelia should be given once daily in accordance with the label dose. If a dog continues to itch after receiving Zenrelia it’s important to revisit the diagnostic workup and ensure other causes for itch have been ruled out, including bacterial and fungal skin infections, ectoparasites (fleas), food sensitivities, etc.

Zenrelia is labeled for use in dogs only; use in other species would be considered off-label use.

The safe use of Zenrelia has not been evaluated in breeding, pregnant, or lactating dogs.

The use of Zenrelia with other medications designed to control allergies has not been specifically evaluated and should be done only at the discretion of the treating veterinarian. In the clinical field trials, common concurrent medications were allowed, including antibiotics, antifungals, non-steroidal topicals and otics, parasiticides, dewormers, vaccinations and prescription diets; glucocorticoids and cyclosporins were not allowed.

The vaccine response study was conducted according to strict quality and animal welfare standards. The lead investigator deemed the dogs fit enough to continue within the established study protocol for this toxicity study, especially as they were beginning to respond to treatment for gastrointestinal parasitism. It is only upon further analysis after study completion that the severity of illness (reduced T helper cells in both control and Zenrelia-treated dogs) and an additional infectious agent (CAV-1) were identified.^{11, 14}

The Zenrelia label contains a boxed safety warning regarding the risk of fatal vaccine-induced disease from modified live virus vaccines and inadequate immune response to vaccines, with instructions to discontinue Zenrelia for at least 28 days to 3 months prior to vaccination and at least 28 days after vaccination. This boxed safety warning is specifically due to the results of a vaccine response study in which 8 young, unvaccinated dogs were treated with 3 times the label dose and were sick at the time of vaccination.¹¹ Future studies should evaluate the response to vaccination in healthy dogs.

A boxed safety warning is not an absolute contraindication but is the most prominent safety warning utilized by the FDA to bring the prescriber’s attention to potentially severe risks associated with the medication.

Within the context of a valid client-patient relationship, it is legal for veterinarians to utilize FDA approved products off-label (also referred to as extra-label), including products with boxed warnings. As with all label safety warnings, veterinarians should take these into account when determining the risk-benefit assessment for all medications, and practice based upon best medicine guidelines and individual patient needs.

Patients should be up-to-date on vaccinations prior to starting Zenrelia. According to the boxed warning, Zenrelia treatment should be withheld for 28 days after vaccination, so another treatment option could be used during this time before starting Zenrelia.

According to the boxed warning, Zenrelia treatment should be withheld at least 28 days to 3 months prior to vaccination and 28 days after, so another treatment option could be used during this time before restarting Zenrelia.

Yes. Common medications, including antibiotics, anti-fungals, parasiticides, non-steroid containing topicals, and vaccines were allowed during the US atopic dermatitis field study, US allergic dermatitis field study and a head to head clinical field study comparing Zenrelia to Apoquel in dogs with atopic dermatitis.^1,3,4 There were adult, client-owned dogs in each of those studies that were vaccinated while receiving the label dose of Zenrelia as part of the study protocol, prior to the label warning regarding concurrent use with vaccines. Refer to Package Insert for full safety information including Boxed Warning.

Vaccine-induced disease refers to disease caused by a modified live vaccine (MLV). This term is used in the boxed safety warning for Zenrelia in reference to a single dog that was euthanized due to adenoviral hepatitis in the Zenrelia vaccine response study¹¹ in which 8 young, unvaccinated dogs intended to be pathogen free were treated with 3 times the label dose of Zenrelia and received a MLV containing canine adenovirus type 2 (CAV-2). After the label was finalized, PCR testing¹⁴ confirmed this dog had Infectious Canine Hepatitis due to infection with canine adenovirus type 1 (CAV-1), which is genetically distinct from the strain of CAV-2 used in the MLV. Furthermore, this dog developed clinical signs of hepatitis (hematemesis) prior to receiving its first MLV.¹¹ CAV-1 is highly contagious and difficult to kill with routine disinfectants; it is unknown how this dog became exposed or if it was a carrier prior to entering the bio-secure facility used for this study.

Although Zenrelia and Apoquel are the same class of drug (JAK inhibitors) with the same indications for treatment, they contain different active ingredients. Apoquel® contains oclacitinib and Zenrelia contains ilunocitinib.

Zenrelia’s dose has been optimized to allow for effective control of allergies with simple, once daily dosing from the start. Apoquel contains a different active ingredient, and was FDA approved based upon twice daily dosing for the first 14 days before decreasing to once daily dosing. An increase in itch levels (“rebound itch”) can occur when Apoquel dosing is decreased from twice to once daily.¹⁵ This phenomenon is not observed in clinical trials with continuous once-daily dosing of Zenrelia.^1,3

The mg/kg dose for each drug is based upon dosage determination studies done during early drug development. Zenrelia and Apoquel are in the same drug class (JAK inhibitors) but contain different active ingredients. It is common for drugs in the same drug class to have different approved dosages. The dosage of Zenrelia has been optimized for simple, continuous, once daily dosing from the start.

Zenrelia and Apoquel are both first generation, non-selective JAK inhibitors that regulate the inflammatory response to allergens by binding to multiple Janus Kinas (JAK) enzymes and interfering with cell signaling.⁵ In laboratory assays, Zenrelia has demonstrated greater potency and subtle differences have been noted in selectivity, with Zenrelia primarily acting on JAK1 and JAK2, and Apoquel primarily acting on JAK1 and JAK3.⁶  However, in vitro laboratory assays do not predict clinical efficacy and safety between JAK inhibitors, so head-to-head clinical trials remain the gold standard for comparison.^7,8,9  In a head to head clinical trial in 338 client-owned dogs, once-daily dosing of Zenrelia showed similar efficacy as Apoquel dosed twice-daily for 14 days then once-daily (primary study endpoint on Day 28), with similar rates of adverse events reported between groups. Results at additional endpoints show promising potential for Zenrelia.*⁴

Both Zenrelia and Apoquel have been deemed safe and effective by the FDA. In a head-to-head clinical trial, adverse events were similar between Zenrelia and Apoquel.⁴ Results of toxicity studies evaluating long term administration of higher than label doses of each drug further confirm that they have similar safety profiles.^6,10 The results of a separate vaccine response study led to the boxed warning on Zenrelia's label.

The Zenrelia boxed safety warning is specifically informed by the results of a vaccine response study in which 8 young, unvaccinated dogs were treated with 3 times the label dose and were sick at the time of vaccination.¹¹ Future studies should evaluate the response to vaccination in healthy dogs. All of the other Zenrelia approval studies, and the head-to-head clinical study with Apoquel, have revealed similar safety profiles between the two products in both laboratory toxicity studies and client-owned dogs.^4,6,10 The FDA concludes on the Apoquel label that young dogs treated with 3X the label dose of Apoquel twice daily developed an adequate immune response (antibody titers) following vaccination with canine distemper virus, canine parvovirus and Rabies vaccines.⁶ The study design was very similar to that of the Zenrelia Vaccine Response study, however the Zenrelia study was complicated by concurrent infections and lymphopenia at the time of vaccination.¹¹  The European Medicines Agency interpreted the Apoquel Vaccine Response study differently than the FDA, concluding that the antibody response to Rabies vaccination was decreased in the dogs treated with Apoquel compared to the control group.¹²

Each dog is an individual and efficacy of any medication in a particular patient cannot be predicted. While Zenrelia and Apoquel are the same class of drug (JAK inhibitors), individual variations in patient response are likely to exist just as can be seen with other classes of drugs (i.e. NSAIDs, antihistamines, etc.). In a head to head clinical trial in 338 client-owned dogs, once-daily dosing of Zenrelia showed similar efficacy as Apoquel dosed twice-daily for 14 days then once-daily (primary study endpoint on Day 28), with similar rates of adverse events reported between groups. Results at additional endpoints show promising potential for Zenrelia.*⁴

The designs of the two studies were different and so a direct comparison cannot be made. In the Apoquel study⁶, treatment success was defined as a 2-point decrease from baseline on a 10-point PVAS (Puritis Visual Analog Score) scale on 5 out of the first 7 days of treatment.  For example, a dog enrolled in the Apoquel study baselining at a PVAS of 10 had to achieve a PVAS of 8 or lower for 5 of the first 7 study days to be considered a treatment success. For Zenrelia, a steeper threshold of 50% reduction in PVAS from baseline was required to achieve treatment success. For example, a dog enrolled in the Zenrelia study baselining at a PVAS of 10 had to achieve a PVAS of 5 or lower to be considered a treatment success. In a head to head clinical trial in 338 client-owned dogs, once-daily dosing of Zenrelia showed similar efficacy as Apoquel dosed twice-daily for 14 days then once-daily (primary study endpoint on Day 28), with similar rates of adverse events reported between groups. Results at additional endpoints show promising potential for Zenrelia.*⁴

The earliest efficacy outcome in the Zenrelia clinical studies was 24 hours, whereas Apoquel has been assessed at earlier time points.¹³ In a head-to-head clinical study, Zenrelia and Apoquel provided similar itch relief on days 1-14 of treatment, while Zenrelia was dosed once daily and Apoquel was dosed twice daily.⁴ The two drugs have the same mechanism of action and very similar pharmacokinetic profiles, including rapid absorption into the bloodstream following oral administration.^6,10

Both drugs have very similar, relatively short half-lives^6,10 and do not accumulate in the body, so no washout period is required when switching.

Efficacy measurements in the Zenrelia clinical field trials included: owner and veterinarian-assessed level of itch using the Pruritus Visual Analog Scale (PVAS) and veterinarian-assessed 4-point Canine Atopic Dermatitis Extent and Severity Index (CADESI-4). Both of these measurement tools are validated outcome measures with established clinical relevance, with PVAS measuring improvement in itch and CADESI-4 measuring improvement in inflammation and skin lesions (which are also a reflection of itch level). For the Allergic Dermatitis field study, the primary outcome of treatment success was defined as ≥ 50% reduction from baseline in PVAS on ≥ 5 out of the first 7 days of treatment, and for the Atopic Dermatitis study it was ≥ 50% reduction from baseline in PVAS and CADESI-4 on Day 28.

Clinical trials for FDA approval are aligned with the FDA prior to being conducted. It is common to include both a primary endpoint, which must be met in order for a drug to be deemed effective, as well as secondary endpoints that elucidate more detail about the drug’s effectiveness.

In dogs with atopic dermatitis, a PVAS score of <2 is considered normal (clinical remission of pruritus).¹⁶ In a head to head clinical trial in 338 client-owned dogs, once-daily dosing of Zenrelia showed similar efficacy as Apoquel dosed twice-daily for 14 days then once-daily (primary study endpoint on Day 28), with similar rates of adverse events reported between groups. Results at additional endpoints show promising potential for Zenrelia.*⁴