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In September 2024, the FDA approved a new drug for controlling symptoms of allergies in adult dogs. The drug is called Zenrelia and specifically targets itching (pruritus) connected to atopic and allergic dermatitis. It has the same mechanism of action as Apoquel, a drug we have already taken under a microscope and examined the hard truths you need to know about its long-term use. For those familiar with Apoquel’s side effects, it’s hard to understand why a similar drug would be allowed on the market.
But some dog owners are only just beginning the journey of searching for treatment options for their itchy dogs and might be very susceptible to drug marketing campaigns that make big promises while concealing the side effects. This article pulls back the curtain on exactly how Zenrelia works, how it compares to Apoquel, and why it comes with a boxed warning — the highest safety warning used by the FDA.
Zenrelia Works by Suppressing the Dog’s Immune System
One of the biggest misconceptions about drugs like Apoquel and Zenrelia is that they treat allergies; they really don’t. What they actually do is suppress the symptoms by altering the proper functioning of the immune system. Both drugs are classified as Janus Kinase (JAK) inhibitors and are the only two drugs of this type available on the veterinary market right now. They bind to JAK enzymes, which play a crucial role in immune responses.
Think of them as messengers that let the rest of the body know when something is wrong. They contribute to the activation of immune cells and help facilitate allergic reactions. Zenrelia and Apoquel both suppress these enzymes. With that, the immune system loses much of its ability to recognize threats. That leaves the dog at risk of diseases and infections, some of which we’ll discuss in more detail later.
The main differences between the two medications are the active ingredient, the specific JAK enzymes they bind to, and the dosage. Zenrelia’s active ingredient is ilunocitinib, which binds to JAK1 and JAK2. The drug is designed as a once-daily medication. Apoquel’s active ingredient is oclacitinib; it binds to JAK1 and JAK3 and begins as a twice-daily medication. Beyond that, they are very much sister drugs.
Since JAK inhibitors only stop the visible response to the allergen, the underlying cause of your dog’s allergy remains unresolved. Once you take the dog off the medication, the symptoms are bound to come back because nothing will be suppressing the immune system anymore. This often means drugs like Zenrelia have to be used long-term, and it’s hard not to wonder whether that’s the reason behind pushing this drug on the market.
Canine dermatology is a booming market, valued at $1.7 billion. In their press release, Elanco (the company behind Zenrelia) made a big deal emphasizing how Zenrelia has a lower price tag than Apoquel. It does, but if dogs have to be on the drug for years, or even an entire lifetime, it doesn’t matter how cheap it is — Elanco can profit for years to come with each dog put on Zenrelia.
The FDA’s Warning: Zenrelia Could Cause Fatal Outcomes When Paired With Vaccines
A boxed warning, sometimes called “the black box,” is the most severe type of warning issued on drugs by the FDA. Zenrelia carries a boxed warning because it might induce life-threatening diseases when paired with vaccines. The FDA makes it very clear that dogs receiving Zenrelia should NOT receive vaccines. In most U.S. states, the rabies vaccine is mandatory; 25 states don’t even allow for medical exemptions.
The package insert for Zenrelia recommends stopping the medication “at least 28 days to 3 months prior to vaccination,” which is a surprisingly broad window for such a serious warning. This recommended timeframe is based on a study that showed dogs needed 27 to 83 days to recover from Zenrelia’s immunosuppression, but including the lowest amount of time in the official recommendation frankly feels irresponsible. According to the FDA, the veterinary guidelines recommend a 3-month discontinuation period.
Why is Zenrelia such an issue for vaccines? The vaccine response study included 16 dogs — eight in the vaccine group and eight in the control group. Two dogs from the vaccine group had to be euthanized because of fatal side effects directly connected to Zenrelia’s immunosuppression. That’s 25% on such a small sample! The first dog developed colonic intussusception, intestinal tract infection, and severe anemia.
The second dog had swollen intestinal lymph nodes, fat necrosis in the abdominal cavity, liver failure, pancreatitis, systemic endotoxemia, severe anemia, and adenoviral infection. Both dogs experienced the symptoms of lethargy, weakness, and depression. For the other six dogs, the vaccines proved ineffective on the titer tests — for four of them, this included the rabies vaccine. As a result, the FDA doesn’t see Zenrelia as compatible with vaccines because it could pose a risk to both animal and human safety.
Elanco is facing a federal lawsuit for misleading investors over Zenrelia safety claims
The results of the vaccine study got Elanco in trouble with their investors, as the company had apparently led them to believe Zenrelia was safer than it ultimately turned out to be. A federal class action lawsuit was filed in October 2024, claiming Elanco made false and misleading statements to investors about the drug’s safety, resulting in potential financial loss — when they announced Zenrelia would have to come with a boxed warning, the company’s stock price dropped overnight, for a whopping 21%.
Meanwhile, Elanco is severely downplaying the findings of the vaccine safety study by claiming the test dogs were previously sick, something they allegedly discovered only after the study was completed. In contrast, the FDA’s freedom of information document states the dogs in the study were “determined as healthy based on physical examination.”
What Side Effects Were Observed in Zenrelia Field Studies?
Protection is the main job of the canine immune system. As previously mentioned, modulating this protective system is a dangerous thing with many adverse effects. Yes, the dog might not be itching, but the body is also not fighting off common diseases and infections anymore, which is arguably a lot more dangerous. The two field studies done to test Zenrelia’s effectiveness for the control of atopic and allergic dermatitis showed this drug can cause some serious side effects, such as:
- Opportunistic infections: Some specific infections that showed up during the studies were demodicosis, ear infections, UTIs, inflammatory lumps between the toes, intestinal infections, and respiratory infections. The FDA advises the owners to closely monitor dogs on Zenrelia for the possible development of such infections, but we would argue that once the infection has already developed, it’s too late. One of the dogs experienced a leg injury (tendonitis and a puncture wound) just four days before the end of the study. The injury was not able to heal; it grew into a serious infection that ended with amputation.
- Blood abnormalities: Several dogs on Zenrelia had abnormal hematology results, such as decreased hematocrit, hemoglobin, and red blood cells. These decreases compromise the transport of oxygen in the bloodstream. A decrease in different types of white blood cells was also noticed; these are the cells that help the body fight infections.
- Tumors, potentially malignant: One of the main warnings in the package insert notes that growths and tumors were observed in Zenrelia-treated dogs during the clinical studies. The tumors were both benign and cancerous.
- Illnesses in the reproductive organs: A few dogs, especially intact ones, developed significant issues in reproductive organs. Decreased prostate glands, testicular cancer, and pyometra (uterus infection) were all observed.
- Gastrointestinal issues: The largest percentage of side effects had to do with GI disruption. Symptoms included vomiting, nausea, diarrhea, lethargy, anorexia, upset stomach, abdominal pain, increased water and/or food intake, weight loss, or weight gain.
How Should We Actually Approach Canine Allergies & Dermatitis?
Allergies are hard, both for the dog and the owner. But on a purely biological level, they are a warning sign that something is wrong. The dog’s body is sending out an alarm. We live in a culture obsessed with instant solutions, so it’s easy to sell us a magic drug that stops the itching — but at what cost? Infections and cancer? No, thank you.
Everything in the body is connected. Allergies and itching are the kind of problems that call for a holistic solution, one that takes the whole body into consideration! For example, a change in diet, eliminating potential allergens, and strengthening the dog’s immune system with natural, non-invasive therapies are all great options. Doing this on your own can be overwhelming, so start with our FREE expert allergy guide that introduces natural and drug-free approaches, even for the most challenging cases.
One of the best healing pathways for canine allergies is through the gut. The addition of probiotics and other allergy-specific supplements can be a game changer. Ultimate Dog’s allergy superfood topper, CHIRP, has countless positive reviews from happy and relieved dog owners. It even comes with a 90-day money-back guarantee. Best of all, it won’t destroy your dog’s immune system, but will work to build it back up after these pharmaceuticals deplete it.
Sources
Zenrelia (ilunocitinib tablets). Elanco, 07/2024.
Zenrelia FAQ. Elanco, 2024.
“Elanco Announces FDA Approval and Launch of Zenrelia™ (ilunocitinib tablets).” PR Newswire, 19/09/2024.
“Rabies Vaccination and Exemption Laws for Dogs.” Animal Legal and Historical Center, Michigan State University, 2023.
“Freedom of Information Summary: Original New Animal Drug Application.” Animal Drugs at FDA, 19/09/2024.
“Lawsuit Alert: Investors who lost money with Elanco Animal Health Incorporated shares should contact the Shareholders Foundation.” PR Newswire, Market Chameleon, 09/12/2014.
Luna’s passion for learning about canine psychology and behavior began when she adopted a severely reactive puppy from a local shelter. She is now a big advocate for positive reinforcement and compassionate training. As a writer, she strives to spotlight the topics that fly under the radar and be the voice for all who cannot speak for themselves.
