Apoquel and its safety: what do we actually know?

Apoquel is probably one of the best-known medications for itching in dogs. In some dogs, its effect can be impressively fast: a dog that was licking, chewing and scratching itself yesterday may be noticeably less itchy after a short time.

That matters. Severe itching is not merely uncomfortable. A dog can damage its skin, sleep poorly, become restless, and secondary infections may develop in injured skin.

But with Apoquel there is another question:

Does getting the itching under control mean that we have found out why the dog is itching?

No.

And in our view, that is exactly where any discussion of Apoquel should begin.

Three perspectives on one medication

You can find very different opinions about Apoquel.

In conventional veterinary medicine, oclacitinib is widely used to control allergic pruritus and atopic dermatitis. In controlled trials, it has shown a rapid and often good antipruritic effect. One large randomised placebo-controlled study included 436 dogs with allergic dermatitis, and itching decreased quickly and significantly more in dogs receiving Apoquel than in the placebo group.

Integrative veterinarians, including Dr Judy Morgan, have for years highlighted another side of the issue: suppressing itching does not necessarily resolve its cause, and long-term use of a drug that interferes with JAK signalling pathways requires attention to its effects on immune function, infections and potentially other health problems.

A third perspective comes from drug-safety surveillance, or pharmacovigilance. The European EudraVigilance Veterinary database collects reports from veterinarians, animal owners and other reporters about suspected adverse reactions after a medication reaches the market.

None of these three perspectives gives the whole answer on its own.

A controlled trial can show very well whether a drug reduces itching, but a small or short study may not detect rare problems or those that appear only years later.

A veterinarian’s years of clinical experience may identify a recurring pattern, but that alone does not prove that the medication caused it.

Pharmacovigilance can reveal signals that were not seen in clinical trials, but a suspected adverse reaction does not automatically mean a proven causal relationship.

That is why we look at all three in this article.

“Not proven” does not mean the same thing as “unfounded”.

And the reverse is equally important: a suspicion or clinical observation is not yet a proven causal relationship.

The dog is itching. But why?

At FendaF, we repeatedly hear quite similar stories from dog owners.

The dog starts itching. An elimination diet may be tried, for example. If that does not help quickly, Apoquel is introduced. Sometimes the owner eventually remains unclear even about what diagnosis the dog actually has.

It almost becomes an equation: itching = Apoquel.

But itching is not a diagnosis.

A dog may itch because of fleas or other parasites. The cause may be a bacterial skin infection, Malassezia yeast overgrowth, a food reaction, environmental allergy, contact reaction, or several problems at the same time.

A dog with atopic dermatitis can also develop secondary infections and other factors during the course of the disease that intensify the itching.

So before starting long-term treatment, it is entirely reasonable to ask:

What is my dog’s diagnosis?

Which possible causes of itching have we investigated or ruled out?

What is Apoquel treating in my dog’s case, and what is it only controlling?

This is not even at odds with the official approach to Apoquel. The product information points to the need to investigate and treat the underlying causes of itching as well as accompanying bacterial, fungal and parasitic infections.

Apoquel can therefore be a simple answer to the question:

“How do we get this dog’s itching under control?”

By itself, it does not answer the more difficult question:

“Why is this dog itching?”

What does Apoquel do in the body?

The active ingredient in Apoquel is oclacitinib. It is an inhibitor of Janus kinases, or JAK enzymes, with stronger activity on signalling pathways associated with JAK1.

One of its most important targets is interleukin 31, or IL-31, which plays an important role in the generation of the itch signal in dogs.

That is why Apoquel can work very quickly.

But JAK signalling pathways do not exist in the body only so that a dog can itch. They transmit signals from different cytokines and participate in the regulation of inflammation and immune responses.

So it is not accurate to call Apoquel simply an “itch tablet”. But it is equally inaccurate to say that Apoquel simply “switches off the immune system”.

The reality is more complex.

How well does Apoquel work?

For many dogs, very well. Controlled studies have shown a rapid reduction in itching, and there is no reason to doubt the drug’s efficacy.

But that does not mean it works for every dog.

Some dogs have an inadequate response from the start. There are also dogs in whom the initial twice-daily dosing controls the itching, but after switching to once-daily maintenance dosing, control is no longer sufficient.

A retrospective study evaluated 53 dogs with atopic dermatitis in which oclacitinib was used twice daily for longer than the usual two weeks specifically because once-daily dosing did not adequately control the disease.

This is also an important nuance in the experience of owners who say: “Apoquel worked at first, but then it stopped working.”

Based on the available evidence, we cannot say that dogs necessarily develop classic pharmacological tolerance and that the body simply “gets used to the drug”.

But inadequate control on maintenance dosing has genuinely been documented.

Can itching return after the dose is reduced?

Yes.

In a randomised study, dogs were first given Apoquel twice daily for 14 days and then reduced to once daily. In the Apoquel monotherapy group, rebound itching occurred after dose reduction in 9 of 20 dogs, or 45%.

Rebound has also been studied in an experimental mouse model. After abrupt withdrawal of oclacitinib, scratching increased rapidly and changes were seen in itch-related inflammatory mediators and markers of nervous-system sensitisation. This study does not prove that exactly the same mechanism occurs in dogs, but it supports the biological plausibility of rebound.

So when a dog starts itching again, we should not automatically assume that the only solution is more Apoquel.

This is a point at which it is worth asking again:

What is causing the itching now?

Infections: where the different perspectives begin to meet

Apoquel’s official product information warns that oclacitinib modulates the immune system and may increase susceptibility to infections.

And this is where real-world drug-safety data become interesting.

When we reviewed reports associated with oclacitinib maleate in the European EudraVigilance Veterinary database, there were 855 reactions related to skin and tissue infections. Of these, 630 were classified as bacterial skin infections.

This DOES NOT mean that Apoquel caused 630 bacterial skin infections.

Dogs with atopic dermatitis already have a higher risk of secondary skin infections because of the disease itself, and a pharmacovigilance report does not prove causality.

But there is no reason to pretend that these data do not exist either.

When we have the drug’s mechanism of action, an official warning about infections, infections described in clinical trials, and a recurring signal in real-world pharmacovigilance at the same time, this is something worth monitoring during long-term treatment.

And here we also encounter a paradox.

If a dog receiving Apoquel starts itching again, one possible cause may be a secondary bacterial or yeast infection, which itself causes itching.

So the answer to renewed itching may not be more antipruritic treatment. The answer may instead be a new skin examination.

What do the blood-count data show?

At the time of our search (September 2026), the European pharmacovigilance database included, among reports associated with oclacitinib maleate:

• anaemia 1,140 times,
• leukopenia 1,109 times,
• neutropenia 826 times,
• lymphopenia 643 times
• and thrombocytopenia 649 times.

These numbers do not show the incidence of these problems among all dogs using Apoquel.

The pharmacovigilance database itself gives a very clear warning: spontaneous adverse-event reports must not be used to prove causality or to calculate the probability of an adverse event simply from the number of reports.

At the same time, blood-count changes are also addressed in the drug’s official safety information and in clinical studies.

So the question of monitoring blood counts during long-term Apoquel use is not merely a concern raised by integrative veterinarians.

But what about cancer?

This is probably the most emotional and one of the most difficult questions surrounding Apoquel.

The official product information includes warnings regarding neoplastic conditions, and lymphoma is addressed in the drug’s safety information.

In our EudraVigilance Veterinary search, 451 cases specifically carrying the lymphoma term were registered among reports associated with oclacitinib maleate.

Again: this does not mean 451 lymphomas caused by Apoquel.

But we also have a retrospective study of 660 dogs examining long-term use. Among 339 dogs receiving Apoquel, malignant neoplasia was diagnosed in 56 dogs, or 16.5%. In the comparison group of 321 dogs, malignant neoplasia occurred in 41 dogs, or 12.8%. The difference was not statistically significant, and the study found no association between Apoquel maintenance dose and malignant neoplasia. The authors concluded that the study did not show an additional risk of malignant neoplasia associated with long-term oclacitinib treatment.

That is an important finding in Apoquel’s favour.

But here too, the exact wording matters.

“The study did not identify a statistically significant additional risk” is not the same statement as “it has been proven that no additional risk exists”.

Likewise, pharmacovigilance reports of lymphoma do not prove that Apoquel caused those tumours.

The two data sources simply answer different questions.

“Very rare” does not mean “irrelevant”

When discussing adverse drug reactions, we often talk about how rare a particular reaction is.

And that information matters. Probability matters. But probability and the severity of the outcome are not the same thing.

If a serious adverse reaction occurs, for example, in one dog out of a very large number, it is very rare at the population level. For the one dog in whom it happens, however, the incidence rate is rather abstract comfort.

This does not mean that necessary treatment should be avoided because of a rare risk. It means that especially with long-term treatment, the decision should be based on an informed assessment of benefits and risks.

We have written in more detail about how to think about rare adverse reactions and the risks of medication use for an individual dog in the FendaF articles “Medications and their long-term use” and “Drug safety: why “safe” does not mean the same thing for everyone”.

Does Apoquel permanently damage the immune system?

Integrative veterinary medicine has raised strong concerns about the long-term immune effects of Apoquel.

Here, however, we need to distinguish between what clinicians have observed in practice and what studies can currently demonstrate.

At present, we do not have good evidence for the claim that a dog’s immune system may never fully recover after Apoquel use.

That does not mean the question is meaningless.

One study followed 13 dogs with atopic dermatitis receiving oclacitinib for 12 months. After a year, the measured cytokine profile of antigen-stimulated T cells was similar to the profile before treatment, and based on the mechanisms measured, the investigators found no evidence of immunosuppression.

That is an important reassuring finding.

But the study included only 13 dogs. Yes, a 12-month study in 13 dogs can provide valuable information about specific measured immune parameters. But it cannot rule out every rare, different, or very long-term effect.

So we do not write: “Apoquel permanently damages the immune system.”

But neither do we write: “It has been proven that long-term use has no effect on the immune system.”

The available evidence does not support either statement in such absolute terms.

But don’t studies say that Apoquel is safe?

In 2025, a comprehensive safety review of Apoquel was published, bringing together the available safety data and reaching an overall reassuring conclusion.

This is an important part of the evidence base.

At the same time, when evaluating scientific literature, we need to look not only at the conclusion but also at the background and methodology of the study or review and at possible conflicts of interest. Nor can the potential risk to an individual patient be ignored.

The authors of this review have ties to Zoetis, the manufacturer of Apoquel.

That does not automatically mean their analysis is wrong. But in the same way, an independent study is not automatically a good study. Funding and conflicts of interest are one part of assessing evidence, not a switch that turns a study on or off.

That is why at FendaF we always look beyond the final sentence of the abstract: how many animals were studied, how long they were followed, which animals were selected, what was actually measured, and what conclusions those data can reasonably support.

Pharmacovigilance: 29,238 cases do not mean 29,238 proven adverse reactions

At the time of our September 2026 search, the European EudraVigilance Veterinary database showed a total of 29,238 cases for oclacitinib maleate.

The reports listed 34,470 treated animals and 31,340 affected animals.

Those last two numbers MUST NOT be divided by one another and called the incidence of Apoquel adverse reactions.

In this view, “treated animals” means animals associated with the reports, not all dogs worldwide that have received Apoquel.

A single report may also contain several reactions and may concern more than one animal.

The European database itself warns that report counts cannot be used to calculate the probability of an adverse reaction or to confirm a causal relationship.

But that does not make pharmacovigilance pointless.

Quite the opposite. The purpose of the system is to detect patterns and rare potential safety signals after a drug reaches the market, including signals that clinical trials may not have detected.

And adverse reactions are not always reported

The other side of spontaneous reporting also deserves attention.

A 2024 veterinary study reviewed 10,565 small-animal clinical records. The researchers identified 827 suspected adverse drug reactions. In about 90% of them, there was no note in the medical record indicating that the case had been reported to the pharmacovigilance system.

This shows that under-reporting is a real problem in veterinary medicine.

But we must not turn that into a mathematical Frankenstein either.

We cannot, for example, take 451 lymphoma reports, multiply them by ten and claim that there were actually 4,510 lymphomas caused by Apoquel.

Different adverse reactions have different probabilities of being reported, and an under-reporting rate found in one study cannot automatically be transferred to a specific drug or a specific adverse reaction.

One important reporting change occurred in 2022

If EudraVigilance reports are viewed by year, a major change can be seen around 2022.

This must not automatically be interpreted as a sudden deterioration in Apoquel’s safety.

Until January 2022, European regulation for the EudraVigilance Veterinary system primarily required reporting of serious adverse reactions, although non-serious cases could also be submitted voluntarily.

After Regulation (EU) 2019/6 came into application, all suspected adverse reactions, both serious and non-serious, must be reported. The European pharmacovigilance database therefore itself warns that data collected before and after January 2022 should be compared cautiously.

Apoquel for a puppy?

Apoquel’s official product information includes an age restriction. The medicine is not intended for dogs under 12 months of age.

For FendaF, this is not merely a theoretical warning on a product leaflet.

Years ago, the owner of a Jack Russell Terrier named Hugo contacted FendaF. At that point Hugo was about one year old, and according to the owner, the dog had already been receiving Apoquel for about nine months.

Based on the treatment history provided by the owner, this means Apoquel had been started when Hugo was about three months old. Apoquel use was later also explicitly recorded in Hugo’s medical record as off-label use.

His story is longer, and we will not retell it here. You can read about Hugo’s medical history, treatment and what happened next in our separate article “Atopic dermatitis”.

But Hugo’s case illustrates very well why, when a medication is prescribed, an animal owner should know the diagnosis, the purpose of the medication and its official restrictions on use.

Especially when the patient is a puppy.

So should Apoquel be used or not?

That is not actually the right question.

For some dogs, Apoquel can be a very valuable medication.

A dog that itches around the clock, chews its paws raw and cannot sleep properly needs help. Uncontrolled inflammation and itching also harm the body and can significantly reduce a dog’s quality of life.

In that situation, Apoquel can be a very effective fire extinguisher.

But a fire extinguisher does not tell us why the house caught fire.

And if the house starts burning again after some time, the only question should not be:

“Do we need a bigger fire extinguisher?”

Perhaps we should look more carefully for where the fire is coming from.

This is where conventional veterinary medicine, integrative veterinary medicine and drug-safety data meet for us.

Observations made by integrative veterinarians do not need to be turned into proven causal relationships in order to be taken seriously.

Nor do controlled studies need to be dismissed simply because they do not answer every question about long-term safety.

The most honest answer emerges when we place these data side by side.

What do we know? What do we suspect? What has actually been documented? What can one particular study prove?

And what can it not prove?

Because with Apoquel, the goal should not be to decide whether the drug is “good” or “bad”.

The goal should be for the owner, together with their veterinarian, to make the most informed decision possible for the individual dog.

And the first question in that decision could still be the simplest one:

Why is my dog itching in the first place?

Sources used

• Cosgrove et al. Randomised placebo-controlled study in dogs with allergic dermatitis. PubMed PMID 23829933. Link
• Apoquel, European Union veterinary medicinal product information. Veterinary Medicines Information / EMA. The product has a valid marketing authorisation in Estonia; the latest product information was published on 28.04.2026. Link
• Extended twice-daily oclacitinib dosing in dogs with atopic dermatitis for which once-daily treatment was insufficient. PubMed PMID 35014745. Link
• Randomised study of rebound pruritus after reduction of oclacitinib dosing. PubMed PMID 36330780. Link
• Experimental mouse model of rebound pruritus after oclacitinib withdrawal. PubMed PMID 27847179. Link
• European veterinary suspected adverse drug reaction reports: disclaimer and interpretation limitations. Link
• Retrospective comparative study of long-term oclacitinib treatment and malignant neoplasia. PubMed PMID 32808904. Link
• Effects of 12 months of oclacitinib treatment on canine immune parameters. PubMed PMID 34747068. Link
• 2025 Apoquel safety review. PubMed PMID 40018984. The authors’ disclosed conflicts of interest should be taken into account when interpreting the results. Link
• Study of under-reporting of suspected adverse reactions to veterinary medicines. PubMed PMID 38441325. Link
• European veterinary adverse drug reaction reports: data source and explanation of the 2022 reporting change. Link
• EudraVigilance Veterinary / European pharmacovigilance database. Oclacitinib maleate query on 27.09.2026. Case counts used in the article are aggregate figures at the time of the query. Link
• FendaF: Atopic dermatitis, Hugo’s case history. Link
• FendaF: Medications and their long-term use. Link

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