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Oclacitinib (Apoquel) has gained popularity in veterinary medicine over the past decade for its ability to control pruritis in dogs (and off-label in cats) secondary to atopic dermatitis. Since the release of the flavored chewable oclacitinib tablets in 2023, unusual and severe adverse effects have been reported following overdose ingestion in cats and dogs. Given the increased potential for overdose exposure, veterinary professionals should be aware of the risks and thoroughly educate clients regarding those risks.
Oclacitinib is a Janus kinus (JAK) enzyme inhibitor approved for use in dogs > 1 year of age to control pruritis secondary to underlying allergic and atopic dermatitis. While only approved for use in canine patients, it is also used off-label by veterinarians in feline patients. Oclacitinib primarily inhibits JAK1, but also exerts some effects on JAK2 and JAK3. Ultimately, oclacitinib inhibits multiple cytokines, including IL-31, which controls pruritis activity and is implicated in the pathogenesis of atopic dermatitis. The recommended dose range for oclacitinib is 0.4 to 0.6 mg/kg PO every 12 hours for up to 14 days, and then every 24 hours thereafter.
The tablet formulation of oclacitinib was approved in the United States by the FDA in May 2013, and a chewable (pork liver) formulation was released in June 2023. With the approval of this highly palatable chewable tablet in 2023, there has been a significant increase in frequency and dosage of accidental exposures reported in dogs and cats.
Currently, there are limited studies available evaluating the side effects of oclacitinib ingested by dogs at supratherapeutic dosages. One study performed prior to FDA approval reported that the most common side effects in dogs being treated with therapeutic doses were diarrhea, vomiting, and anorexia. Another study performed post-FDA approval noted liver enzyme elevation and seizure activity.
As reported by U.S. animal poison control centers, prior to June 2023, there was an annual average of 202 dog exposures and 21 cat exposures. In these cases, more than 88% of exposures were below 10 mg/kg. From June 2023 to early 2025, the number of exposures increased eightfold (annual average of 1,749 dog exposures and 180 cat exposures), and more than 60% of these exposures exceeded a dose of 10 mg/kg.
In symptomatic dogs, reported signs included tachycardia (46%), vomiting (28%), ophthalmic signs such as raised third eyelids and periocular edema (16%), increased ALT activity (10%), hypotension (10%), development of a new heart murmur (6%), leukopenia (5%), acute kidney injury (AKI) (2%), and death (1%).
In symptomatic cats, signs included vomiting (55%), ophthalmic signs (54%), AKI (45%), increased ALT activity (29%), death (21%), development of a new heart murmur (20%), hypocalcemia (18%), and hypotension (15%).
Overall, 36 deaths were reported (eight dogs, 28 cats), secondary to either cardiovascular signs or AKI. Oclacitinib doses resulting in death ranged from 12 to 310 mg/kg.
Dosages of 10–15 mg/kg have been reported to result in GI signs (vomiting, diarrhea, abdominal pain), cardiovascular abnormalities (tachycardia, arrhythmias, new heart murmur, hypotension), CNS signs (severe lethargy, mentation changes, elevated third eyelids), and hepatotoxicity (in some cases leading to coagulopathy and death) in both dogs and cats.
Higher dosages of 12–38 mg/kg have resulted in the development of acute kidney injury in dogs and cats. The degree of AKI ranges from mild (resolving after 48 hours post decontamination and intravenous fluid therapy) to severe (anuric kidney failure requiring hemodialysis) and even death. Marked elevations in BUN and creatinine have been reported within 12 to 72 hours post-exposure, and data thus far suggests that cats appear to be more severely affected by the renal effects of toxicity.
The International Renal Interest Society (IRIS) defines a Grade I AKI as an increase in serum creatinine of 0.3 mg/dL or greater from baseline within 48 hours. While patients with Grade I AKI may not need to be hospitalized, they are at risk of progressing to higher AKI grades, and thus, close monitoring is imperative until renal recovery is achieved. Progression from one grade of AKI to another can occur rapidly (within hours to days), and patients exposed to oclacitinib doses > 10 mg/kg should be monitored daily until stabilization of creatinine occurs.
Currently, a more aggressive management approach is recommended in cats and dogs after an overdose exposure exceeding 10 mg/kg. This includes prompt decontamination via emesis and/or a single dose of oral activated charcoal (when appropriate), judicious IV fluid therapy as indicated by patient status, supportive management of gastrointestinal upset, cardiovascular or neurologic abnormalities, and monitoring serial lab work (chemistry panel, CBC) for 24–72 hours.
In patients with AKI who require hospitalization, fluid therapy should initially be used to correct any dehydration, if present. Once euhydrated, a zero-fluid balance (no net gain or loss of fluids) should be pursued. Patients with AKI may not be able to excrete excessive fluid, leading to the development and clinical consequences of volume overload (chemosis, pulmonary edema, peripheral edema). Additionally, intravenous fluid therapy may contribute to renal tubular edema, exacerbating AKI, after exposure to nephrotoxins. Monitoring of fluid balance includes frequent (at least twice daily) assessment of body weight, urine production, and cardiovascular parameters (for development of hypertension). There is no evidence to support that proactive fluid therapy prevents the development of AKI in a normovolemic and euhydrated patient after oclacitinib exposure.
Patients who develop progressive AKI (increasing creatinine despite euvolemia) should be referred to a facility with 24-hour monitoring and care that is equipped to manage moderate to severe kidney injury. Referral should occur as early as possible to allow directed therapy and intensive monitoring, as patients with AKI can deteriorate rapidly. In patients with severe AKI (creatinine > 5 mg/dL, oliguria/anuria) hemodialysis is indicated.
The underlying mechanism of toxicity due to oclacitinib currently remains unknown. As we gain further information, guidelines for managing overdose situations will be developed. For now, the easiest way to deal with this emerging toxicity is to prevent it from happening. This starts with clear client communication regarding the risks of toxicity, as well as the fact that the highly palatable chewable formulation seems extremely appealing to pets and should be kept safely away from their reach. In the event of an overdose exposure, consultation with an animal poison control center and adverse event reporting to the manufacturer and the FDA are recommended. Encouraging reporting of adverse effects to poison control centers will provide further data on risks, effective management strategies, and morbidity and mortality associated with this medication.
