Ilunocitinib-Induced Pancytopenia in an Australian Shepherd Dog with the MDR1 Mutation

A 5 yr old female spayed Australian shepherd dog with a prior diagnosis of atopy presented for increased pruritus despite immunotherapy. The dog had a history of seizures well controlled by levetiracetam and was genotyped as MDR1 mutant/normal. Ilunocitinib, indicated for controlling pruritus in dogs, was considered. Because the label indicates ilunocitinib can cause cytopenias, a complete blood count (CBC) was performed before initiating treatment. Neutrophils, platelets, and red blood cell numbers were all within reference ranges, so treatment with ilunocitinib was initiated. At a 1 mo follow-up appointment, the dog was bright, alert, and responsive with an improved Pruritus Visual Analog Scale score. A CBC indicated pancytopenia. Ilunocitinib was discontinued and a CBC was repeated after 7 days, indicating resolution of neutropenia and thrombocytopenia, but persisting anemia. One month after discontinuing ilunocitinib, all cytopenias had resolved. Because of the dog's MDR1 genotype, the status of ilunocitinib as a canine P-glycoprotein substrate was assessed. Ilunocitinib was identified as a canine P-glycoprotein substrate. Blunted P-glycoprotein-mediated biliary excretion of ilunocitinib likely resulted in accumulation and a relative overdose. Enhanced penetration of ilunocitinib into hematopoietic stem cells lacking P-glycoprotein expression may have also contributed to dysregulated hematopoiesis. Ilunocitinib should be used cautiously in dogs with P-glycoprotein deficiency.