Neurologic Adverse Events and What TRK Selectivity Explains

Martin Dietrich, MD, PhD, separates an agent working in the brain from an agent acting on the brain, and explains that structural overlap in the adenosine triphosphate (ATP) binding pocket makes TRK family inhibition difficult to avoid. He says the resulting effects, which can present as psychiatric or neurologic, are dose-dependent, and Dietrich counsels patients and families directly, taking particular care when there is a predisposition to falls or psychiatric illness. Wade Iams, MD, says rates of dizziness, ataxia, and tinnitus are roughly halved with the newer agents, that dose reduction is often the right answer, and that recommended doses come from maximum tolerated dose work that may not suit every patient. Ticiana Leal, MD, notes that patients change daily activities, including sport, once dizziness sets in.