A patient on clozapine presents with fever and malaise. What is the most important initial action?

• A. Switch to another antipsychotic immediately.
• B. Immediate evaluation for possible agranulocytosis; obtain CBC with differential and withhold clozapine if ANC is low.
• C. Prescribe antipyretics only without labs.
• D. Ignore symptoms and continue clozapine.

Answer: (B)

Clozapine carries a real risk of agranulocytosis, so fever and malaise in someone taking this drug raise an urgent red flag for a possible dangerous drop in neutrophils. The most important first step is to obtain a CBC with differential to assess the absolute neutrophil count and to withhold clozapine if the neutrophil count is low. This immediate action is crucial because agranulocytosis can progress rapidly to severe infection and sepsis, and continuing the medication in the setting of neutropenia greatly increases risk. If the neutrophil count is low, stop clozapine and manage according to neutropenia guidelines, which may involve hospitalization and close monitoring until counts recover. If the count is not low, fever still warrants prompt evaluation for infection, but starting by rechecking the neutrophil count and reassessing the need to continue clozapine remains essential.