(#32) Clozapine Toxicity in Real-World Practice: The Critical Role of Rapid Therapeutic Drug Monitoring

Abstract: Clozapine is the most effective antipsychotic for treatment-resistant schizophrenia, but it requires careful monitoring due to its narrow therapeutic index and potential for life-threatening toxicity. Therapeutic drug monitoring (TDM) is essential for individualized treatment, especially in medically complex patients. This case series presents three cases of clozapine toxicity triggered by distinct physiological changes: decreased cytochrome P450 1A2 (CYP1A2) metabolism following smoking cessation, impaired hepatic metabolism from sepsis induced by respiratory syncytial virus (RSV), and increased drug concentration due to a urinary infection causing pre-renal acute kidney injury (AKI). All three patients exhibited clozapine toxicity (serum level greater than 1,500 ng/mL) with severe complications, including paralytic ileus, encephalopathy, and recurrent falls. The implementation of an FDA-cleared clozapine assay that reduced significantly the time to clozapine result enabled timely diagnosis and intervention. Dosage adjustments based on serial TDM results facilitated clinical stabilization with all three patients ultimately resuming clozapine at individualized doses. These cases exemplify the benefit of access to rapid TDM in clozapine management, highlighting how same-day clozapine levels can enhance clinical decision-making, reduce the risk of prolonged toxicity, prevent unnecessary discontinuation, and improve patient outcomes. Expanding provider's access to faster clozapine level testing may optimize treatment strategies and enhance patient safety in multiple clinical settings.Short Description: Clozapine toxicity can result from physiological changes affecting metabolism and clearance. This case series highlights three instances of toxicity due to smoking cessation, RSV-induced sepsis, and AKI from a urinary infection. Implementation of an FDA-cleared rapid clozapine assay enabled timely intervention, preventing prolonged toxicity and unnecessary discontinuation. Serial therapeutic drug monitoring guided individualized dosing, improving patient outcomes. Expanding access to same-day clozapine levels can enhance clinical decision-making and patient safety across diverse medical settings.Name of Sponsoring Organization(s): Saladax Biomedical