(1250) Clozapine Metabolism: Dosage, Levels, and the Potential for Toxicity in Non-hispanic Black Patients

Objectives: The purpose of this review is to compare the clozapine level-to-dose ratios of non-Hispanic black patients to white patients. Clozapine is an atypical antipsychotic indicated for treatment-resistant schizophrenia. While it is the most effective antipsychotic medication for schizophrenia, it is not used first line due to its adverse effect profile. The clozapine Risk Evaluation and Mitigation Strategies program is a required safety program to manage the risk of severe neutropenia associated with clozapine treatment. This program requires monthly absolute neutrophil count results, monitoring frequency, and treatment justification. As the field of pharmacogenomics is growing, there are more prescribing strategies being developed using a patient’s genetic composition. Pharmacogenomics may provide insight to the metabolism of clozapine to help decrease the risk of patients developing clozapine toxicity. If results are significant, race may be a prominent factor in the dosing of clozapine as it is already a factor in prescribing other medications within the non-Hispanic black patient population. Through examining a sample of patients on clozapine and their trough levels, the clozapine level-to-dose ratio may provide a better understanding of the rate of the metabolism of clozapine and the potential of toxicity within non-Hispanic black patients as compared to white patients. If differences are noticed, UPMC prescribers may be able to treat patients more adequately with clozapine at doses that are more suitable for them based on patterns seen with possible pharmacogenetic effects on varying metabolism within these two races.

Methods: A retrospective, cross sectional, observational cohort design is used within this study. A sample of 58 patients taking clozapine were included in this study to evaluate the difference in the metabolism of clozapine in African Americans and white patients. Patients who were hospitalized at UPMC Western Psychiatric Hospital and UPMC McKeesport, received treatment at Pathways LTSR, or engaged in services within the WPH CRS service line were included in this study. While receiving care, the patients had trough clozapine blood levels drawn while the medication was at steady state systemically. The clozapine level-to-dose ratios will be collected, analyzed, and compared between the two cohorts of non-Hispanic black patients and white patients. Confounding factors such as drug interactions, signs of infection, history of smoking, and poorly timed trough level draws are considered when examining the metabolism of clozapine. Data will be analyzed using a paired t-test.

Results: Results are in progress.

Conclusions: Conclusion will be determined upon completion of this project.