Baptista T, Motuca M, Serrano A, Perez Lo Presti A, Fernandez-Arana A, Olmos I, Pabon A, Yepez JGA, Alejo Galarza GJ, Rivera Ramirez NM, Elkis H, Sanz EJ, De Las Cuevas C, de Leon J. An expert review of clozapine in Latin American countries: Use, monitoring, and pharmacovigilance. Schizophr Res. 2024 Jun;268:60-65. doi: 10.1016/j.schres.2023.10.025. Epub 2023 Nov 18. PMID: 37985318.

Abstract

There is a growing interest all around the world in clozapine clinical use, monitoring, and research, particularly adverse drug reactions (ADRs) other that agranulocytosis. In this study we focused on clozapine pharmacovigilance. Hence, we contacted clinicians and researchers in Latin America and requested information about local psychiatric services, clozapine availability, clinical use, and ADR monitoring with the VigiBase system. Only two countries have the minimal advisable psychiatric beds (15 per 100.000 habitants): Uruguay (N= 34.9) and Argentine (N= 17). Bolivia is the only country where clozapine is unavailable. Nine out of twenty countries (45%) reported ADRs to VigiBase. Brazil, Chile, Colombia, and Mexico published national guidelines for schizophrenia treatment. Chile is the sole country with clozapine clinics with drug serum monitoring. Ethnicity-related drug titration in not described in package inserts in any country. We examined in detail the 9 most frequent and important clozapine ADRs in the worldwide database (pneumonia, sudden death, cardiac arrest, agranulocytosis, myocarditis, constipation, arrhythmia, seizure, and syncope). These 9 ADRs led to 294 reports with fatal outcomes in Argentine (N=3), Brazil (N=3), Chile (N=2), and Peru (N=1). Agranulocytosis was reported from 7 countries, constipation, or seizures from 8 countries. Only two countries reported pneumonia and one country reported myocarditis. The number of clozapine reports on VigiBase has no relation with the country population. All Latin American countries underreport clozapine associated ADRs. Latin American governments along with clinicians, researchers, and educators should optimize clozapine use and monitoring for the benefit people with severe mental and some neurological disorders.