Clozapine Rechallenge After Neutropenia or Leucopenia

Abstract

To rechallenge with clozapine for a patient who previously has experienced neutropenia or leucopenia or during clozapine treatment is a difficult clinical decision. Herein, we analyzed the results of such a rechallenge in 19 patients. We analyzed all the reports, from the database of the pharmacovigilance department of the Argentine National Administration of Drugs, Foods, and Medical Devices, of patients who were rechallenged with clozapine after a leucopenia or a neutropenia. Nineteen cases of rechallenge after leucopenia or neutropenia were reported between 1996 and 2014. One third of the patients re-exposed to clozapine developed a new hematologic adverse reaction. The second blood dyscrasia was less severe in 83% of the cases and had a shorter median latency as compared with the first (8 weeks vs 182 weeks, P = 0.0045). There were no significant differences for demographic and clinical characteristics of patients who developed a second dyscrasia as compared with those who did not. The present study shows that almost 70% of the patients rechallenged with clozapine after a leucopenia or a neutropenia did not develop a new hematological adverse effect, whereas the remaining 30% had a faster but less serious neutropenia.

Re-titration rates after clozapine-induced neutropenia or agranulocytosis: A case report and literature review

“…The search resulted 467 articles, with 31 relevant to rechallenge after neutropenia or agranulocytosis. Three were systematic reviews (31–33), four were retrospective analysis (34–37), and 24 were case reports (38–61). In all, these reports represented 146 unique patients, of whom 37 (25%) failed rechallenge, comparable to previous rates (31).…”

Clozapine rechallenge and initiation despite neutropenia- a practical, step-by-step guide

“…The majority of dyscrasias occurred within 18 weeks of clozapine treatment; four occurred after this [23]. In 2016 data from a nationwide pharmacovigilance study in Argentina presented the outcomes of 19 patients rechallenged with clozapine; approximately one third of patients experienced a second dyscrasia which mostly occurred sooner during treatment but were less severe and of shorter duration [24]. Evidence from case reports shows a positive outcome in more than 60% of clozapine rechallenges after neutropenia (128 positive outcomes from 203 cases); there is less reported success following agranulocytosis (3 positive outcomes from 17 cases) [1].…”

Isolated Chronic and Transient Neutropenia

“…It is important to evaluate the relative risk of severe agranulocytosis versus discontinuation of clozapine (leading to high mortality due to inadequate treatment for schizophrenia). Caution must be used and regular monitoring of the neutrophil count should be performed if the drug is restarted [31-32].…”