Clozapine

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

In a retrospective chart review of 56 patients, who were receiving clozapine and were diagnosed with severe COVID-19 between March 2020 and May 2020, four patients (3 men and 1 woman) in their 20s−50s were described, who developed neutropenia or neutropenic sepsis during treatment with clozapine [routes, dosages and indications not stated].

Patient A: A woman in her 20s' (age group of 21−30 years) was receiving clozapine for 231 days. Subsequently, she was diagnosed with COVID-19. The day before the diagnosis of COVID-19, she had the first episode of neutropenia with an absolute neutrophil count (ANC) of 1.8 χ10⁹/L. On the next day of COVID-19 diagnosis (on day 1), her ANC level increased to 4.2 χ10⁹/L. However, on days 8 and 9, her ANC level again decreased to 1.2 χ10⁹/L on day 8 and 1.4 χ10⁹/L, respectively. In view of consecutive episodes of neutropenia, treatment with clozapine was stopped for 24h. On day 14, her neutropenia was resolved. In the following 6 months, no recurrence of neutropenia was observed.

Patient B: A man in his 50s' (age group of 51−60 years) was receiving clozapine for 520 days. Subsequently, he was diagnosed with COVID-19. He had a history of 1 unexplained episode of neutropenia during a critical care admission following a road traffic accident. On day 5 of COVID-19 illness, his ANC level was decreased to 0.9 χ10⁹/L, and it remained low at 1.2 χ 10⁹/L and 2.1 χ10⁹/L on day 6 and 8, respectively. Hence, treatment with clozapine was stopped. On day 9, his ANC level recovered. Afterwards, treatment with clozapine was restarted, and no recurrence of neutropenia was observed in the following 6 months.

Patient C: A man in his 30s' (age group of 31−40 years) was receiving clozapine for 339 days. Subsequently, he was diagnosed with COVID-19. On day 6 of COVID-19 illness, he had an episode of neutropenia. Hence, treatment with clozapine was stopped, and on day 8, his ANC level recovered to 2.7 χ10⁹/L. Therefore, on day 10, treatment with clozapine was restarted, and no recurrence of neutropenia was observed in the following 6 months.

Patient D: A man in his 20s' (age group of 21−30 years) was receiving clozapine for 67 days. Subsequently, he was diagnosed with COVID-19. The day before the diagnosis of COVID-19, he had the first episode of neutropenia. On day 1 of COVID-19 illness, his ANC level further decreased to 0.9 χ10⁹/L, followed by 0.5 χ10⁹/L on day 6 and 0.6 χ10⁹/L on day 7. Therefore, treatment with clozapine was stopped. He was also diagnosed with neutropenic sepsis. On day 38, his neutropenia was resolved. Treatment with clozapine was not restarted.