A case report: Clozapine‐induced leukopenia and neutropenia after mRNA COVID‐19 vaccination

Imai, Tomoyuki; Ochiai, Sho; Ishimaru, Takehiro; Daitoku, Hayato; Miyagawa, Yusuke; Fukuhara, Ryuji; Boku, Shuken; Takebayashi, Minoru

doi:10.1002/npr2.12238

Cited by 12 publications

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“…The cumulative prevalence of agranulocytosis and neutropenia in those taking clozapine is approximately 0.9% and 3.8%, respectively, with a peak incidence in the first month after exposure to clozapine treatment. 38 Across the studies analyzed in this review, although a transient but significant drop in the neutrophils' count was reported, only 10.6% of patients presented with neutropenia according to the definition (cut-off value of neutrophils 1500/μL). Recent data suggest that neutropenia is likely to be caused by SARS-CoV-2 infection rather than clozapine treatment.…”

Section: Discussionmentioning

confidence: 86%

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Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Moga

Teodorescu

Dragan³

et al. 2022

American Journal of Therapeutics

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Background: Clozapine is the only approved antipsychotic for treatment-resistant schizophrenia. Despite its therapeutic benefits, it is still widely underused, mainly because of its potential to cause agranulocytosis and neutropenia. Prescribing clozapine in COVID-19-positive patients became more challenging because of this potential side effect. This article is a review of literature on the risk of neutropenia associated with clozapine treatment in patients with COVID-19. Areas of Uncertainty:In clozapine-treated COVID-19-positive patients, neutropenia was reported in some cases; is it a consequence of clozapine treatment or of SARS-Co2 infection?Data Sources: Data were extracted from 2 databases: PubMed/MEDLINE and Google Scholar. We selected all original reports, from March 2020 until May 2022, on neutropenia associated with clozapine treatment in positive COVID-19 patients. Eleven studies were selected for the final analysis.Therapeutic Advances: Before the COVID-19 pandemic, neutropenia in clozapine-treated patients was reported in 3.8% of cases. During the pandemic, neutropenia rates seemed to be higher. As per the cause of neutropenia, studies reported contradictory results. We aim to clarify rates and causes of neutropenia in clozapine-treated COVID-19-positive patients.Results: Three hundred eighty-eight articles were initially selected from the 2 databases. After excluding duplicates, unrelated articles, reviews, and guidelines, 11 studies were analyzed, all centered on clozapine treatment, COVID-19 infection, and associated neutropenia.Conclusions: Clozapine treatment in COVID-19-positive patients may be associated with a transient reduction of absolute neutrophils count, in some cases reaching neutropenia levels. Neutropenia rates reported in SARS-CoV-2-infected patients are higher than the prepandemic reports; therefore, we assume that the cause might be a result of the immunological interference between clozapine and SARS-CoV-2. Clozapine treatment needs to be continued whenever possible, with dose adjustments in relation to blood test results.

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Section: Discussionmentioning

confidence: 86%

“…Blood cell count and clozapine plasma concentration should be both measured before and after the vaccination. 38…”

Section: Resultsmentioning

confidence: 99%

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Moga

Teodorescu

Dragan³

et al. 2022

American Journal of Therapeutics

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“…Takaki et al 89 reported a case of transient neutropenia without agranulocytosis in a patient treated with clozapine and vaccinated with Pfizer-BioNTech. Similarly, Imai et al 90 noticed leukopenia and neutropenia after Pfizer-BioNTech vaccination in a clozapine-treated patient. In both cases, patients had not previously undergone SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 83%

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection

Moga

Petric

Miron

et al. 2023

American Journal of Therapeutics

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Background: The outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic had multiple consequences for the health care system, especially for patients with mental illnesses. Schizophrenia patients particularly appear to have a higher risk of complications due to coronavirus-19 . Clozapine remains the gold standard for treatment-resistant schizophrenia (TRS). However, the COVID-19 pandemic had an important negative impact on clozapine treatment, mainly because of its administration protocol, which was very difficult to follow during the restrictions imposed in the pandemic, and its side effects in patients with COVID-19 infection. Vaccination is an effective method of avoiding SARS-CoV-2 infection or its severe complications, especially in susceptible populations. Data on adverse events after vaccination against COVID-19 are limited, both in the general population and in schizophrenia patients.Study Question: The study aimed to investigate the safety of COVID-19 vaccination in patients treated with clozapine for hematological parameters. Study Design:We conducted an analytical cross-sectional study between July 1, 2021, and June 30, 2022. We compared 2 groups of COVID-19 vaccinated patients who had previously experienced SARS-CoV-2 infection: The first group was treated with clozapine, whereas the second group was treated with other antipsychotics.Measures and outcomes: The primary objective was to identify granulocytopenia, leukocytopenia, and lymphocytopenia. The results were measured after the second dose of the Pfizer-BioNTech vaccine.

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“…Cytochrome P450 genotype of the patient did not explain the increase in clozapine serum level. Recently, Imai et al 33 reported the case of a 44‐year‐old female patient with a good response to clozapine, who experienced an inflammatory reaction and cytopenia after being vaccinated with the BNT162b2 mRNA COVID‐19 vaccine (tozinameran, Pfizer‐ BioNTech). Shortly after the second dose, the patient experienced fatigue and pain in the left parotid gland and had a temperature of 37.5°C and her C‐reactive protein (CRP) level was slightly elevated to 10.1 mg/L.…”

Section: Covid‐19 Vaccine—drug Interactionsmentioning

confidence: 99%

“…Unfortunately, clozapine blood levels were not determined after vaccination. Another case report refers to elevated clozapine levels with toxic effects and mild, transient lymphocytopenia 4 days after the first dose of a BioNTech/Pfizer vaccine 33 . A direct causal relationship between COVID‐19 vaccination and these adverse events could not be established.…”

Section: Covid‐19 Vaccine—drug Interactionsmentioning

confidence: 99%

Implications of potential clinically relevant interactions between COVID‐19 vaccines and concomitant medications

Badary

2023

Reviews in Medical Virology

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COVID‐19 was announced as a global pandemic in 2020. Several types of COVID‐19 vaccines are available such as mRNA vaccines, adenovirus vector vaccines, and protein subunit or inactivated virus vaccines. Vaccines are often administered in patients with chronic diseases who are likely to be treated with several drugs. A growing number of clinical observations indicated the possibility of interactions between COVID‐19 vaccines and drugs. A hyperinflammatory state may spark significant imbalances in drug metabolism that may result in the alteration of drug pharmacokinetics and therapeutic response. Furthermore, interactions may result in additive or antagonistic or synergistic vaccine immune response. Information about COVID‐19 vaccine–drug interactions is needed by physicians and pharmacists to make rational drug‐use decisions. In this review, several individual and categorical evidence‐based potential COVID‐19 vaccine–drug interactions of clinical importance are described. Vigilance is needed to detect previously unreported COVID‐19 drug interactions and to further assess known interactions. The clinical significance of which is not fully determined. Evidence suggests that adverse events to some drugs are rare after COVID‐19 vaccination and their possibility should not affect vaccination of patients at risk. Clinicians prescribing medications should be aware of the likely risk of interaction with COVID‐19 vaccines and may benefit from taking into account present recommendations of the best measures to avoid consequences of such interactions to preserve vaccine efficacy and patient safety.

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A case report: Clozapine‐induced leukopenia and neutropenia after mRNA COVID‐19 vaccination

Cited by 12 publications

References 4 publications

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Neutropenia in Patients With Clozapine-Treated Schizophrenia: An Effect of Clozapine or a Consequence of SARS-CoV-2 Infection? A Systematic Review

Outcome of COVID-19 mRNA Vaccination in Patients Treated With Clozapine WHO Previously Went Through SARS-COV-2 Infection

Implications of potential clinically relevant interactions between COVID‐19 vaccines and concomitant medications

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