Late Onset Neutropenia with Clozapine

Panesar, Narinder; Pai, Nagesh B; Valachova, Iveta

doi:10.3109/00048674.2011.581645

Cited by 7 publications

(5 citation statements)

References 3 publications

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“…Taking these findings into account, it appears that the agranulocytosis occurs the lifelong for clozapine treatment. Our patient's case indicates the necessity of the lifelong monitoring of the WBC count [4][5][6][7]. The mechanism responsible for neutrophil toxicity of clozapine is not fully elucidated.…”

Section: Resultsmentioning

confidence: 96%

Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine

Yoshimura¹,

Takashima²,

Nakamura³

2017

J Clin Case Rep

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We here reported a chronic schizophrenia patient who occurred neutropenia 13 years after starting clozapine. Thus, once clozapine is administered, the lifelong regular monitoring of the patient's total WBC count should be done.Keywords: Clozapine; Neutropenia; Late-onset Case ReportThe patient was a 46-year-old Japanese man who had met the DSM-IV diagnosis of schizophrenia, disorganized-type, for the prior 30 years. He had been on antipsychotic regimens since being diagnosed when he was 16 years old. He had been treated with therapeutic doses of sulpiride, haloperidol, levomepromazine, risperidone, olanzapine, aripiprazole, or lithium on several occasions, after which the treatments were stopped due to inadequate treatment response. After that, clozapine was started during his eighth hospitalization in 33-year-old in which he was brought to the hospital for persistent auditory hallucinations, monologia, persecutory delusion aggressiveness, and psychomotor excitement.After this admission, the clozapine dosage was titrated gradually up to 600 mg/day. The patient's total leucocyte count at baseline was 10,000/mm 3 . After discharge from the hospital, he showed a prominent improvement in his clinical status, with no apparent psychotic symptoms, and he attended a day-care service. During the long follow-up period, his total leucocyte count range was between 5,380 and 11,290/mm 3 with a daily 600 mg clozapine dosage. Twelve years after the start of that clozapine treatment, the patient's total leucocyte count had gradually decreased to 2,255 mm 3 . We therefore added lithium carbonate (600 mg/day) to increase the leucocyte count. However, the total leucocyte count did not recover after the addition of lithium carbonate (2,460 mm 3 , 1,663 mm 3 , 1,584 mm 3 , 1,526 mm 3 ). In 46-year-old (13 years later), the patient's total leucocyte count had gradually declined to 1,330/ mm 3 , and the 600 mg/day clozapine was stopped at the same time. His auditory hallucination, persecutory delusion, irritability, psychomotor excitement were exacerbated after stopping clozapine. Olanzapine (20 mg/day) and levomepromazine (150 mg/day) were re-started; those symptoms were however not ameliorated. Physical symptoms associated with neutropenia including fever, anemia, bleeding, irritability, and hot flashes were not seen. Four weeks after the clozapine was discontinued, the patient's total leucocyte count had recovered to 8,915/mm 3 . Written informed consent to have his case published was obtained from the patient.

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Section: Resultsmentioning

confidence: 96%

Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine

Yoshimura¹,

Takashima²,

Nakamura³

2017

J Clin Case Rep

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“…In another case 27 where this combination was prescribed concurrently for 9 months the pharmacokinetic interaction was not mentioned, and although the patient did relapse, the main focus was the fact that they developed late-onset neutropenia following the introduction of rifampicin. Prior to that he had been mentally and haematologically stable on clozapine for 9 years.…”

Section: Discussionmentioning

confidence: 99%

Prescribing clozapine and rifampicin: clinical impact of their interaction

Parker

2016

BJPsych Bull

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The predictable pharmacokinetic drug interaction between clozapine and rifampicin is listed in most standard reference texts but little detail is given or emphasis on its clinical significance. The interaction is based on theoretical knowledge of both drugs; to date just two case reports have been published. This article describes a third case demonstrating the significance of this interaction. This was potentially devastating for the patient who required an extended psychiatric admission. The enzyme induction was so potent that the dose of clozapine had to be increased approximately sixfold. Careful management of this significant interaction is essential for effective patient care.

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“… 5) In a review of literature, authors reported 16 case reports available prior to 2012. 4 , 8 – 11 , 13 , 16 , 19 – 25) The authors themselves reported the 17th case. In our literature search of PubMed, we came across 3 more cases.…”

Section: Discussionmentioning

confidence: 99%

“… 4 , 6 , 10 , 13 , 15 – 17) In other cases concomitant medication use involved use of antidepressants, anti-tubercular drugs, etc. 7 , 8 , 12 , 15) In 6 cases, late onset agranulocytosis/neutropenia was seen with clozapine monotherapy. In most of these cases, the patients were not rechallenged with clozapine.…”

Section: Discussionmentioning

confidence: 99%

Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature

Singh

Grover

Malhotra

et al. 2016

Clin Psychopharmacol Neurosci

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Agranulocytosis as a side effect of clozapine has been reported to be associated with initial phases of treatment, i.e., first six months. Agranulocytosis with clozapine during the initial phases of treatment has been linked to genetic vulnerability in the form of variations in the human leukocyte-antigen haplotypes. However, there is limited literature on late onset agranulocytosis with clozapine and this has very rarely been linked to human leukocyte-antigen haplotypes vulnerability. In this report we review the existing data on late onset agranulocytosis with clozapine and describe the case of a young man, who developed agranulocytosis with clozapine after 35 months of treatment and was found to have genetic vulnerability in form of being positive for HLA DR4. This case highlights underlying autoimmune immune mechanism in clozapine-induced agranulocytosis and the need for frequent blood count monitoring on clozapine even after the initial 6 months of starting treatment especially in patients with genetic vulnerability to develop this condition.

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Late Onset Neutropenia with Clozapine

Cited by 7 publications

References 3 publications

Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine

Very Late-Onset Neutropenia in a Japanese Schizophrenia Patient Treated with Clozapine

Prescribing clozapine and rifampicin: clinical impact of their interaction

Late Onset Agranulocytosis with Clozapine Associated with HLA DR4 Responding to Treatment with Granulocyte Colony-stimulating Factor: A Case Report and Review of Literature

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