Clozapine and Tuberculosis

Landry, Pierre; Deschamps, René; Tanguay, Nicole; Tessier, Sylvie

doi:10.1176/appi.psy.41.6.539-a

Cited by 4 publications

(4 citation statements)

References 3 publications

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“…The lethality of pneumonia in clozapine patients is explained in that clozapine can contribute to pneumonia, and once pneumonia develops it can cause a clozapine intoxication; therefore, the combination of pneumonia and clozapine intoxication is highly lethal. This complex bidirectional association [162] is described in detail in online supplementary Box S7 [157,[163][164][165][166][167][168][169]. Our recommendations for decreasing the risk and lethality of pneumonia in clozapine patients are described in online supplementary Box S8 [65,162,170,171].…”

Section: Pneumoniamentioning

confidence: 99%

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

Leon

Ruan

Schoretsanitis

et al. 2020

Psychother Psychosom

114

113

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Using Richardson and Davidson's model and the sciences of pharmacokinetics and clinical pharmacopsychology, this article reviewed the: (1) poor life expectancy associated with treatment-resistant schizophrenia (TRS), which may be improved in patients who adhere to clozapine; (2) findings that clozapine is the best treatment for TRS (according to efficacy, effectiveness and well-being); and (3) potential for clozapine to cause vulnerabilities, including potentially lethal adverse drug reactions such as agranulocytosis, pneumonia, and myocarditis. Rational use requires: (1) modification of the clozapine package insert worldwide to include lower doses for Asians and to avoid the lethality associated with pneumonia, (2) the use of clozapine levels for personalizing dosing, and (3) the use of slow and personalized titration. This may make clozapine as safe as possible and contribute to increased life expectancy and well-being. In the absence of data on COVID-19 in clozapine patients, clozapine possibly impairs immunological mechanisms and may increase pneumonia risk in infected patients. Psychiatrists should call their clozapine patients and families and explain to them that if the patient develops fever or flu-like symptoms, the psychiatrist should be called and should consider halving the clozapine dose. If the patient is hospitalized with pneumonia, the treating physician needs to assess for symptoms of clozapine intoxication since halving the dose may not be enough for all patients; consider decreasing it to one-third or even stopping it. Once the signs of inflammation and fever have disappeared, the clozapine dose can be slowly increased to the prior dosage level. 46, 48, 52-67] describes the important pharmacokinetic variables for clozapine clearance. Higher clozapine C/D ratios, indicating lower clearance, are associated with females, non-smokers, Asians, genetic poor metabolizers, inhibitors, obesity, inflammation, and possibly with renal impairment and pregnancy. Lower clozapine C/D ratios indicate lack of adherence or higher clearance associated with males, smokers, non-Asians, and inducers.Two prior TDM review articles [68,69] are summarized in online supplementary Box S3 [31, 44, 50, 51, 55, 58-61, 63, 65, 68-91] which also describe our extensive experience with thousands of inpatient clozapine TDMs under standard conditions (trough and steady-state levels) in the US [44] and China [45,65]. Many of these inpatients were followed for months and/or years after changes in important pharmacokinetic variables [31, 44, 50, 58-61, 63, 65, 74, 79, 86-91].Published review articles [92][93][94] usually insist on the wide variability of clozapine TDM among individuals and the difficulty of interpreting a single clozapine level, but they fail to pay attention to findings from these two sciences: pharmacokinetics and clinical pharmacopsychology, which help in interpreting variability in clozapine levels. In inpatients, repeated measures allow the calculation of average clozapine clearance in an individual through a...

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Section: Pneumoniamentioning

confidence: 99%

A Rational Use of Clozapine Based on Adverse Drug Reactions, Pharmacokinetics, and Clinical Pharmacopsychology

Leon

Ruan

Schoretsanitis

et al. 2020

Psychother Psychosom

114

113

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“…11 The cytotoxic effect of clozapine on leukocytes reduces cellular immunity with an increased risk of infection. 12,13 South Africa, and in particular the Western Cape Province, faces a dual burden of tuberculosis and HIV, 14,15 and it is unknown whether clozapine is an independent risk factor for developing tuberculosis. HIV infection suppresses the immune system, and leukopenia and neutropenia are among the most common hematological aberrations in HIV-positive patients.…”

mentioning

confidence: 99%

“…The cytotoxic effect of clozapine on leukocytes reduces cellular immunity with an increased risk of infection 12,13 . South Africa, and in particular the Western Cape Province, faces a dual burden of tuberculosis and HIV, 14,15 and it is unknown whether clozapine is an independent risk factor for developing tuberculosis.…”

mentioning

confidence: 99%

Clozapine-Associated Leukopenia and Agranulocytosis in Western Cape, South Africa

Geldenhuys

Zunza

Tiffin³

et al. 2021

J Clin Psychopharmacol

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“…The association between antipsychotic agents and tuberculosis is not well documented in the medical literature. For instance, one study reported two cases in which patients were treated with clozapine and subsequently developed pulmonary tuberculosis . However, we found no study using large‐scale systematic datasets to explore the associations between individual antipsychotic agents and tuberculosis.…”

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confidence: 99%