clozapine and Tuberculosis

Clozapine is the only licensed medication for treatment-resistant schizophrenia. The metabolism of clozapine is affected by multiple pharmacokinetic interactions, so the co-administration of adjunct medications can have a significant clinical effect. The anti- tuberculosis medication rifampicin is a potent inducer of the cytochrome P450 system and therefore can cause a reduction in the plasma concentration of clozapine. There is limited clinical evidence regarding co-administration of these medications; in particular there is a lack of data regarding the effect on plasma clozapine levels, which is the key factor determining clinical efficacy. This is clinically relevant given evidence of an increased risk of tuberculosis in patients with schizophrenia.. We present a case of a 28 year old British man with a diagnosis of schizoaffective disorder who presented with persistent psychotic symptoms. He developed a systemic inflammatory condition, diagnosed as tuberculosis, and was commenced on a six month course of treatment that included rifampicin. This case presents comprehensive data to illustrate the effect on clozapine plasma levels of a complete course of tuberculosis therapy.. This case report provides guidance to clinicians in managing drug interactions between clozapine and rifampicin to enable safe and effective treatment. The co-administration of these medications is likely to increase as the existing underuse of clozapine is recognised whilst the incidence of tuberculosis increases.

Topics: Adult; Antibiotics, Antitubercular; Antipsychotic Agents; Clozapine; Drug Interactions; Drug Therapy, Combination; Humans; Male; Psychotic Disorders; Rifampin; Treatment Outcome; Tuberculosis

Patients with schizophrenia have a higher incidence of tuberculosis than do people in the general population. Information is limited regarding the association between antipsychotic agents and the risk of tuberculosis in patients with schizophrenia. This exploratory study assessed the risk of tuberculosis among patients with schizophrenia on antipsychotic therapy.. Among a nationwide schizophrenia cohort derived from the National Health Insurance Research Database in Taiwan (n = 32 399), we identified 284 patients who had developed newly diagnosed tuberculosis after their first psychiatric admission. Ten or fewer matched controls were selected randomly from the cohort for each patient based on risk-set sampling. We categorized exposure to antipsychotic medications by type and defined daily dose. Using multivariate methods, we explored individual antipsychotic agents for the risk of tuberculosis and employed a propensity-scoring method in sensitivity analyses to validate any associations.. Among the antipsychotic agents studied and after adjustment for covariates, current use of clozapine was the only antipsychotic agent associated with a 63% increased risk of tuberculosis (adjusted risk ratio = 1.63, P = 0.014). In addition, the association did not show a clear dose-dependent relationship. Clozapine combined with other antipsychotic agents showed a potential synergistic risk for tuberculosis (adjusted risk ratio = 2.30, P = 0.044).. This exploratory study suggests the potential risk of clozapine on the risk of tuberculosis, especially for those on clozapine in combination with other antipsychotics. Future studies are needed to verify the association.

Topics: Adult; Antipsychotic Agents; Case-Control Studies; Clozapine; Drug Therapy, Combination; Female; Humans; Incidence; Male; Risk Factors; Schizophrenia; Taiwan; Tuberculosis; Young Adult

Topics: Aged; Antipsychotic Agents; Antitubercular Agents; Clozapine; Drug Interactions; Humans; Isoniazid; Male; Schizophrenia, Paranoid; Tuberculosis