Optimising plasma levels of clozapine during metabolic interactions: a review and case report with adjunct rifampicin treatment

Siobhan Gee, Thomas Dixon, Mary Docherty, Sukhwinder S Shergill

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.