Therapeutic monitoring of plasma clozapine and N-desmethylclozapine (norclozapine): practical considerations

SUMMARY Clozapine dose assessment in treatment-refractory schizophrenia is complicated. There is a narrow margin between an effective and a potentially toxic dose and wide inter-individual variation in clozapine metabolic capacity. Moreover, factors such as changes in smoking habit, infection/inflammation, co-prescription of certain drugs, notably fluvoxamine, and age alter the dose requirement within individuals. Therapeutic drug monitoring (TDM) of plasma clozapine and N-desmethylclozapine (norclozapine) can help assess adherence, guide dosage and guard against toxicity. This article gives an overview of clozapine pharmacokinetics and factors affecting clozapine dose requirements. It then outlines the procedures and processes of clozapine TDM, from taking the blood sample for laboratory assay or point-of-contact (finger-prick) testing (POCT) to interpreting and acting on the results.