Drug Interaction Between Clozapine and Rifampicin: Experience in Management Strategies From a Case Report.

Clozapine is the only medication approved for treatment-resistant schizophrenia, which accounts for about 20–33% of individuals with psychotic disorders1. Despite its proven efficacy, clozapine remains underused in real-world clinical practice, with antipsychotic polypharmacy frequently being initiated before considering clozapine 1. For the optimal efficacy, clozapine has a relatively narrow therapeutic range in blood, which is influenced by several factors, some unmodifiable (age, gender or ethnic background) and other subject to variation, such as dose, smoking habit, caffeine intake and concomitant medication2. Clozapine is primarily metabolized in the liver via cytochrome P450 enzymes, notably CYP1A2 and CYP3A4, most of these factors modify clozapine plasma level by inducing or inhibiting the liver cytochromes responsible of clozapine metabolism. This is crucial, because drug–drug interactions (DDIs) that induce or inhibit these enzymes can significantly alter clozapine plasma levels. As in the case presented here, Rifampicin, a first line treatment for tuberculosis and other infections, has a strong cytochrome induction, accelerating clozapine clearance2, reducing its plasma levels and potentially leading to subtherapeutic efficacy or worsening psychotic symptoms3,4. Reports of this interaction are limited but emphasize challenges in maintaining therapeutic clozapine levels during rifampicin treatment.