Co-medication with disulfiram markedly increased serum clozapine levels: Two case reports

BACKGROUND: Alcohol use disorder (AUD) is a significant co-morbidity in patients with schizophrenia. Clozapine offers some benefits in treating patients with refractory schizophrenia and AUD, but co-medicating with disulfiram is also common. PROCEDURES: We report two cases where co-medicating with disulfiram led to a significant increase in clozapine serum levels. FINDINGS: Clozapine serum levels decreased to one-third in Patient 1 when disulfiram was discontinued and started to increase again when disulfiram was reintroduced. Patient 2 developed toxic serum levels of clozapine during disulfiram treatment combined with heavy coffee drinking and symptoms reminiscent of neuroleptic malignant syndrome. CONCLUSIONS: Clozapine and disulfiram are both metabolized by cytochrome P450 CYP1A2 and clinically relevant interaction through this shared pathway is possible.