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Co-medication with disulfiram markedly increased serum clozapine levels: Two case reports
Lydia Hahl-Häkkinen1,2, Susanna Maria Rask1,2, Anssi Solismaa1,2
1Department of Psychiatry, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Journal of Psychopharmacology (Oxford, England)
|January 27, 2023
Summary
Disulfiram may increase clozapine levels in patients with schizophrenia and alcohol use disorder. This drug interaction can lead to toxic clozapine serum levels, requiring careful monitoring.
Area of Science:
- Psychiatry
- Clinical Pharmacology
- Pharmacogenomics
Background:
- Alcohol use disorder (AUD) is a common comorbidity in schizophrenia patients.
- Clozapine is used for refractory schizophrenia and AUD, often with disulfiram.
Observation:
- Two cases highlight significant increases in clozapine serum levels when co-administered with disulfiram.
- Discontinuation of disulfiram led to decreased clozapine levels, with levels rising again upon reintroduction.
Findings:
- Patient 2 experienced toxic clozapine levels during disulfiram treatment, exacerbated by coffee consumption, presenting with neuroleptic malignant syndrome-like symptoms.
- Clozapine and disulfiram share metabolism via cytochrome P450 CYP1A2, indicating a potential drug interaction pathway.
Implications:
- Clinicians should carefully monitor clozapine serum levels in patients co-medicated with disulfiram.
- The shared CYP1A2 metabolism pathway necessitates caution when combining these medications.
- This interaction may impact treatment strategies for patients with schizophrenia and AUD.
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