Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Hahl-Hakkinen L

PROVIDER: S-EPMC9912305 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Hahl-Häkkinen Lydia L Rask Susanna Maria SM Solismaa Anssi A Ruuhonen Sanna S Leinonen Esa E

Journal of psychopharmacology (Oxford, England) 20230126 2

<h4>Background</h4>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.<h4>Procedures</h4>We report two cases where co-medicating with disulfiram led to a significant increase in clozapine serum levels.<h4>Findings</h4>Clozapine serum levels decreased to one-third in Patient 1 when disulfiram was discontinued and started ...[more]

PMID: 36703576

Similar Datasets

Project description:BackgroundDespite its superiority over other drugs for psychosis, clozapine remains underused and is associated with many clinical challenges, including difficulties in predicting therapeutic serum levels (350-600 ng/mL). We found no large or recent study that investigated the determinants of serum clozapine levels in Middle Eastern patients. Therefore, we investigated the association between clozapine dose and serum level, and the clinical predictors of the clozapine serum level, in Middle Eastern patients.MethodsThis cross-sectional study included 94 patients of Middle Eastern ethnicity who attended the Clozapine Clinic in King Saud University Medical City in Riyadh, Saudi Arabia. We used a single measure of the serum clozapine level, which was collected 12 h after the last oral dose of clozapine under steady-state conditions.ResultsThe average clozapine dose and serum level were 400 mg/daily and 705 ng/mL, respectively. The majority of patients (59.8%) had serum levels higher than 600 ng/mL. Clozapine dose and serum level were positively correlated (rs [94] = 0.32, p = 0.002). We generated a predictive model of the serum clozapine level, which revealed that the daily dose, smoking status, use of fluvoxamine or lamotrigine, and body mass index (BMI) predicted 43.6% of the variance in the serum level (p < 0.001). Using this model, we calculated that patients with a BMI of 25 kg/m2 would require a clozapine dose between 50 to 275 mg/daily if they were non-smokers, and a dose of 200 to 450 mg/daily if they were smokers, in order to reach a serum clozapine level between 350 to 600 ng/mL. Patients with higher BMI and those receiving fluvoxamine would require lower doses.ConclusionsThis was a naturalistic study of the clozapine dose-level relationship and the clinical predictors of the serum clozapine level in a sample of Middle Eastern patients. The ratios of clozapine level to dose in our patients more closely resembled those reported in Asian samples than in European samples. These findings do not reduce the value of individualised therapeutic drug monitoring, but may assist clinicians when prescribing clozapine to Middle Eastern patients. Further psychopharmacological studies are needed on this demographic population.

Project description:BackgroundIgE bound on the surface of mast cells contributes to the pathogenesis of chronic spontaneous urticaria (CSU). Atopy is a predisposing factor for CSU, where omalizumab is a widely used monoclonal antibody to control urticaria symptoms via capturing serum free IgE. However, the role of serum free IgE is not clarified in CSU. The present study evaluated the clinical relevance of serum free IgE in patients with CSU.MethodsEighty-eight patients with CSU and 76 healthy controls (HCs) were enrolled in this study. Serum total and Dermatophagoides pteronyssinus (Der p)-specific IgE levels were measured by ImmunoCAPs. The serum free IgE levels were measured by ELISA using a novel IgETRAP, and their associations with clinical parameters, including urticaria activity score (UAS), were evaluated. Changes in serum free and total IgE levels after omalizumab treatment were observed in 23 CSU patients in comparison between responders (≥50% reduction in UAS) and non-responders (<50% reduction).ResultsSignificantly higher serum free/total IgE levels were noted in CSU patients than in HCs with a positive correlation between the 2 values (rho = 0.87, P < 0.001). Among CSU patients, atopics had significantly higher serum free IgE levels than non-atopics, while no associations were noted with UAS, urticaria duration, or the results of serum ANA or autologous serum skin tests. In addition, there were no significant changes in serum free IgE levels during 12 months of omalizumab treatment. No significant differences were noted in serum free/total IgE levels or clinical parameters between responders and non-responders, while responders have higher serum Der p-specific IgE level and its ratio to serum free/total IgE level than non-responders (P < 0.05, respectively).ConclusionsThese findings suggest that increased serum free IgE may be involved in the development of CSU by activating mast cells, especially in atopics. High Der p-specific IgE level and its ratio to serum free IgE level may be a potential biomarker for predicting favorable responses to omalizumab in CSU.

Dataset Information

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

Background

Procedures

Findings

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets