There is a wide interindividual variability in its metabolism, the most important factors being age, ethnicity, gender, genetic polymorphisms of CYP isoenzymes or neurotransmitter receptors, food and drink, smoking status, and drug interactions. Ĭlozapine is metabolized in the liver by the cytochrome P450 (CYP) isoenzyme 1A2 into norclozapine, an active metabolite that could contribute to adverse events. The standard daily dose of clozapine ranges from 300 to 600 mg/day, with a maximum daily dose of 900 mg. Constipation secondary to clozapine intoxication can exacerbate the initial intoxication process.Ĭlozapine is an atypical antipsychotic mainly used for the treatment of refractory schizophrenia. Clinicians must maintain a high level of suspicion in patients taking clozapine who develop and an infectious and/or inflammatory process. This case report illustrates the possibility of severe toxicity associated with an acute infectious and/or inflammatory process in patients on clozapine therapy. She remained stable for years with clozapine 600 mg daily with stable clozapine serum levels. She drastically improved with clozapine dose reduction and antibiotic therapy. Clozapine and norclozapine serum concentrations confirmed the intoxication: 1315 ng/mL and 653 ng/mL, respectively. The initial culprit was determined to be an infectious/inflammatory process of gastrointestinal origin with contribution from dehydration and constipation. The clozapine dose was stable for over 3 years, and there were no recent changes in her medications. She was on clozapine 700 mg daily amongst other medications. Case presentationĪ 64-year-old Caucasian woman known for schizophrenia was brought to the emergency department (ED) with severe signs and symptoms of clozapine intoxication (general deterioration, drowsiness, neutropenia, and ileus). Therefore, clinicians need to rely heavily on case reports describing clozapine intoxication caused by inflammation and/or infection. Although this relationship has been reported previously, the literature is scant of proper research articles describing the presentation and management of this unpredictable interaction. Outside of the common drug–drug interactions, tobacco smoking, and caffeine consumption, infectious and inflammatory processes are important contributors to clozapine intoxication. Clozapine intoxication can be life-threatening.
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