Clozapine intoxication with severe adverse effects induced by an inflammatory and infectious process: a case report

Clozapine intoxication can be life-threatening. Outside of the common drug-drug interactions, tobacco smoking, and caffeine consumption, infectious and inflammatory processes are important contributors to clozapine intoxication. Although this relationship has been reported previously, the literature is scant of proper research articles describing the presentation and management of this unpredictable interaction. Therefore, clinicians need to rely heavily on case reports describing clozapine intoxication caused by inflammation and/or infection.

A 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). She was on clozapine 700 mg daily amongst other medications. The clozapine dose was stable for over 3 years, and there were no recent changes in her medications. The initial culprit was determined to be an infectious/inflammatory process of gastrointestinal origin with contribution from dehydration and constipation. Clozapine and norclozapine serum concentrations confirmed the intoxication: 1315 ng/mL and 653 ng/mL, respectively. She drastically improved with clozapine dose reduction and antibiotic therapy. She remained stable for years with clozapine 600 mg daily with stable clozapine serum levels.

This case report illustrates the possibility of severe toxicity associated with an acute infectious and/or inflammatory process in patients on clozapine therapy. Clinicians must maintain a high level of suspicion in patients taking clozapine who develop and an infectious and/or inflammatory process. Constipation secondary to clozapine intoxication can exacerbate the initial intoxication process.