Caffeine-clozapine interaction associated with severe toxicity and multiorgan system failure: a case report

Caffeine is a known inhibitor of Clozapine metabolism mediated by inhibition of CYP1A2. Hitherto, the effects of caffeine on Clozapine levels have always been modest, as have the clinical manifestations of toxicity resulting from their interaction. We present a case of severe toxicity associated with the co-consumption of caffeine and Clozapine culminating in life-threatening complications requiring management in Intensive Care.

A 34 year old male with a history of chronic schizophrenia, who had been managed stably on 400 mg Clozapine for the previous 5 years, changed his dietary behaviour and began consuming caffeine-containing energy drinks over the course of 3 weeks. The total daily dose of caffeine was estimated as 600 mg/day (four cans of Red Bull). He subsequently presented to the Emergency Department with life-threatening Clozapine toxicity, resulting in a decreased level of consciousness, severe metabolic acidosis, acute respiratory failure, raised inflammatory markers and acute renal failure attributed to interstitial nephritis. Maximum recorded Clozapine level was 1796 ng/ml.

This case describes the interaction between a common caffeine-containing beverage and a commonly prescribed antipsychotic medication, associated with severe adverse effects. We call for clinical and scientific attention to the possible interaction between these substances and draw attention to the implications for prescribing practices and patient counselling.