Risk of intestinal obstruction with clozapine

In a Drug Safety Update, the Medicines and Healthcare products Regulatory Agency (MHRA) has warned of the potentially fatal risk of intestinal obstruction, faecal impaction and paralytic ileus with the antipsychotic drug clozapine.

Clozapine can impair intestinal peristalsis through its anticholinergic effect, which can lead to constipation and, very rarely, intestinal obstruction. The MHRA warns that if constipation occurs during treatment with clozapine, it is important that the patient reports it immediately and that it is actively treated. Particular care should be exercised in patients at higher risk of constipation, including those taking other drugs that can cause constipation (especially those with anticholinergic effects, such as some antipsychotics, antidepressants and antiparkinsonian treatments), patients with a history of colonic disease or lower abdominal surgery, and patients aged 60 years or older. Clozapine is contraindicated in patients with paralytic ileus.

The MHRA says that there have been 370 Yellow Card reports of gastrointestinal obstruction, 135 reports of faecaloma and 86 reports of paralytic ileus associated with clozapine over the past 24 years in the UK.

Warnings of the risk of gastrointestinal events with clozapine are already provided in the summary of product characteristics, patient information leaflets and the BNF; however, in August a coroner alerted the MHRA to the fact that healthcare professionals may lack awareness of these risks.

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