Clozapine: reminder of potentially fatal risk of intestinal obstruction, faecal impaction, and paralytic ileus

If constipation occurs during treatment with clozapine (Clozaril, Denzapine, Zaponex), it is vital that it is recognised and actively treated.

Advice to healthcare professionals:

  • the antipsychotic drug clozapine has been associated with varying degrees of impairment of intestinal peristalsis; this effect can range from constipation, which is very common, to very rare intestinal obstruction, faecal impaction, and paralytic ileus
  • exercise particular care in patients receiving other drugs known to cause constipation (especially those with anticholinergic properties), patients with a history of colonic disease or lower abdominal surgery, and in patients aged 60 years and older
  • clozapine is contraindicated in patients with paralytic ileus
  • advise patients to report constipation immediately
  • actively treat any constipation that occurs

Gastrointestinal disorders

Clozapine has been associated with varying degrees of impairment of intestinal peristalsis. These adverse events are thought to be due to the anticholinergic properties of clozapine. The effects can range from constipation, which is very common, to intestinal obstruction, faecal impaction, and paralytic ileus, which are very rare. On a few occasions, cases have been fatal.

In the UK, there have been 370 Yellow Card reports of gastrointestinal obstruction associated with clozapine between 3 August 1993 and 11 September 2017. In this time period, there have also been 135 reports of faecaloma and 86 of paralytic ileus.

The risk of gastrointestinal adverse effects is long established with clozapine. Warnings are provided in the Summary of Product Characteristics and Patient Information Leaflet and in the BNF. However, in August 2017, a Coroner investigating a death raised concerns to the MHRA that healthcare professionals might have a lack of awareness about the risk of pseudo-obstruction or paralytic ileus and their fast onset.

Reminder of warnings in the product information

Clozapine is contraindicated in patients with paralytic ileus.

When prescribing clozapine, particular care should be taken in patients at risk of constipation, including those:

  • receiving medications known to cause constipation (especially those with anticholinergic properties such as some antipsychotics, antidepressants and antiparkinsonian treatments)
  • with a history of colonic disease or a history of lower abdominal surgery
  • aged 60 years and older

Advise patients that if they develop constipation, they should tell their doctor immediately before taking the next dose of clozapine.

It is vital that constipation is recognised early and actively treated.

Refer to the full summary product of characteristics for a complete list of warnings and recommendations for clozapine.

Call for reporting

All suspected adverse reactions to antipsychotic medicines can be reported via the Yellow Card Scheme.

Further information

BNF – Clozapine

Article citation: Drug Safety Update volume 11, issue 3; October 2017: 4.

Published 26 October 2017