A Drug safety update was issued in October 2017 to remind healthcare professionals of the risk of potentially fatal intestinal obstruction, faecal impaction and paralytic ileus in patients prescribed clozapine.

Clozapine is an atypical antipsychotic drug used in the management of schizophrenia. The risk of agranulocytosis means that clozapine is restricted to use in patients who do not respond to other antipsychotics, including other atypicals, or patients who have severe neurological side effects with these drugs.

Strict procedures for monitoring white blood cell counts are in place for patients prescribed clozapine. In order to enforce patient monitoring the manufacturers of clozapine products (Clozaril, Denzapine and Zaponex) operate a monitoring service for their product, this requires registration of prescribing physicians, supplying pharmacists and patients with the service.

Gastro-intestinal side effects

The gastro-intestinal side effects of clozapine have long been recognised, with the anticholinergic properties of clozapine believed to be the probable cause.

Recognised side effects of clozapine include constipation (very common), intestinal obstruction, paralytic ileus and faecal impaction (very rare).  These side effects can occur very rapidly, which means that it is vital that constipation is recognised early and actively treated.

Between 3^rd  August 1993 and 11^th September 2017 there were 370 yellow card reports submitted to MHRA reporting gastrointestinal obstruction associated with clozapine. Within this time period there were also 86 reports of paralytic ileus and 135 reports of faecaloma.

Pharmacists issuing clozapine should ensure patients are advised of the potential risks associated with constipation.

All patients should be advised to discuss symptoms of constipation with their doctor before taking their next clozapine dose.

Advice to healthcare professionals

• The antipsychotic drug clozapine has been associated with varying degrees of impairment of intestinal peristalsis: this can range from constipation, which is very common, to very rare intestinal obstruction, faecal impaction and paralytic ileus.
• Particular care should be exercised in :
  • patients taking clozapine in conjunction with drugs known to cause constipation (especially those with anticholinergic activity),
  • patients with a history of colonic disease or lower abdominal surgery
  • patients aged 60 or over
  • Clozapine is contraindicated in patients with paralytic ileus
  • Patients should be advised to report constipation immediately
  • Actively treat any constipation that occurs