INFORMATION FOR HEALTH PROFESSIONALS
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Web site: March 2007
Prescriber Update 2007;28(1):7
PM Ellis*, Wellington School of Medicine; RM McLean and M Harrison-Woolrych**, Intensive Medicines Monitoring Programme, University of Otago
Clozapine (Clozaril®, Clopine®) is an atypical antipsychotic that is effective for treatment-resistant schizophrenia. It causes agranulocytosis in up to 1% of patients1 and regular monitoring of neutrophil counts is mandatory throughout treatment. In New Zealand one death from agranulocytosis has been reported to the IMMP. In contrast, four deaths from complications of severe constipation have been reported. This article reminds health professionals that the gastrointestinal effects of clozapine are potentially serious. Awareness of this issue may prevent life-threatening complications.
Clozapine-induced constipation may be fatal
Clozapine affects motility throughout the gut
Mechanism - anticholinergic, serotonergic and more
Take-home messages
Reference
Clozapine-induced constipation may be fatal
Constipation is often regarded as a frequent, minor side effect of clozapine.
However, review of New Zealand reports received by the IMMP shows that clozapine-induced
constipation may be associated with serious effects such as intestinal
obstruction, bowel perforation and toxic megacolon. The four deaths
reported to IMMP demonstrate that these effects can be fatal.
Clozapine affects motility throughout the gut
In addition to reports of constipation associated with clozapine, IMMP has
received three reports of paralytic ileus and a further three reports of
oesophageal dysmotility. These case reports suggest that clozapine may
reduce gastrointestinal (GI)
motility throughout the gut, resulting in complications higher in the GI
tract.
Mechanism - anticholinergic, serotonergic and more
Many anticholinergic drugs can cause GI dysmotility, but clozapine has a
much more potent effect through its interaction with multiple receptors,
(including anticholinergic and serotonergic receptors) affecting GI activity.
This action is exacerbated by co-prescription of anticholinergic agents such as
benztropine and tricyclic antidepressants.
Take-home messages
Competing interests (authors):
* None declared.
**IMMP has in the past received unconditional grants from several pharmaceutical
companies, including Novartis who are one of the sponsors of clozapine in NZ.
However, pharmaceutical companies have no role in the design, analysis or
interpretation of IMMP studies.