The Food and Drug Administration (FDA) is strengthening the warning regarding the risk of serious bowel complications that may occur in patients suffering from clozapine-induced constipation, a common side effect of the antipsychotic medication. 

The update was prompted by an FDA review of 10 cases of constipation in clozapine-treated patients that resulted in serious complications such as necrotizing colitis, intestinal ischemia, intestinal necrosis, volvulus, and death. Patients were receiving doses ranging from 200mg to 600mg daily, with time to onset of serious bowel events ranging from 3 days to 6 months.

Clozapine, an atypical antipsychotic, is indicated for the treatment of severely ill patients with schizophrenia who fail to respond adequately to standard antipsychotic treatment. It is also used for reducing the risk of recurrent suicidal behavior in patients with schizophrenia or schizoaffective disorder who are judged to be at chronic risk for re-experiencing suicidal behavior, based on history and recent clinical state. The drug is marketed under the brand names Clozaril®, Fazaclo®, and Versacloz™.

To reduce the risk of severe bowel problems, the FDA is recommending that healthcare professionals evaluate bowel function before starting patients on clozapine. Once on treatment, clinicians should question patients about the frequency and quality of bowel movements and monitor for symptoms associated with gastrointestinal hypomotility including nausea, abdominal distention/pain, and vomiting. 

Clozapine has potent anticholinergic effects. As other medications with anticholinergic properties could potentially increase the risk of gastrointestinal hypomotility, co-prescribing of these medications with clozapine should be avoided. In addition, higher doses of clozapine have been associated with increased risk.

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Patients on clozapine therapy should be advised frequently about the significant risk of constipation and the potentially life-threatening bowel complications that may result if left untreated. To prevent constipation, adequate hydration is critical, and prophylactic laxatives may be warranted in those with a history of constipation or bowel obstruction. 

“As part of FDA’s routine monitoring, we will continue to monitor clozapine and will report updated information to the public if it becomes available,” the FDA stated in a safety communication.

For more information visit fda.gov.