1. Aschenbrenner, Diane S. MS, RN


* The Food and Drug Administration has strengthened the warning on clozapine's labeling regarding the risk of serious complications from constipation, an adverse effect of this drug.



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The Food and Drug Administration (FDA) has revised the label of clozapine (Clozaril, Versacloz), an atypical antipsychotic used to treat schizophrenia, to include a stronger warning that the adverse effect of constipation could potentially lead to serious bowel complications.


A review of the literature and case reports submitted to the FDA's Adverse Event Reporting System database between July 2006 and August 2016 identified 10 cases of constipation that progressed to serious problems, including necrotizing colitis, intestinal ischemia, intestinal necrosis, and abdominal distention with bowel obstruction (volvulus). These adverse effects required hospitalization or surgery and five patients died.


Clozapine's mechanism of action is believed to be the blocking of dopamine type 2 and serotonin type 2A receptors. Additionally, clozapine blocks adrenergic, cholinergic, histaminergic, and other dopaminergic and serotonergic receptors. Clozapine's effects on various receptor sites may contribute to the risk of constipation with its use. This risk appears to increase if the patient is prescribed other anticholinergics, which also slow intestinal movement, or other medications that can produce constipation such as opioids.


Nurses and NPs should provide patient education on this potential serious adverse effect and encourage taking actions that prevent or minimize constipation. Patients should be encouraged to be physically active, drink plenty of fluids, and eat foods high in fiber. Nurses should carefully assess patients who receive clozapine regarding their bowel habits, especially frequency, characteristics, and any deviation from normal. Nurses should also assess for use of other anticholinergic drugs, including over-the-counter anticholinergics such as diphenhydramine (Benadryl and others), brompheniramine (Bromfed-DM and others), and meclizine (Dramamine and others). NPs should avoid prescribing anticholinergics to patients receiving clozapine if possible and should consider prescribing a prophylactic laxative for those who might be at high risk for constipation. If patients develop constipation, they should be treated with laxatives immediately. A consultation with a gastroenterologist may be necessary. If patients develop constipation or other adverse effects from clozapine, the FDA should be notified via the MedWatch program at


To read the FDA Drug Safety Communication concerning clozapine, go to