Thursday, January 30, 2020

FDA Warns Untreated Constipation From Clozapine Use Can Lead to Serious Bowel Complications

The FDA on Tuesday issued an updated warning that constipation caused by the antipsychotic clozapine may increase the risk of serious bowel complications in some patients.

Constipation is already an identified side effect of clozapine, but “serious and fatal events continue to be reported,” according to the FDA’s website. The medication affects how the intestines function in most patients, and an uncommon but serious problem is complete blockage of the bowel. The risk is greater with clozapine compared with other schizophrenia medications, the FDA wrote.

Higher doses of clozapine and the use of clozapine in combination with anticholinergics and/or other medications known to cause constipation, including opioids, can further increase this risk, the agency warned.

The FDA reviewed cases from 2006 to 2016, some of which were reported to the agency’s Adverse Event Reporting System while others were identified through medical literature in the same time period. They identified 10 cases involving constipation “that resulted in hospitalization, surgery, and five deaths.” The total daily dose of clozapine in these cases ranged from 200 mg to 600 mg, and the time to onset of serious bowel events ranged from three days to six months.

The adverse events “included death of the colon wall (necrotizing colitis), blockage of blood flow to the intestines (intestinal ischemia), death of part of the intestine (intestinal necrosis), and abdominal distention leading to bowel obstruction (volvulus),” according to the FDA website.

The FDA is requiring a new warning and updates about the risk to be added to the prescribing information of all clozapine products. The agency has also recommended that health care professionals evaluate bowel function in patients before starting them on clozapine, and to question patients about their bowel movements throughout treatment. “Consider prophylactic laxative treatment when starting clozapine in patients with a history of constipation or bowel obstruction,” the FDA wrote. Physicians should also avoid co-prescribing the medication with anticholinergic medications.

Health care professionals should report adverse events involving clozapine or other medicines to the FDA MedWatch program.

For related information, see the Psychiatric News article “Updated Clozapine REMS Program Requires Certification With Few Exceptions.”

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