Managing Diarrhea Potentially Caused by Anticholinergic Medications

Critical Safety Warning

The Infectious Diseases Society of America warns that routine use of medications with anticholinergic properties may lead to increased risk of severe outcomes, including death, from diarrhea caused by C. difficile and Clostridium perfringens 1, 2

The National Comprehensive Cancer Network identifies anticholinergics as treatments for diarrhea in palliative care, not causes of it 3, 4
Anticholinergics like cyproheptadine are specifically used to treat gastrointestinal symptoms including diarrhea in mast cell activation syndrome 5

The American College of Physicians and the Infectious Diseases Society of America recommend determining if the diarrhea is complicated and requires hospitalization, and assessing for red flags such as fever, bloody stools, and signs of shock 1, 2, 7
The National Comprehensive Cancer Network recommends performing a digital rectal examination to rule out fecal impaction, and treating it with disimpaction, tap water enemas, and laxatives if present 3, 6

The European Society for Medical Oncology recommends that if the patient is receiving cancer treatment, irinotecan-induced diarrhea should be treated with atropine, and delayed diarrhea should be treated with loperamide 9, 10
The American Geriatrics Society recommends exercising extreme caution with anticholinergics in older adults, as they are more susceptible to cognitive decline, QT prolongation, and cardiac effects 5, 8

The Infectious Diseases Society of America recommends treating C. difficile infection with metronidazole or vancomycin, and avoiding loperamide and other antimotility agents in bloody diarrhea or suspected STEC infection 1, 2, 3
The National Comprehensive Cancer Network recommends using loperamide, diphenoxylate/atropine, and a bland diet to treat non-infectious diarrhea 3
The American College of Physicians recommends using oral rehydration solution for mild-moderate dehydration, and IV isotonic fluids for severe dehydration or inability to tolerate oral intake 7