Diarrhea is a side effect associated with many medications but most commonly associated with antimicrobial use. It is one of the most frequent adverse effects of antibiotic therapy and can range from mild abdominal discomfort to severe diarrhea and colitis. Most cases are mild and self-limited, particularly after cessation of therapy. Drug-induced diarrhea should be distinguished from Clostridioides difficile colitis, which is an infectious complication of antibiotic use in which the suppression of normal flora allows for cytotoxin-producing C difficile to flourish. It is important to establish whether the diarrhea is a side effect of the medication or is related to C difficile or an alternative infectious etiology, as the management strategy may be different.

Some medications (eg, checkpoint inhibitors) can trigger development of a colitis similar to inflammatory bowel disease that may warrant treatment with immune suppressant therapy. In this instance, diarrhea will persist beyond the cessation of the offending agent, and further workup with colonoscopy will likely reveal the diagnosis.

Other medications injure the lining of the bowel causing mucositis, such as chemotherapy, and hence cause diarrhea.