Loperamide have negative effects from rebound constipation. If a suspicion exists of diarrhea associated with organisms that can penetrate the intestinal walls, such as or "Salmonella", loperamide is contraindicated as a primary treatment. Loperamide treatment is not used in symptomatic "C. difficile" infections, as it increases the risk of toxin retention and precipitation of toxic megacolon. Loperamide should be administered with caution to people with liver failure due to reduced first-pass metabolism. Additionally, caution should be used when treating people with advanced HIV, as cases of both viral and bacterial toxic megacolon have been reported. If abdominal distension is noted, therapy
Loperamide abuse were made. In 2015, however, case reports of extremely high-dose loperamide resulting in opioid misuse were published. Dubbing it “the poor man's methadone", clinicians warned that increased restrictions on the availability of prescription opioids passed in response to the opioid epidemic were prompting recreational users to turn to loperamide as an over-the-counter treatment for withdrawal symptoms. The FDA responded to these warnings by calling on drug manufacturers to voluntarily limit the availability of loperamide for public-safety reasons, in an analogous manner to restrictions put on the sales of pseudoephedrine, to be sold only in limited amounts. Since 2015, several