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 physical dependence during preclinical studies, specifically in mice, rats, and rhesus monkeys. Symptoms of mild opiate withdrawal were observed following abrupt discontinuation of long-term treatment of animals with loperamide. When originally approved for medical use in the United States, loperamide was considered a narcotic and was put into Schedule II of the Controlled Substances Act 1970. It was transferred to Schedule V on 17 July 1977 and then decontrolled as of 3 November 1982. Loperamide hydrochloride was first synthesized by Paul Janssen from Janssen Pharmaceutica in Beerse (Belgium), following previous discoveries of diphenoxylate hydrochloride (1956) and fentanyl citrate (1960). The