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 first clinical reports on loperamide were published in 1973 in the" Journal of Medicinal Chemistry" with the inventor being one of the authors. The trial name for it was "R-18553". Loperamide oxide has a different research code: R-58425. The trial against placebo was conducted from December 1972 to February 1974, its results being published in 1977 in "Gut", an edition of British Society of Gastroenterology. In 1973, Janssen started to promote loperamide under the brand name Imodium. In December 1976, Imodium got US FDA approval. During the 1980s, Imodium became the best-selling prescription antidiarrheal in the United States. In March