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
Intention-to-treat analysis be providing benefits if one merely compares the condition before and after the treatment for only those who finish the study (ignoring those who were enrolled originally, but have since been excluded or dropped out). Medical investigators often have difficulties in completing ITT analysis because of clinical trial issues like missing data or poor treatment protocol adherence. To address some of these issues, many clinical trials have excluded participants after the random assignment in their analysis, which is often referred to as "modified intention-to-treat analysis" or mITT. Trials employing mITT have been linked to industry sponsorship and conflicts of interest