Coadministration of ritonavir (600 mg) and loperamide (16 mg single dose) increased loperamide AUC (~165%) and Cmax (17%). The pharmacokinetic changes did not result in opioid CNS effects. Because the amount of active parent compound was substantially increased and because the site of antidiarrhoeal action is outside the CNS compartment, it appears likely that loperamide will be sufficiently effective even when reduced doses are administered. Note: The US Food and Drug Administration has issued a safety alert over the use of high doses of loperamide from abuse and misuse with case reports of cardiac events including QT interval prolongation. Cardiac events are unlikely to occur when loperamide is dosed as an antidiarrheal even if coadministered with ritonavir. However caution is advised when loperamide is used at high doses for reducing stoma output, particularly as patients may be at increased risk of cardiac events due to electrolytes disturbances.