The reported cases of cardiac arrhythmia associated with the prolongation of QT-interval and incidence of apparent TdP with loperamide overdose are likely attributable to loperamide’s inhibition of the IKr (hERG) channel and potential additive effects when administered with other drugs that inhibit hERG and/or PGP (e.g., Sotalol, hydroxyzine). Here, PGP is linked to cardiac rhythm disease.