Interaction between Loperamide and Quinidine
Major Synergy Absorption

ID DDInter1088 and DDInter1556
Interaction Coadministration with quinidine may increase the concentrations of loperamide in plasma and central nervous system (CNS). Opioid and other adverse effects may be enhanced. The proposed mechanism is inhibition of P-glycoprotein (P-gp) efflux transporter by quinidine, resulting in increased gastrointestinal absorption as well as increased penetration of loperamide across the blood brain barrier. The use of higher than recommended dosages of loperamide (e.g., through abuse or misuse) has been associated with serious and potentially fatal cardiac adverse events, including syncope, cardiac arrest, and arrhythmia related to prolongation of the QT interval. Under such circumstances, coadministration with other agents that can prolong the QT interval such as quinidine or quinine may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
anaemia asthenia Fatigue Excess potassium Multiple Myeloma osteoporosis sarcoidosis sick sinus syndrome tremor loss of consciousness More
Management Caution is recommended if loperamide is used with quinidine, a drug that can prolong the QT interval as well as increase the plasma and CNS concentrations of loperamide. Patients should be counseled to not exceed the recommended dosage and frequency or duration of use of loperamide, and to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. If loperamide-induced cardiotoxicity is suspected, promptly discontinue loperamide and initiate therapy to manage and prevent cardiac arrhythmias and adverse outcomes. Electrical pacing or cardioversion may be necessary if torsade de pointes persists despite pharmacotherapy. In many of the reported cases of loperamide-induced cardiotoxicity, standard antiarrhythmic drugs were ineffective, and electrical pacing or cardioversion was necessary.
References
Alternative for Loperamide A07D
Opium
Difenoxin
Morphine (liposomal)
Diphenoxylate
Alternative for Quinidine C01B
Bretylium
Mexiletine
Lidocaine (topical)
Lidocaine (ophthalmic)
Moricizine
Tocainide

Potential Metabolism Interactions

Substrate-Substrate Interaction：If more than one drug is metabolized by the same CYP, it is possible that its metabolism is inhibited because of the competition between the drugs. That means, it can be useful to lower the dosage of the drugs in the drug-cocktail because they remain longer in the organism than in monotherapy.
Inhibitor-Inhibitor Interaction：Combining two or more inhibitors of one CYP, should be compensated by lowering the dosage of these drugs because the metabolism is reduced and the drugs remain longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.
Inhibitor-Substrate Interaction：Combining drugs that have inhibitory effect and are substrates of one particular CYP, should be compensated by lowering the dosage. They rest longer in the organism than in monotherapy. Not adapting the dosage bears the risk of even more side effects.