Loperamide is a peripherally effective μ-opioid receptor agonist, which is frequently used for the therapy of diarrhea. In normal dose loperamide has no central opioid effects. This is due to the efflux transporter P-gp, which transports any loperamide at the blood-brain barrier back to the peripheral blood system which might have been absorbed before from the blood capillaries into the endothelial cells. if P-gp in these cells is blocked, however, loperamide may penetrate the CNS and develop opioid effects including central and respiratory depression. This is probably the mechanism which was responsible for the fatal outcome of a case published in the german journal “NeuroTransmitter” under the original title “Tod durch Limonade” (Death by Lemonade) (1). A comprehensive discussion and the consequences of the underlying drug - food and beverage interaction for E-prescribing have been presented in the Mega Journal of Case Reports in December 2024 (2).
Please read all the details here.
This case demonstrates another time that not only drug drug interactions but also drug - food and drug - beverage interactions cause possibly serious adverse drug effects with fatal outcome. Therefore, when e-prescribing or dispensing drugs, providers should rely on decision support systems supported by drug interaction checkers focussing not only on drug to drug interactions but also on drug to food and beverage interactions. The complexity of medication scenarios, in particular in polypharmacy, requires furthermore that multiple mechanism driven interactions where diverse enzymes and transporters are involved become instantly transparent to the doctor or the pharmacist.
Please read all the details here.
This case demonstrates another time that not only drug drug interactions but also drug - food and drug - beverage interactions cause possibly serious adverse drug effects with fatal outcome. Therefore, when e-prescribing or dispensing drugs, providers should rely on decision support systems supported by drug interaction checkers focussing not only on drug to drug interactions but also on drug to food and beverage interactions. The complexity of medication scenarios, in particular in polypharmacy, requires furthermore that multiple mechanism driven interactions where diverse enzymes and transporters are involved become instantly transparent to the doctor or the pharmacist.
SCHOLZ DataBank is a U.S. drug database supporting e-prescribing with a strong focus on avoiding drugs risks, in particular adverse drug effects due to drug interactions as well as pharmacogenetics and stages of renal failure/CKD of the patient. Users are enabled to check drug drug as well as drug food and beverage interactions. Such interactions are displayed in a transparant and fast manner either as traditional pairwise interactions or complex multiple drug interactions if needed. The listing of food and beverages consists for example of alcohol containing beverages such as Cognac, Gin, Wine, Whisky, or Chianti, containing additionally tyramine interacting with MAO inhibitors. Due to the case described and the underlying mechanism Tonic Water and Bitter Lemon have been added to this listing in order to help to avoid the hidden and possibly fatal drug food interaction between loperamide and quinine contained in lemonades.
Literature:
1) Hülya Kursun, Ekkehard Haen, Markus Weih; Death by Lemonade, original in german: Tod durch Limonade. NeuroTransmitter 2024;35(6),43-45
2) Scholz W. Loperamide: Death by Lemonade and Conclusions for E-prescribing. Mega J Case Rep. 2024;7(12):2001-2005