Loperamide & Omeprazole: Potential for Abuse?

As pharmacists, it is important to stay aware of potential drugs of abuse. In the Colleagues Interact section of Pharmacists Letter, there was a conversation feed about surprising drugs of abuse. One pharmacist stated that they had seen omeprazole and loperamide being used together inappropriately. The science behind it does appear to make sense... Loperamide is a peripherally acting mu-receptor agonist. Not only does omeprazole inhibit CYP3A4, one of the enzymes responsible for metabolizing loperamide, but also inhibits p-glycoprotein which plays a large role in keeping drugs from crossing the blood brain barrier. This combination means loperamide would not only be at higher concentrations in the body, but also have greater potential to cross the blood brain barrier and affect the central nervous system. However, a 2010 review by Vandenbossche et al noted that of 10 studies performed, only one trial supported that inhibition of p-gp could lead to the development of clinically relevant central nervous system effects. It does not appear as though omeprazole has any sort of substantial contribution to the effects that people observe when abusing loperamide.

Vaults of Erowid, a member-supported website that includes information about drugs of abuse does show that loperamide is quite frequently abused. This was a reference frequently utilized in the substance abuse class at the University of Iowa College of Pharmacy. A normal dose of loperamide is 8 mg or less per day. Individuals on this site report using upwards of 30mg, and frequently use it as a way of controlling opiate withdrawal symptoms and inducing a "mild euphoria." It goes without saying that doses of loperamide this high can have disastrous effects on gastrointestinal health, risking severe constipation, intestinal obstruction, if not complete ileus. While making a substance abuse intervention of this nature would be difficult, it is important to be cognizant of what these drugs may be being used for when individuals buy them in combination.



1.Vandenbossche J, Huisman M, Xu Y, Sanderson-Bongiovanni D, Soons P. Loperamide and P-glycoprotein inhibition: assessment of the clinical relevance. J Pharm Pharmacol. 2010;62:(4)401-12. [pubmed]