Loperamide, sold under the brand name Imodium, among others,[1] is a medication of the opioid receptor agonist class used to decrease the frequency of diarrhea.

[4] Common side effects include abdominal pain, constipation, sleepiness, vomiting, and dry mouth.

Loperamide should not be used as the primary treatment in cases of bloody diarrhea, acute exacerbation of ulcerative colitis, or bacterial enterocolitis.

[16][17][18] Adverse drug reactions most commonly associated with loperamide are constipation (which occurs in 1.7–5.3% of users), dizziness (up to 1.4%), nausea (0.7–3.2%), and abdominal cramps (0.5–3.0%).

If suspicion exists of diarrhea associated with organisms that can penetrate the intestinal walls, such as E. coli O157:H7 or Salmonella, loperamide is contraindicated as a primary treatment.

[15] Loperamide treatment is not used in symptomatic C. difficile infections, as it increases the risk of toxin retention and precipitation of toxic megacolon.

[23] Additionally, caution should be used when treating people with advanced HIV/AIDS, as cases of both viral and bacterial toxic megacolon have been reported.

The study reported that the use of loperamide should be contraindicated in children who are under 3, systemically ill, malnourished, moderately dehydrated, or have bloody diarrhea.

[27] The National Health Service in the United Kingdom recommends that loperamide should only be given to children under the age of twelve if prescribed by a doctor.

[30] One controlled, prospective study of 89 women exposed to loperamide during their first trimester of pregnancy showed no increased risk of malformations.

[33] Loperamide is an opioid-receptor agonist and acts on the μ-opioid receptors in the myenteric plexus of the large intestine.

[39] Efflux by P-glycoprotein also prevents circulating loperamide from effectively crossing the blood-brain barrier,[40] so it can generally only antagonize muscarinic receptors in the peripheral nervous system, and currently has a score of one on the anticholinergic cognitive burden scale.

[41] Concurrent administration of P-glycoprotein inhibitors such as quinidine potentially allows loperamide to cross the blood-brain barrier and produce central morphine-like effects.

[43] High doses of loperamide have been shown to cause a mild physical dependence during preclinical studies, specifically in mice, rats, and rhesus monkeys.

Symptoms of mild opiate withdrawal were observed following abrupt discontinuation of long-term treatment of animals with loperamide.

[58] In the late 1980s, before the US patent expired on 30 January 1990,[55] McNeil started to develop Imodium Advanced containing loperamide and simethicone for treating both diarrhea and gas.

[4][11] In 2016, Imodium was one of the biggest-selling branded over-the-counter medications sold in Great Britain, with sales of £32.7 million.

[71][72] The primary intent of users has been to manage symptoms of opioid withdrawal such as diarrhea, although a small portion derive psychoactive effects at these higher doses.

[73] At these higher doses central nervous system penetration occurs and long-term use may lead to tolerance, dependence, and withdrawal on abrupt cessation.

[74] The FDA responded to these warnings by calling on drug manufacturers to voluntarily limit the package size of loperamide for public-safety reasons.