Loperamide, sold under the brand name Imodium, among others,
[Drugs.co]
Page accessed September 4, 2015 is a medication used to decrease the frequency of
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
.
It is often used for this purpose in
inflammatory bowel disease
Inflammatory bowel disease (IBD) is a group of inflammation, inflammatory conditions of the colon (anatomy), colon and small intestine, Crohn's disease and ulcerative colitis being the principal types. Crohn's disease affects the small intestine a ...
and
short bowel syndrome
Short bowel syndrome (SBS, or simply short gut) is a rare malabsorption disorder caused by a lack of functional small intestine. The primary symptom is diarrhea, which can result in dehydration, malnutrition, and weight loss. Other symptoms may in ...
.
[ It is not recommended for those with ]blood in the stool
Blood in stool looks different depending on how early it enters the digestive tract—and thus how much digestive action it has been exposed to—and how much there is. The term can refer either to melena, with a black appearance, typically orig ...
, mucus in the stool, or fevers.[ The medication is taken by mouth.][
Common side effects include abdominal pain, ]constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
, sleepiness, vomiting, and a dry mouth.[ It may increase the risk of ]toxic megacolon
Toxic megacolon is an acute form of colonic distension. It is characterized by a very dilated colon (megacolon), accompanied by abdominal distension (bloating), and sometimes fever, abdominal pain, or shock.
Toxic megacolon is usually a complica ...
.[ Loperamide's safety in ]pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
is unclear, but no evidence of harm has been found. It appears to be safe in breastfeeding
Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that br ...
. It is an opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
with no significant absorption from the gut and does not cross the blood–brain barrier
The blood–brain barrier (BBB) is a highly selective semipermeable membrane, semipermeable border of endothelium, endothelial cells that prevents solutes in the circulating blood from ''non-selectively'' crossing into the extracellular fluid of ...
when used at normal doses. It works by slowing the contractions of the intestines
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans ...
.[
Loperamide was first made in 1969 and used medically in 1976.] It is on the World Health Organization's List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
. Loperamide is available as a generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
. In 2020, it was the 330th most commonly prescribed medication in the United States, with more than 700thousand prescriptions.
Medical uses
Loperamide is effective for the treatment of a number of types of diarrhea. This includes control of acute nonspecific diarrhea, mild traveler's diarrhea
Travelers' diarrhea (TD) is a stomach and intestinal infection. TD is defined as the passage of unformed stool (one or more by some definitions, three or more by others) while traveling. It may be accompanied by abdominal cramps, nausea, fever, ...
, irritable bowel syndrome, chronic diarrhea due to bowel resection, and chronic diarrhea secondary to inflammatory bowel disease. It is also useful for reducing ileostomy
Ileostomy is a stoma (surgical opening) constructed by bringing the end or loop of small intestine (the ileum) out onto the surface of the skin, or the surgical procedure which creates this opening. Intestinal waste passes out of the ileostomy an ...
output. Off-label use
Off-label use is the use of pharmaceutical drugs for an unapproved indication (medicine), indication or in an unapproved age group, dose (biochemistry), dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) ...
s for loperamide also include chemotherapy-induced diarrhea, especially related to irinotecan
Irinotecan, sold under the brand name Camptosar among others, is a medication used to treat colon cancer, and small cell lung cancer. For colon cancer it is used either alone or with fluorouracil. For small cell lung cancer it is used with cispl ...
use.
Loperamide should not be used as the primary treatment in cases of bloody diarrhea
Dysentery (UK pronunciation: , US: ), historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications ...
, acute exacerbation of ulcerative colitis
Ulcerative colitis (UC) is a long-term condition that results in inflammation and ulcers of the colon and rectum. The primary symptoms of active disease are abdominal pain and diarrhea mixed with blood (hematochezia). Weight loss, fever, and a ...
, or bacterial enterocolitis
Enterocolitis is an inflammation of the digestive tract, involving enteritis of the small intestine and colitis of the colon. It may be caused by various infections, with bacteria, viruses, fungi, parasites, or other causes. Common clinical manif ...
.
Loperamide is often compared to diphenoxylate
Diphenoxylate is a centrally active opioid drug of the phenylpiperidine series that is used as a combination drug with atropine for the treatment of diarrhea. Diphenoxylate is an opioid and acts by slowing intestinal contractions; the atropine i ...
. Studies suggest that loperamide is more effective and has lower neural side effects.
Side effects
Adverse drug reaction
An adverse drug reaction (ADR) is a harmful, unintended result caused by taking medication. ADRs may occur following a single dose or prolonged administration of a drug or result from the combination of two or more drugs. The meaning of this term ...
s 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%). Rare, but more serious, side effects include toxic megacolon, paralytic ileus
Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction.
The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...
, angioedema
Angioedema is an area of swelling ( edema) of the lower layer of skin and tissue just under the skin or mucous membranes. The swelling may occur in the face, tongue, larynx, abdomen, or arms and legs. Often it is associated with hives, which ...
, anaphylaxis/allergic reactions, toxic epidermal necrolysis
Toxic epidermal necrolysis (TEN) is a type of severe skin reaction. Together with Stevens–Johnson syndrome (SJS) it forms a spectrum of disease, with TEN being more severe. Early symptoms include fever and flu-like symptoms. A few days later th ...
, Stevens–Johnson syndrome
Stevens–Johnson syndrome (SJS) is a type of severe skin reaction. Together with toxic epidermal necrolysis (TEN) and Stevens–Johnson/toxic epidermal necrolysis (SJS/TEN), it forms a spectrum of disease, with SJS being less severe. Erythema ...
, erythema multiforme
Erythema multiforme (EM) is a skin condition that appears with red patches evolving into target lesions, typically on both hands.
It is a type of erythema possibly mediated by deposition of immune complexes (mostly IgM-bound complexes) in the s ...
, urinary retention
Urinary retention is an inability to completely empty the bladder. Onset can be sudden or gradual. When of sudden onset, symptoms include an inability to urinate and lower abdominal pain. When of gradual onset, symptoms may include loss of bladd ...
, and heat stroke
Heat stroke or heatstroke, also known as sun stroke, is a severe heat illness that results in a body temperature greater than , along with red skin, headache, dizziness, and confusion. Sweating is generally present in exertional heatstroke, ...
. The most frequent symptoms of loperamide overdose are drowsiness, vomiting, and abdominal pain, or burning. High doses may result in heart problems such as abnormal heart rhythm
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
s.
Contraindications
Treatment should be avoided in the presence of high fever
Fever, also referred to as pyrexia, is defined as having a body temperature, temperature above the human body temperature, normal range due to an increase in the body's temperature Human body temperature#Fever, set point. There is not a single ...
or if the stool is bloody. Treatment is not recommended for people who could have negative effects from rebound constipation
Constipation is a bowel dysfunction that makes bowel movements infrequent or hard to pass. The stool is often hard and dry. Other symptoms may include abdominal pain, bloating, and feeling as if one has not completely passed the bowel movement ...
. If a suspicion exists of diarrhea associated with organisms that can penetrate the intestinal walls, such as ''E. coli ''O157:H7 or ''Salmonella
''Salmonella'' is a genus of rod-shaped (bacillus) Gram-negative bacteria of the family Enterobacteriaceae. The two species of ''Salmonella'' are ''Salmonella enterica'' and ''Salmonella bongori''. ''S. enterica'' is the type species and is fur ...
'', loperamide is contraindicated
In medicine, a contraindication is a condition that serves as a reason not to take a certain medical treatment due to the harm that it would cause the patient. Contraindication is the opposite of indication, which is a reason to use a certain tre ...
as a primary treatment.[ Loperamide treatment is not used in symptomatic '' C. difficile'' infections, as it increases the risk of toxin retention and precipitation of toxic megacolon.
Loperamide should be administered with caution to people with liver failure due to reduced ]first-pass metabolism
The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemi ...
. Additionally, caution should be used when treating people with advanced HIV/AIDS
Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual ...
, as cases of both viral and bacterial toxic megacolon have been reported. If abdominal distension is noted, therapy with loperamide should be discontinued.
Children
The use of loperamide in children under two years is not recommended. Rare reports of fatal paralytic ileus
Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction.
The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...
associated with abdominal distention
Abdominal distension occurs when substances, such as air (gas) or fluid, accumulate in the abdomen causing its expansion. It is typically a symptom of an underlying disease or dysfunction in the body, rather than an illness in its own right. Pe ...
have been made. Most of these reports occurred in the setting of acute dysentery
Dysentery (UK pronunciation: , US: ), historically known as the bloody flux, is a type of gastroenteritis that results in bloody diarrhea. Other symptoms may include fever, abdominal pain, and a feeling of incomplete defecation. Complications ...
, overdose, and with very young children less than two years of age. A review of loperamide in children under 12 years old found that serious adverse events occurred only in children under three years old. 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. In 1990, all formulations for children of the antidiarrheal loperamide were banned in Pakistan
Pakistan ( ur, ), officially the Islamic Republic of Pakistan ( ur, , label=none), is a country in South Asia. It is the world's List of countries and dependencies by population, fifth-most populous country, with a population of almost 24 ...
.
Pregnancy and breast feeding
Loperamide is not recommended in the United Kingdom for use during pregnancy
Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins.
Pregnancy usually occurs by sexual intercourse, but ca ...
or by nursing mothers. In the U.S., loperamide is classified by the U.S. Food and Drug Administration
The United States Food and Drug Administration (FDA or US FDA) is a List of United States federal agencies, federal agency of the United States Department of Health and Human Services, Department of Health and Human Services. The FDA is respon ...
(FDA) as pregnancy category
The pregnancy category of a medication is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. It does ''not'' include any risks conferred by pharmaceutical agents or their ...
C. Studies in rat models have shown no teratogenicity, but sufficient studies in humans have not been conducted. One controlled, prospective study of 89 women exposed to loperamide during their first trimester of pregnancy showed no increased risk of malformations. This, however, was only one study with a small sample size. Loperamide can be present in breast milk, and is not recommended for breast-feeding mothers.[
]
Drug interactions
Loperamide is a substrate of P-glycoprotein
P-glycoprotein 1 (permeability glycoprotein, abbreviated as P-gp or Pgp) also known as multidrug resistance protein 1 (MDR1) or ATP-binding cassette sub-family B member 1 (ABCB1) or cluster of differentiation 243 (CD243) is an important protein ...
; therefore, the concentration of loperamide increases when given with a P-glycoprotein inhibitor.[ Common P-glycoprotein inhibitors include ]quinidine
Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...
, ritonavir
Ritonavir, sold under the brand name Norvir, is an antiretroviral drug used along with other medications to treat HIV/AIDS. This combination treatment is known as highly active antiretroviral therapy (HAART). Ritonavir is a protease inhibitor a ...
, and ketoconazole
Ketoconazole, sold under the brand name Nizoral among others, is an antiandrogen and antifungal medication used to treat a number of fungal infections. Applied to the skin it is used for fungal skin infections such as tinea, cutaneous candid ...
. Loperamide is capable of decreasing the absorption of some other drugs. As an example, saquinavir
Saquinavir (SQV), sold under the brand names Invirase and Fortovase, is an antiretroviral drug used together with other medications to treat or prevent HIV/AIDS. Typically it is used with ritonavir or lopinavir/ritonavir to increase its effect ...
concentrations can decrease by half when given with loperamide.[
Loperamide is an antidiarrheal agent, which decreases intestinal movement. As such, when combined with other antimotility drugs, the risk of constipation is increased. These drugs include other ]opioid
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid us ...
s, antihistamine
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provides re ...
s, antipsychotic
Antipsychotics, also known as neuroleptics, are a class of Psychiatric medication, psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but ...
s, and anticholinergic
Anticholinergics (anticholinergic agents) are substances that block the action of the neurotransmitter called acetylcholine (ACh) at synapses in the central and peripheral nervous system.
These agents inhibit the parasympathetic nervous system ...
s.
Mechanism of action
Loperamide is an opioid-receptor agonist
An agonist is a chemical that activates a receptor to produce a biological response. Receptors are cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an antagonist blocks the action of the ago ...
and acts on the μ-opioid receptors in the myenteric plexus of the large intestine. It works like morphine
Morphine is a strong opiate that is found naturally in opium, a dark brown resin in poppies (''Papaver somniferum''). It is mainly used as a analgesic, pain medication, and is also commonly used recreational drug, recreationally, or to make ...
, decreasing the activity of the myenteric plexus, which decreases the tone of the longitudinal and circular smooth muscle
Smooth muscle is an involuntary non-striated muscle, so-called because it has no sarcomeres and therefore no striations (''bands'' or ''stripes''). It is divided into two subgroups, single-unit and multiunit smooth muscle. Within single-unit mus ...
s of the intestinal wall. This increases the time material stays in the intestine, allowing more water to be absorbed from the fecal matter. It also decreases colonic mass movements and suppresses the gastrocolic reflex
The gastrocolic reflex or gastrocolic response is a physiological reflex that controls the motility, or peristalsis, of the gastrointestinal tract following a meal. It involves an increase in motility of the colon consisting primarily of giant mi ...
.
Loperamide's circulation in the bloodstream is limited in two ways. Efflux by P-glycoprotein in the intestinal wall reduces passage of loperamide, and the fraction of drug crossing is then further reduced through first-pass metabolism
The first pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentration of a drug, specifically when administered orally, is greatly reduced before it reaches the systemi ...
by the liver. Loperamide metabolizes into an MPTP
MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is a prodrug to the neurotoxin MPP+, which causes permanent symptoms of Parkinson's disease by destroying dopaminergic neurons in the substantia nigra of the brain. It has been used to study d ...
-like compound, but is unlikely to exert neurotoxicity.
Blood–brain barrier
Efflux by P-glycoprotein also prevents circulating loperamide from effectively crossing the blood–brain barrier, so it can generally only antagonize muscarinic receptors in the peripheral nervous system
The peripheral nervous system (PNS) is one of two components that make up the nervous system of bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside the brain ...
, and currently has a score of one on the anticholinergic cognitive burden scale. Concurrent administration of P-glycoprotein inhibitors such as quinidine
Quinidine is a class I antiarrhythmic agent, class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of Antimalarial medication, antimalarial agent quinine, originally derived from the bark of the cinchona tre ...
potentially allows loperamide to cross the blood–brain barrier and produce central morphine-like effects. Loperamide taken with quinidine was found to produce respiratory depression, indicative of central opioid action.
Loperamide has been shown to cause a mild physical dependence
Physical dependence is a physical condition caused by chronic use of a tolerance-forming drug, in which abrupt or gradual drug withdrawal causes unpleasant physical symptoms. Physical dependence can develop from low-dose therapeutic use of certai ...
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.
When originally approved for medical use in the United States, loperamide was considered a narcotic and was put into Schedule II of the Controlled Substances Act 1970. It was transferred to Schedule V on 17 July 1977, and then decontrolled on 3 November 1982.
History
Loperamide hydrochloride was first synthesized in 1969 by Paul Janssen
Paul Adriaan Jan, Baron Janssen (12 September 1926 - 11 November 2003) was a Belgian physician. He was the founder of Janssen Pharmaceutica, a pharmaceutical company with over 20,000 employees which is now a subsidiary of Johnson & Johnson.
Ea ...
from Janssen Pharmaceuticals
Janssen Pharmaceuticals is a pharmaceutical company headquartered in Beerse, Belgium, and wholly-owned by Johnson & Johnson. It was founded in 1953 by Paul Janssen.
In 1961, Janssen Pharmaceuticals was purchased by New Jersey-based American c ...
in Beerse
Beerse () is a municipality located in the Belgian province of Antwerp. The municipality comprises the towns of Beerse proper and . In 2021, Beerse had a total population of 18,194. The total area is 37.48 km2 (14.5 sq mi). The pharmaceutica ...
, Belgium, following previous discoveries of diphenoxylate hydrochloride (1956) and fentanyl citrate
Fentanyl, also spelled fentanil, is a very potent synthetic opioid used as a pain medication. Together with other drugs, fentanyl is used for anesthesia. It is also used illicitly as a recreational drug, sometimes mixed with heroin, cocain ...
(1960).
The first clinical reports on loperamide were published in 1973 in the'' Journal of Medicinal Chemistry
A journal, from the Old French ''journal'' (meaning "daily"), may refer to:
*Bullet journal, a method of personal organization
*Diary, a record of what happened over the course of a day or other period
*Daybook, also known as a general journal, a ...
'' with the inventor being one of the authors. The trial name for it was "R-18553". Loperamide oxide
Loperamide, sold under the brand name Imodium, among others,Drugs.co Page accessed September 4, 2015 is a medication used to decrease the frequency of diarrhea. It is often used for this purpose in inflammatory bowel disease and short bowel synd ...
has a different research code: R-58425.
The trial against placebo
A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures.
In general ...
was conducted from December 1972 to February 1974, its results being published in 1977 in the journal ''Gut''.
In 1973, Janssen started to promote loperamide under the brand name Imodium. In December 1976, Imodium got US FDA approval.
During the 1980s, Imodium became the best-selling prescription antidiarrheal in the United States.[
]
In March 1988, McNeil Pharmaceutical began selling loperamide as an over-the-counter drug
Over-the-counter (OTC) drugs are medicines sold directly to a consumer without a requirement for a prescription from a healthcare professional, as opposed to prescription drugs
A prescription drug (also prescription medication or prescripti ...
under the brand name Imodium A-D.
In the 1980s, loperamide also existed in the form of drops (Imodium Drops) and syrup. Initially, it was intended for children's usage, but Johnson & Johnson
Johnson & Johnson (J&J) is an American multinational corporation founded in 1886 that develops medical devices, pharmaceuticals, and consumer packaged goods. Its common stock is a component of the Dow Jones Industrial Average and the company i ...
voluntarily withdrew it from the market in 1990 after 18 cases of paralytic ileus
Ileus is a disruption of the normal propulsive ability of the intestine. It can be caused by lack of peristalsis or by mechanical obstruction.
The word 'ileus' is from Ancient Greek ''eileós'' (, "intestinal obstruction"). The term 'subileus' re ...
(resulting in six deaths) were registered in Pakistan and reported by the World Health Organization
The World Health Organization (WHO) is a specialized agency of the United Nations responsible for international public health. The WHO Constitution states its main objective as "the attainment by all peoples of the highest possible level of h ...
(WHO). In the following years (1990-1991), products containing loperamide have been restricted for children's use in a number of countries (ranging from two to five years of age).
In the late 1980s, before the US patent expired on 30 January 1990,[ McNeil started to develop Imodium Advanced containing loperamide and simethicone for treating both ]diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin wi ...
and gas
Gas is one of the four fundamental states of matter (the others being solid, liquid, and plasma).
A pure gas may be made up of individual atoms (e.g. a noble gas like neon), elemental molecules made from one type of atom (e.g. oxygen), or ...
. In March 1997, the company patented such combination. The drug was approved in June 1997, by the FDA as Imodium Multi-Symptom Relief in the form of a chewable tablet. A caplet formulation was approved in November 2000.
In November 1993, loperamide was launched as an orally disintegrating tablet
An orally disintegrating tablet or orally dissolving tablet (ODT) is a drug dosage form available for a limited range of over-the-counter (OTC) and prescription medications. ODTs differ from traditional tablets in that they are designed to be ...
based on Zydis
Zydis is a technology used to manufacture orally disintegrating tablets developed by R.P. Scherer Corporation. Zydis tablets dissolve in the mouth within 3 seconds.
History
Zydis technology was developed by R.P. Scherer Corporation (currentl ...
technology.
In 2013, loperamide in the form of 2-mg tablets was added to the WHO Model List of Essential Medicines
The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...
.
In 2020, it was discovered by researchers at Goethe University
Goethe University (german: link=no, Johann Wolfgang Goethe-Universität Frankfurt am Main) is a university located in Frankfurt am Main, Germany. It was founded in 1914 as a citizens' university, which means it was founded and funded by the wealt ...
that Loperamide was effective at killing glioblastoma
Glioblastoma, previously known as glioblastoma multiforme (GBM), is one of the most aggressive types of cancer that begin within the brain. Initially, signs and symptoms of glioblastoma are nonspecific. They may include headaches, personality ch ...
cells.
Society and culture
Economics
Loperamide is sold as a generic medication
A generic drug is a pharmaceutical drug that contains the same chemical substance as a drug that was originally protected by chemical patents. Generic drugs are allowed for sale after the patents on the original drugs expire. Because the active ch ...
.[ In 2016, Imodium was one of the biggest-selling branded over-the-counter medications sold in Great Britain, with sales of £32.7 million.
]
Brand names
Loperamide was originally marketed as Imodium, and many generic brands are sold.[
]
Off-label/unapproved use
Loperamide has typically been deemed to have a relatively low risk of misuse. In 2012, no reports of loperamide abuse were made. In 2015, however, case reports of extremely high-dose loperamide use were published. 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.[ At these higher doses central nervous system penetration occurs and long term use may lead to tolerance, dependence, and withdrawal on abrupt cessation.] Dubbing it "the poor man's methadone
Methadone, sold under the brand names Dolophine and Methadose among others, is a synthetic opioid agonist used for chronic pain and also for opioid dependence. It is used to treat chronic pain, and it is also used to treat addiction to heroin ...
", clinicians warned that increased restrictions on the availability of prescription opioids passed in response to the opioid epidemic
The opioid epidemic, also referred to as the opioid crisis, is the rapid increase in the overuse, misuse/abuse, and overdose deaths attributed either in part or in whole to the class of drugs opiates/opioids since the 1990s. It includes the sign ...
were prompting recreational users to turn to loperamide as an over-the-counter treatment for withdrawal symptoms. The FDA responded to these warnings by calling on drug manufacturers to voluntarily limit the package size of loperamide for public-safety reasons. However, there is no quantity restriction on number of packages that can be purchased, and most pharmacies do not feel capable of restricting its sale, so it is unclear that this intervention will have any impact without further regulation to place loperamide behind the counter. Since 2015, several reports of sometimes-fatal cardiotoxicity
Cardiotoxicity is the occurrence of heart dysfunction as electric or muscle damage, resulting in heart toxicity. The heart becomes weaker and is not as efficient in pumping blood. Cardiotoxicity may be caused by chemotherapy (a usual example is th ...
due to high-dose loperamide abuse have been published.
See also
* Methylnaltrexone
Methylnaltrexone (MNTX, brand name Relistor), used in form of methylnaltrexone bromide (INN, USAN, BAN), is a medication that acts as a peripherally acting μ-opioid receptor antagonist that acts to reverse some of the side effects of opioid dr ...
, another peripheral-acting opioid antagonist, is similar to naloxegol and is indicated to reduce opioid-induced constipation
Opioids are substances that act on opioid receptors to produce morphine-like effects. Medically they are primarily used for pain relief, including anesthesia. Other medical uses include suppression of diarrhea, replacement therapy for opioid use ...
without significantly affecting analgesia.
* Naloxegol
Naloxegol (INN; PEGylated naloxol; trade names Movantik and Moventig) is a peripherally acting μ-opioid receptor antagonist developed by AstraZeneca, licensed from Nektar Therapeutics, for the treatment of opioid-induced constipation. It was app ...
, a peripheral-acting opioid antagonist, is indicated to reduce opioid-induced constipation without significantly affecting analgesia. As such, it can be considered the antithesis of the peripheral-acting opiate agonist loperamide.
* Simethicone
Simeticone (INN), also known as simethicone (USAN), is an anti-foaming agent used to reduce bloating, discomfort or pain caused by excessive gas.
Medical uses
Simeticone is used to relieve the symptoms of excessive gas in the gastrointestinal ...
, a silicone
A silicone or polysiloxane is a polymer made up of siloxane (−R2Si−O−SiR2−, where R = organic group). They are typically colorless oils or rubber-like substances. Silicones are used in sealants, adhesives, lubricants, medicine, cooking ...
unrelated to opioids, is combined with loperamide in some formulations. It is an antifoaming agent used to reduce bloating, discomfort, or pain caused by excessive gas.
References
External links
*
*
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