loperamide

Action and Spectrum

Actions and Spectrum: 

Loperamide is a lipophilic synthetic phenylpiperidine opioid that acts as a μ-opioid receptor agonist. At therapeutic doses, it exerts its effects locally on μ-opioid receptors in the circular and longitudinal muscles of the intestine, resulting in reduced gastrointestinal motility, increased intestinal transit time, decreased electrolyte and fluid loss, and enhanced rectal tone. These actions help control diarrhea by improving fluid and electrolyte absorption while decreasing bowel frequency. However, at higher doses, loperamide becomes a substrate for P-glycoprotein, a transporter that typically limits its penetration into the central nervous system (CNS). When P-glycoprotein is inhibited, loperamide can cross the blood-brain barrier, potentially producing central opioid effects and leading to CNS toxicity. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Fatigue 

Dizziness 

Constipation 

Abdominal pain 

Dry Mouth  

Nausea 

Flatulence 

Rash 

Angioedema 

Bullous eruptions 

Black Box Warning

Black-Box Warning: 

Cases have been reported cases of Torsades de Pointes, cardiac arrest, and death associated with the use of higher than recommended dosages of a particular medication. Therefore, it is crucial to avoid exceeding the recommended dosages, especially in patients who are 2 years of age or older, to reduce the risk of serious cardiac adverse reactions. 

Furthermore, the medication is contraindicated in patients who are under the age of 2 years, meaning it should not be used in this patient population due to potential risks. It is important to follow dosing instructions carefully and to consult with a healthcare provider if there are any concerns about the appropriate use of the medication. 

Contraindication / Caution

Contraindications: 

• Allergy or hypersensitivity to loperamide 

• Children under the age of 2 years old 

Caution: 

• Patients with liver disease 

• Patients with kidney disease 

• Patients taking medications that can affect the heart’s electrical activity (such as some antiarrhythmic drugs, antipsychotics, and antibiotics) 

• Pregnant or breastfeeding women (should consult a doctor before taking loperamide) 

Pregnancy / Lactation

Pregnancy consideration: loperamide is safe for consumption during pregnancy 

Breastfeeding warnings: loperamide is secreted in breast milk in small amounts 

Lactating females should not breastfeed during this medication 

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 

• Category B: There is no affirmation of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women. 

• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a product in humans; Pregnant women must take care of the potential risks. 

• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergency cases for potential benefits. 

• Category X: Drugs listed in this category outweigh risks over benefits. The drug is not for pregnant women. 

• Category N: No data is available for the drug under this category. 

Pharmacology

loperamide is an antidiarrheal medication that works by slowing down the movement of the intestines, which reduces the frequency and urgency of bowel movements. It acts on the opioid receptors in the intestinal wall to inhibit the release of acetylcholine and other neurotransmitters, which normally stimulate contractions of the intestinal muscles. 

loperamide is not absorbed significantly into the bloodstream when taken orally, so it primarily acts on the gastrointestinal tract. It is metabolized mainly in the liver and excreted in the feces. 

The onset of action of loperamide is typically within one hour, and the effects can last for several hours. It is available in various forms, including tablets, capsules, and liquid formulations. 

loperamide is a relatively safe medication when used as directed, but it can cause side effects such as constipation, abdominal pain, nausea, and vomiting. In rare cases, it can cause serious cardiac adverse effects such as Torsades de Pointes, especially when taken at higher than recommended dosages or in combination with other medications that affect the heart’s electrical activity. It is important to follow dosing instructions carefully and to consult with a healthcare provider if there are any concerns about the appropriate use of loperamide. 

Pharmacodynamics: 

loperamide is an opioid agonist that primarily acts on the mu-opioid receptors in the gastrointestinal tract, which are responsible for regulating bowel motility. By binding to these receptors, loperamide inhibits the release of acetylcholine and other neurotransmitters, which normally stimulate contractions of the intestinal muscles. 

The inhibition of intestinal motility by loperamide reduces the frequency and urgency of bowel movements, allowing the body to reabsorb more water from the stools and thereby producing more formed stools. This effect can help relieve diarrhea symptoms. 

loperamide does not cross the blood-brain barrier to a significant extent, so it has little to no effect on the central nervous system and does not produce significant analgesic or euphoric effects like other opioids. 

The onset of action of loperamide is typically within one hour, and the effects can last for several hours. The duration of action may be prolonged in patients with liver disease or those taking certain medications that affect the metabolism of loperamide. 

Pharmacokinetics: 

Absorption 

Loperamide exhibits low oral bioavailability (<1%) due to extensive first-pass metabolism. After oral administration, the peak plasma concentration is reached in 4 to 5 hours, and the plasma half-life ranges from 7 to 19 hours. 

Distribution 

Loperamide demonstrates high protein binding and a large volume of distribution, indicating extensive distribution throughout body tissues. 

Metabolism 

Loperamide undergoes extensive hepatic metabolism, primarily by the cytochrome P450 enzymes CYP2C8 and CYP3A4, converting it to desmethyl-loperamide. It is also extracted in the gastrointestinal tract, with minimal systemic absorption at therapeutic doses. The metabolism favors biliary excretion and limits systemic activity. 

Elimination/Excretion 

The elimination half-life of loperamide ranges between 9.1 to 14.4 hours. Excretion is mainly via the feces, both as unchanged drug and metabolites, with minimal renal elimination. 

Adminstartion

loperamide is available in various forms, including tablets, capsules, and liquids. The medication is typically taken orally, and the dosage and frequency of administration depend on the condition being treated and the patient’s age and health status. 

For the treatment of acute diarrhea in adults, the recommended initial dose of loperamide is 4 mg, followed by 2 mg after each loose stool, up to a maximum daily dose of 16 mg. The medication should be taken with a full glass of water and can be taken with or without food. If symptoms persist for more than 48 hours, a healthcare provider should be consulted. 

For the treatment of chronic diarrhea in adults, the recommended initial dose is 4 mg, taken twice daily, with a maximum daily dose of 16 mg. The medication should be taken with a full glass of water and can be taken with or without food. If symptoms persist for more than 10 days, a healthcare provider should be consulted. 

For children aged 2-12 years, the recommended initial dose of loperamide is 0.08 mg/kg (up to a maximum of 2 mg), followed by 0.04 mg/kg after each loose stool, up to a maximum daily dose of 6 mg or the weight-based equivalent. Children under the age of 2 years should not be given loperamide unless directed by a healthcare provider. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: loperamide 

Pronounced: Loh-per-uh-mahyd 

Why do we use loperamide? 

loperamide is used to treat acute and chronic diarrhea in adults and children over the age of two. It works by slowing down the movement of the intestines and reducing the frequency and urgency of bowel movements, which can help relieve diarrhea symptoms such as loose stools, stomach cramps, and dehydration. 

loperamide is particularly useful for treating diarrhea caused by non-specific or functional disorders, such as irritable bowel syndrome (IBS) or inflammatory bowel disease (IBD).  

Overall, loperamide is an effective and widely used medication for the symptomatic relief of diarrhea. However, it should be used with caution and under the guidance of a healthcare provider, as it may not be appropriate for all patients, especially those with underlying medical conditions or taking certain medications.