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Loperamide

Class: Antidiarrhea Agents
CAS Number: 34552-83-5
Brands: Imodium A-D, Imodium Multi-Symptom Relief

Medically reviewed by Drugs.com. Last updated on Jan 27, 2020.

Warning

    Torsades de Pointes and Sudden Death
  • Cases of torsades de pointes, cardiac arrest, and death reported with use of higher than recommended dosage. (See Cardiovascular Effects under Cautions.)

  • Contraindicated in pediatric patients <2 years of age. (See Pediatric Use under Cautions.)

  • Avoid dosages higher than recommended in adults and pediatric patients ≥2 years of age due to risk of serious adverse cardiac effects. (See Dosage under Dosage and Administration.)

Introduction

Antiperistaltic antidiarrhea agent; synthetic piperidine-derivative.

Uses for Loperamide

Diarrhea

Control and symptomatic relief of acute, nonspecific diarrhea.

Control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease. Also has been effective in controlling chronic functional (idiopathic) diarrhea and chronic diarrhea caused by bowel resection or organic lesions.

Self-medication for symptomatic control of diarrhea, including travelers’ diarrhea.

Self-medication (in fixed combination with simethicone) for symptomatic control of diarrhea and symptomatic control of gas (gastric bloating, pressure, cramps).

Antiperistaltics (e.g., loperamide, diphenoxylate) used for symptomatic treatment of mild or uncomplicated travelers’ diarrhea, including that occurring in adult travelers with HIV infection. Short-term (1–3 days) empiric treatment with an appropriate anti-infective recommended if travelers’ diarrhea is moderate to severe, associated with fever or bloody stools, or extremely disruptive to travel plans; adjunctive use of antiperistaltics during first few days may shorten duration of illness or reduce frequency of bowel movements and allow traveler to continue with travel plans while waiting for beneficial effects of the anti-infective. Antiperistaltics not usually recommended in travelers with high fever or bloody diarrhea or in young children. (See Cautions.)

Ileostomy Discharge

Reduction of discharge volume from ileostomies.

Loperamide Dosage and Administration

General

  • Administer appropriate fluid and electrolyte replacement as needed.

  • If used for self-medication, advise patients to drink plenty of clear fluids to help prevent dehydration caused by diarrhea.

Administration

Oral Administration

Capsules: Administer orally in adults, adolescents, and children ≥2 years of age.

Solution (1 mg/5 mL), suspension (1 mg/7.5 mL), tablets (film-coated or chewable): Administer orally in adults, adolescents, and children ≥6 years of age.

Administer oral solution or suspension using only the calibrated measuring cup provided by the manufacturer. Shake suspension well prior to each dose.

Dosage

Available as loperamide hydrochloride; dosage expressed in terms of the salt.

Pediatric Patients

Acute Diarrhea
Oral

Children 2–12 years of age: Base initial dosage on age and body weight. (See Table 1 for recommended initial dosage for first day of therapy.) On second and subsequent days of therapy, administer 0.1 mg/kg only after each unformed stool; do not exceed total daily dosage recommended for initial 24 hours.

Table 1. Initial Dosage of Loperamide Hydrochloride for Children 2–12 Years of Age108

Age (weight)

Dosage (initial 24 hours)

2–5 years (13–20 kg)

1 mg 3 times daily

6–8 years (20–30 kg)

2 mg twice daily

8–12 years (>30 kg)

2 mg 3 times daily

Self-medication in children <6 years of age: Do not use (alone or in fixed combination with simethicone) unless directed by a clinician.

Self-medication in children ≥6 years of age (alone or in fixed combination with simethicone): Base dosage on body weight, if possible; otherwise use age. (See Table 2 for dosage for self-administration in children ≥6 years of age.)

Table 2. Dosage for Self-Medication in Children ≥6 Years of Age109110111112113114

Age (weight)

Dosage

<6 years (≤21.4 kg)

Do not use unless directed by a clinician

6–8 years (21.8–26.8 kg)

2 mg after first unformed stool, followed by 1 mg after each subsequent unformed stool (not to exceed 4 mg in 24 hours)

9–11 years (27.3–43.2 kg)

2 mg after first unformed stool, followed by 1 mg after each subsequent unformed stool (not to exceed 6 mg in 24 hours)

≥12 years

4 mg after first unformed stool, followed by 2 mg after each subsequent unformed stool (not to exceed 8 mg in 24 hours)

Discontinue and consult a clinician if acute diarrhea does not improve after 48 hours of therapy.

Chronic Diarrhea
Oral

Children: Therapeutic dosage for chronic diarrhea not established. Dosage of 0.08–0.24 mg/kg daily in 2 or 3 divided doses has been used in a limited number of children and has been recommended by some clinicians.

Adults

Acute Diarrhea
Oral

Initially, 4 mg, followed by 2 mg after each unformed stool, up to a maximum of 16 mg daily.

Self-medication: Initial dosage (alone or in fixed combination with simethicone) is 4 mg, followed by 2 mg after each subsequent unformed stool. Do not exceed 8 mg in a 24-hour period unless directed by a clinician.

Discontinue and consult a clinician if acute diarrhea does not improve after 48 hours of therapy.

Chronic Diarrhea
Oral

Initially, 4 mg, followed by 2 mg after each unformed stool until symptoms are controlled and then reduce for maintenance as required. When optimal dosage established, may administer as single or divided doses.

In clinical trials, average maintenance dosage was 4–8 mg daily.

If improvement not observed after 10 days of therapy with maximum dosage of 16 mg daily, symptoms are unlikely to be controlled by further administration of the drug. May continue therapy if diarrhea cannot be adequately controlled with diet or specific treatment.

Prescribing Limits

Pediatric Patients

Acute Diarrhea
Oral

Children 2–5 years of age: Maximum 3 mg daily; not for self-medication unless directed by a clinician.

Children 6–8 years of age: Maximum 4 mg daily. If used for self-medication, do not exceed 2 days unless otherwise directed by a clinician.

Children 9–11 years of age: Maximum 6 mg daily. If used for self-medication, do not exceed 2 days unless otherwise directed by a clinician.

Children ≥12 years of age: Maximum 8 mg daily. If used for self-medication, do not exceed 2 days unless otherwise directed by a clinician.

Adults

Acute Diarrhea
Oral

Maximum 16 mg daily.

For self-medication, maximum 8 mg in a 24-hour period; do not exceed 2 days unless otherwise directed by a clinician.

Chronic Diarrhea
Oral

Maximum 16 mg daily.

Special Populations

Hepatic Impairment

Use with caution. (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustments not needed. (See Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustments not needed. (See Geriatric Use under Cautions.)

Cautions for Loperamide

Contraindications

  • Pediatric patients <2 years of age. (See Pediatric Use under Cautions.)

  • Known hypersensitivity to loperamide or any ingredient in the formulation.

  • Abdominal pain in the absence of diarrhea.

  • Acute dysentery (characterized by blood in stools and high fever), acute ulcerative colitis, bacterial enterocolitis caused by invasive organisms (e.g., Salmonella, Shigella, Campylobacter), or pseudomembranous colitis associated with anti-infective therapy.

Warnings/Precautions

Warnings

Use only for control and symptomatic relief of diarrhea. Whenever underlying etiology for the diarrhea can be determined, use specific treatment whenever indicated or appropriate.

Discontinue if clinical improvement of acute diarrhea does not occur within 48 hours. Also discontinue if there is blood in the stool or if fever or abdominal distention develops.

For self-medication, do not use for >2 days unless directed by a clinician; do not use if diarrhea is accompanied by fever or if mucus or blood is present in the stool; do not use if rash or other allergic reaction to the drug occurred previously. Consult clinician before using for self-medication in patients who have a history of liver disease or are receiving an anti-infective.

Fluid and Electrolyte Replacement Therapy

Fluid and electrolyte depletion often occurs in patients with diarrhea; in such cases, administration of appropriate fluid and electrolytes is important. Use of loperamide does not preclude administration of appropriate fluid and electrolyte therapy.

When used for self-medication, patients should drink plenty of clear fluids to help prevent dehydration caused by diarrhea.

Risk of Ileus, Megacolon, and Toxic Megacolon

Should not be used when inhibition of peristalsis should be avoided; possible risk of serious sequelae (e.g., ileus, megacolon, toxic megacolon).

Loperamide must be discontinued promptly if constipation, abdominal distention, or ileus occurs.

Based on rare reports of toxic megacolon in HIV-infected patients with infectious colitis associated with viral or bacterial pathogens, discontinue loperamide in HIV-infected patients at earliest signs of abdominal distention.

Cardiovascular Effects

Potentially fatal, serious cardiovascular effects (e.g., QT interval prolongation, torsades de pointes or other ventricular arrhythmias, syncope, cardiac arrest) have occurred. Reported rarely in patients receiving recommended loperamide dosages; majority of cases have involved higher than recommended dosages, usually in individuals misusing or abusing the drug. (See Misuse and Abuse Potential under Cautions.)

Use with caution in patients predisposed to QT interval prolongation, torsades de pointes, or other serious arrhythmias. Also use with caution in patients receiving drugs that inhibit loperamide metabolism or transport (i.e., CYP3A4 or CYP2C8 inhibitors, P-glycoprotein inhibitors) since increased loperamide plasma concentrations may increase risk of serious cardiovascular effects. (See Interactions.)

Misuse and Abuse Potential

FDA has warned clinicians to consider the potential for misuse and abuse of loperamide.

Serious cardiovascular effects, including fatalities, reported in individuals intentionally misusing and abusing high dosages of loperamide in an attempt to self-treat opiate withdrawal symptoms or to achieve a feeling of euphoria. Maximum recommended adult dosage is 8 mg daily for self-medication or 16 mg daily for prescription use; in some cases of misuse and abuse, individuals ingested dosages of 70–1600 mg daily.

FDA recommends that clinicians consider loperamide as a possible cause of unexplained cardiac events (e.g., QT interval prolongation, torsades de pointes or other ventricular arrhythmias, syncope, cardiac arrest).

If loperamide-induced cardiotoxicity is suspected, promptly discontinue loperamide and initiate appropriate therapy to manage and prevent cardiac arrhythmias and severe outcomes. In some cases of torsades de pointes, drug treatment may be ineffective and electrical pacing or cardioversion may be required. Refer patients with opiate use disorders for treatment. When excessive loperamide ingestion is suspected, consider that specific testing may be required to measure blood levels of the drug; standard drug screens for opiates may not include a loperamide assay and may yield negative results even in the presence of loperamide.

Individuals abusing loperamide often take other drugs with the antidiarrheal agent in an attempt to increase loperamide absorption and penetration across the blood-brain barrier, inhibit loperamide metabolism, and enhance its euphoric effects. FDA warns that the risk of serious cardiac problems (e.g., abnormal heart rhythms) may be increased if high loperamide dosages are taken with drugs that interact with loperamide (e.g., cimetidine, clarithromycin, erythromycin, gemfibrozil, itraconazole, ketoconazole, quinidine, quinine, ranitidine, ritonavir). (See Interactions.)

Advise patients and consumers to take loperamide only in the dosage prescribed by their clinician or stated on the label of the OTC product. Warn patients and consumers that taking larger doses of loperamide (either intentionally or unintentionally) may lead to abnormal heart rhythms and serious cardiac events that can be fatal and that taking loperamide with some commonly used medications also may increase the risk of serious cardiac adverse events.

To help deter misuse and abuse of OTC loperamide products, FDA has approved packaging changes for several tablet and capsule formulations of the drug (including Imodium brand-name products) that limit total loperamide hydrochloride content of the package to 48 mg and require use of single-dose (e.g., blister) packaging. FDA continues to work with manufacturers, including manufacturers of OTC generic and liquid loperamide formulations, to institute appropriate packaging changes.

Advise patients and consumers to immediately seek medical attention if they or someone taking loperamide experiences fainting, rapid heartbeat or irregular heart rhythm, or are unresponsive (i.e., can’t be wakened or is not answering or reacting normally).

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, reported.

Severe hypersensitivity reactions (e.g., anaphylactic shock, anaphylactoid reactions) and bullous eruptions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported rarely.

General Precautions

Use of Fixed Combination

When fixed combination containing loperamide and simethicone used, consider cautions, precautions, contraindications, and drug interactions associated with both drugs. Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for both loperamide and simethicone.

Specific Populations

Pregnancy

Category C.

Use only if potential benefits in the woman justify potential risks to the fetus. No adequate or controlled studies in pregnant women.

Lactation

Distributed into human milk in low concentrations.

Not recommended in nursing women.

Pediatric Use

Contraindicated in children <2 years of age because of the risks of respiratory depression and serious adverse cardiac reactions.

Rare reports of paralytic ileus associated with abdominal distention; most cases occurred in the setting of acute dysentery, overdosage, and in infants <2 years of age.

Use for self-medication in children <6 years of age only under direction of clinician.

Use particular caution in young children due to greater variability of response to the drug; presence of dehydration, especially in younger children, may further influence variability of response.

Children may be more sensitive to CNS effects than adults.

Geriatric Use

No formal studies conducted in geriatric patients; no apparent differences in disposition of the drug in elderly patients with diarrhea relative to younger adults.

Hepatic Impairment

Use with caution and monitor closely for manifestations of CNS toxicity; first-pass metabolism may be decreased in such patients. Specific pharmacokinetic data not available.

Do not use for self-medication in patients with a history of liver disease without consulting a clinician.

Renal Impairment

Although specific pharmacokinetic data not available, dosage adjustments not needed in patients with renal impairment since unchanged drug and metabolites excreted principally in feces.

Common Adverse Effects

Nausea, constipation, abdominal cramps, dizziness.

Interactions for Loperamide

Metabolized principally by CYP3A4 and CYP2C8.

P-glycoprotein (P-gp) substrate.

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 or CYP2C8 inhibitors: Possible increased loperamide plasma concentrations and possible increased risk of serious cardiovascular effects.

Drugs Affecting P-glycoprotein Transport

P-gp inhibitors: Possible increased loperamide plasma concentrations and possible increased risk of enhanced central effects or serious cardiovascular effects.

Specific Drugs

Drug

Interaction

Comments

Antifungal agents (itraconazole, ketoconazole)

Itraconazole, ketoconazole: May increase loperamide concentrations and increase risk of serious cardiovascular effects

Use concomitantly with caution

Cimetidine

Potential interaction

Gemfibrozil

May increase loperamide concentrations and increase risk of serious cardiovascular effects

Use concomitantly with caution

Macrolides (erythromycin, clarithromycin)

Erythromycin, clarithromycin: May increase loperamide concentrations and increase risk of serious cardiovascular effects

Use concomitantly with caution

Quinidine

Increased loperamide concentrations; may increase risk of serious cardiovascular effects

Use concomitantly with caution

Quinine

May increase loperamide concentrations and increase risk of serious cardiovascular effects

Use concomitantly with caution

Ranitidine

Potential interaction

Ritonavir

Increased loperamide concentrations; may increase risk of serious cardiovascular effects

Use concomitantly with caution

Saquinavir

Decreased saquinavir concentrations and possible loss of antiretroviral therapeutic efficacy

Closely monitor for saquinavir efficacy

Loperamide Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained about 5 or 2.5 hours after administration of capsules or oral solution, respectively. Oral bioavailability of capsules and oral solution, as determined by AUC, is similar.

Peak plasma concentrations of loperamide metabolites are reached 8 hours following oral administration of capsules.

Distribution

Not known whether loperamide crosses the placenta.

Distributed into milk in low concentrations.

Elimination

Metabolism

Oxidative metabolism occurs, principally by CYP2C8 and 3A4; CYP2B6 and 2D6 may also be involved.

Elimination Route

Unchanged drug and metabolites excreted principally in feces.

Half-life

10.8 hours (range 9.1–14.4 hours) in healthy adults receiving recommended dosages.

Half-lives as high as 41 hours reported in individuals ingesting higher than recommended dosages.

Stability

Storage

Oral

Capsules

20–25°C in well-closed container.

Solution or Suspension

20–25°C.

Tablets

20–25°C. Protect fixed combination containing loperamide and simethicone from light.

Actions

  • Slows intestinal motility and affects water and electrolyte movement through the bowel. Inhibits peristaltic activity by a direct effect on circular and longitudinal muscles of the intestinal wall.

  • Prolongs the transit time of intestinal contents; reduces fecal volume, increases fecal viscosity and bulk density, and diminishes loss of fluid and electrolytes.

Advice to Patients

  • Advise patients to discontinue the drug and contact clinician if diarrhea does not improve after 2 days of therapy, if blood is present in stools, or if fever or abdominal distention develops.

  • Importance of adequate hydration and drinking plenty of clear fluids to help prevent dehydration caused by diarrhea.

  • Advise patients that tiredness, dizziness, or drowsiness may occur in the setting of diarrheal syndromes treated with loperamide; importance of using caution when driving a car or operating machinery.

  • When used for self-medication, importance of reading product labeling.

  • Do not use for self-medication for longer than 2 days or in children <6 years of age unless directed by a clinician.

  • Do not use for self-medication if diarrhea is accompanied by fever, if mucus or blood is present in the stool, or if rash or other allergic reaction to the drug has occurred previously. Importance of consulting clinician before use if patient has history of liver impairment or is currently taking an anti-infective.

  • If using for self-medication, advise patients to discontinue the drug and contact a clinician if diarrhea symptoms worsen or last >2 days or if abdominal swelling or bulging develops.

  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.

  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Loperamide Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

2 mg*

Loperamide Hydrochloride Capsules

Solution

1 mg/5 mL*

Imodium A-D

McNeil

Loperamide Hydrochloride Oral Solution

Suspension

1 mg/7.5 mL*

Loperamide Hydrochloride Oral Suspension

Imodium A-D

McNeil

Tablets, film-coated

2 mg*

Imodium A-D Caplets

McNeil

Loperamide Hydrochloride Tablets

Tablets, chewable

2 mg

Imodium A-D EZ Chews

McNeil

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Loperamide Hydrochloride Combinations

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets

2 mg with Simethicone 125 mg*

Imodium Multi-Symptom Relief Caplets

McNeil

Loperamide Hydrochloride and Simethicone Tablets

Tablets, chewable

2 mg with Simethicone 125 mg*

Imodium Multi-Symptom Relief Chewable Tablets

McNeil

Loperamide Hydrochloride and Simethicone Chewable Tablets

AHFS DI Essentials™. © Copyright 2021, Selected Revisions January 27, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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