Brand names: Imodium A-D, Imodium Multi-Symptom Relief
Drug class: Antidiarrhea Agents
CAS number: 34552-83-5

Medically reviewed by Drugs.com on Jan 17, 2024. Written by ASHP.

Introduction

Antiperistaltic antidiarrhea agent;¹⁰⁸ synthetic piperidine-derivative.¹⁰⁸

Uses for Loperamide

Diarrhea

Control and symptomatic relief of acute, nonspecific diarrhea.¹⁰⁸

Control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease.¹⁰⁸ Also has been effective in controlling chronic functional (idiopathic) diarrhea^{† [off-label]} and chronic diarrhea caused by bowel resection or organic lesions^{† [off-label]}.^a

Self-medication for symptomatic control of diarrhea, including travelers’ diarrhea.^{109 110 111 112 113}

Self-medication (in fixed combination with simethicone) for symptomatic control of diarrhea and symptomatic control of gas (gastric bloating, pressure, cramps).¹¹⁴

Antiperistaltics (e.g., loperamide, diphenoxylate) used for symptomatic treatment of mild or uncomplicated travelers’ diarrhea, including that occurring in adult travelers with HIV infection.^{104 105 106} 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;¹⁰⁶ 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.^{105 106} Antiperistaltics not usually recommended in travelers with high fever or bloody diarrhea or in young children.^{104 105} (See Cautions.)

Ileostomy Discharge

Reduction of discharge volume from ileostomies.¹⁰⁸

Loperamide Dosage and Administration

General

• Administer appropriate fluid and electrolyte replacement as needed.¹⁰⁸

• If used for self-medication, advise patients to drink plenty of clear fluids to help prevent dehydration caused by diarrhea.^{109 110 111 112 113}

Administration

Oral Administration

Capsules: Administer orally in adults, adolescents, and children ≥2 years of age.¹⁰⁸

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.^{109 110 111 112 113}

Administer oral solution or suspension using only the calibrated measuring cup provided by the manufacturer.^{109 111 112} Shake suspension well prior to each dose.^{109 112}

Dosage

Available as loperamide hydrochloride; dosage expressed in terms of the salt.^{108 109 110 111 112 113 114}

Pediatric Patients

Acute Diarrhea

Oral

Children 2–12 years of age: Base initial dosage on age and body weight.¹⁰⁸ (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;¹⁰⁸ do not exceed total daily dosage recommended for initial 24 hours.¹⁰⁸

Self-medication in children <6 years of age: Do not use (alone or in fixed combination with simethicone) unless directed by a clinician.^{109 110 111 112 113 114}

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.^{109 110 111 112 113 114} (See Table 2 for dosage for self-administration in children ≥6 years of age.)

Discontinue and consult a clinician if acute diarrhea does not improve after 48 hours of therapy.^{108 109 110 111 112 113 114}

Chronic Diarrhea

Oral

Children: Therapeutic dosage for chronic diarrhea not established.¹⁰⁸ Dosage of 0.08–0.24 mg/kg daily in 2 or 3 divided doses^{† [off-label]} has been used in a limited number of children and has been recommended by some clinicians.^{107 115}

Adults

Acute Diarrhea

Oral

Initially, 4 mg, followed by 2 mg after each unformed stool, up to a maximum of 16 mg daily.¹⁰⁸

Self-medication: Initial dosage (alone or in fixed combination with simethicone) is 4 mg, followed by 2 mg after each subsequent unformed stool.^{106 109 110 111 112 113 114} Do not exceed 8 mg in a 24-hour period unless directed by a clinician.^{106 109 110 111 112 113 114}

Discontinue and consult a clinician if acute diarrhea does not improve after 48 hours of therapy.^{108 109 110 111 112 113 114}

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.¹⁰⁸ When optimal dosage established, may administer as single or divided doses.¹⁰⁸

In clinical trials, average maintenance dosage was 4–8 mg daily.¹⁰⁸

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.¹⁰⁸ May continue therapy if diarrhea cannot be adequately controlled with diet or specific treatment.¹⁰⁸

Prescribing Limits

Pediatric Patients

Acute Diarrhea

Oral

Children 2–5 years of age: Maximum 3 mg daily;¹⁰⁸ not for self-medication unless directed by a clinician.^{109 110}

Children 6–8 years of age: Maximum 4 mg daily.^{108 109 110 111 112 113} If used for self-medication, do not exceed 2 days unless otherwise directed by a clinician.^{109 110 111 112 113}

Children 9–11 years of age: Maximum 6 mg daily.^{108 109 110 111 112 113} If used for self-medication, do not exceed 2 days unless otherwise directed by a clinician.^{109 110 111 112 113}

Children ≥12 years of age: Maximum 8 mg daily.^{109 110 111 112 113} If used for self-medication, do not exceed 2 days unless otherwise directed by a clinician.^{109 110 111 112 113}

Adults

Acute Diarrhea

Oral

Maximum 16 mg daily.¹⁰⁸

For self-medication, maximum 8 mg in a 24-hour period;^{106 109 110 111 112 113 114} do not exceed 2 days unless otherwise directed by a clinician.^{109 110 111 112 113}

Chronic Diarrhea

Oral

Maximum 16 mg daily.¹⁰⁸

Special Populations

Hepatic Impairment

Use with caution.¹⁰⁸ (See Hepatic Impairment under Cautions.)

Renal Impairment

Dosage adjustments not needed.¹⁰⁸ (See Renal Impairment under Cautions.)

Geriatric Patients

Dosage adjustments not needed.¹⁰⁸ (See Geriatric Use under Cautions.)

Cautions for Loperamide

Contraindications

• Pediatric patients <2 years of age.¹²⁴ (See Pediatric Use under Cautions.)

• Known hypersensitivity to loperamide or any ingredient in the formulation.¹⁰⁸

• Abdominal pain in the absence of diarrhea.¹⁰⁸

• 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.¹²⁴

Warnings/Precautions

Warnings

Use only for control and symptomatic relief of diarrhea.¹⁰⁸ Whenever underlying etiology for the diarrhea can be determined, use specific treatment whenever indicated or appropriate.¹⁰⁸

Discontinue if clinical improvement of acute diarrhea does not occur within 48 hours.¹⁰⁸ Also discontinue if there is blood in the stool or if fever or abdominal distention develops.¹⁰⁸

For self-medication, do not use for >2 days unless directed by a clinician;^{109 110 111 112 113} do not use if diarrhea is accompanied by fever or if mucus or blood is present in the stool;^{109 110 111 112 113} do not use if rash or other allergic reaction to the drug occurred previously.^{109 110 111 112 113} Consult clinician before using for self-medication in patients who have a history of liver disease or are receiving an anti-infective.^{109 110 111 112 113}

Fluid and Electrolyte Replacement Therapy

Fluid and electrolyte depletion often occurs in patients with diarrhea;¹⁰⁸ in such cases, administration of appropriate fluid and electrolytes is important.¹⁰⁸ Use of loperamide does not preclude administration of appropriate fluid and electrolyte therapy.¹⁰⁸

When used for self-medication, patients should drink plenty of clear fluids to help prevent dehydration caused by diarrhea.^{109 110 111 112 113}

Risk of Ileus, Megacolon, and Toxic Megacolon

Should not be used when inhibition of peristalsis should be avoided;¹⁰⁸ possible risk of serious sequelae (e.g., ileus, megacolon, toxic megacolon).¹⁰⁸

Loperamide must be discontinued promptly if constipation, abdominal distention, or ileus occurs.¹⁰⁸

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.¹⁰⁸

Cardiovascular Effects

Potentially fatal, serious cardiovascular effects (e.g., QT interval prolongation, torsades de pointes or other ventricular arrhythmias, syncope, cardiac arrest) have occurred.^{116 117 119 120 121 125} Reported rarely in patients receiving recommended loperamide dosages;¹¹⁶ majority of cases have involved higher than recommended dosages, usually in individuals misusing or abusing the drug.^{116 117 119 120 121 125} (See Misuse and Abuse Potential under Cautions.)

Use with caution in patients predisposed to QT interval prolongation, torsades de pointes, or other serious arrhythmias.¹¹⁶ 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.¹¹⁶ (See Interactions.)

Misuse and Abuse Potential

FDA has warned clinicians to consider the potential for misuse and abuse of loperamide.¹¹⁶

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.^{116 117 119 120 121 125} Maximum recommended adult dosage is 8 mg daily for self-medication^{106 109 110 111 112 113 114 116 125} or 16 mg daily for prescription use;^{108 116 125} in some cases of misuse and abuse, individuals ingested dosages of 70–1600 mg daily.^{116 117 119 120 122}

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).^{116 125}

If loperamide-induced cardiotoxicity is suspected, promptly discontinue loperamide and initiate appropriate therapy to manage and prevent cardiac arrhythmias and severe outcomes.^{116 125} In some cases of torsades de pointes, drug treatment may be ineffective and electrical pacing or cardioversion may be required.^{116 125} Refer patients with opiate use disorders for treatment.¹¹⁶ When excessive loperamide ingestion is suspected, consider that specific testing may be required to measure blood levels of the drug;¹¹⁶ standard drug screens for opiates may not include a loperamide assay and may yield negative results even in the presence of loperamide.¹¹⁶

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.^{116 125} 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).¹¹⁶ (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.^{116 125} 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.^{116 125}

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.¹²⁷ FDA continues to work with manufacturers, including manufacturers of OTC generic and liquid loperamide formulations, to institute appropriate packaging changes.^{125 126 127}

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).^{116 125}

Sensitivity Reactions

Hypersensitivity

Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, reported.¹⁰⁸

Severe hypersensitivity reactions (e.g., anaphylactic shock, anaphylactoid reactions) and bullous eruptions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported rarely.¹⁰⁸

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.¹¹⁴ 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.¹¹⁴

Specific Populations

Pregnancy

Category C.¹⁰⁸

Use only if potential benefits in the woman justify potential risks to the fetus.¹⁰⁸ No adequate or controlled studies in pregnant women.¹⁰⁸

Lactation

Distributed into human milk in low concentrations.¹⁰⁸

Not recommended in nursing women.¹⁰⁸

Pediatric Use

Contraindicated in children <2 years of age because of the risks of respiratory depression and serious adverse cardiac reactions.¹²⁴

Rare reports of paralytic ileus associated with abdominal distention;¹⁰⁸ most cases occurred in the setting of acute dysentery, overdosage, and in infants <2 years of age.¹⁰⁸

Use for self-medication in children <6 years of age only under direction of clinician.^{109 110 111 112 113}

Use particular caution in young children due to greater variability of response to the drug;¹⁰⁸ presence of dehydration, especially in younger children, may further influence variability of response.¹⁰⁸

Children may be more sensitive to CNS effects than adults.¹⁰⁸

Geriatric Use

No formal studies conducted in geriatric patients;¹⁰⁸ no apparent differences in disposition of the drug in elderly patients with diarrhea relative to younger adults.¹⁰⁸

Hepatic Impairment

Use with caution and monitor closely for manifestations of CNS toxicity;¹⁰⁸ first-pass metabolism may be decreased in such patients.¹⁰⁸ Specific pharmacokinetic data not available.¹⁰⁸

Do not use for self-medication in patients with a history of liver disease without consulting a clinician.^{109 110 111 112 113}

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.¹⁰⁸

Common Adverse Effects

Nausea, constipation, abdominal cramps, dizziness.¹⁰⁸

Drug Interactions

Metabolized principally by CYP3A4 and CYP2C8.¹⁰⁸

P-glycoprotein (P-gp) substrate.¹⁰⁸

Drugs Affecting Hepatic Microsomal Enzymes

CYP3A4 or CYP2C8 inhibitors: Possible increased loperamide plasma concentrations and possible increased risk of serious cardiovascular effects.¹¹⁶

Drugs Affecting P-glycoprotein Transport

P-gp inhibitors: Possible increased loperamide plasma concentrations and possible increased risk of enhanced central effects¹⁰⁸ or serious cardiovascular effects.¹¹⁶

Specific Drugs

Loperamide Pharmacokinetics

Absorption

Bioavailability

Peak plasma concentrations attained about 5 or 2.5 hours after administration of capsules or oral solution, respectively.¹⁰⁸ Oral bioavailability of capsules and oral solution, as determined by AUC, is similar.¹⁰⁰

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

Distribution

Not known whether loperamide crosses the placenta.^a

Distributed into milk in low concentrations.¹⁰⁸

Elimination

Metabolism

Oxidative metabolism occurs, principally by CYP2C8 and 3A4;¹⁰⁸ CYP2B6 and 2D6 may also be involved.¹⁰⁸

Elimination Route

Unchanged drug and metabolites excreted principally in feces.¹⁰⁸

Half-life

10.8 hours (range 9.1–14.4 hours) in healthy adults receiving recommended dosages.^{100 108 116}

Half-lives as high as 41 hours reported in individuals ingesting higher than recommended dosages.¹¹⁶

Stability

Storage

Oral

Capsules

20–25°C in well-closed container.¹⁰⁸

Solution or Suspension

20–25°C.^{109 111 112}

Tablets

20–25°C.^{110 113 114} Protect fixed combination containing loperamide and simethicone from light.¹¹⁴

Actions

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

• Prolongs the transit time of intestinal contents;¹⁰⁸ reduces fecal volume, increases fecal viscosity and bulk density, and diminishes loss of fluid and electrolytes.^{a 108}

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.^{108 109 110 111 112 113}

• Importance of adequate hydration and drinking plenty of clear fluids to help prevent dehydration caused by diarrhea.^{108 109 110 111 112 113}

• Advise patients that tiredness, dizziness, or drowsiness may occur in the setting of diarrheal syndromes treated with loperamide;^{108 109 110 111 112 113} importance of using caution when driving a car or operating machinery.^{108 109 110 111 112 113}

• When used for self-medication, importance of reading product labeling.^{109 110 111 112 113}

• Do not use for self-medication for longer than 2 days or in children <6 years of age unless directed by a clinician.^{109 110 111 112 113}

• 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.^{109 110 111 112 113} Importance of consulting clinician before use if patient has history of liver impairment or is currently taking an anti-infective.^{109 110 111 112 113}

• 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.^{109 110 111 112 113}

• Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.¹⁰⁸

• Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.^{108 109 110 111 112 113}

• Importance of informing patients of other important precautionary information.¹⁰⁸ (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

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

Frequently asked questions

• How long does Imodium stop diarrhea for?

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