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Loperamide Hydrochloride

Pronunciation

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

Warning(s)

    Torsades de Pointes and Sudden Death
  • Cases of torsades de pointes, cardiac arrest, and death reported with use of higher than recommended dosage.124 (See Cardiovascular Effects under Cautions.)

  • Contraindicated in pediatric patients <2 years of age.124 (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.124 (See Dosage under Dosage and Administration.)

Introduction

Antiperistaltic antidiarrhea agent;108 synthetic piperidine-derivative.108

Uses for Loperamide Hydrochloride

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 and chronic diarrhea caused by bowel resection or organic lesions.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 Hydrochloride 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

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.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.)

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.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 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 Hydrochloride

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 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 (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 opioid withdrawal symptoms or to achieve a feeling of euphoria.116 117 119 120 121 Maximum recommended adult dosage is 8 mg daily for self-medication106 109 110 111 112 113 114 116 or 16 mg daily for prescription use;108 116 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

If loperamide-induced cardiotoxicity is suspected, promptly discontinue loperamide and initiate appropriate therapy to manage and prevent cardiac arrhythmias and severe outcomes.116 In some cases of torsades de pointes, drug treatment may be ineffective and electrical pacing or cardioversion may be required.116 Refer patients with opioid 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 opioids 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 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 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

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

FDA is continuing to evaluate this safety issue regarding misuse and abuse of loperamide and will determine if additional FDA actions are needed.116

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

Interactions for Loperamide Hydrochloride

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

Drug

Interaction

Comments

Antifungal agents (itraconazole, ketoconazole)

Itraconazole, ketoconazole: May increase loperamide concentrations and increase risk of serious cardiovascular effects116

Use concomitantly with caution116

Cimetidine

Potential interaction116

Gemfibrozil

May increase loperamide concentrations and increase risk of serious cardiovascular effects116

Use concomitantly with caution116

Macrolides (erythromycin, clarithromycin)

Erythromycin, clarithromycin: May increase loperamide concentrations and increase risk of serious cardiovascular effects116

Use concomitantly with caution116

Quinidine

Increased loperamide concentrations;108 may increase risk of serious cardiovascular effects116

Use concomitantly with caution108 116

Quinine

May increase loperamide concentrations and increase risk of serious cardiovascular effects116

Use concomitantly with caution116

Ranitidine

Potential interaction116

Ritonavir

Increased loperamide concentrations;108 may increase risk of serious cardiovascular effects116

Use concomitantly with caution108 116

Saquinavir

Decreased saquinavir concentrations and possible loss of antiretroviral therapeutic efficacy108

Closely monitor for saquinavir efficacy108

Loperamide Hydrochloride 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

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 2017, Selected Revisions December 2, 2016. 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.

References

Only references cited for selected revisions after 1984 are available electronically.

100. Killinger JM, Weintraub HS, Fuller BL. Human pharmacokinetics and comparative bioavailability of loperamide hydrochloride. J Clin Pharmacol. 1979; 19:211-8. [PubMed 438356]

104. Panel on Opportunistic Infection in HIV-infected Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from the Centers for Disease Control and Prevention, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America (September 17, 2015). Updates may be available at HHS AIDS Information (AIDSinfo) website.

105. Centers for Disease Control and Prevention. CDC health information for international travel, 2016. Atlanta, GA: US Department of Health and Human Services. Updates may be available at CDC website.

106. . Advice for travelers. Med Lett Drugs Ther. 2015; 57:52-8. [PubMed 25853663]

107. Robertson J, Shilkofski N, eds. The Harriet Lane handbook: a manual for pediatric house officers. 17th ed. Philadelphia, PA: Elsevier Mosby: 2005:865.

108. Teva. Loperamide hydrochloride capsules, USP prescribing information. North Wales, PA; 2014 Sep.

109. McNeil Consumer Healthcare. Imodium A-D (loperamide hydrochloride) solution (1 mg/7.5 mL) patient information. Fort Washington, PA. 2015 Nov.

110. McNeil Consumer Healthcare. Imodium A-D Caplets (loperamide hydrochloride) film-coated tablets patient information. Fort Washington, PA. 2015 Oct.

111. Rite Aid. Loperamide hydrochloride solution (1 mg/5 mL) patient information. Camp Hill, PA. 2009 Jun.

112. CVS. Loperamide hydrochloride suspension (1 mg/7.5 mL) patient information. Woonsocket, RI. 2015 Oct.

113. McNeil Consumer Healthcare. Imodium A-D (loperamide hydrochloride) EZ chews patient information. Fort Washington, PA.

114. McNeil Consumer Healthcare. Imodium Multi-Symptom Relief Caplets (loperamide hydrochloride and dimethicone) tablets patient information. Fort Washington, PA. 2015 Aug.

115. Buts JP, Petit BF, de Meyer R. Letter: Loperamide in treatment of persistent diarrhoea in children. Br Med J. 1975; 3:766-7. [PubMed 1174894]

116. US Food and Drug Administration. FDA drug safety communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. Silver Spring, MD; 2016 Jun 7. From FDA website.

117. Wightman RS, Hoffman RS, Howland MA et al. Not your regular high: cardiac dysrhythmias caused by loperamide. Clin Toxicol (Phila). 2016; 54:454-8. [PubMed 27022002]

118. Litovitz T, Clancy C, Korberly B et al. Surveillance of loperamide ingestions: an analysis of 216 poison center reports. J Toxicol Clin Toxicol. 1997; 35:11-9. [PubMed 9022646]

119. Spinner HL, Lonardo NW, Mulamalla R et al. Ventricular tachycardia associated with high-dose chronic loperamide use. Pharmacotherapy. 2015; 35:234-8. [PubMed 25645123]

120. Mukarram O, Hindi Y, Catalasan G et al. Loperamide Induced Torsades de Pointes: A Case Report and Review of the Literature. Case Rep Med. 2016; 2016:4061980. [PubMed 26989420]

121. Eggleston W, Clark KH, Marraffa JM. Loperamide Abuse Associated With Cardiac Dysrhythmia and Death. Ann Emerg Med. 2016; :. [PubMed 27140747]

122. MacDonald R, Heiner J, Villarreal J et al. Loperamide dependence and abuse. BMJ Case Rep. 2015; 2015:. [PubMed 25935922]

123. Di Rosa E, Di Rosa AE. Loperamide overdose-induced catatonia: potential role of brain opioid system and P-glycoprotein. Acta Neuropsychiatr. 2014; 26:58-60. [PubMed 25142101]

124. Mylan Pharmaceuticals Inc. Loperamide hydrochloride capsule prescribing information. Morgantown, WV; 2016 Nov.

a. AHFS Drug Information 2016. McEvoy, GK, ed. Loperamide Hydrochloride. Bethesda, MD: American Society of Health-System Pharmacists; 2016:2970-1.

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