ATC Class:A07DA03
Loperamide hydrochloride, a synthetic piperidine-derivative, is an antiperistaltic antidiarrhea agent.108
Loperamide hydrochloride is used in the control and symptomatic relief of acute, nonspecific diarrhea108 and in the control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease.108 The drug has also been effective in controlling chronic functional (idiopathic) diarrhea† and chronic diarrhea caused by bowel resection or organic lesions†.
For self-medication , loperamide hydrochloride is used for symptomatic control of diarrhea, including travelers' diarrhea.109, 110, 111, 112, 113 The fixed combination containing loperamide hydrochloride and simethicone is used for self-medication for symptomatic control of diarrhea and symptomatic control of gas (gastric bloating, pressure, cramps).114
Double-blind clinical studies have shown that loperamide is at least as effective as diphenoxylate for control of acute diarrhea and more effective than diphenoxylate in decreasing daily stool frequency, improving fecal consistency, and controlling chronic diarrhea.
Loperamide should not be used as primary therapy in patients with 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 the use of anti-infectives.108 Fluid and electrolyte depletion may occur in patients who have diarrhea, and the use of loperamide does not preclude administration of appropriate fluid and electrolyte therapy.108
Antiperistaltic agents (e.g., loperamide, diphenoxylate) are used for symptomatic treatment of mild or uncomplicated travelers' diarrhea, including that occurring in adult travelers with human immunodeficiency virus (HIV) infection, and also have been used for adjunctive therapy when anti-infectives are indicated for the treatment of moderate to severe travelers' diarrhea.104, 105, 106
The most common cause of travelers' diarrhea (80-90% of cases) is bacteria (e.g., enterotoxigenic Escherichia coli , Campylobacter jejuni , Shigella , Salmonella , Aeromonas , Plesiomonas ).105, 106 Travelers' diarrhea caused by bacteria often is self-limited and resolves within 3-7 days without treatment.105, 106 In travelers with only mild diarrhea (without fever or bloody stools), use of loperamide may provide symptomatic relief in less that 24 hours.106 If diarrhea is moderate to severe, associated with fever or bloody stools, or extremely disruptive to travel plans, short-term (1-3 days) empiric treatment with an appropriate anti-infective (e.g., ciprofloxacin or levofloxacin, azithromycin, rifaximin) is recommended.106 Adjunctive therapy with an antiperistaltic agent during the first few days may shorten the duration of illness or reduce the frequency of bowel movements so that travelers can continue with travel plans while waiting for the beneficial effects of anti-infective treatment.105, 106 However, loperamide and diphenoxylate are not usually recommended in travelers with high fever or bloody diarrhea or in young children.104, 105 (See Cautions.)
Loperamide hydrochloride is used to reduce the volume of discharge from ileostomies.108 Although not statistically significant, in one study loperamide appeared to have a greater effect on ileostomy discharge than did diphenoxylate with atropine. The greater the initial ileostomy discharge, the more benefit obtained by the patient from loperamide therapy.
Loperamide hydrochloride is administered orally.108, 109, 110, 111, 112, 113
The oral solution or suspension should be administered using only the calibrated measuring cup provided by the manufacturer; the suspension should be shaken well prior to each dose.109, 111, 112
Patients should receive appropriate fluid and electrolyte replacement as needed.108 Patients using the drug for self-medication should be advised to drink plenty of clear fluids to help prevent dehydration caused by diarrhea.109, 110, 111, 112, 113
Dosage of loperamide hydrochloride is expressed in terms of the salt.108, 109, 110, 111, 112, 113, 114
For control and symptomatic relief of acute, nonspecific diarrhea in adults, the initial dosage of loperamide hydrochloride is 4 mg, followed by 2 mg after each unformed stool.108 The maximum recommended dosage of loperamide hydrochloride for adults is 16 mg daily.108
For self-medication to control symptoms of diarrhea, including travelers' diarrhea, in adults, the initial dosage of loperamide hydrochloride (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 The maximum recommended dosage of loperamide hydrochloride for self-medication in adults is 8 mg in a 24-hour period;106, 109, 110, 111, 112, 113, 114 the duration of therapy should not exceed 2 days unless directed by a clinician.109, 110, 111, 112, 113, 114
Clinical improvement of acute diarrhea usually occurs within 48 hours after initiation of loperamide.108 The drug should be discontinued and a clinician consulted if there is no improvement after 48 hours of therapy.104, 108, 109, 110, 111, 112, 113, 114
For control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease in adults, the initial dosage of loperamide hydrochloride is 4 mg, followed by 2 mg after each unformed stool until symptoms are controlled;108 dosage should then be reduced for maintenance as required.108 When the optimal dosage for maintenance therapy has been established, the daily dosage may then be administered as a single dose or in divided doses.108 In clinical trials, the average adult maintenance dosage was 4-8 mg daily and only rarely exceeded 16 mg daily.108 If improvement does not occur in patients with chronic diarrhea after treatment with loperamide hydrochloride given in a dosage of 16 mg daily for at least 10 days, symptoms are unlikely to be controlled by further administration of the drug.108 Loperamide therapy may be continued if diarrhea cannot be adequately controlled with diet or specific treatment.108
For control and symptomatic relief of acute, nonspecific diarrhea in children 2-12 years of age, dosage of loperamide hydrochloride is based on age and body weight.108 (See Table 1 for initial pediatric dosage for the first day of therapy.) On the second and subsequent days of therapy, children 2-12 years of age should receive a dosage of 0.1 mg/kg only after each unformed stool.108 Dosage on the second and subsequent days should not exceed the age-appropriate dosages recommended for the initial 24 hours of therapy.108
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 |
For self-medication in children 12 years of age or older to control symptoms of diarrhea, including travelers' diarrhea, the initial dosage of loperamide hydrochloride (alone or in fixed combination with simethicone) is 4 mg, followed by 2 mg after each subsequent unformed stool.109, 110, 111, 112, 113, 114 The maximum recommended dosage of loperamide hydrochloride for self-medication in children 12 years of age or older is 8 mg in a 24-hour period;109, 110, 111, 112, 113, 114 the duration of therapy should not exceed 2 days unless directed by a clinician.109, 110, 111, 112, 113, 114
For self-medication in children 9-11 years of age (27.3-43.2 kg) to control symptoms of diarrhea, including travelers' diarrhea, the usual dosage of loperamide hydrochloride (alone or in fixed combination with simethicone) is 2 mg after the first unformed stool, followed by 1 mg after each subsequent unformed stool.109, 110, 111, 112, 113, 114 The maximum recommended dosage of loperamide hydrochloride for self-medication in children 9-11 years of age is 6 mg daily in a 24-hour period;109, 110, 111, 112, 113, 114 the duration of therapy should not exceed 2 days unless directed by a clinician.109, 110, 111, 112, 113, 114
For self-medication in children 6-8 years of age (21.8-26.8 kg) to control symptoms of diarrhea, including travelers' diarrhea, the usual dosage of loperamide hydrochloride (alone or in fixed combination with simethicone) is 2 mg after the first unformed stool, followed by 1 mg after each subsequent unformed stool.109, 110, 111, 112, 113, 114 The maximum recommended dosage of loperamide hydrochloride for self-medication in children 6-8 years of age is 4 mg in a 24-hour period;109, 110, 111, 112, 113, 114 the duration of therapy should not exceed 2 days unless directed by a clinician.109, 110, 111, 112, 113, 114
Loperamide hydrochloride (alone or in fixed combination with simethicone) should not be used for self-medication in children younger than 6 years of age unless directed by a clinician.109, 110, 111, 112, 113, 114
Clinical improvement of acute diarrhea usually occurs within 48 hours after initiation of loperamide.108 The drug should be discontinued and a clinician consulted if there is no improvement after 48 hours of therapy.104, 108, 109, 110, 111, 112, 113, 114
A therapeutic dosage of loperamide hydrochloride for the treatment of chronic diarrhea in pediatric patients has not been established.108 A dosage of 0.08-0.24 mg/kg daily in 2 or 3 divided doses† has been used in a limited number of children for the management of chronic diarrhea and has been recommended by some clinicians.107, 115
Dosage in Renal and Hepatic Impairment
Dosage adjustments are not necessary when loperamide hydrochloride is used in patients with renal impairment.108
Loperamide hydrochloride should be used with caution in patients with hepatic impairment since first-pass metabolism may be decreased in such patients.108 (See Cautions: Precautions and Contraindications.)
In clinical trials evaluating loperamide hydrochloride for the treatment of diarrhea, adverse effects generally were minor and self-limiting and were reported more frequently in patients receiving the drug for treatment of chronic diarrhea than in those receiving the drug for treatment of acute diarrhea.108 Some adverse effects reported with loperamide during clinical trials and postmarketing experience are difficult to distinguish from symptoms of the underlying diarrheal syndrome.108
The most frequently reported adverse effects in patients receiving recommended dosages of the drug are nausea, constipation, abdominal cramps, and dizziness.108 Dry mouth, abdominal pain, abdominal distention or discomfort, vomiting, flatulence, dyspepsia, drowsiness, fatigue, and urinary retention also have been reported.108 Children may be more sensitive to adverse CNS effects of the drug than adults.108
Paralytic ileus and megacolon (including toxic megacolon) have been reported in patients receiving loperamide.108 There have been rare reports of toxic megacolon in patients with human immunodeficiency virus (HIV) infection who had infectious colitis associated with viral or bacterial pathogens and received loperamide.108 (See Cautions: Precautions and Contraindications.)
Hypersensitivity reactions, including rash, pruritus, urticaria, and angioedema, have been reported in patients receiving loperamide.108 There have been rare reports of severe hypersensitivity reactions (e.g., anaphylactic shock, anaphylactoid reactions) and bullous eruptions (e.g., erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis).108
Potentially fatal, serious cardiovascular effects (e.g., QT interval prolongation, torsades de pointes or other ventricular arrhythmias, syncope, cardiac arrest) have been reported in patients taking loperamide.116, 117, 119, 120, 121, 125 Cardiovascular effects have been reported rarely in patients receiving recommended dosages of loperamide hydrochloride;116 the majority of reported cases 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: Precautions and Contraindications.)
Precautions and Contraindications
Loperamide is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.108
Loperamide is contraindicated in patients with abdominal pain in the absence of diarrhea.108
The drug is used only for control and symptomatic relief of diarrhea.108 Whenever an underlying etiology for the diarrhea can be determined, specific treatment should be given if indicated or appropriate.108
Loperamide is contraindicated in patients with 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
Because of the possible risk of serious sequelae, including ileus, megacolon, and toxic megacolon, loperamide should not be used when inhibition of peristalsis should be avoided.108 The drug 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, loperamide should be discontinued in HIV-infected patients at the earliest signs of abdominal distention.108
Fluid and electrolyte depletion often occurs in patients with diarrhea, and administration of appropriate fluid and electrolytes is important in such cases.108 Loperamide therapy does not preclude administration of appropriate fluid and electrolyte therapy.108 When loperamide is used for self-medication , patients should be advised to drink plenty of clear fluids to help prevent dehydration caused by diarrhea.109, 110, 111, 112, 113
Because tiredness, dizziness, or drowsiness may occur in the setting of diarrheal syndromes treated with loperamide, patients should be advised to use caution when driving a car or operating machinery.108, 109, 110, 111, 112, 113
Loperamide should be used with caution in patients with hepatic impairment.108 Such patients should be monitored closely for signs and symptoms of CNS toxicity during loperamide therapy, since first-pass metabolism of the drug may be decreased in patients with hepatic impairment.108
Patients receiving loperamide should be advised to consult a clinician if diarrhea persists for longer than 2 days, if blood is present in stools, or if fever or abdominal distention develops.108
Loperamide should be used with caution in patients predisposed to QT interval prolongation, torsades de pointes, or other serious arrhythmias.116 The drug also should be used with caution in patients who are receiving drugs that inhibit loperamide metabolism or transport (i.e., inhibitors of hepatic cytochrome P-450 [CYP] isoenzymes 3A4 and 2C8, inhibitors of P-glycoprotein [P-gp]) since increased plasma concentrations of loperamide may increase the risk of serious cardiovascular effects.116 (See Misuse and Abuse Potential under Cautions: Precautions and Contraindications and see Drug Interactions.)
Precautions Related to Self-medication
For self-medication , loperamide should not be used for longer than 2 days unless directed by a clinician.109, 110, 111, 112, 113 Loperamide also should not be used 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
If a patient is receiving an anti-infective or has a history of liver disease, a clinician should be consulted before the drug is used for self-medication .109, 110, 111, 112, 113
When loperamide is used for self-medication , patients should be advised to discontinue the drug and contact a clinician if diarrhea symptoms worsen or last longer than 2 days or if abdominal swelling or bulging develops.109, 110, 111, 112, 113
Precautions Related to Use of Fixed Combinations
When the fixed combination containing loperamide and simethicone is used, the cautions, precautions, contraindications, and drug interactions associated with both drugs should be considered.114 Cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) should be considered for both loperamide and simethicone.114
FDA has warned clinicians to consider the potential for misuse and abuse of loperamide hydrochloride.116
Serious cardiovascular effects, including fatalities, have occurred when loperamide hydrochloride was used at dosages higher than recommended.116, 117, 119, 120, 121, 125 The majority of serious cardiovascular effects reported with loperamide have occurred in individuals who were intentionally misusing and abusing high dosages of the drug in an attempt to self-treat opiate withdrawal symptoms or to achieve a feeling of euphoria.116, 117, 119, 120, 121, 125 The maximum recommended adult dosage of loperamide hydrochloride 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 loperamide hydrochloride 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, loperamide should be promptly discontinued and appropriate therapy initiated 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 Patients with opiate use disorders should be referred for treatment.116 When excessive loperamide ingestion is suspected, specific testing may be required to measure blood levels of the drug;116 standard drug screens for opiates may not include an assay for loperamide 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 Drug Interactions.)
FDA states that patients and consumers should be advised to take loperamide only in the dosage prescribed by their clinician or stated on the label of the over-the-counter (OTC, nonprescription) product and should be warned that taking larger doses of loperamide (either intentionally or unintentionally) may lead to abnormal heart rhythms and serious cardiac events that can be fatal.116, 125 In addition, patients and consumers should be warned that taking loperamide with some commonly used drugs 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 the 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 formulations of the drug, to institute appropriate packaging changes.125, 126, 127
Patients and consumers should be advised to immediately seek medical attention if they or someone else 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
Loperamide is contraindicated in children younger than 2 years of age because of the risks of respiratory depression and serious adverse cardiac reactions.124
There have been rare reports of paralytic ileus associated with abdominal distention in patients receiving loperamide;108 most cases occurred in the setting of acute dysentery, overdosage, and with infants younger than 2 years of age.108
Loperamide should not be used for self-medication in children younger than 6 years of age unless directed by a clinician.109, 110, 111, 112, 113
Loperamide should be used with particular caution in young children because of the greater variability of response in this age group.108 The presence of dehydration, especially in younger children, may further influence the variability of response to the drug.108
Formal studies have not been conducted to evaluate loperamide in geriatric patients.108 There are no apparent differences in disposition of the drug in elderly patients with diarrhea relative to younger adults.108
Mutagenicity and Carcinogenicity
In a study in rats using loperamide hydrochloride dosages up to 40 mg/kg daily (21 times the maximum human dose of 16 mg daily based on body surface area comparison) for 18 months, there was no evidence of carcinogenicity.108
Loperamide was not genotoxic in the Ames test, the SOS chromotest in Escherichia coli , the dominant lethal test in female mice, or the mouse embryo cell transformation assay.108
Pregnancy, Fertility, and Lactation
There are no adequate and well-controlled studies using loperamide in pregnant women, and the drug should be used during pregnancy only if potential benefits to the woman justify potential risks to the fetus.108
Reproduction studies in rats and rabbits using loperamide hydrochloride dosages up to 40 mg/kg daily (43 times the human dosage based on body surface comparison) did not reveal evidence of teratogenicity;108 however, a dosage of 40 mg/kg daily in rats produced impaired growth and survival of offspring.108
Although reproduction studies in female and male rats using loperamide hydrochloride dosages up to 10 mg/kg daily (5 times the human dosage based on body surface area comparison) did not reveal evidence of impaired fertility, a dosage of 20 or 40 mg/kg daily resulted in marked impairment of fertility in females and a dosage of 40 mg/kg daily resulted in impairment of fertility in males.108
Because loperamide is distributed into milk in low concentrations, the drug is not recommended in nursing women.108
Drugs Affecting Hepatic Microsomal Enzymes
Loperamide hydrochloride is metabolized principally by hepatic cytochrome P-450 (CYP) isoenzymes 3A4 and 2C8.108
Concomitant use of loperamide with drugs that are CYP3A4 inhibitors (e.g., clarithromycin, erythromycin, itraconazole, ketoconazole) or CYP2C8 inhibitors (e.g., gemfibrozil) may increase plasma loperamide concentrations and may increase the risk of serious cardiovascular effects.116 Caution is advised if loperamide is used in patients receiving a CYP3A4 or CYP2C8 inhibitor.116
Drugs Affecting P-glycoprotein Transport
Loperamide hydrochloride is a P-glycoprotein (P-gp) substrate.108
Concomitant use of loperamide with drugs that are P-gp inhibitors (e.g., quinidine, quinine, ritonavir) may increase plasma loperamide concentrations and may increase the risk of enhanced central effects108 or serious cardiovascular effects.116 Caution is advised if loperamide is used in patients receiving a P-gp inhibitor.108, 116
Cimetidine or ranitidine can potentially interact with loperamide if the drugs are used concomitantly.116
Concomitant use of loperamide hydrochloride (single 16-mg dose) and ritonavir (single 600-mg dose) resulted in up to a threefold increase in plasma loperamide concentrations.108 Loperamide should be used concomitantly with ritonavir with caution since increased plasma loperamide concentrations may result in enhanced central effects of the drug.108
Concomitant use of loperamide hydrochloride (single 16-mg dose) and saquinavir (single 600-mg dose) resulted in a 54% decrease in saquinavir exposure, which may result in decreased efficacy of the antiretroviral agent.108 If loperamide and saquinavir are used concomitantly, therapeutic efficacy of saquinavir should be closely monitored.108
Concomitant use of loperamide hydrochloride (single 16-mg dose) and quinidine (single 600-mg dose) resulted in up to a threefold increase in plasma loperamide concentrations.108 Loperamide should be used concomitantly with quinidine with caution since increased plasma loperamide concentrations may result in enhanced central effects of the drug and may increase the risk of serious cardiovascular effects.108, 116
Overdosage of loperamide hydrochloride (including relative overdosage due to hepatic dysfunction) may be manifested by urinary retention, paralytic ileus, CNS depression, and GI effects (e.g., vomiting, abdominal pain or burning).108, 118 Children may be more sensitive to CNS effects than adults.108 An adult who took three 20-mg doses of loperamide hydrochloride within 24 hours was nauseated after the second dose and vomited after the third dose.108 In studies designed to evaluate the potential for adverse effects, intentional ingestion of single doses of up to 60 mg did not result in any clinically important adverse effects.108
Intentional or unintentional overdosage of loperamide (intentional misuse or abuse in an attempt to self-treat opioid withdrawal symptoms or to achieve a feeling of euphoria, suspected suicide attempt) or long-term use of high loperamide dosages has resulted in serious cardiovascular effects, including fatalities.116, 117, 119, 120 Use of excessive loperamide dosage also has resulted in severe CNS effects (e.g., catatonia).123 In some cases of misuse and abuse, individuals ingested loperamide hydrochloride dosages of 70-1600 mg daily.116, 117, 119, 120 (See Misuse and Abuse Potential under Cautions: Precautions and Contraindications.)
In the treatment of loperamide overdosage, gastric lavage is recommended, followed by administration of 100 g of activated charcoal slurry through the gastric tube.108 If vomiting has occurred spontaneously, 100 g of activated charcoal slurry should be administered orally as soon as fluids can be retained.108 Patients should be monitored for signs of CNS depression for at least 24 hours.108 Naloxone may be administered if CNS depression occurs.108 Because the duration of action of loperamide is greater than that of naloxone, the patient must be closely watched and additional doses of naloxone administered as necessary.108 Vital signs should be monitored for recurrence of symptoms of drug overdose for at least 24 hours after the last dose of naloxone.108 Forced diuresis would not be expected to be effective in loperamide overdosage, since relatively little drug is excreted in urine.108
Loperamide hydrochloride slows intestinal motility through a direct effect on the nerve endings and/or intramural ganglia of the intestinal wall. The drug is generally believed to act by interfering with the cholinergic and noncholinergic mechanisms involved in the peristaltic reflex, decreasing the activity of circular and longitudinal muscles in the intestinal wall. However, some data indicate that the drug may act, like diphenoxylate and morphine, by enhancing contractions of intestinal circular musculature, thus increasing segmentation and retarding forward motion through the intestine.
Loperamide prolongs the transit time of intestinal contents and therefore reduces fecal volume, increases fecal viscosity and bulk density, and diminishes loss of fluid and electrolytes.108 As an antidiarrhea agent, loperamide is reported to be more specific, longer acting, and 2-3 times more potent on a weight basis than diphenoxylate. Tolerance to the antidiarrheal effect of loperamide has not been reported.108
In animals, loperamide has no analgesic activity even in extremely high doses. Although loperamide binds to opiate receptors in the brain and myenteric plexus, the drug has not produced opiate-like CNS effects in rats, even in large doses. Studies in monkeys, however, have demonstrated that high doses of loperamide can produce morphine-like symptoms of physical dependence and prevent signs of morphine withdrawal in morphine-dependent animals. In humans, the naloxone challenge pupil test, which when positive indicates opiate-like effects, was negative when performed after a single 16-mg dose of loperamide, and after more than 2 years of therapeutic use of the drug. Physical dependence on loperamide has not been reported in humans.
Peak plasma concentrations of loperamide occur about 5 or 2.5 hours following administration of loperamide hydrochloride capsules or oral solution, respectively.108 After a 2-mg oral dose of loperamide hydrochloride capsules, peak plasma concentrations of 2 ng/mL have been reported. The oral bioavailability of capsules and solution of the drug, as determined by area under the plasma concentration-time curve (AUC), is reportedly similar.100 Peak plasma concentrations of loperamide metabolites are reached 8 hours following oral administration of capsules of the drug.
It is not known whether loperamide crosses the placenta. The drug is distributed into milk in low concentrations.108
Loperamide undergoes oxidative metabolism, principally by hepatic cytochrome P-450 (CYP) isoenzymes 2C8 and 3A4;108 CYP2B6 and CYP2D6 may also be involved.108
The unchanged drug and metabolites are excreted principally in feces.108 A manufacturer reports that after oral administration of 4 mg of loperamide hydrochloride, less than 2% of the dose is excreted in urine and 30% of the dose is excreted in feces as intact drug. In animals, loperamide has been shown to undergo enterohepatic circulation.
The apparent elimination half-life of loperamide in healthy adults receiving recommended dosages of the drug is 10.8 hours (range 9.1-14.4 hours).100, 108, 116 Half-lives as high as 41 hours have been reported in individuals who ingested higher than recommended dosages of the drug.116
Loperamide hydrochloride is a synthetic piperidine-derivative antidiarrhea agent.108 The drug occurs as a white to slightly yellow powder and is slightly soluble in water and freely soluble in alcohol.108 Loperamide hydrochloride oral solution has a pH of about 5. The drug has a pKa of 8.6.
Loperamide hydrochloride capsules should be stored at 20-25°C in a well-closed container.108
Loperamide hydrochloride solutions, suspensions, film-coated tablets, and chewable tablets commercially available for self-administration should be stored at 20-25°C.109, 110, 111, 112, 113
Tablets containing a fixed combination of loperamide hydrochloride and simethicone commercially available for self-administration should be stored at 20-25°C and protected from light.114
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Oral | Capsules | 2 mg* | Loperamide Hydrochloride Capsules | |
Solution | 1 mg/5 mL* | Imodium® A-D | ||
Loperamide Hydrochloride Oral Solution | ||||
Suspension | 1 mg/7.5 mL* | Imodium® A-D | McNeil | |
Loperamide Hydrochloride Oral Suspension | ||||
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
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 |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
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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.
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