Cases of torsades de pointes, cardiac arrest, and death have been reported with the use of a higher than recommended dosage of loperamide.
Loperamide is contraindicated in pediatric patients <2 years of age.
Avoid dosages higher than recommended in adults and pediatric patients ≥2 years due to the risk of serious cardiac adverse reactions.
Diarrhea, acute (including Travelers' diarrhea):
Note: In patients with known or suspected dysentery (eg, fever ≥38.3°C [101°F] and bloody or mucoid stools), some experts consider use of loperamide with close monitoring as long as antibiotics are also given (ACG [Riddle 2016]; IDSA [Hill 2006]; LaRocque 2022). Although often avoided in patients with Clostridioides difficile infection, some experts consider use of loperamide with close monitoring as an adjunct to antibiotic therapy if such patients have major fluid losses and no ileus or colonic distention (IDSA/SHEA [McDonald 2018]; Kelly 2021).
Oral: Initial: 4 mg, followed by 2 mg after each loose stool; maximum: 16 mg/day (OTC: 8 mg/day). Limit use to ≤48 hours (ACG [Riddle 2016]; manufacturer's labeling).
Diarrhea, cancer treatment-induced (off-label use): Oral: Initial: 4 mg, followed by 2 mg every 2 to 4 hours or after each loose stool; for diarrhea persisting >24 hours, administer 2 mg every 2 hours (or 4 mg every 4 hours). Continue until 12 hours have passed without a loose bowel movement (Andreyev 2014; Benson 2004; Sharma 2005). Note: Doses >16 mg/day may not provide benefit; consider alternative therapy for diarrhea persisting ≥48 hours (Andreyev 2014; Benson 2004).
Neratinib-induced diarrhea, prophylaxis: Oral: 4 mg 3 times daily (days 1 to 14 of neratinib therapy), followed by 4 mg twice daily (days 15 to 56 of neratinib therapy), followed by 4 mg as needed up to a maximum of 16 mg/day (days 57 to 365 of neratinib therapy) (Nerlynx prescribing information). Note: Antidiarrheal prophylaxis is recommended during the first 56 days of neratinib therapy; initiate with the first neratinib dose. After day 56, titrate dose to achieve 1 to 2 bowel movements/day. Additional antidiarrheal medication may be required for loperamide-refractory diarrhea.
Irinotecan-induced delayed diarrhea: Oral: 4 mg after first loose stool or first sign of frequent bowel movements, then 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours have passed without a loose bowel movement (Rothenberg 1996; Sharma 2005).
Diarrhea, chronic:
Oral: Initial: 4 mg, followed by 2 mg after each loose stool; maximum: 16 mg/day (manufacturer's labeling). Note: Doses >16 mg/day (eg, up to 40 to 64 mg/day) may be required in some cases (eg, short bowel syndrome). Experience with doses >16 mg/day is generally limited to observational data in specialized centers with close monitoring (DiBaise 2021; Hollington 2004; Mackowski 2015).
Maintenance dosage: Once diarrhea is controlled, use lowest dosage required to control symptoms; usual maintenance dose: 4 to 8 mg/day as a single dose or in divided doses (eg, 2 mg before meals) (Wald 2021; manufacturer's labeling). If clinical improvement is not observed after ≥10 days of maximally tolerated dosage, symptoms are unlikely to be controlled by further administration. Note: In patients with irritable bowel syndrome with alternating diarrhea and constipation, treatment should be limited to short courses as needed (Wald 2021; manufacturer's labeling).
Enterocutaneous fistula (off-label use) or ileostomy (labeled use), high-output:
Note: Avoid use of liquid formulations; propylene glycol content may increase output (de Vries 2017; Parli 2018).
Initial:
Enterocutaneous fistula: Oral: 4 mg administered 3 to 4 times per day (Parli 2018; Stein 2021).
Ileostomy: Oral: 2 mg administered 2 to 3 times per day (Landmann 2021; Parli 2018).
Dosage adjustment: May increase dose in 2 mg/day increments if fistula output remains elevated (maximum: 16 mg/day) (Parli 2018; manufacturer's labeling). Note: Doses >16 mg/day may be required in refractory cases. Experience with doses >16 mg/day is generally limited to observational data in specialized centers with close monitoring (de Vries 2017; Hollington 2004; Mackowski 2015; Parli 2018).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Mild to severe impairment: No dosage adjustment necessary (manufacturer's labeling).
Hemodialysis, intermittent (thrice weekly): Unlikely to be dialyzed (highly protein bound): No supplemental dose or dosage adjustment necessary (expert opinion).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound): No dosage adjustment necessary (expert opinion).
CRRT: No dosage adjustment necessary (expert opinion).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment necessary (expert opinion).
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
(For additional information see "Loperamide: Pediatric drug information")
Acute diarrhea: Note: Loperamide is not recommended for management of infectious diarrhea in pediatric patients (IDSA [Shane 2017]). For patients who are small for chronological age, consider dosing according to weight range and not by age group. Use lowest effective dose for shortest duration.
Children 2 to <12 years: Oral:
2 to 5 years weighing 13 to <21 kg: Initial: 1 mg with first loose stool followed by 1 mg/dose after each subsequent loose stool; maximum daily dose: 3 mg/day
6 to 8 years weighing 21 to 27 kg: Initial: 2 mg with first loose stool followed by 1 mg/dose after each subsequent loose stool; maximum daily dose: 4 mg/day
9 to 11 years weighing 27.1 to 43 kg: Initial: 2 mg with first loose stool followed by 1 mg/dose after each subsequent loose stool; maximum daily dose: 6 mg/day
Children ≥12 years and Adolescents: Oral: Initial: 4 mg with first loose stool followed by 2 mg/dose after each subsequent loose stool; maximum daily dose: 8 mg/day
Chronic diarrhea; secondary to intestinal failure, short-bowel syndrome, or other noninfectious causes: Limited data available; dosing regimens variable: Infants ≥2 months and Children: Oral: 0.08 to 0.24 mg/kg/day divided 2 to 3 times/day was reported in a case series of 10 pediatric patients (age range: 2 to 52 months) (Buts 1975). In a case series of six infants and young children, higher dosing was described: Initial: 1 to 1.5 mg/kg/day in 4 divided doses with subsequent dose decreased as stool output and diet tolerance improved and patient weight increased. Reported final dose range of 0.25 to 0.5 mg/kg/day in 2 divided doses was used long-term until patient achieved target weight and dietary goals; reported duration of therapy: 6 months to ~2 years (Sandhu 1983); maximum single dose: 2 mg
Irinotecan-induced (delayed) diarrhea: Limited data available; consult individual protocols; some organizations have used the following:
Fixed dosing (Children's Oncology Group 2009):
Children ≥2 to 12 years:
<13 kg: Initial: 0.5 mg after the first loose bowel movement, followed by 0.5 mg every 3 hours while awake; during the night, may administer every 4 hours; maximum daily dose: 4 mg/day
13 kg to <20 kg: Initial: 1 mg after the first loose bowel movement, followed by 1 mg every 4 hours; maximum daily dose: 6 mg/day
20 kg to <30 kg: Initial: 2 mg after the first loose bowel movement, followed by 1 mg every 3 hours while awake; during the night, may administer every 4 hours; maximum daily dose: 8 mg/day
30 kg to <43 kg: Initial: 2 mg after the first loose bowel movement, followed by 1 mg every 2 hours while awake; during the night, may administer every 4 hours; maximum daily dose: 12 mg/day
Adolescents weighing ≥43 kg: Initial: 4 mg after the first loose bowel movement, followed by 2 mg after each loose stool; maximum daily dose: 16 mg/day
Weight-directed dosing (Vassal 2007): Children and Adolescents 2 to <15 years:
Grade 1 or 2: 0.03 mg/kg/dose every 4 hours
Grade 3 or 4: 0.06 mg/kg/dose every 4 hours
Maximum single dose dependent upon weight:
<13 kg: 0.5 mg
13 to <20 kg: 1 mg
20 to <43 kg: Initial: 2 mg; subsequent doses: 1 mg
≥43 kg: Initial: 4 mg; subsequent doses: 2 mg
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Altered kidney function: Children ≥2 years: Oral:
Mild to severe impairment: No dosage adjustment necessary.
Hemodialysis, intermittent: Unlikely to be dialyzed (highly protein bound).
Peritoneal dialysis: Unlikely to be dialyzed (highly protein bound).
There are no dosage adjustments provided in the manufacturer labeling. Due to possible effects on first-pass metabolism, use with caution and monitor closely for signs of CNS toxicity.
Refer to adult dosing; use with caution.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral, as hydrochloride:
Imodium A-D: 2 mg [contains brilliant blue fcf (fd&c blue #1), peg-40 hydrogenated castor oil]
Generic: 2 mg
Liquid, Oral, as hydrochloride:
Imodium A-D: 1 mg/7.5 mL (120 mL, 240 mL) [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), propylene glycol, sodium benzoate]
Imodium A-D: 1 mg/7.5 mL (120 mL, 240 mL) [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow), propylene glycol, sodium benzoate; mint flavor]
Generic: 1 mg/5 mL (5 mL [DSC], 10 mL [DSC], 118 mL [DSC]); 1 mg/7.5 mL (120 mL)
Solution, Oral, as hydrochloride:
Generic: 1 mg/7.5 mL (7.5 mL); 2 mg/15 mL (15 mL)
Suspension, Oral, as hydrochloride:
Generic: 1 mg/7.5 mL (120 mL [DSC])
Tablet, Oral, as hydrochloride:
Anti-Diarrheal: 2 mg [scored]
Anti-Diarrheal: 2 mg [contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]
Anti-Diarrheal: 2 mg [scored; contains corn starch, fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake]
Anti-Diarrheal: 2 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 (quinoline yellow)]
Diamode: 2 mg [scored]
Imodium A-D: 2 mg [scored]
Loperamide A-D: 2 mg [DSC]
Generic: 2 mg
Yes
Oral: Administer with plenty of clear fluids to prevent dehydration.
Oral solution: Shake well before administering dose.
Cancer treatment-induced diarrhea: Consider administering 30 minutes prior to eating 4 times daily to slow gastrocolic reflex (Andreyev 2014).
Oral: Drink plenty of fluids to help prevent dehydration.
Oral solution: Shake well before administering dose.
Diarrhea:
Rx labeling: Control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease in adults and of acute nonspecific diarrhea in patients ≥2 years of age; to reduce volume of ileostomy discharge.
OTC labeling: Control of symptoms of diarrhea, including Travelers' diarrhea.
Diarrhea, cancer treatment-induced; Enterocutaneous fistula, high-output
Imodium A-D may be confused with Indocin
Loperamide may be confused with furosemide, Lomotil
KIDs List: Loperamide, when used in pediatric patients <2 years of age with acute infectious diarrhea, is identified on the Key Potentially Inappropriate Drugs in Pediatrics (KIDs) list and should be avoided due to risk of ileus and lethargy (strong recommendation; high quality of evidence) (PPA [Meyers 2020]).
Indiaral [France] may be confused with Inderal and Inderal LA brand names for propranolol [US, Canada, and multiple international markets]
Lomotil: Brand name for loperamide [Mexico, Philippines], but also the brand name for diphenoxylate [US, Canada, and multiple international markets]
Lomotil [Mexico, Philippines] may be confused with Ludiomil brand name for maprotiline [multiple international markets]
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
1% to 10%:
Central nervous system: Dizziness (1%)
Gastrointestinal: Constipation (2% to 5%), abdominal cramps (≤3%), nausea (≤3%)
<1%, postmarketing, and/or case reports: Abdominal discomfort, abdominal distention, abdominal pain, anaphylactic shock, anaphylactoid reaction, angioedema, bullous rash (rare), drowsiness, dyspepsia, erythema multiforme (rare), fatigue, flatulence, hypersensitivity reaction, megacolon, paralytic ileus, pruritus, skin rash, Stevens-Johnson syndrome (rare), toxic epidermal necrolysis (rare), toxic megacolon, urinary retention, urticaria, vomiting, xerostomia
Hypersensitivity to loperamide or any component of the formulation; abdominal pain without diarrhea; children <2 years; acute dysentery; acute ulcerative colitis; bacterial enterocolitis (caused by Salmonella, Shigella, and Campylobacter); pseudomembranous colitis associated with broad-spectrum antibiotic use.
Canadian labeling: Additional contraindications (not in the US labeling): When constipation should be avoided; when the inhibition of peristalsis should be avoided
OTC labeling: When used for self-medication, do not use if stool is bloody or black.
Documentation of allergenic cross-reactivity for antidiarrheals is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.
Concerns related to adverse effects:
• Allergic reactions: Rare cases of anaphylaxis and anaphylactic shock have been reported.
• CNS effects: May cause drowsiness or dizziness, which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).
• GI effects: Discontinue promptly if constipation, abdominal pain, abdominal distension, blood in stool, or ileus develop. Do not use when peristalsis inhibition should be avoided due to potential for ileus, megacolon and/or toxic megacolon.
• Torsades de pointes and sudden death: [US Boxed Warning]: Cases of torsades de pointes, cardiac arrest, and death have been reported with the use of a higher than recommended dosage. Contraindicated in pediatric patients <2 years. Avoid dosages higher than recommended in patients ≥2 years due to the risk of serious cardiac adverse reactions. Cases of syncope and ventricular tachycardia have been reported in adults receiving the recommended dose of loperamide. Cases of cardiac arrest, syncope, and respiratory depression have been reported in pediatric patients <2 years. Avoid use in patients with risk factors for QT prolongation (eg, congenital long QT syndrome, history of cardiac arrhythmias or other cardiac conditions, elderly, electrolyte abnormalities) and in combination with others drugs known to prolong the QT interval.
Disease-related concerns:
• AIDS: Stop therapy at the first sign of abdominal distention; cases of toxic megacolon have occurred in patients with AIDS and infectious colitis (due to viral or bacterial pathogens).
• Hepatic impairment: Use with caution in patients with hepatic impairment due to reduced first-pass metabolism; monitor for signs of CNS toxicity.
Special populations:
• Elderly: Use with caution in elderly patients; may be more susceptible to drug-associated effects on the QT interval.
• Pediatric: Use with caution in young children as response may be variable because of dehydration. Contraindicated in children <2 years.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Loperamide is a symptom-directed treatment; if an underlying diagnosis is made, other disease-specific treatment may be indicated. Concurrent fluid and electrolyte replacement is often necessary in all age groups depending upon severity of diarrhea.
• Duration of use: If diarrhea lasts longer than 2 days, symptoms worsen, or abdominal swelling or bulging develops, discontinue use and consult healthcare provider.
• Self medication (OTC use): Consult health care provider prior to using, if taking antibiotics, if pregnant or breastfeeding, or in the presence of fever, mucus in stool, or a history of liver disease. Serious heart problems may occur if taken more than directed.
When managing acute dysentery, concurrent fluid and electrolyte replacement is often necessary in all age groups depending upon severity of diarrhea; young pediatric patients are particularly susceptible to dehydration and electrolyte imbalances. Antidiarrheal agents are not recommended as part of the management of acute gastroenteritis in infants and children because they do not address the underlying cause (ie, do not treat the infection) and have a risk of serious adverse events (CDC 2003). A meta-analysis evaluating the use of loperamide for adjunct treatment of acute bacterial gastroenteritis in pediatric patients identified that infants and children <3 years, malnourished, moderately to severely dehydrated, or those with bloody diarrhea have a higher risk of serious adverse events (ileus, lethargy, death) even at therapeutic doses (≤0.25 mg/kg/day of loperamide); the potential benefit of loperamide therapy does not outweigh risks; use should be avoided in pediatric patients (IDSA [Shane 2017]; Li 2007). Although data suggests that older children with milder infection and adolescents may see benefit from loperamide therapy, including decreased duration of diarrhea and stool counts, use is not recommended (IDSA [Shane 2017]); if used, patients should be monitored closely for adverse effects or worsening of infection (CDC 2003; Li 2007).
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP 1997; Shehab 2009).
Substrate of CYP2B6 (minor), CYP2C8 (minor), CYP2D6 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Desmopressin: Loperamide-Loperamide Oxide may increase the serum concentration of Desmopressin. Risk C: Monitor therapy
Eluxadoline: Loperamide-Loperamide Oxide may enhance the constipating effect of Eluxadoline. Risk C: Monitor therapy
Haloperidol: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Haloperidol. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of Loperamide-Loperamide Oxide. Risk X: Avoid combination
Levoketoconazole: QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of Levoketoconazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Lonafarnib: May increase the serum concentration of Loperamide. Management: When first using loperamide with lonafarnib, do not exceed a loperamide dose of 1 mg/day. If needed, the loperamide dose can then be slowly and cautiously increased according to the loperamide labeling. Risk D: Consider therapy modification
QT-prolonging Agents (Highest Risk): QT-prolonging Agents (Indeterminate Risk - Avoid) may enhance the QTc-prolonging effect of QT-prolonging Agents (Highest Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QuiNIDine: May enhance the CNS depressant effect of Loperamide-Loperamide Oxide. Loperamide-Loperamide Oxide may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Loperamide-Loperamide Oxide. Risk C: Monitor therapy
Ramosetron: Loperamide-Loperamide Oxide may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Sincalide: Drugs that Affect Gallbladder Function may diminish the therapeutic effect of Sincalide. Management: Consider discontinuing drugs that may affect gallbladder motility prior to the use of sincalide to stimulate gallbladder contraction. Risk D: Consider therapy modification
Adverse effects have not been observed in animal reproduction studies. Information related to loperamide use in pregnancy is limited and data is conflicting (Einarson 2000; Källén 2008). For acute diarrhea in pregnant women, some clinicians recommend oral rehydration and dietary changes; loperamide in small amounts may be used only if symptoms are disabling (Wald 2003).
Loperamide may be present in breast milk.
Studies evaluating milk concentrations of loperamide following maternal use have not been located. Available information is based on studies using loperamide oxide, the prodrug of loperamide, conducted in six women given 2 doses of oral loperamide oxide 12 hours apart, within 47 hours of delivery. Loperamide concentrations in breast milk ranged from not detectable (<0.1 ng/mL) to 0.61 ng/mL, compared to maternal plasma concentrations of 0.2 ng/mL to 1.71 ng/mL (Nikodem 1992). Therapeutic use of loperamide is contraindicated in children <2 years of age. Breastfeeding is not recommended by the manufacturer.
Some products may contain sodium.
Signs of CNS toxicity in patients with hepatic impairment.
Acts directly on circular and longitudinal intestinal muscles, through the opioid receptor, to inhibit peristalsis and prolong transit time; reduces fecal volume, increases viscosity, and diminishes fluid and electrolyte loss; demonstrates antisecretory activity. Loperamide increases tone on the anal sphincter
Absorption: Poor.
Distribution: Poor penetration into brain.
Protein binding: ~95%.
Metabolism: Hepatic via oxidative N-demethylation; CYP2C8 and CYP3A4 (major) and CYP2B6 and CYP2D6 (minor) role in N-demethylation.
Half-life elimination: 9.1 to 14.4 hours.
Time to peak, plasma: Liquid: 2.5 hours; Capsule: ~5 hours.
Excretion: Feces.
Capsules (Imodium A-D Oral)
2 mg (per each): $0.46
Capsules (Loperamide HCl Oral)
2 mg (per each): $0.87 - $1.37
Liquid (Imodium A-D Oral)
1 mg/7.5 mL (per mL): $0.04
Liquid (Loperamide HCl Oral)
1 mg/7.5 mL (per mL): $0.04
Solution (Loperamide HCl Oral)
2 mg/15 mL (per mL): $0.19
Tablets (Imodium A-D Oral)
2 mg (per each): $0.49
Tablets (Loperamide HCl Oral)
2 mg (per each): $0.12
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