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Loperamide


General


Pronunciation

(loe PER a mide)


Brand Names: U.S.

  • Anti-Diarrheal [OTC]
  • Diamode [OTC]
  • Imodium A-D [OTC]
  • Loperamide A-D [OTC]

Indications


Use: Labeled Indications

Control and symptomatic relief of chronic diarrhea associated with inflammatory bowel disease and of acute nonspecific diarrhea; to reduce volume of ileostomy discharge

OTC labeling: Control of symptoms of diarrhea, including Traveler 's diarrhea


Contraindications


Hypersensitivity to loperamide or any component of the formulation; abdominal pain without diarrhea; children <2 years of age

Avoid use as primary therapy in patients with acute dysentery (bloody stools and high fever), acute ulcerative colitis, bacterial enterocolitis (caused by Salmonella, Shigella, and Campylobacter), pseudomembranous colitis associated with broad-spectrum antibiotic use


Dosing and Administration


Dosing: Adult

Acute diarrhea: Oral: Initial: 4 mg, followed by 2 mg after each loose stool, up to 16 mg/day

Chronic diarrhea: Oral: Initial: Follow acute diarrhea; maintenance dose should be slowly titrated downward to minimum required to control symptoms (typically, 4-8 mg/day in divided doses)

Travelers diarrhea: Oral: Initial: 4 mg after first loose stool, followed by 2 mg after each subsequent stool (maximum dose: 8 mg/day)

Cancer treatment-induced diarrhea (off-label use): Oral: 4 mg followed by 2 mg every 4 hours or after each unformed stool; Maximum: 16 mg/day (Benson, 2004) or 4 mg followed by 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours have passed without a loose bowel movement (Sharma, 2005)

Irinotecan-induced delayed diarrhea (off-label use): Oral: 4 mg after first loose or frequent bowel movement, then 2 mg every 2 hours (4 mg every 4 hours at night) until 12 hours have passed without a bowel movement (Rothenberg, 1996)


Dosing: Geriatric

Refer to adult dosing.


Dosing: Pediatric

Acute diarrhea: Initial doses (in first 24 hours):

2-5 years (13-20 kg): 1 mg 3 times/day

6-8 years (20-30 kg): 2 mg twice daily

8-12 years (>30 kg): 2 mg 3 times/day

Maintenance: After initial dosing, 0.1 mg/kg doses after each loose stool, daily dose should not exceed the recommended dose for the initial 24 hours

Travelers diarrhea:

6-8 years: 2 mg after first loose stool, followed by 1 mg after each subsequent stool (maximum dose: 4 mg/day)

9-11 years: 2 mg after first loose stool, followed by 1 mg after each subsequent stool (maximum dose: 6 mg/day)

≥12 years: Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment necessary.


Dosing: Hepatic Impairment

No dosage adjustment provided in manufacturer 's labeling; use with caution.


Dietary Considerations

Some products may contain sodium.


Storage

Store at 20 � �C to 25 � �C (68 � �F to 77 � �F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral, as hydrochloride:

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 (30 mL, 120 mL, 240 mL, 360 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, 10 mL, 118 mL)

Suspension, Oral, as hydrochloride:

Generic: 1 mg/7.5 mL (120 mL)

Tablet, Oral, as hydrochloride:

Anti-Diarrheal: 2 mg [DSC]

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 brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

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; contains brilliant blue fcf (fd&c blue #1), fd&c yellow #10 (quinoline yellow)]

Imodium A-D: 2 mg [scored; contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake]

Loperamide A-D: 2 mg

Tablet Chewable, Oral, as hydrochloride:

Imodium A-D: 2 mg [contains fd&c blue #1 aluminum lake, fd&c yellow #10 aluminum lake; cool mint flavor]


Drug Interactions

Eluxadoline: Loperamide may enhance the constipating effect of Eluxadoline. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

Lumacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

QuiNIDine: May enhance the adverse/toxic effect of Loperamide. Specifically, the combination may result in enhanced CNS effects of loperamide (eg, miosis, respiratory depression) and/or possible proarrhythmic effects. QuiNIDine may increase the serum concentration of Loperamide. Monitor therapy

Ramosetron: Loperamide may enhance the constipating effect of Ramosetron. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy


Adverse Reactions


1% to 10%:

Central nervous system: Dizziness (1%)

Gastrointestinal: Constipation (2% to 5%), abdominal cramps ( ≤3%), nausea ( ≤3%)

<1% (Limited to important or life-threatening): 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


Warnings/Precautions


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.

Disease-related concerns:

- AIDS patients: Stop therapy at the first sign of abdominal distention; cases of toxic megacolon have occurred in AIDS patients with 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:

- Pediatric: Use with caution in young children as response may be variable because of dehydration. Contraindicated in children <2 years of age.

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. Contraindicated if diarrhea is accompanied by high fever or blood in stool. Should not be used when inhibition of peristalsis is undesirable or dangerous. Concurrent fluid and electrolyte replacement is often necessary in all age groups depending upon severity of diarrhea. If improvement in acute diarrhea does not occur in 2 days, discontinue use and consult healthcare provider.

- Duration of use: If diarrhea lasts longer than 2 days, symptoms worsen, or abdominal swelling or bulging develops, discontinue use and consult healthcare provider.


Pregnancy Risk Factor

C


Pregnancy Considerations

Teratogenic effects were not observed in animal reproduction studies. Information related to loperamide use in pregnancy is limited and data is conflicting (Einarson, 2000; K � �llen, 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).


Actions


Pharmacology

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


Metabolism

Hepatic via oxidative N-demethylation


Time to Peak

Liquid: 2.5 hours; Capsule: 5 hours


Half-Life Elimination

9-14 hours


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience fatigue or loss of strength and energy. Have patient report immediately to prescriber severe dizziness, passing out, tachycardia, abnormal heartbeat, severe nausea; severe vomiting; abdominal pain; constipation; abdominal edema; bloating; black, tarry, or bloody stools; urinary retention; or change in amount of urine passed (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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