Imodium - Drug Monograph

Introduction

Imodium (loperamide hydrochloride) is an over-the-counter antidiarrheal medication belonging to the opioid receptor agonist class. Originally approved by the FDA in 1976, it has become one of the most widely used medications for the symptomatic treatment of acute and chronic diarrhea. Unlike other opioids, loperamide has limited central nervous system effects due to its poor penetration of the blood-brain barrier.

Mechanism of Action

Loperamide acts primarily as a μ-opioid receptor agonist in the myenteric plexus of the large intestine. It inhibits the release of acetylcholine and prostaglandins, thereby reducing intestinal peristalsis and prolonging intestinal transit time. Additionally, it enhances anal sphincter tone and reduces daily fecal volume while increasing viscosity and decreasing fluid and electrolyte loss.

Indications

• Acute nonspecific diarrhea
• Chronic diarrhea associated with inflammatory bowel disease
• Traveler's diarrhea (as adjunctive therapy)
• Reduction of ileostomy output

Dosage and Administration

• Initial dose: 4 mg (2 capsules or 20 mL liquid)
• Maintenance dose: 2 mg after each loose stool
• Maximum: 16 mg/day (prescription) or 8 mg/day (OTC)

• Ages 2-5: 1 mg after each loose stool (maximum 3 mg/day)
• Ages 6-8: 2 mg after each loose stool (maximum 4 mg/day)
• Ages 8-12: 2 mg after each loose stool (maximum 6 mg/day)

• Hepatic impairment: Reduced dosing recommended
• Renal impairment: Use with caution
• Elderly: Consider reduced dosing

Pharmacokinetics

• Absorption: Poor systemic absorption (<1%)
• Distribution: Primarily confined to intestinal wall
• Metabolism: Extensive hepatic metabolism via CYP3A4 and CYP2C8
• Elimination: Half-life approximately 11 hours; primarily excreted in feces
• Protein binding: 97%

Contraindications

• Hypersensitivity to loperamide or any components
• Abdominal pain without diarrhea
• Acute dysentery (bloody diarrhea with fever)
• Bacterial enterocolitis caused by invasive organisms
• Pseudomembranous colitis associated with broad-spectrum antibiotics

Warnings and Precautions

• Cardiac effects: FDA black box warning for serious cardiac events with excessive dosing
• Torsades de pointes and other arrhythmias reported with misuse/abuse
• Avoid in patients with prolonged QT interval or concomitant QT-prolonging drugs
• Discontinue if abdominal distension occurs
• Use caution in patients with hepatic impairment
• Not recommended for children under 2 years

Drug Interactions

• QT-prolonging agents: Increased risk of torsades de pointes (quinolones, antipsychotics, antiarrhythmics)
• CYP3A4 inhibitors: Ketoconazole, ritonavir, clarithromycin (increased loperamide levels)
• P-glycoprotein inhibitors: Increased systemic absorption
• Other CNS depressants: Additive effects (though minimal CNS penetration)

Adverse Effects

• Constipation
• Abdominal pain/discomfort
• Nausea
• Dizziness
• Dry mouth

• Toxic megacolon
• Ileus
• Cardiac arrhythmias (with overdose)
• Allergic reactions
• Pancreatitis (rare)

Monitoring Parameters

• Bowel function and pattern
• Hydration status and electrolyte balance
• ECG monitoring in cases of suspected overdose
• Signs of toxic megacolon (abdominal distension, fever)
• Therapeutic response and need for continued treatment

Patient Education

• Use only as directed for diarrhea relief
• Do not exceed recommended dosage
• Maintain adequate fluid intake to prevent dehydration
• Discontinue and contact healthcare provider if:

- Diarrhea persists beyond 48 hours - Fever develops - Blood appears in stool - Abdominal distension or pain occurs

• Store safely away from children
• Avoid alcohol during treatment
• Be aware of potential drowsiness or dizziness

References

1. FDA. (2016). FDA Drug Safety Communication: FDA warns about serious heart problems with high doses of the antidiarrheal medicine loperamide (Imodium), including from abuse and misuse. 2. Lexicomp Online. (2023). Loperamide: Drug Information. 3. UpToDate. (2023). Loperamide: Drug information. 4. Micromedex Solutions. (2023). Loperamide Hydrochloride. 5. American Gastroenterological Association. (2021). Guidelines on the Management of Acute Diarrhea. 6. WHO Model Formulary. (2021). Loperamide Monograph. 7. Clinical Pharmacology [database online]. (2023). Loperamide.