Lopesim

Approved Indications:

• Acute nonspecific diarrhea: For relief of symptoms such as frequent loose stools, bloating, and abdominal discomfort.
• Traveler’s diarrhea: Short-term symptomatic relief in adults and children over 12 years.
• Functional or chronic diarrhea with gas-related symptoms: For associated bloating and flatulence.

Clinically Accepted Off-Label Uses:

• Irritable Bowel Syndrome with Diarrhea (IBS-D): Symptomatic management of diarrhea and abdominal bloating.
• Post-infectious diarrhea: Adjunct therapy during the recovery phase.
• Postoperative diarrhea or diarrhea in short bowel syndrome: Used cautiously under medical supervision.

Adults and Children ≥12 years:

• Initial dose: 2 tablets (each containing Loperamide 2 mg + Simethicone 125 mg).
• Maintenance dose: 1 tablet after each loose stool.
• Maximum daily dose: 4 tablets (8 mg Loperamide) for over-the-counter use; up to 8 tablets (16 mg Loperamide) under physician supervision.

Children 6–11 years:

• 20–30 kg: 1 tablet initially, then ½ tablet after each loose stool.
• >30 kg: 1 tablet initially, then 1 tablet after each loose stool.
• Maximum dose: Do not exceed 3 tablets (6 mg Loperamide) per day.

Children <6 years:

• Not recommended unless prescribed and closely monitored by a physician.

Elderly:

• No specific dose adjustment is required; start at the lower end of dosing range and monitor closely.

Renal Impairment:

• No dosage adjustment required.

Hepatic Impairment:

• Use with caution. Due to reduced metabolism, accumulation of loperamide may occur. Start with low doses and monitor for CNS effects.

Route of Administration:

• Oral. Chew tablets completely before swallowing. Ensure adequate hydration during treatment.

Loperamide is a synthetic opioid agonist that selectively binds to μ-opioid receptors in the intestinal wall. This inhibits peristalsis, increases transit time, and enhances water and electrolyte absorption, thereby reducing stool frequency and volume. It acts peripherally and does not cross the blood-brain barrier significantly at therapeutic doses.
Simethicone is an oral anti-foaming agent that reduces the surface tension of gas bubbles in the gastrointestinal tract, promoting their coalescence and easier elimination, thus relieving bloating, discomfort, and flatulence.

Loperamide:

• Absorption: Incomplete; ~40%
• Bioavailability: ~0.3% due to first-pass metabolism
• Onset of action: Within 1 hour
• Peak plasma time: 2.5–5 hours
• Metabolism: Hepatic, primarily via CYP3A4 and CYP2C8
• Half-life: 10.8 hours (range 9–14 hours)
• Excretion: Mainly in feces; <2% in urine

Simethicone:

• Absorption: Not systemically absorbed
• Metabolism: Not applicable
• Excretion: Excreted unchanged in feces

Pregnancy:

• Loperamide: FDA Category C. Animal studies show adverse effects; human data are limited. Use only if clearly needed.
• Simethicone: Generally considered safe; not absorbed systemically.

Lactation:

• Loperamide: Small amounts may pass into breast milk; use with caution.
• Simethicone: Safe; not excreted into breast milk.

Summary: Short-term use may be considered during pregnancy and lactation under medical supervision.

• Antidiarrheal and Antiflatulent Combination
• Subclass: Peripheral μ-opioid receptor agonist (Loperamide) + Anti-foaming agent (Simethicone)

• Known hypersensitivity to loperamide, simethicone, or any formulation components
• Children under 2 years of age
• Acute dysentery with high fever and bloody stools
• Bacterial enterocolitis (caused by Salmonella, Shigella, or Campylobacter)
• Pseudomembranous colitis associated with antibiotic use
• Abdominal pain without diarrhea
• Severe hepatic impairment

• Pediatric Use: Not recommended in children under 2 years due to risk of serious adverse effects, including respiratory and CNS depression.
• Overdose Risk: High doses can lead to QT prolongation, torsades de pointes, and cardiac arrest.
• Hepatic Impairment: Increased risk of loperamide accumulation and toxicity.
• Symptom Persistence: Discontinue if no improvement within 48 hours.
• Hydration: Fluid and electrolyte replacement should accompany treatment.

Common (by system):

• Gastrointestinal: Constipation, abdominal cramps, flatulence, nausea
• Nervous system: Drowsiness, dizziness

Less Common:

• Dry mouth, fatigue

Serious/Rare:

• Paralytic ileus, toxic megacolon (particularly in inflammatory bowel disease)
• CNS depression, respiratory depression (mainly in overdose or young children)
• Cardiac arrhythmias, including QT prolongation and torsades de pointes (in excessive doses)

Onset: Most occur within 12–24 hours
Dose-dependence: Higher risk with increased or prolonged dosing

Major Interactions:

• CYP3A4/CYP2C8 inhibitors (e.g., ketoconazole, ritonavir): Increase plasma loperamide levels, heightening toxicity risk.
• P-glycoprotein inhibitors (e.g., quinidine, verapamil): May reduce loperamide efflux from CNS, increasing CNS toxicity risk.
• Other CNS depressants: May exacerbate sedative effects.
• Alcohol: Increases CNS depression risk; should be avoided.

Simethicone: No significant drug interactions reported.

• FDA Warning: High doses of loperamide may lead to serious heart problems or death. Doses should never exceed the recommended maximum.
• OTC labeling revision: Limits maximum daily dose to 8 mg of loperamide for safety.
• Clinical guidelines: Emphasize that antidiarrheal agents are adjunctive therapy; rehydration remains the primary treatment for acute diarrhea per WHO/CDC.

• Storage temperature: Store below 25°C (77°F)
• Humidity: Protect from moisture
• Light: Store in original packaging, away from direct light
• Handling: Keep tightly closed
• Oral liquid (if applicable): Shake well before use; do not freeze