Lopera

Approved Indications:

• Acute nonspecific diarrhea in adults and children ≥6 years
• Chronic diarrhea associated with inflammatory bowel disease (e.g., Crohn’s disease, ulcerative colitis)
• Traveler’s diarrhea
• Reduction of ileostomy output in patients with an ileostomy

Clinically Accepted Off-Label Uses:

• Irritable Bowel Syndrome with Diarrhea (IBS-D): Symptomatic control
• Chemotherapy-induced diarrhea: Adjunctive management
• Post-infectious diarrhea: Short-term supportive care
• Short bowel syndrome-associated diarrhea: Use with caution under medical supervision

Adults and Children ≥12 years:

• Initial dose: 4 mg (2 mg capsule/tablet × 2)
• Maintenance dose: 2 mg after each loose stool
• Maximum daily dose:
• OTC use: 8 mg/day
• Prescription use: 16 mg/day

Children 6–11 years:

• 20–30 kg: 2 mg initial dose, then 1 mg after each loose stool (max 4 mg/day)
• >30 kg: 2 mg initial dose, then 2 mg after each loose stool (max 6 mg/day)

Children <6 years:

• Not recommended unless prescribed by a physician and closely monitored

Elderly:

• No specific dose adjustment required; use with caution and monitor for adverse effects

Renal Impairment:

• No dosage adjustment necessary

Hepatic Impairment:

• Use with extreme caution due to reduced metabolism; start at the lowest effective dose and monitor for central nervous system toxicity

Route of Administration:

• Oral (capsule, tablet, syrup)

Duration:

• Discontinue if no clinical improvement is observed within 48 hours of initiation

Loperamide Hydrochloride acts as a peripherally acting μ-opioid receptor agonist. It binds to opioid receptors in the intestinal wall, thereby inhibiting acetylcholine and prostaglandin release, reducing peristalsis and intestinal motility. This increases the time substances remain in the intestine, allowing more water and electrolytes to be absorbed, and results in firmer stools and decreased stool frequency. Loperamide does not significantly penetrate the central nervous system at therapeutic doses due to its P-glycoprotein-mediated efflux.

• Absorption: ~40% absorbed orally; significant first-pass effect
• Bioavailability: ~0.3%
• Time to peak concentration: 2.5 to 5 hours
• Protein Binding: ~95%
• Metabolism: Hepatic (CYP3A4, CYP2C8-mediated)
• Half-life: 10.8 hours (range: 9–14 hours)
• Elimination: Mostly excreted in feces; <2% via urine
• Onset of action: Within 1 hour

Pregnancy:

• FDA Pregnancy Category C
• Animal studies show adverse effects; there are no adequate well-controlled studies in pregnant women. Should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation:

• Loperamide is excreted in small amounts in breast milk. While adverse effects are unlikely, caution is advised when administering to nursing mothers.

Summary:

• Use with caution during pregnancy and breastfeeding. Short-term therapy may be considered under medical supervision.

• Class: Antidiarrheal agent
• Subclass: Peripheral μ-opioid receptor agonist
• Chemical Class: Synthetic piperidine derivative

• Known hypersensitivity to Loperamide or any component of the formulation
• Children under 2 years of age
• Acute dysentery (fever and blood in stool)
• Bacterial enterocolitis caused by invasive pathogens (e.g., Salmonella, Shigella, Campylobacter)
• Pseudomembranous colitis associated with the use of broad-spectrum antibiotics
• Abdominal pain in the absence of diarrhea
• Severe hepatic impairment

• Cardiotoxicity: High doses may cause QT prolongation, torsades de pointes, and cardiac arrest
• CNS Depression: Risk increases with hepatic impairment or overdose
• Pediatric risk: Contraindicated in children <2 years due to life-threatening respiratory and CNS depression
• Overdose risk: Misuse or abuse for opioid-like effects can lead to serious arrhythmias and death
• Hydration required: Always ensure appropriate rehydration therapy in acute diarrhea
• Discontinue use if no improvement within 48 hours

Common:

• Gastrointestinal: Constipation, abdominal cramps, nausea, dry mouth
• Neurological: Dizziness, drowsiness

Less Common:

• Flatulence, vomiting, fatigue

Serious/Rare:

• Paralytic ileus
• Toxic megacolon (especially in inflammatory bowel disease)
• CNS depression or respiratory depression (especially in children and overdose)
• Serious cardiac events (QT prolongation, torsades de pointes, cardiac arrest)
• Hypersensitivity reactions (rash, pruritus, urticaria)

Onset & Severity:

• Most side effects occur within 12–24 hours
• Severity is dose-dependent; serious events are rare but potentially fatal in overdose

Major Interactions:

• CYP3A4/CYP2C8 inhibitors (e.g., ketoconazole, ritonavir): Increase plasma levels of loperamide, raising toxicity risk
• P-glycoprotein inhibitors (e.g., quinidine, verapamil): Increase CNS penetration, elevating risk of sedation and toxicity
• CNS depressants (e.g., benzodiazepines, opioids): May enhance sedation and respiratory depression
• Alcohol: May potentiate CNS depression; should be avoided

Food:

• Food may delay absorption but does not significantly impact efficacy

FDA Black Box Warning: High doses of loperamide are associated with fatal cardiac arrhythmias (QT prolongation, torsades de pointes, and cardiac arrest)

• OTC Dosing Limitations: Maximum allowed OTC dose is 8 mg/day; higher doses allowed only under prescription
• WHO and CDC Guidelines: Recommend oral rehydration as primary therapy for diarrhea; loperamide is supportive only
• Regulatory Actions: Packaging and sales restrictions implemented to reduce abuse potential

• Temperature: Store below 25°C (77°F)
• Humidity: Protect from excessive moisture
• Light: Store in original packaging, away from direct light
• Handling: Keep container tightly closed
• Liquid preparations: Shake well before use; do not freeze