LOPERAMIDE HYDROCHLORIDE
Clinical safety rating: safe
QT prolongation has been reported with high doses Can cause toxic megacolon in patients with infectious diarrhea.
Loperamide binds to µ-opioid receptors in the intestinal wall, reducing propulsive peristalsis and increasing intestinal transit time. It also inhibits calcium-calmodulin-dependent pathways, decreasing electrolyte and water secretion, and enhances anal sphincter tone.
| Metabolism | Primarily metabolized by CYP2C8 and CYP3A4 to N-desmethylloperamide; also O-demethylation via CYP2D6. Extensive first-pass metabolism. |
| Excretion | Primarily fecal (30-40% as unchanged drug, 50-60% as metabolites); renal excretion accounts for <5% of unchanged drug and ~10% of metabolites. |
| Half-life | Terminal elimination half-life is 9-14 hours (mean 10.8 hours) in adults; may be prolonged in hepatic impairment. |
| Protein binding | Approximately 95-97% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | 9-20 L/kg (mean 14 L/kg), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 40-60% due to extensive first-pass metabolism (primarily N-dealkylation via CYP3A4 and CYP2C8). |
| Onset of Action | Oral: 0.5-1 hour (tablets) or 0.5-2 hours (liquid); onset is faster with liquid formulation. |
| Duration of Action | Antidiarrheal effect lasts 4-6 hours after a single dose; maximal effect at 2-3 hours; duration may be longer with higher doses. |
4 mg orally initially, followed by 2 mg after each unformed stool; maximum 16 mg per day. For chronic diarrhea, 4 mg orally once, then 2 mg after each unformed stool until diarrhea controlled; typical maintenance 4-8 mg daily in divided doses. Traveler's diarrhea: 4 mg initially, then 2 mg after each loose stool; maximum 8 mg per day for up to 2 days.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR < 30 mL/min), use with caution due to potential accumulation; consider dose reduction or extended interval. No specific GFR-based guidelines available; clinical monitoring advised. |
| Liver impairment | Child-Pugh Class A: No adjustment. Child-Pugh Class B: Reduce dose by 50% or extend interval; maximum 8 mg/day. Child-Pugh Class C: Avoid use or use with extreme caution; maximum 6 mg/day with close monitoring for CNS toxicity. Loperamide is hepatically metabolized; accumulation may occur. |
| Pediatric use | Children 2-5 years (13-20 kg): 1 mg orally three times daily (maximum 3 mg/day). 6-8 years (20-30 kg): 2 mg orally twice daily (maximum 4 mg/day). 8-12 years (>30 kg): 2 mg orally three times daily (maximum 6 mg/day). For acute diarrhea: initial dose based on weight, then 0.1 mg/kg after each unformed stool; not to exceed initial dose per 24 hours. Use only under medical supervision; contraindicated in children <2 years. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
QT prolongation has been reported with high doses Can cause toxic megacolon in patients with infectious diarrhea.
| FDA category | Animal |
| Breastfeeding | Loperamide is excreted into breast milk in low concentrations. The milk-to-plasma (M/P) ratio is approximately 0.5:1. The estimated relative infant dose is 0.1-0.2% of the maternal weight-adjusted dose. Due to low oral bioavailability and limited transfer, it is considered compatible with breastfeeding, but caution is advised in premature infants or those with compromised gastrointestinal function. |
| Teratogenic Risk |
■ FDA Black Box Warning
None.
| Common Effects | Constipation |
| Serious Effects |
["Hypersensitivity to loperamide or any component","Acute dysentery (bloody stools, high fever)","Abdominal conditions where constipation may be dangerous (e.g., ileus, acute ulcerative colitis)","Pediatric patients <2 years of age","Mechanism-related: Avoid in patients with known prolonged QT interval or cardiac arrhythmias"]
| Precautions | ["Do not use for diarrhea with high fever or bloody stools (risk of bacterial enterocolitis)","Prolonged use may lead to constipation and toxic megacolon in IBD","Avoid use in children <2 years due to risk of respiratory depression","Risk of cardiac arrhythmias (QT prolongation, Torsades de Pointes) with high doses or when combined with drugs inhibiting CYP3A4 or P-glycoprotein","Dehydration and electrolyte imbalances should be corrected before use"] |
Loading safety data…
| Geriatric use |
| Initiate at lower doses (e.g., 2 mg initially) due to increased sensitivity and risk of CNS effects, constipation, and dehydration. Monitor for electrolyte imbalances and prolonged QT interval. Maximum 8 mg/day for acute diarrhea; adjust based on response and tolerability. Avoid in patients with advanced age and multiple comorbidities unless necessary. |
| Loperamide hydrochloride is classified as FDA Pregnancy Category C. Animal studies have shown no evidence of teratogenicity at doses up to 40 mg/kg/day in rats (maternal toxic doses). In humans, data from postmarketing reports and small studies suggest no increased risk of major malformations after first-trimester exposure, but there is insufficient data for second and third trimesters. Potential for neonatal opioid withdrawal syndrome if used near term. |
| Fetal Monitoring | No specific maternal-fetal monitoring is routinely required. However, in pregnant women, monitor for signs of constipation, ileus, or CNS depression, especially with prolonged use. Fetal monitoring is not indicated unless maternal adverse effects occur. For neonates, monitor for signs of opioid withdrawal if loperamide was used near term. |
| Fertility Effects | Preclinical studies in animals at high doses (40 mg/kg/day) showed no effects on fertility or reproductive performance. In humans, there are no controlled studies; however, due to minimal systemic absorption and short-term use, loperamide is not expected to impair fertility. Chronic high-dose use might theoretically affect male or female reproductive function via opioid receptor activity, but clinical evidence is lacking. |