LONOX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LONOX (LONOX).
Loperamide is an opioid receptor agonist that acts on mu-opioid receptors in the myenteric plexus of the large intestine, inhibiting peristalsis and prolonging transit time. It also reduces colonic water and electrolyte secretion, enhancing fluid and electrolyte absorption. Loperamide has low systemic bioavailability due to extensive first-pass metabolism and is not significantly absorbed into the central nervous system due to P-glycoprotein efflux transport.
| Metabolism | Primarily metabolized via oxidative N-demethylation by CYP3A4 and CYP2C8 in the liver, with minor contribution from CYP2C9. Forms inactive metabolites, mainly N-desmethylloperamide, excreted in feces and urine. |
| Excretion | Primarily renal (60-70% as unchanged drug and active metabolite); biliary/fecal ~20%. |
| Half-life | Terminal half-life 12-15 hours; prolonged (up to 30 h) in elderly and renal impairment. |
| Protein binding | 75-95% bound, primarily to albumin. |
| Volume of Distribution | Vd 2.5-5 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Oral: 40-50% (first-pass metabolism varies); Rectal: ~50-60%; Intravenous: 100%. |
| Onset of Action | Oral: 30-60 minutes; Rectal (suppository): 20-30 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | 3-6 hours depending on dose and route; clinical antidiarrheal effect may persist longer. |
1-2 mg orally every 6 hours as needed for diarrhea; maximum 8 mg per day.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (eGFR <30 mL/min/1.73 m²), reduce dose by 50% and monitor for increased CNS effects. |
| Liver impairment | Child-Pugh Class A: no adjustment. Child-Pugh Class B: reduce dose by 50% and monitor. Child-Pugh Class C: avoid use due to risk of CNS toxicity. |
| Pediatric use | Children 2-5 years: 0.5 mg orally after first loose stool, then 0.5 mg after each subsequent stool, maximum 3 mg/day. Children 6-12 years: 1 mg initially, then 0.5 mg after each loose stool, maximum 4 mg/day. |
| Geriatric use | Initiate at lower dose (1 mg orally every 8 hours), monitor for constipation and CNS effects; avoid prolonged use. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LONOX (LONOX).
| Breastfeeding | Limited data; present in breast milk. M/P ratio unknown. Potential for infant toxicity (methemoglobinemia, hemolysis). Use caution; consider alternative agents. |
| Teratogenic Risk | Pregnancy category C: Animal studies show fetal harm; no adequate human studies. First trimester: Potential teratogenicity (neural tube defects, cardiovascular anomalies) based on animal data. Second/third trimester: Risk of premature closure of ductus arteriosus, oligohydramnios, and neonatal renal impairment. Avoid in late pregnancy. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to loperamide or any component of the formulation","Acute dysentery characterized by bloody diarrhea, high fever, or systemic toxicity","Abdominal pain without diarrhea","Constipation or suspected ileus/obstruction","Acute ulcerative colitis","Pseudomembranous colitis (antibiotic-associated diarrhea)","Children under 2 years of age"]
| Precautions | ["Increased risk of cardiac adverse events (QT prolongation, torsade de pointes) at high doses (>16 mg/day) or with overdose, especially in patients with cardiac risk factors or those taking QT-prolonging drugs","Potential for central nervous system depression (drowsiness, dizziness) when used at high doses or with concomitant central nervous system depressants","Do not use in patients with acute dysentery (bloody stools, high fever) due to risk of toxic megacolon","Use with caution in patients with hepatic impairment due to reduced first-pass metabolism, increasing risk of toxicity"] |
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| Fetal Monitoring |
| Monitor maternal renal function, complete blood count, and fetal ultrasound for ductus arteriosus closure and oligohydramnios. Serial fetal echocardiography in third trimester. Assess neonatal blood count and methemoglobin levels at birth. |
| Fertility Effects | No definitive human studies; animal studies suggest decreased implantation rates and increased embryo resorption. Potential for reversible impairment of spermatogenesis in males. |