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. |
| Molecular Weight | 489.09 |
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 | Contraindicated: Risk of fetal alcohol spectrum disorders due to ethanol content. |
| 2nd trimester | Contraindicated: Continued risk of fetal alcohol exposure; ethanol crosses placenta. |
| 3rd trimester | Contraindicated: Risk of neonatal withdrawal and alcohol-related birth defects. |
Clinical note
Comprehensive clinical and safety monograph for LONOX (LONOX).
| Placental transfer | Ethanol component readily crosses the placenta; diphenoxylate crosses in minimal amounts but active metabolite may transfer. |
| Breastfeeding | Drug contains alcohol (ethanol) which is excreted into breast milk; may impair infant development. Use is not recommended during breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to diphenoxylate or atropineObstructive jaundiceDiarrhea associated with pseudomembranous colitis or enterotoxin-producing bacteriaChildren <2 years of ageLactation
| 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 |
| Food/Dietary | Avoid alcohol and grapefruit juice as they may increase CNS depression and risk of toxicity. Take on an empty stomach for faster relief, but can be taken with food if GI upset occurs. Maintain adequate fluid intake to prevent dehydration. |
Loading safety data…
| L5 (Avoid) |
| 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. |
| 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. |
| Clinical Pearls | Lonox (diphenoxylate/atropine) is contraindicated in children under 6 years old due to risk of respiratory depression. Monitor for signs of atropinism (flushing, tachycardia, dry skin) especially in elderly. Use with caution in hepatic impairment and ulcerative colitis. Do not exceed 20 mg/day of diphenoxylate. Discontinue if diarrhea persists >48 hours. |
| Patient Advice | Take exactly as prescribed; do not increase dose without consulting your doctor. · This medication can cause drowsiness or dizziness; avoid driving or operating heavy machinery until you know how it affects you. · Do not take with alcohol or other CNS depressants. · Report any signs of severe constipation, blurred vision, difficulty urinating, or rapid heartbeat. · Keep out of reach of children; overdose can be fatal. · If diarrhea does not improve within 2 days or if you have a fever, contact your healthcare provider. |