LOMANATE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LOMANATE (LOMANATE).
LOMANATE is a combination of diphenoxylate (a peripheral opioid receptor agonist that slows GI motility) and atropine (an anticholinergic that discourages abuse).
| Metabolism | Diphenoxylate is metabolized by ester hydrolysis to difenoxin (active metabolite), both primarily metabolized by CYP3A4. Atropine undergoes hepatic metabolism via CYP450 enzymes. |
| Excretion | Primarily renal (80% as unchanged drug and metabolites); biliary/fecal (15%); 5% eliminated via other routes. |
| Half-life | Terminal elimination half-life is 18-24 hours in adults with normal renal function; prolonged to 40-60 hours in severe renal impairment (CrCl < 30 mL/min), requiring dose adjustment. |
| Protein binding | 98% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 2.5-3.5 L/kg, indicating extensive extravascular distribution and tissue binding. |
| Bioavailability | Oral: 90% (high first-pass metabolism yields 60-70% systemic bioavailability); IM: 95%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes; Intramuscular: 15-30 minutes. |
| Duration of Action | Oral: 4-6 hours; IV: 2-4 hours; IM: 3-5 hours. Duration extended in hepatic impairment due to reduced clearance. |
100 mg orally twice daily
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-50: 50 mg twice daily; GFR <30: 50 mg once daily |
| Liver impairment | Child-Pugh A: 75 mg twice daily; Child-Pugh B: 50 mg twice daily; Child-Pugh C: contraindicated |
| Pediatric use | 3 mg/kg/dose orally twice daily (max 100 mg/dose) |
| Geriatric use | Initiate at 50 mg twice daily; titrate cautiously based on renal function |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LOMANATE (LOMANATE).
| Breastfeeding | Propranolol is excreted into breast milk in small amounts; M/P ratio is approximately 0.5 to 1.5. Infant exposure is low, but monitor for bradycardia and hypoglycemia. Generally considered compatible with breastfeeding, but use with caution. |
| Teratogenic Risk | LOMANATE (propranolol) is FDA Pregnancy Category C. First trimester: limited human data, but animal studies show increased fetal resorptions. Second/third trimester: risk of intrauterine growth restriction, bradycardia, hypoglycemia, and respiratory depression in the neonate. Should be used only if potential benefit justifies risk. |
■ FDA Black Box Warning
WARNING: ABUSE POTENTIAL. Diphenoxylate is a controlled substance (C-II) and can cause opioid dependence, respiratory depression, and lethal overdose if misused.
| Serious Effects |
Hypersensitivity to diphenoxylate or atropine; intestinal obstruction; acute diarrhea with fever or bloody stools; pseudomembranous colitis; children under 6 years; jaundice; concurrent use with MAO inhibitors.
| Precautions | Risk of respiratory depression at high doses; use with caution in hepatic impairment; risk of toxic megacolon in patients with inflammatory bowel disease; anticholinergic effects (urinary retention, blurred vision); hypokalemia or electrolyte disturbances; pediatric sensitivity due to atropine content. |
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| Fetal Monitoring | Maternal: heart rate, blood pressure, signs of heart failure, bronchospasm. Fetal: ultrasound for growth restriction, fetal heart rate monitoring. Neonatal: observe for bradycardia, hypoglycemia, respiratory depression for 24-48 hours after delivery. |
| Fertility Effects | Limited data. Propranolol may impair male fertility through effects on sperm motility and function. In females, no significant impact on fertility reported. |