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. |
| Molecular Weight | 387.45 |
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 | Contraindicated due to risk of teratogenicity; avoid use. |
| 2nd trimester | Contraindicated; potential fetal harm. |
| 3rd trimester | Contraindicated; may cause fetal/neonatal adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for LOMANATE (LOMANATE).
| Placental transfer | Significant placental transfer demonstrated; crosses placenta readily in animal studies. |
| Breastfeeding | Excreted in breast milk; contraindicated due to potential toxicity in nursing infants. |
| Lactation Rating | L5 - Contraindicated |
■ 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 |
PregnancyHypersensitivity to lomanate or any componentLactationSevere hepatic impairment
| 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. |
| Food/Dietary | No specific food interactions are documented. However, grapefruit juice may theoretically increase diphenoxylate levels due to CYP3A4 inhibition; monitor for increased sedation. Limit high-fiber or fatty meals which may worsen diarrhea or alter drug absorption. |
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| 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. |
| 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. |
| Clinical Pearls | LOMANATE (diphenoxylate/atropine) is an antidiarrheal agent; avoid use in patients with infectious diarrhea (e.g., C. difficile, Shigella) due to risk of toxic megacolon. Concomitant use with MAOIs may precipitate hypertensive crisis. Monitor for CNS depression when used with other central depressants. Onset of action is 45-60 minutes; maximum effect at 2 hours. |
| Patient Advice | Take exactly as prescribed; do not exceed recommended dose as it may cause serious side effects including slowed breathing. · Avoid alcohol and other sedatives during treatment. · Do not use for more than 2 days unless directed by your provider; if diarrhea persists, seek medical attention. · Stop use and contact your doctor if you develop fever, bloody stool, or severe abdominal pain. · Keep out of reach of children; accidental overdose can be fatal in children. · May cause dry mouth, blurred vision, or dizziness – avoid driving if affected. |