LOMOTIL - diphenoxylate hydrochloride and atropine sulfate tablet
Physicians Total Care, Inc.
Each Lomotil tablet and each 5 ml of Lomotil liquid for oral use contains:
diphenoxylate hydrochloride 2.5 mg
atropine sulfate �����.. 0.025 mg
Diphenoxylate hydrochloride, an antidiarrheal, is ethyl 1-(3-cyano-3,3-diphenylpropyl)-4-phenylisonipecotate monohydrochloride and has the following structural formula:
image of chemical structure for diphenoxylate hcl
Atropine sulfate, an anticholinergic, is endo-(�)-?-(hydroxymethyl) benzeneacetic acid 8-methyl-8-azabicyclo[3.2.1] oct-3-yl ester sulfate (2:1) (salt) monohydrate and has the following structural formula:
image of chemical structure for atropine sulfate
(click image for full-size original)
Inactive ingredients of Lomotil tablets include acacia, corn starch, magnesium stearate, sorbitol, sucrose, and talc. Inactive ingredients of Lomotil liquid include cherry flavor, citric acid, ethyl alcohol 15%, glycerin, sodium phosphate, sorbitol, and water.
Diphenoxylate is rapidly and extensively metabolized in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. After a 5-mg oral dose of carbon-14 labeled diphenoxylate hydrochloride in ethanolic solution was given to three healthy volunteers, an average of 14% of the drug plus its metabolites was excreted in the urine and 49% in the feces over a four-day period. Urinary excretion of the unmetabolized drug constituted less than 1% of the dose, and diphenoxylic acid plus its glucuronide conjugate constituted about 6% of the dose. In a 16-subject crossover bioavailability study, a linear relationship in the dose range of 2.5 to 10 mg was found between the dose of diphenoxylate hydrochloride (given as Lomotil liquid) and the peak plasma concentration, the area under the plasma concentration-time curve, and the amount of diphenoxylic acid excreted in the urine. In the same study the bioavailability of the tablet compared with an equal dose of the liquid was approximately 90%. The average peak plasma concentration of diphenoxylic acid following ingestion of four 2.5-mg tablets was 163 ng/ml at about 2 hours, and the elimination half-life of diphenoxylic acid was approximately 12 to 14 hours.
In dogs, diphenoxylate hydrochloride has a direct effect on circular smooth muscle of the bowel that conceivably results in segmentation and prolongation of gastrointestinal transit time. The clinical antidiarrheal action of diphenoxylate hydrochloride may thus be a consequence of enhanced segmentation that allows increased contact of the intraluminal contents with the intestinal mucosa.
Lomotil Indications and Usage
Lomotil is effective as adjunctive therapy in the management of diarrhea.
Lomotil is contraindicated in patients with
Known hypersensitivity to diphenoxylate or atropine.
Diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria.