DailyMed Label: Lomotil

DailyMed Label: Lomotil

2009

DailyMed Prescription

Lomotil

Diphenoxylate Hydrochloride

Physicians Total Care, Inc.

NDC: 54868-0427

NDC: 54868-0427

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: Atropine sulfate, an anticholinergic, is endo-(±)-α-(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: A subtherapeutic amount of atropine sulfate is present to discourage deliberate overdosage. 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. image of chemical structure for diphenoxylate hcl image of chemical structure for atropine sulfate

Lomotil is effective as adjunctive therapy in the management of diarrhea.

DO NOT EXCEED RECOMMENDED DOSAGE. Adults: The recommended initial dosage is two Lomotil tablets four times daily or 10 ml (two regular teaspoonfuls) of Lomotil liquid four times daily (20 mg per day). Most patients will require this dosage until initial control has been achieved, after which the dosage may be reduced to meet individual requirements. Control may often be maintained with as little as 5 mg (two tablets or 10 ml of liquid) daily. Clinical improvement of acute diarrhea is usually observed within 48 hours. If clinical improvement of chronic diarrhea after treatment with a maximum daily dose of 20 mg of diphenoxylate hydrochloride is not observed within 10 days, symptoms are unlikely to be controlled by further administration. Children: Lomotil is not recommended in children under 2 years of age and should be used with special caution in young children (see Warnings and Precautions ) . The nutritional status and degree of dehydration must be considered. In children under 13 years of age, use Lomotil liquid. Do not use Lomotil tablets for this age group. Only the plastic dropper should be used when measuring Lomotil liquid for administration to children. Dosage schedule for children: The recommended initial total daily dosage of Lomotil liquid for children is 0.3 to 0.4 mg/kg, administered in four divided doses. The following table provides an approximate initial daily dosage recommendation for children. Age (years) Approximate weight Dosage in ml (four times daily) (kg) (lb) 2 11–14 24–31 1.5–3.0 3 12–16 26–35 2.0–3.0 4 14–20 31–44 2.0–4.0 5 16–23 35–51 2.5–4.5 6–8 17–32 38–71 2.5–5.0 9–12 23–55 51–121 3.5–5.0 These pediatric schedules are the best approximation of an average dose recommendation which may be adjusted downward according to the overall nutritional status and degree of dehydration encountered in the sick child. Reduction of dosage may be made as soon as initial control of symptoms has been achieved. Maintenance dosage may be as low as one-fourth of the initial daily dosage. If no response occurs within 48 hours, Lomotil is unlikely to be effective. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.

Lomotil is contraindicated in patients with Known hypersensitivity to diphenoxylate or atropine. Obstructive jaundice. Diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria.

General Since a subtherapeutic dose of atropine has been added to the diphenoxylate hydrochloride, consideration should be given to the precautions relating to the use of atropine. In children, Lomotil should be used with caution since signs of atropinism may occur even with recommended doses, particularly in patients with Down's syndrome. Information For Patients INFORM THE PATIENT (PARENT OR GUARDIAN) NOT TO EXCEED THE RECOMMENDED DOSAGE AND TO KEEP LOMOTIL OUT OF THE REACH OF CHILDREN AND IN A CHILD-RESISTANT CONTAINER. INFORM THE PATIENT OF THE CONSEQUENCES OF OVERDOSAGE, INCLUDING SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH. Lomotil may produce drowsiness or dizziness. The patient should be cautioned regarding activities requiring mental alertness, such as driving or operating dangerous machinery. Potentiation of the action of alcohol, barbiturates, and tranquilizers with concomitant use of Lomotil should be explained to the patient. The physician should also provide the patient with other information in this labeling, as appropriate. Drug Interactions Known drug interactions include barbiturates, tranquilizers, and alcohol. Lomotil may interact with MAO inhibitors (see Warnings ). In studies with male rats, diphenoxylate hydrochloride was found to inhibit the hepatic microsomal enzyme system at a dose of 2 mg/kg/day. Therefore, diphenoxylate has the potential to prolong the biological half-lives of drugs for which the rate of elimination is dependent on the microsomal drug metabolizing enzyme system. Carcinogenesis, Mutagenesis, Impairment Of Fertility No long-term study in animals has been performed to evaluate carcinogenic potential. Diphenoxylate hydrochloride was administered to male and female rats in their diets to provide dose levels of 4 and 20 mg/kg/day throughout a three-litter reproduction study. At 50 times the human dose (20 mg/kg/day), female weight gain was reduced and there was a marked effect on fertility as only 4 of 27 females became pregnant in three test breedings. The relevance of this finding to usage of Lomotil in humans is unknown. Pregnancy Pregnancy Category C. Diphenoxylate hydrochloride has been shown to have an effect on fertility in rats when given in doses 50 times the human dose (see above discussion). Other findings in this study include a decrease in maternal weight gain of 30% at 20 mg/kg/day and of 10% at 4 mg/kg/day. At 10 times the human dose (4 mg/kg/day), average litter size was slightly reduced. Teratology studies were conducted in rats, rabbits, and mice with diphenoxylate hydrochloride at oral doses of 0.4 to 20 mg/kg/day. Due to experimental design and small numbers of litters, embryotoxic, fetotoxic, or teratogenic effects cannot be adequately assessed. However, examination of the available fetuses did not reveal any indication of teratogenicity. There are no adequate and well-controlled studies in pregnant women. Lomotil should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus. Nursing Mothers Caution should be exercised when Lomotil is administered to a nursing woman, since the physicochemical characteristics of the major metabolite, diphenoxylic acid, are such that it may be excreted in breast milk and since it is known that atropine is excreted in breast milk. Pediatric Use Lomotil may be used as an adjunct to the treatment of diarrhea but should be accompanied by appropriate fluid and electrolyte therapy, if needed. LOMOTIL IS NOT RECOMMENDED FOR CHILDREN UNDER 2 YEARS OF AGE. Lomotil should be used with special caution in young children because of the greater variability of response in this age group. See Warnings and Dosage and Administration . In case of accidental ingestion by children, see Overdosage for recommended treatment.

At

Tablets —round, white, with SEARLE debossed on one side and 61 on the other side and containing 2.5 mg of diphenoxylate hydrochloride and 0.025 mg of atropine sulfate, supplied as: NDC Number          Size 54868-0427-5        bottle of 10 54868-0427-4        bottle of 12 54868-0427-3         bottle of 30 54868-0427-0         bottle of 100 Rx only

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 Tablets image of 2 package labels (2_a) image of 2 package labels (2_b)