Data from FDA - Curated by EPG Health - Last updated 22 November 2019

Indication(s)

INDICATIONS AND USAGE Diphenoxylate hydrochloride and atropine sulfate is effective as adjunctive therapy in the management of diarrhea.

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Advisory information

contraindications
CONTRAINDICATIONS Diphenoxylate hydrochloride and atropine sulfate is contraindicated in patients with: Known hypersensitivity to diphenoxylate or atropine. Obstructive jaundice. Diarrhea associated with pseudomembranous enterocolitis or enterotoxin-producing bacteria.
Special warnings and precautions
PRECAUTIONS 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, diphenoxylate hydrochloride and atropine sulfate 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 DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE 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. Diphenoxylate hydrochloride and atropine sulfate 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 diphenoxylate hydrochloride and atropine sulfate 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. Diphenoxylate hydrochloride and atropine sulfate 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 diphenoxylate hydrochloride and atropine sulfate in humans in 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 tetratogenicity. There are no adequate and well-controlled studies in pregnant women. Diphenoxylate hydrochloride and atropine sulfate should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus. Nursing Mothers Caution should be exercised when diphenoxylate hydrochloride and atropine sulfate 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 Diphenoxylate hydrochloride and atropine sulfate may be used as an adjunct to the treatment of diarrhea but should be accompanied by appropriate fluid and electrolyte therapy, if needed. DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE IS NOT RECOMMENDED FOR CHILDREN UNDER 2 YEARS OF AGE. Diphenoxylate hydrochloride and atropine sulfate 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.
Adverse reactions
ADVERSE REACTIONS At therapeutic doses, the following have been reported; they are listed in decreasing order of severity, but not of frequency: Nervous system: numbness of extremities, euphoria, depression, malaise/lethargy, confusion, sedation/drowsiness, dizziness, restlessness, headache. Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus. Gastrointestinal system: toxic megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort. The following atropine sulfate effects are listed in decreasing order of severity, but not of frequency: hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes. These effects may occur, especially in children. THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN SINCE AN OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION DO NOT EXCEED RECOMMENDED DOSAGE. Adults The recommended initial dosage is 10 mL (two regular teaspoonfuls) of oral solution 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 (10 mL of solution) 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 Diphenoxylate hydrochloride and atropine sulfate 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 the oral solution. Do not use the tablets for this age group. Only the plastic dropper should be used when measuring the oral solution for administration to children. Dosage Schedule for Children The recommended initial total daily dosage of the oral solution 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 Approximate Weight Dosage in mL (Years) (kg) (lbs.) (four times daily) 2 11 to 14 24 to 31 1.5 to 3.0 3 12 to 16 26 to 35 2.0 to 3.0 4 14 to 20 31 to 44 2.0 to 4.0 5 16 to 23 35 to 51 2.5 to 4.5 6 to 8 17 to 32 38 to 71 2.5 to 5.0 9 to 12 23 to 55 51 to 121 3.5 to 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, diphenoxylate hydrochloride and atropine sulfate is unlikely to be effective. KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
Pregnancy and lactation
Nursing Mothers Caution should be exercised when diphenoxylate hydrochloride and atropine sulfate 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.

Interactions

Drug Interactions Known drug interactions include barbiturates, tranquilizers, and alcohol. Diphenoxylate hydrochloride and atropine sulfate 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.

More information

Category Value
Authorisation number ANDA087708
Agency product number W24OD7YW48
Orphan designation No
Product NDC 70166-630
Date Last Revised 10-09-2019
Type HUMAN PRESCRIPTION DRUG
RXCUI 1190568
Marketing authorisation holder Lohxa