Data from FDA - Curated by EPG Health - Last updated 05 July 2018

Indication(s)

INDICATIONS AND USAGE Diphenoxylate hydrochloride and atropine sulfate tablets are indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older.

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Advisory information

contraindications
CONTRAINDICATIONS Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in: Pediatric patients less than 6 years of age due to the risks of respiratory and central nervous system (CNS) depression (see WARNINGS). Patients with diarrhea associated with pseudomembranous enterocolitis ( Clostridium difficile) or other enterotoxin-producing bacteria due to the risk of gastrointestinal (GI) complications, including sepsis (see WARNINGS). Patients with known hypersensitivity to diphenoxylate or atropine. Patients with obstructive jaundice.
Special warnings and precautions
PRECAUTIONS Atropinism Since a subtherapeutic dose of atropine has been added to diphenoxylate hydrochloride and atropine sulfate tablets, consideration should be given to the development of adverse reactions associated with of atropine (see WARNINGS). Diphenoxylate hydrochloride and atropine sulfate tablets have caused atropinism (hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes) particularly in pediatric patients with Down’s syndrome. Diphenoxylate hydrochloride and atropine sulfate tablets are not indicated for use in pediatric patients (see CONTRAINDICATIONS and WARNINGS). Monitor patients for signs of atropinism. Information for Patients Advise patients: Accidental ingestion of diphenoxylate hydrochloride and atropine sulfate tablets in children, especially in those less than 6 years of age, may result in severe respiratory depression or coma. Instruct patients to take steps to store diphenoxylate hydrochloride and atropine sulfate tablets securely and out of reach of children, and to dispose of unused diphenoxylate hydrochloride and atropine sulfate tablets (see WARNINGS). To take diphenoxylate hydrochloride and atropine sulfate tablets at the prescribed dosage. Use of a higher than prescribed dosage may include opioid and/or anticholinergic effects (see OVERDOSAGE). Report to a healthcare facility if they develop anticholinergic symptoms such as hyperthermia, flushing, tachycardia, tachypnea, hypotonia, lethargy, hallucinations, febrile convulsion, dry mouth, mydriasis or opioid symptoms such as progressive CNS and respiratory depression, miosis, seizures, or paralytic ileus. Diphenoxylate hydrochloride and atropine sulfate tablets may produce drowsiness or dizziness. Concomitant use of alcohol or other drugs that also cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, and muscle relaxants) may increase this effect. Inform patients not to operate motor vehicles or other dangerous machinery until they are reasonably certain that diphenoxylate hydrochloride and atropine sulfate tablets do not affect them adversely. To use fluid and electrolyte therapy, if prescribed along with diphenoxylate hydrochloride and atropine sulfate tablets, as instructed by their healthcare provider. Clinical improvement of diarrhea is usually observed within 48 hours. If clinical improvement is not seen within 10 days, discontinue diphenoxylate hydrochloride and atropine sulfate tablets and contact their healthcare provider. Drug Interactions Alcohol Alcohol may increase the CNS depressant effects of diphenoxylate hydrochloride and atropine sulfate tablets and may cause drowsiness (see WARNINGS). Avoid concomitant use of diphenoxylate hydrochloride and atropine sulfate tablets with alcohol. Other Drugs that Cause CNS Depression The concurrent use of diphenoxylate hydrochloride and atropine sulfate tablets with other drugs that cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, muscle relaxants), may potentiate the effects of diphenoxylate hydrochloride and atropine sulfate tablets (see WARNINGS). Either diphenoxylate hydrochloride and atropine sulfate tablets or the other interacting drug should be chosen, depending on the importance of the drug to the patient. If CNS-acting drugs cannot be avoided, monitor patients for CNS adverse reactions. MAO Inhibitors Diphenoxylate may interact with monoamine oxidase inhibitors (MAOIs) and precipitate a hypertensive crisis . Avoid use of diphenoxylate hydrochloride and atropine sulfate tablets in patients who take MAOIs and monitor for signs and symptoms of hypertensive crisis (headache, hyperthermia, hypertension). 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 tablets in humans is unknown. Pregnancy 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. Diphenoxylate hydrochloride and atropine sulfate tablets 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 tablets are 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 The safety and effectiveness of diphenoxylate hydrochloride and atropine sulfate tablets have been established in pediatric patients 13 years of age and older as adjunctive therapy in the management of diarrhea. The safety and effectiveness of diphenoxylate hydrochloride and atropine sulfate tablets have not been established in pediatric patients less than 13 years of age. Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in pediatric patients less than 6 years of age due to the risks of severe respiratory depression and coma, possibly resulting in permanent brain damage or death (see CONTRAINDICATIONS). Diphenoxylate hydrochloride and atropine sulfate tablets have caused atropinism, particularly in pediatric patients with Down’s syndrome (see PRECAUTIONS). In case of accidental ingestion of diphenoxylate hydrochloride and atropine sulfate tablets by pediatric patients, see OVERDOSAGE for recommended treatment.
Adverse reactions
ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in labeling: Respiratory and/or CNS depression (see WARNINGS) Anticholinergic and opioid-toxicities, including atroponism (see WARNINGS and PRECAUTIONS) Dehydration and electrolyte imbalance (see WARNINGS) GI Complications in patients with infectious diarrhea (see WARNINGS) Toxic megacolon in patients with acute ulcerative colitis (see WARNINGS) At therapeutic doses of diphenoxylate hydrochloride and atropine sulfate tablets, the following other adverse reactions 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, hallucination Allergic: anaphylaxis, angioneurotic edema, urticaria, swelling of the gums, pruritus Gastrointestinal system: megacolon, paralytic ileus, pancreatitis, vomiting, nausea, anorexia, abdominal discomfort The following adverse reactions related to atropine sulfate are listed in decreasing order of severity, but not of frequency: hyperthermia, tachycardia, urinary retention, flushing, dryness of the skin and mucous membranes.

Usage information

Dosing and administration
DOSAGE AND ADMINISTRATION Management of Diarrhea in Patients 13 Years of Age and Older Diphenoxylate hydrochloride and atropine sulfate tablets are recommended as adjunctive therapy for the management of diarrhea in patients 13 years of age and older. Consider the nutritional status and degree of dehydration in patients prior to initiating therapy with diphenoxylate hydrochloride and atropine sulfate tablets. The use of diphenoxylate hydrochloride and atropine sulfate tablets should be accompanied by appropriate fluid and electrolyte therapy, when indicated. If severe dehydration or electrolyte imbalance is present, do not administer diphenoxylate hydrochloride and atropine sulfate tablets until appropriate corrective therapy has been indicated (see WARNINGS). Initial and Maximum Recommended Dosage in Patients 13 Years of Age and Older The initial adult dosage is 2 diphenoxylate hydrochloride and atropine sulfate tablets four times daily (maximum total daily dose of 20 mg per day of diphenoxylate hydrochloride). Most patients will require this dosage until initial control of diarrhea has been achieved. Clinical improvement of acute diarrhea is usually observed within 48 hours. Dosage after Initial Control of Diarrhea After initial control has been achieved, the diphenoxylate hydrochloride and atropine sulfate tablet dosage may be reduced to meet individual requirements. Control may often be maintained with as little as two diphenoxylate hydrochloride and atropine sulfate tablets daily. Duration of Treatment If clinical improvement of chronic diarrhea after treatment with the maximum recommended daily dosage is not observed within 10 days, discontinue diphenoxylate hydrochloride and atropine sulfate tablets as symptoms are unlikely to be controlled by further administration.
Pregnancy and lactation
Nursing Mothers Caution should be exercised when diphenoxylate hydrochloride and atropine sulfate tablets are 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 Alcohol Alcohol may increase the CNS depressant effects of diphenoxylate hydrochloride and atropine sulfate tablets and may cause drowsiness (see WARNINGS). Avoid concomitant use of diphenoxylate hydrochloride and atropine sulfate tablets with alcohol. Other Drugs that Cause CNS Depression The concurrent use of diphenoxylate hydrochloride and atropine sulfate tablets with other drugs that cause CNS depression (e.g., barbiturates, benzodiazepines, opioids, buspirone, antihistamines, muscle relaxants), may potentiate the effects of diphenoxylate hydrochloride and atropine sulfate tablets (see WARNINGS). Either diphenoxylate hydrochloride and atropine sulfate tablets or the other interacting drug should be chosen, depending on the importance of the drug to the patient. If CNS-acting drugs cannot be avoided, monitor patients for CNS adverse reactions. MAO Inhibitors Diphenoxylate may interact with monoamine oxidase inhibitors (MAOIs) and precipitate a hypertensive crisis . Avoid use of diphenoxylate hydrochloride and atropine sulfate tablets in patients who take MAOIs and monitor for signs and symptoms of hypertensive crisis (headache, hyperthermia, hypertension).

More information

Category Value
Authorisation number ANDA085762
Agency product number W24OD7YW48
Orphan designation No
Product NDC 55289-102
Date Last Revised 28-06-2018
Type HUMAN PRESCRIPTION DRUG
Marketing authorisation holder PD-Rx Pharmaceuticals, Inc.