Diphenoxylate Hydrochloride And Atropine Sulfate

FDA Drug Information • Also known as: Diphenoxylate Hydrochloride And Atropine Sulfate, Lomotil

Brand Names: Diphenoxylate Hydrochloride And Atropine Sulfate, Lomotil
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

DESCRIPTION Each Diphenoxylate Hydrochloride and Atropine Sulfate Tablet USP contains: 2.5 mg of diphenoxylate hydrochloride USP (equivalent to 2.3 mg of diphenoxylate) and 0.025 mg of atropine sulfate USP (equivalent to 0.01 mg of atropine) 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. Each diphenoxylate hydrochloride and atropine sulfate tablet contains the following inactive ingredients: confectioner’s sugar, corn starch, lactose monohydrate, magnesium stearate, and sodium starch glycolate.

What Is Diphenoxylate Hydrochloride And Atropine Sulfate Used For?

INDICATIONS AND USAGE Diphenoxylate Hydrochloride and Atropine Sulfate Tablets USP are indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older.

Dosage 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. The use of this product 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 two 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 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.

Side Effects (Adverse Reactions)

ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling:

Respiratory and/or CNS depression (see WARNINGS )

Anticholinergic and opioid-toxicities, including atropinism (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, 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.

Warnings and Precautions

WARNINGS Respiratory and/or CNS Depression in Pediatric Patients Less than 6 Years of Age Cases of severe respiratory depression and coma, leading to permanent brain damage or death have been reported in patients less than 6 years of age who received diphenoxylate hydrochloride and atropine sulfate tablets. Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in patients less than 6 years of age due to these risks (see CONTRAINDICATIONS ). Anticholinergic and Opioid-Toxicities Toxicities associated with the atropine and diphenoxylate components of this product have been reported. The initial presenting symptoms may be delayed by up to 30 hours due to prolonged gastric emptying time induced by the diphenoxylate hydrochloride. Clinical presentations vary in terms of which toxicity (anticholinergic vs. opioid) will present first or predominate; non-specific findings have been reported and include symptoms such as drowsiness (see OVERDOSAGE ). Dehydration and Electrolyte Imbalance 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, diphenoxylate hydrochloride and atropine sulfate tablets should be withheld until appropriate corrective therapy has been initiated. Drug-induced inhibition of peristalsis may result in fluid retention in the intestine, which may further aggravate dehydration and electrolyte imbalance. Gastrointestinal Complications in Patients with Infectious Diarrhea Diphenoxylate hydrochloride and atropine sulfate tablets are contraindicated in patients with diarrhea associated with organisms that penetrate the GI mucosa (toxigenic E. coli , Salmonella , Shigella ), and pseudomembranous enterocolitis ( Clostridium difficile ) associated with broad-spectrum antibiotics (see CONTRAINDICATIONS ). Antiperistaltic agents, including diphenoxylate hydrochloride and atropine sulfate, slow gastrointestinal motility and may enhance bacterial overgrowth and the release of bacterial exotoxins. Diphenoxylate hydrochloride and atropine sulfate has been reported to result in serious GI complications in patients with infectious diarrhea, including sepsis, prolonged and/or worsened diarrhea. Prolonged fever and the delay in the resolution of stool pathogens were reported in study of Shigellosis in adults who used diphenoxylate hydrochloride and atropine sulfate vs. placebo. Toxic Megacolon in Patients with Acute Ulcerative Colitis In some patients with acute ulcerative colitis, agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Consequently, patients with acute ulcerative colitis should be carefully observed and diphenoxylate hydrochloride and atropine sulfate therapy should be discontinued promptly if abdominal distention occurs or if other untoward symptoms develop. Interaction with Meperidine...

Drug Interactions

Drug Interactions Alcohol Alcohol may increase the CNS depressant effects of diphenoxylate hydrochloride and atropine sulfate 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 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 (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).

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.

Pregnancy and Breastfeeding

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.

Overdosage

OVERDOSAGE Diagnosis Overdosage can be life-threatening. Symptoms of overdosage may include opioid and/or anticholinergic effects including respiratory depression, coma, delirium, lethargy, dryness of the skin and mucous membranes, mydriasis or miosis, flushing, hyperthermia, tachycardia, hypotonia, tachypnea, toxic encephalopathy, seizures and incoherent speech. Respiratory depression has been reported up to 30 hours after ingestion and may recur despite an initial response to narcotic antagonists. Treat all possible diphenoxylate hydrochloride and atropine sulfate overdosages as serious and maintain medical observation/hospitalization until patients become asymptomatic without naloxone use. Treatment A pure narcotic antagonist (e.g., naloxone) should be used in the treatment of respiratory depression caused by diphenoxylate hydrochloride and atropine sulfate. Refer to the prescribing information for naloxone. Consider diphenoxylate hydrochloride and atropine sulfate toxicity even in settings of negative toxicology tests. Following initial improvement of respiratory function, repeated doses of naloxone hydrochloride may be required to counteract recurrent respiratory depression. If over-exposure occurs, call your Poison Control Center at 1-800-222-1222 for current information of the management of poisoning or overdosage.

How Supplied

HOW SUPPLIED Diphenoxylate Hydrochloride and Atropine Sulfate Tablets USP are available as round white tablets debossed ‘490’ on one side and plain on the other side. Each tablet contains 2.5 mg of diphenoxylate hydrochloride and 0.025 mg of atropine sulfate and are supplied as: NDC Number Size 63629-1933-1 Bottle of 100 tablets Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [See USP controlled room temperature]. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.