Get your patient on Diphenoxylate Hydrochloride And Atropine Sulfate - Diphenoxylate Hydrochloride And Atropine Sulfate tablet (Diphenoxylate Hydrochloride And Atropine Sulfate)

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

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.

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.

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.

CALL YOUR DOCTOR FOR MEDICAL ADVICE ABOUT SIDE EFFECTS. YOU MAY REPORT SIDE EFFECTS TO THE FDA AT 1-800-FDA-1088 OR LEADING PHARMA, LLC AT 1-844-740-7500.

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).

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-(±)-alpha-(hydroxymethyl) benzeneacetic acid 8-methyl-8- azabicylo[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 diphenoxylate hydrochloride and atropine sulfate tablets include colloidal silicon dioxide, lactose monohydrate, microcrystalline cellulose, pregelatinized starch and stearic acid.

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 diphenoxylate hydrochloride and atropine sulfate 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.

Tablets - White to off-white, round, tablet debossed with "LP" over "910" on one side and plain on the other side and containing 2.5 mg of diphenoxylate hydrochloride, USP and 0.025 mg of atropine sulfate, USP.

Supplied as:

NDC 69315-910-09

bottles of 90 tablets

NDC 69315-910-01

bottles of 100 tablets

NDC 69315-910-10

bottles of 1000 tablets

Store below 25°C (77°F).

Rx only

Manufactured and Distributed by :

Leading Pharma, LLC

Fairfield, NJ 07004

Rev. 03 10/22