DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE tablet

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

DIPHENOXYLATE HYDROCHLORIDE (UNII: W24OD7YW48) (DIPHENOXYLATE - UNII:73312P173G), ATROPINE SULFATE (UNII: 03J5ZE7KA5) (ATROPINE - UNII:7C0697DR9I)

Available from:

Bayshore Pharmaceuticals, LLC

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Diphenoxylate hydrochloride and atropine sulfate tablets are indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older. 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. Diphenoxylate hydrochloride and atropine sulfate tablets are classified as a Schedule V controlled substance by federal regulation. Diphenoxylate hydrochloride is chemically related to the narcotic analgesic meperidine. In doses used for the treatment of diarrhea, whether acute or chronic, diphenoxylate has not produced addiction. Diphenoxylate hydrochloride is devoid of morphine-like subjective effects at therapeutic doses. At high doses it exhibits codeine-like subjective effects. The dose which produces antidiarrheal action is widely separated from the dose which causes central nervous system effects. The insolubility of diphenoxylate hydrochloride in commonly available aqueous media precludes intravenous self-administration. A dose of 100 to 300 mg/day, which is equivalent to 40 to 120 tablets, administered to humans for 40 to 70 days, produced opiate withdrawal symptoms. Since addiction to diphenoxylate hydrochloride is possible at high doses, the recommended dosage should not be exceeded.

Product summary:

Tablets — round, off-white to white tablet with BY3 on one side; and plain on the other side and containing 2.5 mg of diphenoxylate hydrochloride and 0.025 mg of atropine sulfate, supplied as: Store below 25°C (77°F). Rx only Distributed By: Bayshore Pharmaceuticals, LLC Short Hills, NJ 07078 Revised 02/2019

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE- DIPHENOXYLATE
HYDROCHLORIDE AND ATROPINE SULFATE TABLET
BAYSHORE PHARMACEUTICALS, LLC
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DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE TABLETS, FOR ORAL
USE, C-V
DESCRIPTION
Each diphenoxylate hydrochloride and atropine sulfate tablet 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.
Inactive ingredients of diphenoxylate hydrochloride and atropine
sulfate tablets include
mannitol, pregelatinized starch, hypromellose, colloidal silicon
dioxide, magnesium
stearate
CLINICAL PHARMACOLOGY
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-