DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE solution

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:

Hikma Pharmaceuticals USA Inc.

INN (International Name):

DIPHENOXYLATE HYDROCHLORIDE

Composition:

DIPHENOXYLATE HYDROCHLORIDE 2.5 mg in 5 mL

Administration route:

ORAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Diphenoxylate hydrochloride and atropine sulfate is indicated as adjunctive therapy in the management of diarrhea in patients 13 years of age and older. Diphenoxylate hydrochloride and atropine sulfate is contraindicated in: Diphenoxylate hydrochloride and atropine sulfate oral solution is 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

Product summary:

Diphenoxylate Hydrochloride 2.5 mg and Atropine Sulfate 0.025 mg per 5 mL Oral Solution, USP The 2.5 mg/0.025 mg per 5 mL oral solution is supplied as a (cherry-flavored) clear, orange-colored solution. NDC 0054-3194-46: Bottle of 60 mL Oral Solution: Dispense only in original container. A plastic oral syringe calibrated in increments of 1/2 mL (1/4 mg) with a capacity of 3 mL (1.5 mg) accompanies each 2 oz bottle of Diphenoxylate Hydrochloride and Atropine Sulfate Oral Solution, USP. Only this plastic oral syringe should be used when measuring Diphenoxylate Hydrochloride and Atropine Sulfate Oral Solution, USP for administration to children. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Discard open bottle after 90 days. Distributed by: Hikma Pharmaceuticals USA Inc. Berkeley Heights, NJ 07922 C50000486/01 Revised February 2023

Authorization status:

Abbreviated New Drug Application

Summary of Product characteristics

DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE- DIPHENOXYLATE
HYDROCHLORIDE AND ATROPINE SULFATE SOLUTION
HIKMA PHARMACEUTICALS USA INC.
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DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE ORAL SOLUTION, USP
FOR ORAL USE, C-V
RX ONLY
DESCRIPTION
Each 5 mL of oral solution contains:
2.5 mg of diphenoxylate hydrochloride (equivalent to 2.3 mg of
diphenoxylate),
0.025 mg of atropine sulfate (equivalent to 0.01 mg of atropine), and
15% alcohol.
Diphenoxylate hydrochloride, an antidiarrheal, is ethyl
1-(3-cyano-3,3-diphenylpropyl)-4-
phenylisoni-pecotate monohydrochloride and has the following
structural formula:
C
H
N O · HCL M.W. 489.05
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:
30 32 2
2
(C
H
NO ) · H SO · H O M.W. 694.83
A subtherapeutic amount of atropine sulfate is present to discourage
deliberate
overdosage.
Inactive ingredients of diphenoxylate hydrochloride and atropine
sulfate oral solution
include alcohol, anhydrous citric acid, FD&C Red No. 40, FD&C Yellow
No. 6, glycerin,
maltol, potassium sorbate, purified water, sorbitol solution and wild
cherry flavor.
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
hydrochlori