diphenoxylate HCl 2.5 MG / atropine sulfate 0.025 MG Oral Tablet
Generic Name: DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE
Brand Name: Diphenoxylate Hydrochloride and Atropine Sulfate
- Substance Name(s):
- ATROPINE SULFATE
- DIPHENOXYLATE HYDROCHLORIDE
WARNINGS
DIPHENOXYLATE HYDROCHLORIDE IS NOT AN INNOCUOUS DRUG AND DOSAGE RECOMMENDATIONS SHOULD BE STRICTLY ADHERED TO, ESPECIALLY IN CHILDREN.
DIPHENOXYLATE HYDROCHLORIDE IS NOT RECOMMENDED FOR CHILDREN UNDER 2 YEARS OF AGE.
OVERDOSAGE MAY RESULT IN SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH (SEE OVERDOSAGE ).
THEREFORE, KEEP THIS MEDICATION OUT OF THE REACH OF CHILDREN.
THE USE OF DIPHENOXYLATE HYDROCHLORIDE SHOULD BE ACCOMPANIED BY APPROPRIATE FLUID AND ELECTROLYTE THERAPY, WHEN INDICATED.
IF SEVERE DEHYDRATION OR ELECTROLYTE IMBALANCE IS PRESENT, DIPHENOXYLATE HYDROCHLORIDE 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.
DIPHENOXYLATE HYDROCHLORIDE SHOULD BE USED WITH SPECIAL CAUTION IN YOUNG CHILDREN BECAUSE THIS AGE GROUP MAY BE PREDISPOSED TO DELAYED DIPHENOXYLATE TOXICITY AND BECAUSE OF THE GREATER VARIABILITY OF RESPONSE IN THIS AGE GROUP.
Antiperistaltic agents may prolong and/or worsen diarrhea associated with organisms that penetrate the intestinal mucosa (toxigenic E.
coli, Salmonella, Shigella), and pseudomembranous enterocolitis associated with broad-spectrum antibiotics.
Antiperistaltic agents should not be used in these conditions.
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 therapy should be discontinued promptly if abdominal distention occurs or if other untoward symptoms develop.
Since the chemical structure of diphenoxylate hydrochloride is similar to that of meperidine hydrochloride, the concurrent use of diphenoxylate hydrochloride with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis.
Diphenoxylate hydrochloride should be used with extreme caution in patients with advanced hepatorenal disease and in all patients with abnormal liver function since hepatic coma may be precipitated.
Diphenoxylate hydrochloride may potentiate the action of barbiturates, tranquilizers, and alcohol.
Therefore, the patient should be closely observed when any of these are used concomitantly.
DRUG INTERACTIONS
Drug interactions Known drug interactions include barbiturates, tranquilizers, and alcohol.
Diphenoxylate hydrochloride may interact with MAO inhibitors (see Warnings ).
In studies with male rats, diphenoxylate hydrochloride was found to inhibit the hepatic microsomal enzyme system at a dose of 2 mg/kg/day.
Therefore, diphenoxylate has the potential to prolong the biological half-lives of drugs for which the rate of elimination is dependent on the microsomal drug metabolizing enzyme system.
OVERDOSAGE
RECOMMENDED DOSAGE SCHEDULES SHOULD BE STRICTLY FOLLOWED.
THIS MEDICATION SHOULD BE KEPT IN A CHILD-RESISTANT CONTAINER AND OUT OF THE REACH OF CHILDREN, SINCE AN MAY RESULT IN SEVERE, EVEN FATAL, RESPIRATORY DEPRESSION.
Diagnosis Initial signs of overdosage may include dryness of the skin and mucous membranes, mydriasis, restlessness, flushing, hyperthermia, and tachycardia followed by lethargy or coma, hypotonic reflexes, nystagmus, pinpoint pupils, and respiratory depression.
Respiratory depression may be evidenced as late as 30 hours after ingestion and may recur despite an initial response to narcotic antagonists.
TREAT ALL POSSIBLE DIPHENOXYLATE HYDROCHLORIDE S AS SERIOUS AND MAINTAIN MEDICAL OBSERVATION FOR AT LEAST 48 HOURS, PREFERABLY UNDER CONTINUOUS HOSPITAL CARE.
Treatment In the event of overdose, induction of vomiting, gastric lavage, establishment of a patent airway, and possibly mechanically assisted respiration are advised.
In vitro and animal studies indicate that activated charcoal may significantly decrease the bioavailability of diphenoxylate.
In noncomatose patients, a slurry of 100 g of activated charcoal can be administered immediately after the induction of vomiting or gastric lavage.
A pure narcotic antagonist (e.g., naloxone) should be used in the treatment of respiratory depression caused by diphenoxylate hydrochloride.
When a narcotic antagonist is administered intravenously, the onset of action is generally apparent within two minutes.
It may also be administered subcutaneously or intramuscularly, providing a slightly less rapid onset of action but a more prolonged effect.
To counteract respiratory depression caused by diphenoxylate hydrochloride overdosage, the following dosage schedule for the narcotic antagonist naloxone hydrochloride should be followed: Adult dosage An initial dose of 0.4 mg to 2 mg of naloxone hydrochloride may be administered intravenously.
If the desired degree of counteraction and improvement in respiratory functions is not obtained, it may be repeated at 2- to 3-minute intervals.
If no response is observed after 10 mg of naloxone hydrochloride has been administered, the diagnosis of narcotic-induced or partial narcotic-induced toxicity should be questioned.
Intramuscular or subcutaneous administration may be necessary if the intravenous route is not available.
Children The usual initial dose in children is 0.01 mg/kg body weight given I.V.
If this dose does not result in the desired degree of clinical improvement, a subsequent dose of 0.1 mg/kg body weight may be administered.
If an I.V.
route of administration is not available, naloxone hydrochloride may be administered I.M.
or S.C.
in divided doses.
If necessary, naloxone hydrochloride can be diluted with sterile water for injection.
Following initial improvement of respiratory function, repeated doses of naloxone hydrochloride may be required to counteract recurrent respiratory depression.
Supplemental intramuscular doses of naloxone hydrochloride may be utilized to produce a longer-lasting effect.
Since the duration of action of diphenoxylate hydrochloride is longer than that of naloxone hydrochloride, improvement of respiration following administration may be followed by recurrent respiratory depression.
Consequently, continuous observation is necessary until the effect of diphenoxylate hydrochloride on respiration has passed.
This effect may persist for many hours.
The period of observation should extend over at least 48 hours, preferably under continuous hospital care.
Although signs of overdosage and respiratory depression may not be evident soon after ingestion of diphenoxylate hydrochloride, respiratory depression may occur from 12 to 30 hours later.
DESCRIPTION
Each diphenoxylate hydrochloride and atropine sulfate tablet contains: diphenoxylate hydrochloride 2.5 mg atropine sulfate 0.025 mg 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 tablets include acacia, corn starch, magnesium stearate, sorbitol, sucrose, and talc.
Chemical Structure Chemical Structure
HOW SUPPLIED
Product: 50436-3763 NDC: 50436-3763-5 10 TABLET in a BOTTLE
INDICATIONS AND USAGE
Diphenoxylate hydrochloride is effective as adjunctive therapy in the management of diarrhea.
PEDIATRIC USE
Pediatric use Diphenoxylate hydrochloride may be used as an adjunct to the treatment of diarrhea but should be accompanied by appropriate fluid and electrolyte therapy, if needed.
DIPHENOXYLATE HYDROCHLORIDE IS NOT RECOMMENDED FOR CHILDREN UNDER 2 YEARS OF AGE.
Diphenoxylate hydrochloride should be used with special caution in young children because of the greater variability of response in this age group.
See Warnings and Dosage and Administration .
In case of accidental ingestion by children, see Overdosage for recommended treatment.
PREGNANCY
Pregnancy Pregnancy Category C 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 should be used during pregnancy only if the anticipated benefit justifies the potential risk to the fetus.
NUSRING MOTHERS
Nursing mothers Caution should be exercised when diphenoxylate hydrochloride is 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.
INFORMATION FOR PATIENTS
Information for patients INFORM THE PATIENT (PARENT OR GUARDIAN) NOT TO EXCEED THE RECOMMENDED DOSAGE AND TO KEEP DIPHENOXYLATE HYDROCHLORIDE OUT OF THE REACH OF CHILDREN AND IN A CHILD-RESISTANT CONTAINER.
INFORM THE PATIENT OF THE CONSEQUENCES OF OVERDOSAGE, INCLUDING SEVERE RESPIRATORY DEPRESSION AND COMA, POSSIBLY LEADING TO PERMANENT BRAIN DAMAGE OR DEATH.
Diphenoxylate hydrochloride may produce drowsiness or dizziness.
The patient should be cautioned regarding activities requiring mental alertness, such as driving or operating dangerous machinery.
Potentiation of the action of alcohol, barbiturates, and tranquilizers with concomitant use of diphenoxylate hydrochloride should be explained to the patient.
The physician should also provide the patient with other information in this labeling, as appropriate.
DOSAGE AND ADMINISTRATION
DO NOT EXCEED RECOMMENDED DOSAGE.
Adults The recommended initial dosage is two diphenoxylate hydrochloride tablets four times daily .
Most patients will require this dosage until initial control has been achieved, after which the dosage may be reduced to meet individual requirements.
Control may often be maintained with as little as 5 mg (two tablets) daily.
Clinical improvement of acute diarrhea is usually observed within 48 hours.
If clinical improvement of chronic diarrhea after treatment with a maximum daily dose of 20 mg of diphenoxylate hydrochloride is not observed within 10 days, symptoms are unlikely to be controlled by further administration.
Children Diphenoxylate hydrochloride is not recommended in children under 2 years of age and should be used with special caution in young children (see Warnings and Precautions ).
The nutritional status and degree of dehydration must be considered.
Do not use diphenoxylate hydrochloride tablets for children under 13 years of age .
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.