Diphenoxylate and atropine

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 OVERDOSAGE 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 LOMOTIL OVERDOSAGES 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 (eg, naloxone) should be used in the treatment of respiratory depression caused by Lomotil. 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 Lomotil 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 narcoticinduced 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.

• Diarrhea
• Travelers' Diarrhea

If diphenoxylate and atropine upsets your stomach, your doctor may want you to take it with food.

Take diphenoxylate and atropine only as directed by your doctor . Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. If too much is taken, it may become habit-forming.

For patients taking the liquid form of diphenoxylate and atropine:

• diphenoxylate and atropine is to be taken by mouth even if it comes in a dropper bottle. The amount to be taken is to be measured with the specially marked dropper.

Importance of diet and fluids while treating diarrhea :

• In addition to using medicine for diarrhea, it is very important that you replace the fluid lost by the body and follow a proper diet. For the first 24 hours you should eat gelatin and drink plenty of caffeine-free clear liquids, such as ginger ale, decaffeinated cola, decaffeinated tea, and broth. During the next 24 hours you may eat bland foods, such as cooked cereals, bread, crackers, and applesauce. Fruits, vegetables, fried or spicy foods, bran, candy, caffeine, and alcoholic beverages may make the condition worse.
• If too much fluid has been lost by the body due to the diarrhea a serious condition may develop. Check with your doctor as soon as possible if any of the following signs or symptoms of too much fluid loss occur:
  • Decreased urination
  • Dizziness and light-headedness
  • Dryness of mouth
  • Increased thirst
  • Wrinkled skin

Dosing

The dose of diphenoxylate and atropine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of diphenoxylate and atropine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For severe diarrhea:
  • For oral dosage form (oral solution):
    • Adults and teenagers—At first, the dose is 5 milligrams (mg) (2 teaspoonfuls) three or four times a day. Then, the dose is usually 5 mg (2 teaspoonfuls) once a day, as needed.
    • Children up to 12 years of age—Use is not recommended.
  • For oral dosage form (tablets):
    • Adults and teenagers—At first, the dose is 5 mg (2 tablets) three or four times a day. Then, the dose is usually 5 mg (2 tablets) once a day, as needed.
    • Children up to 12 years of age—Use is not recommended.

Missed Dose

If you miss a dose of diphenoxylate and atropine, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Bloating
• constipation
• loss of appetite
• stomach pain (severe) with nausea and vomiting

Check with your doctor immediately if any of the following side effects occur:

• Blurred vision (continuing) or changes in near vision
• drowsiness (severe)
• dryness of mouth, nose, and throat (severe)
• fast heartbeat
• shortness of breath or troubled breathing (severe)
• unusual excitement, nervousness, restlessness, or irritability
• unusual warmth, dryness, and flushing of the skin

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blurred vision
• confusion
• difficult urination
• dizziness or light-headedness
• drowsiness
• dryness of skin and mouth
• fever
• headache
• increased body temperature
• mental depression
• numbness of hands or feet
• skin rash or itching
• swelling of the gums

After you stop using diphenoxylate and atropine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:

• Increased sweating
• muscle cramps
• nausea or vomiting
• shivering or trembling
• stomach cramps

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

THIS IS NOT AN INNOCUOUS DRUG AND DOSAGE RECOMMENDATIONS SHOULD BE STRICTLY ADHERED TO, ESPECIALLY IN CHILDREN. DIPHENOXYLATE HYDROCHLORIDE AND ATROPINE SULFATE 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 AND ATROPINE SULFATE SHOULD BE ACCOMPANIED BY APPROPRIATE FLUID AND ELECTROLYTE THERAPY, WHEN INDICATED. IF SEVERE DEHYDRATION OR ELECTROLYTE IMBALANCE IS PRESENT, THIS PRODUCT 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 AND ATROPINE SULFATE 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 and atropine sulfate 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 this product with monoamine oxidase (MAO) inhibitors may, in theory, precipitate hypertensive crisis.

This product 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.

Controlled Substance

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.

Drug Abuse and Dependence

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.

Diphenoxylate Hydrochloride and Atropine Sulfate Tablets USP, CV
2.5 mg / 0.025 mg
NDC 62559-490-01
Rx Only
100 Tablets

Diphenoxylate inhibits excessive GI motility and GI propulsion; commercial preparations contain a subtherapeutic amount of atropine to discourage abuse

Absorption

Diphenoxylate: Well absorbed

Metabolism

Diphenoxylate: Extensively hepatic via ester hydrolysis to diphenoxylic acid (active)

Excretion

Diphenoxylate: Primarily feces (49% as unchanged drug and metabolites); urine (~14%, [<1%] and metabolites)

There are no specific dosage adjustments provided in the manufacturer’s labeling. Use with extreme caution in patients with abnormal hepatic function and in advanced hepatorenal disease.

Use of the liquid preparation is recommended in children <13 years of age; use only plastic dropper provided when measuring liquid. Dropper has a 2 mL (1 mg) capacity and is calibrated in increments of 1/2 mL (0.25 mg).