In the U.S.—

• Antidiarrheal, antiperistaltic

Difenoxin and atropine (dye-fen-OX-in and A-troe-peen ) combination medicine is used along with other measures to treat severe diarrhea in adults. Difenoxin helps stop diarrhea by slowing down the movements of the intestines.

Since difenoxin is chemically related to some narcotics, it may be habit-forming if taken in doses that are larger than prescribed. To help prevent possible abuse, atropine (an anticholinergic) has been added. If higher-than-normal doses of the combination are taken, the atropine will cause unpleasant effects, making it unlikely that such doses will be taken again.

Difenoxin and atropine combination medicine should not be used in children. Children with diarrhea should be given solutions of carbohydrates (sugars) and electrolytes (important salts) to replace the water and important salts that are lost from the body during diarrhea.

This medicine is available only with your doctor's prescription, in the following dosage form:

Oral
• Tablets (U.S.)

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For difenoxin and atropine, the following should be considered:

Allergies—Tell your doctor if you have ever had any unusual or allergic reaction to difenoxin or atropine. Also tell your health care professional if you are allergic to any other substances, such as foods, preservatives, or dyes.

Pregnancy—Difenoxin and atropine combination has not been studied in pregnant women. However, studies in rats have shown that difenoxin and atropine combination, when given in doses many times the human dose, increases the delivery time and the chance of death of the newborn.

Breast-feeding—Both difenoxin and atropine pass into the breast milk. Although it is not known how much of these drugs pass into the breast milk, difenoxin and atropine combination could cause serious effects in the nursing baby. Be sure you have discussed the risks and benefits of this medicine with your doctor.

Children—This medicine should not be used in children. Children, especially very young children, are very sensitive to the effects of difenoxin and atropine. This may increase the chance of side effects during treatment. Also, the fluid loss caused by diarrhea may result in a severe condition. For this reason, it is very important that a sufficient amount of liquids be given to replace the fluid lost by the body. If you have any questions about this, check with your health care professional.

Older adults—Shortness of breath or difficulty in breathing may be more likely to occur in elderly patients, who are usually more sensitive than younger adults to the effects of difenoxin. Also, the fluid loss caused by diarrhea may result in a severe condition. For this reason, elderly persons should not take this medicine without first checking with their doctor. It is also very important that a sufficient amount of liquids be taken to replace the fluid lost by the body. If you have any questions about this, check with your health care professional.

Other medicines—Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking difenoxin and atropine, it is especially important that your health care professional know if you are taking any of the following:

• Antibiotics, such as cephalosporins (e.g., Ceftin, Keflex), clindamycin (e.g., Cleocin), erythromycins (e.g., E.E.S., PCE), tetracyclines (e.g., Achromycin, Doryx)—These antibiotics may cause diarrhea. Difenoxin and atropine may make the diarrhea caused by antibiotics worse or make it last longer

• Central nervous system (CNS) depressants (medicines that cause drowsiness)—Effects, such as drowsiness, of CNS depressants or of difenoxin and atropine may become greater

• Monoamine oxidase (MAO) inhibitors (furazolidone [e.g., Furoxone], isocarboxazid [e.g., Marplan], phenelzine [e.g., Nardil], procarbazine [e.g., Matulane], tranylcypromine [e.g., Parnate])—Taking difenoxin and atropine while you are taking or within 2 weeks of taking MAO inhibitors may cause severe side effects; these medicines should not be used together

• Naltrexone (e.g., Trexan)—Withdrawal side effects may occur in patients who have become addicted to the difenoxin in this combination medicine; also, naltrexone will make this medicine less effective against diarrhea

• Other anticholinergics (medicine to help reduce stomach acid and abdominal or stomach spasms or cramps)—Use of other anticholinergics with this combination medicine may increase the effects of the atropine in this combination; however, this is not likely to happen with the usual doses of difenoxin and atropine

• Alcohol abuse (or history of) or
• Drug abuse (history of)—There is a greater chance that this medicine may become habit-forming

• Colitis (severe)—A more serious problem of the colon may develop if you use this medicine

• Down's syndrome—Side effects may be more likely and severe in these patients

• Dysentery—This condition may get worse; a different kind of treatment may be needed

• Emphysema, asthma, bronchitis, or other chronic lung disease—There is a greater chance that this medicine may cause breathing problems in patients who have any of these conditions

• Enlarged prostate or
• Urinary tract blockage or difficult urination—Problems with urination may develop with the use of this medicine

• Gallbladder disease or gallstones—Use of this medicine may cause spasms of the biliary tract and make the condition worse

• Glaucoma—Severe pain in the eye may occur with the use of this medicine; however, the chance of this happening is low

• Heart disease—This medicine may have some effects on the heart, which may make the condition worse

• Hiatal hernia—The atropine in this medicine may make this condition worse; however, the chance of this happening is low

• High blood pressure (hypertension)—The atropine in this medicine may cause an increase in blood pressure; however, the chance of this happening is low

• Intestinal blockage—This medicine may make the condition worse

• Kidney disease—The atropine in this medicine may build up in the body and cause side effects

• Liver disease—The chance of central nervous system (CNS) side effects, including coma, may be greater in patients who have this condition

• Myasthenia gravis—This medicine may make the condition worse

• Overactive or underactive thyroid—Unwanted effects on breathing and heart rate may occur

• Overflow incontinence—This medicine may make the condition worse

If this medicine upsets your stomach, your doctor may want you to take it with food.

Take this medicine 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.

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 symptoms of too much fluid loss occur:
  • Decreased urination
  • Dizziness and lightheadedness
  • Dryness of mouth
  • Increased thirst
  • Wrinkled skin

Dosing—

The dose of difenoxin and atropine combination medicine 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 difenoxin and atropine combination. If your dose is different, do not change it unless your doctor tells you to do so.

• For oral dosage form (tablets):
  • For severe diarrhea:
    • Adults and teenagers—The first dose is usually 2 milligrams (mg). After that, the dose is 1 mg taken after each loose stool or every three or four hours as needed. Do not take more than 8 mg in any twenty-four-hour period.
    • Children—Use is not recommended.

Missed dose—

If you are taking this medicine on a regular schedule and you miss a dose, 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—

To store this medicine:

• Keep out of the reach of children. Overdose is especially dangerous in children, and even part of an adult's pill can cause serious problems in children.
• Store away from heat and direct light.
• Do not store in the bathroom, near the kitchen sink, or in other damp places. Heat or moisture may cause the medicine to break down.
• Do not keep outdated medicine or medicine no longer needed. Be sure that any discarded medicine is out of the reach of children.

Your doctor should check your progress at regular visits if you will be taking this medicine regularly for a long time.

Check with your doctor if your diarrhea does not stop after 2 days or if you develop a fever.

This medicine will add to the effects of alcohol and other CNS depressants (medicines that slow down the nervous system, possibly causing drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies, or colds; sedatives, tranquilizers, or sleeping medicine; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are taking this medicine.

If you think you or someone else in your home may have taken an overdose of this medicine, get emergency help at once. Taking an overdose of this medicine may lead to unconsciousness and possibly death. Symptoms of overdose include severe drowsiness; fast heartbeat; shortness of breath or troubled breathing; and unusual warmth, dryness, and flushing of skin.

Before having any kind of surgery (including dental surgery) or emergency treatment, tell the medical doctor or dentist in charge that you are using this medicine.

This medicine may cause some people to become dizzy, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are dizzy or are not alert.

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.

When this medicine is used for short periods of time at low doses, side effects usually are rare. However, check with your doctor immediately if any of the following side effects are severe and occur suddenly, since they may be signs of a more severe and dangerous problem with your bowels:

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

Check with your doctor also if any of the following effects occur, since they may be signs of an overdose of this medicine:

• 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 skin 

Other 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. However, check with your doctor if any of the following side effects continue, worsen, or are bothersome:

• Less common or rare
  • Blurred vision;  confusion;  difficult urination;  dizziness or lightheadedness ;  drowsiness;  dryness of skin and mouth;  fever;  headache;  trouble in sleeping;  unusual tiredness or weakness 
  
  

After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on the amount of medicine you were using and how long you used it. During this period of time check with your doctor if you notice any of the following side effects:

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

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