Antidiarrheal Agents

Key Terms: Anticholinergic agent.

Definition

Antidiarrheal agents are prescription and non-prescription medicines that are used to treat diarrhea.

Purpose

Some types of cancer may cause diarrhea. In addition, diarrhea is a common side effect of chemotherapy treatments for cancer. This is because anticancer drugs can damage the cells of the intestines. Radiation treatment for cancer directed at the abdominal region also may cause diarrhea. Diarrhea can result in dehydration and the loss of minerals such as potassium. It may prevent the elimination of waste products in the urine, as the body attempts to conserve water.

Description

The common medicines for treating diarrhea that results from cancer and cancer treatments are:

• atropine and diphenoxylate
• loperamide
• octreotide
• opium tincture

Atropine and diphenoxylate are prescribed as a combination medicine with the brand names:

• Lofene
• Logen
• Lomocot
• Lomotil
• Lonox
• Vi-Atro The generic name product also may be available. Atropine and diphenoxylate, antiperistaltic and anticholinergic agents, relax muscles and slow down the movements of the gastrointestinal tract. Diphenoxylate is similar to some narcotics and may be habit-forming if taken in dosages higher than prescribed. Since higher doses of atropine have unpleasant effects, it is unlikely that the combination medicine will be taken in high enough doses to cause diphenoxylate dependence.

Loperamide slows down the movements of the intestines. The common brand names for this medicine are:

• Imodium
• Kaopectate II
• Maalox Anti-Diarrheal
• Pepto Diarrhea Control

Octreotide (brand name Sandostatin) is used to treat diarrhea and other symptoms of some types of intestinal cancers. It also is used to treat insulin-producing tumors of the pancreas and diarrhea caused by chemotherapy.

Opium tincture, also known as camphorated opium tincture or laudanum, is a narcotic that is used to treat severe diarrhea.

Except for loperamide liquid or tablets, all of these medicines require a prescription. Dosages vary with the individual.

Recommended Dosage

The atropine-diphenoxylate combination is taken by mouth as a solution or a tablet. It may be taken with food to reduce stomach upset. The initial average dosage is 5 mg (2 tsp or two tablets) three to four times daily. Subsequent doses are once daily, as needed.

Loperamide is taken orally, as a liquid, tablet, or capsule. The usual dosage for adults and teenagers is 4 mg (2 capsules or tablets, 4 tsp of liquid) after the first loose bowel movement, followed by 2 mg after each successive loose bowel movement. The maximum dose is 16 mg of the capsules or 8 mg of the tablets or liquid in 24 hours. Loperamide should not be taken for more than two days unless ordered by a physician.

Following therapy with irinotecan (Camptosar), loperamide doses of 2 mg every two hours while awake and 4 mg every four hours at night are utilized at the onset of diarrhea to prevent severe dehydration and possible hospitalization.

Octreotide is packaged as a kit, for injection into a vein. For treating severe diarrhea from intestinal tumors, the average initial dosage of the long-acting form, for adults and teenagers, is 20 mg injected into the gluteal muscle of the buttocks, once every four weeks for two months. The dosage may then be adjusted by the physician. For the short-acting form, the average initial dose is 50 micrograms (mcg) injected under the skin, two to three times per day. The dosage may be gradually increased up to 600 mcg per day for the first two weeks. The average dosage after two weeks is 50–1500 mcg per day. For children, the usual dosage is 1–10 mcg per kg (0.45–4.5 mcg per lb) of body weight per day.

Opium tincture is taken orally, as a liquid. It may be taken with food to prevent stomach upset. The average adult dose is 5–16 drops, measured from the dropper in the bottle, four times per day, until diarrhea is controlled. It may be diluted with water. After several weeks of treatment, it may be necessary to lower the dosage gradually before stopping the medicine, to lessen the risk of side effects from opium withdrawal.

Precautions

Antidiarrheal agents may cause allergic reactions in some individuals. Atropine and diphenoxylate should not be given to children. Loperamide should not be given to children under six. Opium may cause breathing problems in children up to two years of age. Older adults are more sensitive to diphenoxylate and opium than younger individuals and these drugs may cause breathing problems. Diphenoxylate and loperamide may mask the symptoms of dehydration caused by diarrhea in older individuals, so it is very important to drink sufficient fluids.

Atropine and Diphenoxylate

Other medical conditions may affect the use of atropine and diphenoxylate:

• alcohol or drug abuse may increase the risk of diphenoxylate addiction
• colitis (inflammation of the colon) may become more severe
• Down syndrome may cause more severe side effects
• dysentery may worsen
• emphysema, asthma, bronchitis, or other chronic lung diseases increase the risk of breathing problems
• enlarged prostate or urinary tract blockage may cause severe problems with urination
• gall bladder disease or gallstones may worsen
• glaucoma may result in severe eye pain (rare)
• heart disease may worsen
• hiatal hernia may worsen with atropine (rare)
• high blood pressure may increase (rare)
• intestinal blockage may worsen
• kidney disease may cause atropine to accumulate in the body, resulting in side effects
• liver disease may cause central nervous system side effects, including coma
• myasthenia gravis may become worse
• overactive or underactive thyroid may cause effects on breathing and heart rate
• incontinence may worsen

An overdose of atropine and diphenoxylate can lead to unconsciousness and death. Symptoms of overdose include:

• severe drowsiness
• breathing problems
• fast heartbeat
• warmth, dryness, and flushing of skin
• vision problems
• severe dryness of mouth, nose, and throat
• nervousness or irritability

Loperamide and Octreotide

Other medical conditions may affect the use of loperamide:

• colitis (inflammation of the colon) may worsen
• dysentery may worsen
• liver disease may increase the risk of side effects Loperamide should not be used in the presence of fever or blood or mucus in stools.

Medical conditions that may affect the use of octreotide include:

• diabetes mellitus, since octreotide may affect blood sugar levels
• gallbladder disease or gallstones, since octreotide may cause gallstones
• severe kidney disease that may cause octreotide to remain in the body longer

Opium Tincture

Side effects of opium tincture may be increased or become dangerous when combined with the following medical conditions:

• alcohol or drug abuse
• colitis (inflammation of the colon)
• heart disease
• kidney disease
• liver disease
• underactive thyroid
• head injury or brain disease
• emphysema, asthma, bronchitis, or other chronic lung disease
• problems with urination or enlarged prostate
• gallbladder disease or gallstones
• seizures

Opium tincture may be habit-forming, causing mental or physical dependence that can lead to side effects of withdrawal when stopping the medicine. The use of opium tincture during pregnancy can cause dependency in the fetus and symptoms of drug withdrawal or breathing problems in the newborn infant.

Symptoms of opium overdose include:

• seizures
• confusion
• severe restlessness or nervousness
• severe dizziness
• severe drowsiness
• slow or irregular breathing
• severe weakness
• cold, clammy skin
• low blood pressure
• slow heartbeat
• contracted eye pupils

Side Effects

Atropine and Diphenoxylate

At low doses, taken for short periods of time, side effects of atropine and diphenoxylate are rare. However, serious side effects may include:

• bloating
• constipation
• loss of appetite
• stomach pain with nausea and vomiting

Other, less common or rare side effects of atropine and diphenoxylate include:

• dizziness
• drowsiness
• blurred vision
• confusion
• difficult urination
• dry skin or mouth
• fever
• headache
• depression
• numbness in hands or feet
• skin rash or itching
• swelling of gums

Rare side effects that may occur after stopping atropine and diphenoxylate include:

• sweating
• trembling or chills
• muscle cramps
• nausea or vomiting
• stomach cramps

Loperamide

Side effects are rare with low dosages of loperamide, taken for a short time. However, severe side effects may include:

• bloating
• constipation
• loss of appetite
• stomach pain with nausea and vomiting
• skin rash
• dry mouth
• dizziness or drowsiness

Octreotide

More common side effects of octreotide may include:

• irregular or slow heartbeat
• constipation
• diarrhea
• flatulence
• discomfort at the site of injection

Less common or rare side effects of octreotide may include:

• dizziness or light-headedness
• fever
• flushing or redness of the face
• swelling of feet or lower legs
• inflammation of the pancreas with stomach pain, nausea, or vomiting
• hair loss
• seizures
• unconsciousness

Symptoms of high blood sugar (hyperglycemia) from octreotide include:

• blurred vision
• drowsiness and fatigue
• dry mouth
• flushed, dry skin
• fruity breath odor
• increased urination
• ketones in urine
• loss of appetite
• increased thirst
• nausea or vomiting
• stomach ache
• rapid, deep breathing

Symptoms of low blood sugar (hypoglycemia) from octreotide include:

• anxiety and nervousness
• confusion
• blurred vision
• cold sweats
• cool, pale skin
• drowsiness, fatigue, weakness
• hunger
• fast heartbeat
• headache
• nausea
• nightmares and restless sleep
• shakiness
• slurred speech

Opium Tincture

Side effects of opium tincture that are more common with higher dosages may include:

• drowsiness
• dizziness, light-headedness, faintness
• nervousness
• weakness or fatigue
• painful or strained urination
• frequent urination
• decreased volume of urine Lying down and rising slowly from a seated or lying position may help relieve dizziness.

Rare side effects of opium tincture include:

• bloating
• constipation
• loss of appetite
• nausea or vomiting
• stomach cramps
• fast or slow heartbeat
• sweating
• rash, hives, or itching
• redness or flushing of the face
• depression
• troubled breathing
• convulsions (seizures)

The following side effects may occur after stopping treatment with opium tincture:

• runny nose or sneezing
• body aches
• loss of appetite
• diarrhea
• stomach cramps
• nausea or vomiting
• fever
• sweating
• nervousness or irritability
• trembling
• insomnia
• dilated pupils
• severe weakness

Interactions

Atropine and Diphenoxylate

Other drugs may interact with atropine and diphenoxylate:

• Antibiotics (cephalosporins, clindamycin, erythromycins, tetracyclines) can counteract the effects of atropine and diphenoxylate and make the diarrhea worse.
• Central nervous system depressants (alcohol, anti-histamines, sedatives, pain medicines or narcotics, barbiturates, seizure medicine, muscle relaxants, anesthetics) may increase effects, such as drowsiness, from both the depressant and the antidiarrheal agent.
• Monoamine oxidase inhibitors may cause severe side effects if taken within two weeks of diphenoxylate and atropine.
• Opioid antagonists (naltrexone) may cause withdrawal from diphenoxylate addiction; naltrexone will counteract the antidiarrheal effects of the medicine.
• Other anticholinergics to reduce stomach acid or cramps may increase the effects of atropine.

Loperamide and Octreotide

Antibiotics may interact with loperamide and make the diarrhea worse. Narcotic pain medicines in combination with loperamide may cause severe constipation.

Because octreotide may cause high or low blood sugar, it can interact with the following medicines:

• antidiabetic medicines, sulfonylurea
• diazoxide (Proglycem)
• glucagon
• insulin
• growth hormone

Opium Tincture

The following medicines may increase side effects from opium tincture:

• anticholinergics for abdominal or stomach cramps
• other antidiarrheal medicines
• tricyclic antidepressants Naltrexone (Trexan) makes opium less effective for treating diarrhea. Alcohol, narcotics, and other central nervous system depressants, including antihistamines, sedatives, prescription pain medicines, barbiturates, seizure medicines, muscle relaxants, or anesthetics, may lead to unconsciousness or death in combination with opium tincture.

—Margaret Alic, Ph.D.