Kaolin, Pectin, and Paregoric (Systemic)


VA CLASSIFICATION
Primary: GA208

Note: Controlled substance classification—

Note: Controlled substance classification


Canada—N
Commonly used brand name(s): Donnagel-PG.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.



Category:


Antidiarrheal (adsorbent)—

Indications

Note: The efficacy of any antidiarrheal medication for treatment of most cases of nonspecific diarrhea is questionable, especially in children. {03} {14} Preferred treatment for acute, nonspecific diarrhea consists of fluid and electrolyte replacement, nutritional therapy, {03} {15} and, if possible, elimination of the underlying cause of the diarrhea.


Unaccepted
The U.S. Food and Drug Administration (FDA) has banned the inclusion of paregoric in antidiarrheal preparations because of lack of proof of its effectiveness. FDA has requested that manufacturers wishing to obtain the agency's approval for inclusion of this ingredient in their product provide FDA with evidence that the ingredient is safe and effective for its intended use. {13} Paregoric-containing medications have been replaced by equally or more effective, and safer, agents for the treatment of diarrhea. {05}


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Kaolin and pectin—Adsorbent and protectant. Kaolin is a natural hydrated aluminum silicate that is believed to adsorb large numbers of bacteria and toxins and to reduce water loss. Pectin is a polyuronic polymer for which the mechanism of action is unknown. Pectin consists of purified carbohydrate extracted from citrus fruit or apple pomace. {03} Studies have shown no decrease in stool frequency or fecal weight and water content with this combination even though stools appeared more formed. {03} {07}

Paregoric—Most of the effects of paregoric are due to the morphine component. Usefulness in the treatment of diarrhea appeared to be due to alteration of intestinal motility; however, its efficacy in the treatment of diarrhea has not been demonstrated. {07} {13}

Absorption:

Kaolin and pectin—Not absorbed (up to 90% of pectin is decomposed in gastrointestinal tract). {09} {10}

Paregoric—Morphine: Well absorbed from the gastrointestinal tract but undergoes rapid metabolism so that the effect is less than after parenteral administration.

Protein binding:

Paregoric—Morphine: Low.

Biotransformation:

Paregoric—Hepatic.

Half-life:

Paregoric—Morphine: 2 to 3 hours.

Duration of action:

3 to 4 hours.

Elimination:
    Paregoric—Renal and biliary.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other opium alkaloids may be sensitive to this medication also.

Pregnancy/Reproduction

Pregnancy—

First trimester

Opium alkaloids cross the placenta. Problems in humans have not been documented.

Morphine has been shown to be teratogenic in animals in very high doses.



Third trimester

Regular use of an opiate by a pregnant woman late in pregnancy may cause physical dependence in the fetus, leading to withdrawal symptoms in the neonate.


Breast-feeding

Opium alkaloids (particularly morphine) are distributed into breast milk. However, problems in humans have not been documented.

Pediatrics

Children up to 2 years of age may be more susceptible to the effects, especially the respiratory depressant effects, of opiates. Preferred measures for treating childhood diarrhea consist of fluid and electrolyte replacement, nutritional therapy, and, if possible, elimination of the cause of the diarrhea; whether antidiarrheals are beneficial for this condition is questionable. {16} {17} It is recommended that paregoric not be used for treatment of diarrhea in infants and children up to 2 years of age. In older children, paregoric should be used with caution (if at all), for as short a time as possible, and only in addition to the preferred treatment measures. {01}

Paregoric contains 45% alcohol, which is considered an undesirable ingredient in medications administered to pediatric patients. {01}


Geriatrics


In geriatric patients with diarrhea, caution is recommended because of the risk of fluid and electrolyte loss; these patients should be referred to a physician. {07}

Geriatric patients may be more susceptible to the effects, especially the respiratory depressant effects, of opiates. Also, geriatric patients are more likely to have prostatic hyperplasia or obstruction and age-related renal function impairment, and are therefore more likely to be adversely affected by opiate-induced urinary retention.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

Addictive medications, other, especially central nervous system (CNS) depressants with habituating potential    (prolonged concurrent use with paregoric may increase the risk of habituation; caution is recommended)


» Alcohol or
» Antidiarrheals, antiperistaltic, such as:
» Difenoxin and atropine
» Diphenoxylate and atropine
» Loperamide
» Opium tincture or
» CNS depression–producing medications, other (See Appendix II )    (concurrent use of these medications with paregoric may result in increased CNS depressant, respiratory depressant, and hypotensive effects; concurrent use should be undertaken with caution, and dosage of one or both agents should be reduced)

    (concurrent use of any opioid-containing analgesic may increase the risk of severe constipation)


Anticholinergics or other medications with anticholinergic activity (See Appendix II )    (concurrent use with paregoric may result in increased risk of severe constipation, which may lead to paralytic ileus, and/or urinary retention)


Digitalis glycosides or
Lincomycins    (concurrent use with kaolin and pectin combinations may impair absorption of digitalis glycosides and lincomycins, resulting in decreased therapeutic effectiveness of these medications when administered orally; it is recommended that kaolin and pectin–containing medications be administered not less than 2 hours before or 3 to 4 hours after oral lincomycins; patients receiving digitalis glycosides concurrently with kaolin and pectin-containing medications should be monitored closely for evidence of altered effect {03})


Metoclopramide    (paregoric may antagonize the effects of metoclopramide on gastrointestinal motility)


Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline    (caution is recommended when using any opioid in patients who have received an MAO inhibitor within 14 days because concurrent use of MAO inhibitors with meperidine has resulted in unpredictable, severe, and sometimes fatal reactions, including immediate excitation, sweating, rigidity, and severe hypertension, or, in some patients, hypotension, severe respiratory depression, coma, convulsions, hyperpyrexia, and vascular collapse)


» Naloxone{02}{23}{24}    (naloxone reverses the effects of paregoric and may precipitate withdrawal symptoms in opioid-dependent patients)


» Naltrexone{22}    (naltrexone blocks the therapeutic effects of paregoric and may precipitate withdrawal symptoms in opioid-dependent patients; naltrexone therapy should not be initiated in a patient receiving paregoric; patients receiving naltrexone should be treated with nonopioid medications when antidiarrheal treatment is required)


Oral medications, other{09}{10}    (prolonged use of adsorbents may interfere with absorption of other oral agents administered concurrently; it is recommended that medications containing kaolin and pectin be administered at least 2 to 3 hours before or after other oral medications)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Gastric emptying studies    (paregoric may delay gastric emptying, thereby invalidating test results)


Hepatobiliary imaging using technetium Tc 99m disofenin, technetium Tc 99m lidofenin, or technetium Tc 99m mebrofenin    (delivery of technetium Tc 99m-labeled agent to the small bowel may be prevented because paregoric may cause constriction of the sphincter of Oddi and increased biliary tract pressure; these actions result in delayed visualization and thus resemble obstruction of the common bile duct {11} {12})

With physiology/laboratory test values
Amylase, plasma and
Lipase, plasma    (values may be increased because opiates can cause contractions of the sphincter of Oddi and increased biliary tract pressure; the diagnostic utility of determinations of these enzymes may be compromised for up to 24 hours after medication has been given)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problems exist:
» Diarrhea associated with Clostridium difficile caused by cephalosporins, lincomycins (possibly including topical clindamycin), or penicillins or
» Diarrhea caused by poisoning until the toxic material is eliminated from the gastrointestinal tract    (paregoric may delay removal of toxins from the colon, thereby prolonging and/or worsening the diarrhea)


» Respiratory depression, acute    (may be exacerbated)


Risk-benefit should be considered when the following medical problems exist
Alcohol abuse, or history of or
Drug abuse or dependence, history of    (patient predisposition to drug abuse)


» Asthma, acute attack or
» Respiratory disease or impairment, especially chronic obstructive pulmonary disease{02}    (paregoric may decrease respiratory drive and increase airway resistance in patients with these conditions)


Cardiac arrhythmias or
Seizures, history of    (paregoric may exacerbate condition)


» Dehydration    (although adsorbent antidiarrheals may increase the consistency of feces and decrease the frequency of evacuation, they do not reduce the amount of fluid loss, but only mask its extent; rehydration therapy is essential if signs or symptoms of dehydration, such as dryness of mouth, excessive thirst, wrinkled skin, decreased urination, and dizziness or lightheadedness, are present; fluid loss may have serious consequences, such as circulatory collapse and renal failure, especially in young children {07} {08} and the elderly {20})


Diarrhea, parasite-associated, suspected{07}    (use of adsorbent antidiarrheals may make recognition of parasitic causes of diarrhea more difficult; if parasitic agents are suspected pathogens, appropriate stool analyses should be performed prior to therapy with adsorbents)


» Dysentery, acute, characterized by bloody stools and elevated temperature{07}    (sole treatment with adsorbent antidiarrheals may be inadequate; antibiotic therapy may be required)


Gallbladder disease or gallstones    (paregoric may cause biliary contraction)


Head injury or
Increased intracranial pressure, pre-existing or
Intracranial lesions    (risk of respiratory depression and further increase in cerebrospinal fluid pressure)


Hepatic function impairment{07}
Hypothyroidism    (paregoric may increase risk of respiratory depression and CNS depression)


Incontinence, overflow    (secondary to constipation, but often mistaken for diarrhea; {19} {20} use of kaolin, pectin, and paregoric combination may worsen constipation {20})


» Inflammatory bowel disease, severe    (risk of toxic megacolon may be increased, especially with repeated dosing of paregoric)


Prostatic hyperplasia or obstruction or
Urethral stricture    (paregoric may cause urinary retention)


Renal function impairment    (components of this formulation excreted primarily via kidneys; also, paregoric may cause urinary retention)


Sensitivity to paregoric{05} or other opiates


Side/Adverse Effects

Note: At high doses, paregoric exhibits effects of opiates.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence rare
    
Allergic reaction (hives; itching; skin rash)
    
histamine release (decreased blood pressure; fast heartbeat; increased sweating; redness or flushing of face; shortness of breath, troubled breathing or wheezing)
    
mental depression
    
toxic megacolon (bloating; loss of appetite; nausea or vomiting; severe constipation; severe stomach pain)



Those indicating need for medical attention only if they continue or are bothersome
Incidence dose-related
    
Antidiuretic effect (decreased urination)
    
CNS effects or hypotension, including orthostatic hypotension (dizziness; feeling faint; lightheadedness; unusual tiredness or weakness)
    
constipation —usually mild and transient, but may rarely lead to fecal impaction
    
drowsiness
    
nervousness or restlessness
    
ureteral spasm (difficult or painful urination; frequent urge to urinate)





Overdose
For specific information on the agents used in the management of opiate overdose, see:
   • Charcoal, Activated (Oral-Local) monograph;
   • Ipecac (Oral-Local) monograph; and/or
   • Naloxone (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (See Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:
    
Bradycardia (slow heartbeat )
    
cold, clammy skin
    
confusion
    
hypotension (low blood pressure)
    
pinpoint pupils
    
respiratory depression (slow or irregular breathing)
    
seizures
    
severe dizziness, drowsiness, nervousness, restlessness, or weakness
    
unconsciousness


Treatment of overdose
Treatment of respiratory depression or other potentially life-threatening adverse effects should be instituted first.

To decrease absorption—The stomach may be emptied by induction of emesis with ipecac syrup if the patient is awake and alert {18} or by gastric lavage. {05} {18} If bowel sounds are present, activated charcoal may be administered, followed by a cathartic. {18}

Specific treatment—The opioid antagonist, naloxone, may be administered. {05} Initial treatment may be followed by continuous intravenous infusion of naloxone, with the rate of infusion being adjusted according to patient response. The fact that naloxone may precipitate withdrawal symptoms in physically dependent patients must be kept in mind.

Monitoring—The patient's heart and respiratory rate, blood pressure, and mental status should be closely monitored for a minimum of 24 hours. {18} The patient must also be monitored so that additional naloxone may be administered, if needed. The duration of action of the opiate may exceed that of naloxone. {18}

Supportive care—Adequate respiratory exchange should be established through provision of a patent airway and institution of assisted or controlled respiration. {05} {18} Intravenous fluids, vasopressors, and other supportive measures may be instituted, as needed. Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Kaolin, Pectin, and Paregoric (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to paregoric or other opiates

Pregnancy—Opium alkaloids cross placenta; possible fetal dependence with regular use late in pregnancy





Breast-feeding—Opium alkaloids distributed into breast milk





Use in children—Not using in infants and children up to 2 years of age because of risk of dehydration associated with diarrhea; oral rehydration therapy recommended in children with diarrhea; increased sensitivity to opiate effects






Use in the elderly—Risk of dehydration associated with diarrhea; increased sensitivity to opiate effects
Other medications, especially antiperistaltic antidiarrheals, CNS depressants, naloxone, and naltrexone; spacing doses of other oral medications 2 to 3 hours before or after doses of kaolin and pectin–containing medication is recommended
Other medical problems, especially acute dysentery, acute respiratory depression, asthma or respiratory disease, dehydration, diarrhea associated with C. difficile or caused by poisoning, and severe inflammatory bowel disease

Proper use of this medication
Taking with food or meals if gastric irritation occurs

» Importance of not taking more medication than the amount prescribed because of habit-forming potential

Using specially marked spoon or measuring device

» Importance of maintaining adequate hydration and proper diet

» Proper dosing

» Proper storage

Precautions while using this medication
» Consulting physician if diarrhea is not controlled within 48 hours and/or fever develops

» Caution if taking alcohol or other central nervous system (CNS) depressants

» Caution if drowsiness occurs


Side/adverse effects
Signs of potential side effects, especially allergic reaction, histamine-release related effects, mental depression, and toxic megacolon


General Dosing Information
This medication may be taken with food or meals to lessen gastric irritation

Reduction of intestinal motility in patients with traveler's diarrhea may result in prolonged fever by slowing expulsion of infectious organisms that penetrate intestinal mucosa (for example, Shigella, Salmonella, and certain strains of Escherichia coli ). {07}

Inhibition of peristalsis may produce fluid retention in the bowel, which may aggravate and mask dehydration and depletion of electrolytes, especially in young children, and may also increase variability of response to the medication. If dehydration or electrolyte imbalance occurs, antidiarrheal medication should be withheld until appropriate corrective therapy has begun. {07}

To reduce the risk of toxic megacolon in patients with acute ulcerative colitis, treatment with paregoric-containing medications should be discontinued promptly if abdominal distention or other specific gastrointestinal symptoms occur.

Prolonged use of larger than usual therapeutic doses may result in physical and psychological dependence.

Following prolonged administration of high doses, paregoric should be withdrawn gradually in order to avoid the possibility of precipitating withdrawal symptoms.

This medication may suppress respiration, especially in the elderly, the very ill, and those patients with respiratory problems. Lower doses may be required for these patients.

A reduction in dosage is recommended for patients with impaired hepatic function who require prolonged treatment with this medication.

Treatment with antidiarrheal medication should be continued for 24 to 36 hours before it is considered ineffective in the treatment of acute diarrhea.


Oral Dosage Forms

KAOLIN, PECTIN, AND PAREGORIC ORAL SUSPENSION

Usual adult and adolescent dose
Antidiarrheal—Oral, 30 mL {05} after each loose bowel movement. {21}

Usual adult prescribing limits
Four doses within twelve hours. {21}

Usual pediatric dose
Antidiarrheal


Children up to 2 years of age:
Use is not recommended.



Children 2 years of age and over:
Children up to 4.5 kg of body weight—Dosage must be individualized by physician.

Children 4.5 to 9 kg of body weight—Oral, 2.5 mL {05} after each loose bowel movement.

Children 9 to 13.5 kg of body weight—Oral, 5 mL {05} after each loose bowel movement.

Children 13.5 kg of body weight and over—Oral, 5 to 10 mL {05} after each loose bowel movement.



Note: No more than 4 doses should be administered within twelve hours.
In general, oral rehydration therapy and dietary treatment of diarrhea in children are preferred whenever possible.


Usual geriatric dose
See Usual adult and adolescent dose .

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—


6 grams of kaolin, 142.8 mg of pectin, and 6 mL of paregoric, per 30 mL (N) [Donnagel-PG (alcohol 5%) ( sodium <1 mmol per 5 mL)]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Do not take other medicines without your doctor"s advice.
   • Keep out of reach of children.
   • May be habit-forming.
   • Shake well before using.

Note: Controlled substance in Canada.
Refer patients with recurrent or persistent diarrhea to a physician.




Revised: 04/26/1995



References
  1. Reviewers' consensus on paregoric monograph revision of 5/92.
  1. Panel comment on paregoric monograph, 1/92.
  1. Diarrhoeal Disease Control Programme. Guide for improving diarrhoea treatment practices of pharmacists and licensed drug sellers. Geneva: World Health Organization, 1993; 53-5.
  1. Binder HJ. Net fluid and electrolyte secretion: the pathophysiologic basis of diarrhea. In: Binder HJ, editor. Mechanism of intestinal secretion. New York: Alan R Liss Inc., 1979: 1-15.
  1. Donnagel-PG (Wyeth-Ayerst). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 402.
  1. Brownlee HJ. Family practitioner's guide to patient self-treatment of acute diarrhea. Am J Med 1990; 88(6A Suppl): 27S-29S.
  1. DuPont HL. Using OTC drugs for acute diarrhea. Drug Ther 1983: 127-36.
  1. Burdock N. The pharmacist's role in patient counseling OTC antidiarrheals. Kentucky Pharmacist 1981: 323.
  1. Longe LR. Antidiarrheal and other gastrointestinal products. In: Handbook of nonprescription drugs. 8th ed. Washington, DC: American Pharmaceutical Association, 1986: 59-74.
  1. AMA Drug evaluations. 6th ed. Chicago: American Medical Association, September 1986: 963.
  1. Hladik WB, et al. Drug-induced changes. Biodistribution. Semin Nucl Med 1982: 201.
  1. Hladik WB, Saha GB, Study KT. Essentials of nuclear medicine science. Williams & Wilkins, 1987: 126-7, 191-3, 417.
  1. U.S. Department of Health and Human Services. Food and Drug Administration, HHS News. Nov 1990.
  1. Kenyon J, Caldwell M, editors. Oral rehydration is the cornerstone of diarrhoea therapy in children. Drugs Ther Perspect 1993; 1: 15-6.
  1. International Health Advisory Panel Meeting, 6/10/94.
  1. The rational use of drugs in the management of acute diarrhoea in children. Geneva: World Health Organization, 1990.
  1. de L Costello AM, Bhutta TI. Antidiarrhoeal drugs for acute diarrhoea in children. None work, and many may be dangerous. Br Med J 1992; 304: 1-2.
  1. Easom JM, Lovejoy FH. Opiates. In: Haddad LM, Winchester JF, editors. Clinical management of poisoning and drug overdose. Philadelphia: W.B. Saunders Co., 1983: 424-33.
  1. Abrams WB, Berkow R, editors. The Merck manual of geriatrics. Rahway, NJ: Merck Sharp & Dohme Research Laboratories, 1990: 508.
  1. Panel comment, 2/95.
  1. Reviewers' consensus on monograph revision of 2/95.
  1. Reviewer comment on paregoric monograph, 8/92.
  1. Reviewer comment on paregoric monograph, 1/92.
  1. Panel comment on paregoric monograph, 1/92.
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