Paregoric (Systemic)


VA CLASSIFICATION
Primary: GA400
Secondary: CN101

Note: Controlled substance classification—

U.S.—III.

Canada—N.
A commonly used name is camphorated opium tincture. In the U.S., however, camphor is no longer a required ingredient in the formulation.
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).



Category:


Antidiarrheal—

Indications

Unaccepted
Paregoric has been replaced by equally or more effective, and safer, agents for treatment of diarrhea {08}. However, the efficacy of any antidiarrheal medication for treatment of childhood diarrhea is questionable; preferred treatment consists of fluid and electrolyte replacement, nutritional therapy, and, if possible, elimination of the underlying cause of the diarrhea {01} {02} {08}.

Paregoric is not recommended for ameliorating withdrawal symptoms in opioid-dependent neonates {12}. Because paregoric contains ingredients that are potentially hazardous to infants (alcohol, benzoic acid, and, in most products, camphor), it has been replaced for this purpose by other opioid preparations having fewer or no hazardous additional ingredients, such as diluted tincture of opium or morphine sulfate oral solution, {04} {08} or by benzodiazepines, barbiturates, and/or clonidine {03} {08}.

Although paregoric was at one time applied to the gums of a teething infant (to provide local anesthesia and permit sleep), such use is not recommended {08}.


Pharmacology/Pharmacokinetics

Mechanism of action/Effect:

Most of the effects of paregoric are due to the morphine component. Usefulness in the treatment of diarrhea is due to alteration of intestinal motility.

Absorption:

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

Protein binding:

Morphine—Low.

Biotransformation:

Hepatic.

Half-life:

Morphine—2 to 3 hours.

Elimination:
    Renal and biliary.


Precautions to Consider

Cross-sensitivity and/or related problems

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

Pregnancy/Reproduction

Pregnancy—

First trimester

Problems in humans have not been documented; however, opium alkaloids cross the placenta. Camphor, which may be present in some formulations, and alcohol {05} also cross the placenta.

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. Also, administration of an opiate to a pregnant woman shortly before delivery may cause respiratory depression in the neonate, especially the premature neonate.

Camphor, which may be present in some formulations, may cause respiratory depression and death in the neonate if administered to a pregnant woman shortly before delivery.


Breast-feeding

Problems in humans have not been documented; however, opium alkaloids (particularly morphine) are distributed into breast milk.

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, eliminating the cause of the diarrhea; whether antidiarrheals are beneficial for this condition is questionable. {01} {02} It is recommended that paregoric not be used for treatment of diarrhea in infants and children up to 2 years of age {08}. 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 {08}.

Paregoric contains 45% alcohol, which is considered an undesirable ingredient in medications administered to pediatric patients {08}.

Neonates may also be susceptible to serious toxicity induced by camphor, including convulsions and respiratory depression, and to benzoic acid–induced hyperbilirubinemia. Whenever possible, other medications (e.g., diluted tincture of opium, morphine sulfate oral solution, barbiturates, benzodiazepines, clonidine) should be used for ameliorating withdrawal symptoms in opioid-dependent neonates. {03} {04} {08}


Geriatrics


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 hypertrophy or obstruction and age-related renal function impairment; opiate-induced urinary retention may be detrimental to these patients.

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 may increase the risk of habituation; caution is recommended)


» Alcohol or
» Antidiarrheals, antiperistaltic, other, such as:
» Difenoxin and atropine
» Diphenoxylate and atropine
» Kaolin, pectin, belladonna alkaloids and opium
» 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 or antidiarrheal with paregoric may also 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)


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    (naloxone reverses the effects of paregoric and may precipitate withdrawal symptoms in opioid-dependent patients {03} {05} {06})


» Naltrexone    (naltrexone blocks the therapeutic effects of paregoric and may precipitate withdrawal symptoms in opioid-dependent patients; {10} 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)



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    (delivery of technetium Tc 99m disofenin 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)

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 pseudomembranous colitis caused by cephalosporins; lincomycins, possibly including topical clindamycin; or penicillins or
» Diarrhea caused by poisoning, until after the toxic material has been eliminated from the gastrointestinal tract    (paregoric may delay removal of toxins from the colon, thereby prolonging and/or worsening the diarrhea)


» Diarrhea caused by infectious organisms, including:
» Dysentery, acute, characterized by bloody stools and elevated temperature    (paregoric may slow recovery by delaying removal of infectious organisms or toxins, prolonging contact between infectious organisms and the mucosa, and delaying other appropriate treatment; antimicrobial treatment may be necessary {02})


» Respiratory depression, acute    (may be exacerbated)


Risk-benefit should be considered (if paregoric is to be used over prolonged periods) 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{03}    (paregoric may decrease respiratory drive and increase airway resistance in these patients)


Cardiac arrhythmias or
Convulsions, history of    (may be exacerbated)


» Dehydration, especially in infants{06} and children    (rehydration therapy is essential if signs of dehydration, such as dry mouth, excessive thirst, wrinkled skin, decreased urination, rapid or racing pulse, {07} and dizziness or lightheadedness, are present [especially when caused by diarrhea]; fluid loss may have serious consequences, such as circulatory collapse and renal failure, especially in young children)


Gallbladder disease or gallstones    (paregoric may cause biliary contraction)


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


Hepatic function impairment
Hypersensitivity to paregoric or other opiates, history of
Hypothyroidism    (increased risk of respiratory depression and CNS depression)


» Inflammatory bowel disease, severe    (risk of toxic megacolon may be increased, especially with repeated dosing, although antidiarrheals may be used in moderation to provide symptomatic relief {07})


Prostatic hypertrophy 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)


Caution is also advised in administration to very young, elderly, or very ill or debilitated patients, who may be more sensitive to the effects, especially the respiratory depressant effects, of opiates.


Side/Adverse Effects

Note: At high doses, paregoric exhibits effects of opiates.
Physical dependence with or without psychological dependence may occur with chronic administration of high doses of paregoric; an abstinence syndrome may occur when the medication is discontinued.
Dizziness, feeling faint, or lightheadedness occurs more frequently in ambulatory patients receiving opiates and may be a sign of orthostatic hypotension; however, these effects may also reflect the CNS depressant effects of opiates and may occur independently of hypotension.

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 (skin rash, hives, itching)
    
histamine release (decreased blood pressure; fast heartbeat; increased sweating; redness or flushing of face; shortness of breath, wheezing, or troubled breathing)
    
mental depression
    
toxic megacolon (bloating; constipation; loss of appetite; nausea or vomiting; stomach pain)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent with large doses
    
Antidiuretic effect (decreased urination)
    
CNS effects (dizziness; feeling faint; lightheadedness; unusual tiredness or weakness ; drowsiness; nervousness or restlessness)
    
hypotension, including orthostatic hypotension (dizziness; feeling faint; lightheadedness; unusual tiredness or weakness)
    
ureteral spasm (difficult or painful urination; frequent urge to urinate)



Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued
    
Body aches
    
diarrhea
    
fast heartbeat
    
fever, runny nose, or sneezing
    
gooseflesh
    
increased sweating
    
increased yawning
    
loss of appetite
    
nausea or vomiting
    
nervousness, restlessness, or irritability
    
shivering or trembling
    
stomach cramps
    
trouble in sleeping
    
unusually large pupils
    
weakness, severe




Overdose
For specific information on the agents use in the management of paregoric overdose, see:    • Naloxone (Systemic) mongraph.


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:
Acute and chronic
    
Cold, clammy skin
    
confusion
    
convulsions
    
severe dizziness, drowsiness, nervousness, restlessness, or weakness
    
low blood pressure
    
pinpoint pupils
    
respiratory depression (slow or irregular breathing)
    
slow heartbeat
    
unconsciousness


Treatment of overdose
To decrease absorption—Emptying the stomach by induction of emesis or gastric lavage. However, treatment of respiratory depression or other potentially life-threatening adverse effects must take precedence.

Specific treatment—Use of the opioid antagonist naloxone. See the package insert or Naloxone (Systemic) for specific dosing guidelines for use of this product.

Monitoring—Continuing to monitor the patient (mandatory because the duration of action of the opioid may exceed that of naloxone) so that additional antagonist may be administered as needed. Alternatively, 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.

Supportive care—Establishing adequate respiratory exchange through provision of a patent airway and institution of assisted or controlled respiration. Administration of intravenous fluids, vasopressors, and other supportive measures as needed. Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.


Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Opium Preparations (Systemic).

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

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

Pregnancy—Opiates and camphor cross the placenta; regular use of opiates may cause physical dependence in the fetus, leading to withdrawal symptoms in the neonate; camphor may cause respiratory depression and other serious adverse effects in the neonate





Breast-feeding—Opium alkaloids distributed into breast milk





Use in children—Increased sensitivity to respiratory depressant effects in children up to 2 years of age






Use in the elderly—Increased sensitivity to respiratory depressant effects in geriatric patients
Other medications, especially alcohol or other CNS depressants, other antiperistaltic antidiarrheals, and naltrexone
Other medical problems, especially asthma or other respiratory disease or impairment; and severe inflammatory bowel disease

Proper use of this medication
Proper administration

Taking with food or meals if gastrointestinal irritation occurs

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

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose; not doubling doses

» Proper storage

Precautions while using this medication
» Consulting physician if diarrhea continues and/or fever develops

» Avoiding use of alcoholic beverages or other CNS depressants during therapy unless prescribed or otherwise approved by physician

» Caution if drowsiness, dizziness, or lightheadedness occurs

Caution when getting up suddenly from a lying or sitting position

» Checking with physician before discontinuing medication after prolonged use of high doses; gradual dosage reduction may be necessary to avoid possible withdrawal symptoms

» Suspected overdose: Getting emergency help at once


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


General Dosing Information
Alteration of intestinal motility in patients with traveler's diarrhea may result in prolonged fever by slowing expulsion of infectious organisms that penetrate the intestinal mucosa (for example, Shigella, Salmonella, and certain strains of Escherichia coli ).

Paregoric may produce fluid retention in the bowel, which may mask dehydration and electrolyte depletion caused by severe diarrhea, especially in infants and young children. Patients with severe or prolonged diarrhea should be monitored for signs of dehydration or electrolyte imbalances, and corrective therapy administered as required.

To reduce the risk of toxic megacolon in patients with acute inflammatory bowel disease, treatment with paregoric should be discontinued promptly if abdominal distention or other gastrointestinal symptoms occur.

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

Tolerance to the antidiarrheal effects of paregoric may develop with prolonged use.

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

This medication may suppress respiration, especially in very young, elderly, very ill, or debilitated patients, and 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.

The effect of 4 mL of paregoric is similar to that of 2.5 mg of diphenoxylate.


Oral Dosage Forms

PAREGORIC USP

Usual adult dose
Antidiarrheal
Oral, 5 to 10 mL (the equivalent of 2 to 4 mg of anhydrous morphine) one to four times a day until diarrhea is controlled.


Usual adult prescribing limits
Oral, 10 mL four times a day.

Usual pediatric dose
Antidiarrheal
Children 2 years of age and older: Oral, 0.25 to 0.5 mL (the equivalent of 100 to 200 mcg [0.1 to 0.2 mg] of anhydrous morphine) per kg of body weight one to four times a day.


Note: For treatment of neonatal opioid withdrawal—Oral, 0.2 mL (the equivalent of 80 mcg [0.08 mg] of anhydrous morphine) every three hours. The dose may be increased, if necessary, by 0.05 mL (the equivalent of 20 mcg [0.02 mg] of anhydrous morphine) every three hours until symptoms are controlled, up to a maximum of 0.7 mL (the equivalent of 280 mcg [0.28 mg] of anhydrous morphine) per dose. After symptoms have remained stable for three to five days, dosage should be reduced gradually over a period of two to four weeks before treatment is discontinued.
It is recommended that a standard scoring system that provides objective assessment of symptom severity be used as a guide to the treatment of opioid-dependent neonates. {11}


Strength(s) usually available
U.S.—


The equivalent of 2 mg of anhydrous morphine per 5 mL (Rx)[Generic]

Canada—


The equivalent of 2 mg of anhydrous morphine per 5 mL (Rx)[Generic]

Note: Paregoric contains:

Powdered opium
4.3 grams
Suitable essential oil(s)
 
Benzoic acid
3.8 grams
Diluted alcohol
900 mL
Glycerin
38 mL
To make about
950 mL



Note: Paregoric may also be prepared with opium or opium tincture instead of powdered opium, the anhydrous morphine content being adjusted to 40 mg in each 100 mL and the alcohol content being adjusted to 45%.
Paregoric may also be prepared using 3.8 grams of camphor instead of the suitable essential oil(s).


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. Avoid exposure to direct sunlight and to excessive heat. 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 both the U.S. and Canada.
Caution: Be careful not to confuse paregoric (Camphorated opium tincture) with Opium tincture (Laudanum).
Refrigeration is not recommended because decreased solubility and precipitation of some of the ingredients may occur. If this occurs, filtration may be used to remove the sediment.




Revised: 09/08/1994



References
  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. Panelist comment, draft 1/92.
  1. Panelist comment, draft 1/92.
  1. Reviewer comment, draft 1/92.
  1. Panelist comment, draft 1/92.
  1. Panelist comment, draft 1/92.
  1. Panel consensus, ballot 5/92.
  1. Panel consensus, Pediatrics Panel meeting 10/10/92.
  1. Reviewer comment, 8/92.
  1. Panel consensus, ballot 5/92.
  1. Pediatrics Panel meeting 1993.
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