Medication Guide App

Antihistamines, Decongestants, and Anticholinergics (Systemic )

This monograph includes information on the following:

1) Chlorpheniramine, Phenylephrine, and Methscopolamine 
2) Chlorpheniramine, Pseudoephedrine, and Methscopolamine 

VA CLASSIFICATION
Primary: RE599


Note: For other combinations containing decongestants, see Antihistamines and Decongestants (Systemic) , Antihistamines, Decongestants, and Analgesics (Systemic) , Cough/Cold Combinations (Systemic) , and Decongestants and Analgesics (Systemic) .




Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000{53}

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

Not commercially available in Canada.



Category:


Antihistaminic (H 1-receptor)-decongestant-anticholinergic—

Indications

Accepted

Congestion, nasal (treatment)
Cold symptoms (treatment) and
Rhinitis, perennial and seasonal allergic or vasomotor (treatment) —Antihistamine, decongestant, and anticholinergic combinations are indicated in the symptomatic treatment of allergic rhinitis, sinusitis, and the common cold. {01} {41} {42} {44}
—The therapeutic effectiveness of oral phenylephrine as a nasal decongestant has been questioned, especially at the usual oral dose. {45} {47}

Note: In November 2000, the Food and Drug Administration (FDA) issued a public health warning regarding phenylpropanolamine (PPA) due to the risk of hemorrhagic stroke. The FDA, supported by the final report of The Hemorrhagic Stroke Project (HSP){54}, requested that manufacturers voluntarily discontinue marketing products that contain PPA and that consumers work with their healthcare providers to select alternative products.{53}



Pharmacology/Pharmacokinetics

Physicochemical characteristics:

Chemical group—
    Antihistaminic (H 1-receptor): Propylamine derivatives (alkylamines)—Chlorpheniramine.
    Decongestant: Sympathomimetic amines—Phenylephrine; Pseudoephedrine.
    Anticholinergic: Atropine; Hyoscyamine; Methscopolamine; Scopolamine.
Molecular weight—
    Atropine: 289.37
    Chlorpheniramine maleate: 390.87
    Hyoscyamine sulfate: 712.85
    Methscopolamine bromide: 398.3
    Phenylephrine hydrochloride: 203.67
    Pseudoephedrine hydrochloride: 201.7
    Scopolamine hydrobromide: 438.31

pKa—
    Atropine: 9.8
    Chlorpheniramine maleate: 9.2
    Scopolamine: 7.55–7.81

Mechanism of action/Effect:


Antihistaminic (H 1-receptor):

Antihistamines used in the treatment of allergy act by competing with histamine for H 1-receptor sites on effector cells. They thereby prevent, but do not reverse, responses mediated by histamine alone. The anticholinergic actions of most antihistamines provide a drying effect on the nasal mucosa. {41} {44} {45}



Decongestant:

Sympathomimetic amines act on alpha-adrenergic receptors in the mucosa of the respiratory tract to produce vasoconstriction, which temporarily reduces the swelling associated with inflammation of the mucous membranes lining the nasal passages. {44} {46}



Anticholinergic:

The naturally occurring belladonna alkaloids (e.g., atropine, hyoscyamine, scopolamine) and the quaternary ammonium compounds (e.g., methscopolamine) inhibit the muscarinic actions of acetylcholine on structures innervated by postganglionic cholinergic nerves as well as on smooth muscles that respond to acetylcholine but lack cholinergic innervation. These postganglionic receptor sites are present in the autonomic effector cells of the smooth muscle, cardiac muscle, sinoatrial and atrioventricular nodes, and exocrine glands. {10}



Other actions/effects:


Anticholinergics:

Depending on the dose, anticholinergics may reduce the motility and secretory activity of the gastrointestinal system and the tone of the ureter and urinary bladder, and may have a slight relaxant action on the bile ducts and gallbladder. In general, the smaller doses of anticholinergics inhibit salivary and bronchial secretions, sweating, and accommodation; cause dilatation of the pupil; and increase the heart rate. Larger doses are required to decrease motility of the gastrointestinal and urinary tracts and to inhibit gastric acid secretion. {10}


Absorption:


Antihistamines:

Well absorbed from the gastrointestinal tract after oral administration.



Sympathomimetic amines:

Sympathomimetic amines (except phenylephrine) are well absorbed from the gastrointestinal tract after oral administration. {47} Phenylephrine has reduced bioavailability (about 38%) from the gastrointestinal tract because of first-pass metabolism by monoamine oxidase in the intestinal wall and liver. {47}



Anticholinergics:

Atropine, hyoscyamine, and scopolamine are rapidly absorbed from the gastrointestinal tract. Methscopolamine's gastrointestinal absorption is poor and irregular. Total absorption of methscopolamine after an oral dose is about 10 to 25%.


Protein binding:

Atropine—Moderate.

Chlorpheniramine—High (72%).

Hyoscyamine—Moderate.

Scopolamine hydrobromide—Low.

Biotransformation:


Antihistamines:

Hepatic (cytochrome P-450 system); some renal.



Sympathomimetic amines:

Phenylephrine: Extensive in the intestinal wall and in the liver. Sulfate conjugates are formed largely in the intestinal wall. Also, phenylephrine undergoes oxidative deamination by monoamine oxidase. {47}

Pseudoephedrine: Hepatic, incomplete.



Anticholinergics:

Hepatic, by enzymatic hydrolysis.


Half-life:


Antihistamines:

Chlorpheniramine: 21 to 27 hours.



Sympathomimetic amines:

Phenylephrine: 2.1 to 3.4 hours. {47}



Anticholinergics:

Atropine: 2.5 hours. {10}

Hyoscyamine: 3.5 hours.

Scopolamine: 8 hours.


Time to peak concentration:


Antihistamines:

Chlorpheniramine: 2 to 6 hours.



Sympathomimetic amines:

Phenylephrine: 0.75 to 2 hours (to achieve peak levels ranging from 0.9 to 298 nanograms per mL, respectively). {47}


Elimination:


Antihistamines—
        Renal. Most of the antihistamines studied are excreted as metabolites within 24 hours.



Sympathomimetic amines—
        Renal.
        Phenylephrine: 2.6% of the administered oral dose is excreted unchanged. Eighty to 86% of unchanged phenylephrine and metabolites is recovered in 48 hours after oral administration. {47}
        Pseudoephedrine: About 55 to 75% of a dose is excreted unchanged. The rate of excretion is accelerated in acidic urine.



Anticholinergics—
        Renal.



Precautions to Consider

Cross-sensitivity and/or related problems

For antihistamines—Patients sensitive to one antihistamine may be sensitive to the other antihistamines also.

For sympathomimetic amines—Patients sensitive to one sympathomimetic amine (e.g., amphetamines, ephedrine, epinephrine, isoproterenol, metaproterenol, norepinephrine, terbutaline) may be sensitive to the other sympathomimetic amines also.

For anticholinergics—Patients sensitive to one belladonna alkaloid or derivative may be sensitive to the other belladonna alkaloids or derivatives also.

Pregnancy/Reproduction

Pregnancy—

For sympathomimetic amines


Phenylephrine—

Studies on teratogenic effects with phenylephrine have not been done in humans. {01}

Studies have not been done in animals. {01}



Pseudoephedrine—

Studies in humans have not been done.

Studies in animals have not shown that pseudoephedrine causes teratogenic effects in the fetus. However, pseudoephedrine reduced average weight, length, and rate of skeletal ossification in the animal fetus.


FDA Pregnancy Category B. {51}



For anticholinergics


Atropine—

Atropine crosses the placenta. Well-controlled studies in humans have not been done. {01}

Studies in mice have not shown that atropine, given in doses of 50 mg per kg of body weight (mg/kg), has adverse effects on the fetus. {01}

FDA Pregnancy Category C. {11}



Hyoscyamine—

Hyoscyamine crosses the placenta. Studies with hyoscyamine have not been done in humans. {01}

Studies with hyoscyamine have not been done in animals. {01}

FDA Pregnancy Category C. {12}



Methscopolamine—

Studies have not been done with methscopolamine in humans.

Studies have not been done in animals.

FDA Pregnancy Category C. {34}



Scopolamine—

Scopolamine crosses the placenta. Studies with scopolamine have not been done in humans. {01}

At plasma concentrations 100 times greater than those produced by the usual adult dose, scopolamine had marginal embryotoxic effects in pregnant rabbits. Studies performed in pregnant rats showed no adverse effects. {35}

FDA Pregnancy Category C. {36}



Breast-feeding


For antihistamines:

Small amounts of antihistamines are distributed into breast milk; use is not recommended in nursing mothers because of the risk of antihistamines causing excitement or irritability in infants. Also, antihistamines may inhibit lactation because of their anticholinergic action.



For sympathomimetic amines:

Small amounts of sympathomimetic amines are distributed into breast milk; use is not recommended in nursing mothers because of the high risk to infants from sympathomimetic amines. {31}



For anticholinergics:

Anticholinergics may inhibit lactation. {13} {14} Atropine and hyoscyamine are distributed into breast milk, although amounts have not been quantified. The chronic use of these medications should be avoided during breast-feeding since infants are usually very sensitive to the effects of anticholinergics. {15} It is unlikely that methscopolamine is distributed into breast milk since it is incompletely absorbed from the gastrointestinal tract and has poor lipid solubility.


Pediatrics


For antihistamines:

Use of antihistamines is not recommended in newborn or premature infants. This age group may be at higher risk than other age groups of developing side effects because of an increased susceptibility to anticholinergic effects, such as CNS excitation, and an increased tendency toward convulsions. {32}

A paradoxical reaction characterized by hyperexcitability may occur in children taking antihistamines.



For sympathomimetic amines:

Very young children may be particularly sensitive to the effects, especially the vasopressor effects, of sympathomimetic amines. {04} Pseudoephedrine should be used with caution in infants, especially newborn and premature infants, because of higher-than-usual risk of side/adverse effects.



For anticholinergics:

Infants and young children are especially susceptible to the toxic effects of anticholinergics.

Close supervision is recommended for infants and children with spastic paralysis or brain damage since an increased response to anticholinergics has been reported in these patients and dosage adjustments are often required.

When anticholinergics are given to children where the environmental temperature is high, there is risk of a rapid increase in body temperature because of these medications" suppression of sweat gland activity.

A paradoxical reaction characterized by hyperexcitability may occur in children taking large doses of anticholinergics.



Geriatrics



For antihistamines:

Confusion, dizziness, sedation, hypotension, hyperexcitability, and anticholinergic side effects, such as dryness of mouth and urinary retention (especially in males), may be more likely to occur in geriatric patients taking antihistamines. If the anticholinergic side effects occur and continue or are severe, medication should probably be discontinued.



For sympathomimetic amines:

Confusion, hallucinations, seizures, and CNS depression may be more likely to occur in geriatric patients taking sympathomimetic amines. {04} {33} Geriatric patients may also be more sensitive to the other effects, especially the vasopressor effects, of sympathomimetic amines.



For anticholinergics:

Geriatric patients may respond to usual doses of anticholinergics with excitement, agitation, drowsiness, or confusion.

Geriatric patients are especially susceptible to anticholinergic side effects, such as constipation, dryness of mouth, and urinary retention (especially in males). If these side effects occur and continue or are severe, the medication should probably be discontinued.

Caution is also recommended when anticholinergics are given to geriatric patients, because of the danger of precipitating undiagnosed glaucoma.

Memory may become severely impaired in geriatric patients, especially those who already have memory problems, with the continued use of anticholinergics, since these drugs block the actions of acetylcholine, which is responsible for many functions of the brain, including memory functions. {15} {16} {17} {18}



Dental

Prolonged use of antihistamines and anticholinergics may decrease or inhibit salivary flow, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

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.

» Alcohol or
» CNS depression–producing medications, other (see Appendix II ) {01}    (concurrent use may potentiate the CNS depressant effects of either these medications or antihistamines)


Alkalizers, urinary, such as: {19}
Antacids, calcium- and/or magnesium-containing
Carbonic anhydrase inhibitors
Citrates
Sodium bicarbonate    (urinary excretion of pseudoephedrine or anticholinergics may be delayed by alkalinization of the urine, thus potentiating the therapeutic and/or side effects of pseudoephedrine or the anticholinergic)


» Anesthetics, hydrocarbon inhalation, such as:
Chloroform
Cyclopropane
Enflurane
Halothane
Isoflurane
Methoxyflurane
Trichloroethylene or
» Digitalis glycosides    (cardiac arrhythmias may occur when sympathomimetic amines are used prior to anesthesia or concurrently with digitalis glycosides, since anesthetics and digitalis glycosides may sensitize the myocardium to the effects of the sympathomimetics)


» Anticholinergics, other, or other medications with anticholinergic activity (see Appendix II ) or
Antihistamines, other    (anticholinergic effects may be potentiated when these medications are used concurrently with antihistamines and anticholinergics; patients should be advised to report occurrence of gastrointestinal problems promptly, since paralytic ileus may occur with concurrent therapy)


» Antidepressants, tricyclic or
Maprotiline    (concurrent use may potentiate the CNS depressant effects of these medications or the antihistamine contained in these combinations)

    (concurrent use may potentiate the cardiovascular effects of sympathomimetic amines)


Antihypertensives or
Diuretics used as antihypertensives    (antihypertensive effects may be reduced when these medications are used concurrently with sympathomimetic amines; the patient should be carefully monitored to confirm that the desired effect is being obtained)


Antimyasthenics    (concurrent use with anticholinergics may further reduce intestinal motility; caution is recommended {20} {21})


» Beta-adrenergic blocking agents, oral    (concurrent use with sympathomimetic amines may result in significant hypertension and excessive bradycardia with possible heart block; concurrent use requires careful monitoring)


» CNS stimulation–producing medications, other (see Appendix II)    (concurrent use may result in additive CNS stimulation to excessive levels, which may cause unwanted effects, such as nervousness, irritability, insomnia, or possibly convulsions or cardiac arrhythmias)


» Cocaine, mucosal-local    (in addition to increasing CNS stimulation, concurrent use with pseudoephedrine may increase the cardiovascular effects of either or both medications and the risk of adverse effects {50})


Doxapram    (concurrent use may increase the pressor effects of either doxapram or sympathomimetic amines)


Haloperidol {22} {23}    (antipsychotic effectiveness of haloperidol in schizophrenic patients may be decreased by the anticholinergics)


Ketoconazole    (although this effect is unlikely with usual doses of these combinations, large doses of anticholinergics may increase gastrointestinal pH, possibly resulting in a marked reduction in ketoconazole absorption; patients should be advised to take these combination medications at least 2 hours after ketoconazole {20})


Levodopa    (concurrent use with pseudoephedrine may increase the possibility of cardiac arrhythmias; dosage reduction of the sympathomimetic is recommended)


Metoclopramide    (although this effect is unlikely with usual doses of these combinations, concurrent use of metoclopramide with anticholinergics may antagonize metoclopramide's effects on gastrointestinal motility {21} {23})


» Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and possibly selegiline {01} {42}    (concurrent use with antihistamine and anticholinergic combinations may prolong and intensify the anticholinergic and CNS depressant effects; concurrent use is not recommended)

    (concurrent use with sympathomimetic amines may prolong and intensify the cardiac stimulant and vasopressor effects [including headache, cardiac arrhythmias, vomiting, sudden and severe hypertensive and hyperpyretic crises] of the sympathomimetic amines because of release of catecholamines, which accumulate in intraneuronal storage sites during MAO inhibitor therapy; these combination medications should not be administered during or within 14 days following the administration of an MAO inhibitor {45} {47})

    (concurrent use of MAO inhibitors may inhibit metabolism of anticholinergics, thus potentiating their action {37} {38})


Nitrates    (concurrent use with pseudoephedrine may reduce the antianginal effects of these medications)


Opioid (narcotic) analgesics    (concurrent use with anticholinergics may result in increased risk of severe constipation, which may lead to paralytic ileus, and/or urinary retention {24} {25})


Ototoxic medications (see Appendix II )    (antihistamines may mask the symptoms of ototoxicity, such as tinnitus, dizziness, or vertigo)


» Potassium chloride, especially wax-matrix preparations     (concurrent use with anticholinergics may increase severity of potassium chloride–induced gastrointestinal lesions {13} {26} {27})


» Rauwolfia alkaloids    (in addition to possibly decreasing the hypotensive effects of rauwolfia alkaloids, concurrent use with phenylephrine may theoretically prolong the direct-acting sympathomimetic action of phenylephrine by preventing its uptake into storage granules {48})


Sympathomimetics, other    (in addition to possibly increasing CNS stimulation, concurrent use may increase the cardiovascular effects of either the other sympathomimetics or pseudoephedrine and the potential for side effects)


Thyroid hormones    (concurrent use may increase the effects of either these medications or pseudoephedrine; thyroid hormones enhance risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease; dosage adjustment is recommended, although problem is reduced in euthyroid patients)



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 acid secretion test    (anticholinergics may antagonize the effect of pentagastrin and histamine in the evaluation of gastric acid secretory function; administration of anticholinergics is not recommended during the 24 hours preceding the test)


» Phenolsulfonphthalein (PSP) excretion test    (atropine utilizes the same tubular mechanism of excretion as PSP, resulting in decreased urinary excretion of PSP; PSP excretion test is not recommended in patients taking atropine)


Radionuclide gastric emptying studies    (although this effect is unlikely with usual doses of these combinations, use of anticholinergics may result in delayed gastric emptying {29})


Skin tests using allergen extracts    (antihistamines contained in these combinations may inhibit the cutaneous histamine response, thus producing false-negative results; it is recommended that antihistamine-containing medication be discontinued at least 72 hours before testing begins)


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).


Risk-benefit should be considered when the following medical problems exist
» Bladder neck obstruction or
» Prostatic hypertrophy, symptomatic or
» Urinary retention, or predisposition to    (anticholinergic effects of antihistamines and anticholinergics, and stimulation of alpha-adrenergic receptors on the trigone and sphincter muscles of the bladder by the sympathomimetic amines, may precipitate or aggravate urinary retention {01} {46})


Brain damage, in children    (CNS effects may be exacerbated by the anticholinergics)


» Cardiovascular disease    (pressor effects and increase in heart rate may be exacerbated due to anticholinergic- and sympathomimetic amine–induced cardiovascular effects {01} {46})


» Diabetes mellitus    (sympathomimetic amines may increase risk of cardiovascular disease {46})


Down syndrome    (abnormal increase in pupillary dilation and acceleration of heart rate may occur with use of anticholinergics)


Esophagitis, reflux    (although these effects are unlikely with usual doses of these combinations, large doses of anticholinergics may decrease esophageal and gastric motility and cause relaxation of the lower esophageal sphincter, thus promoting gastric retention by delaying gastric emptying and increased gastroesophageal reflux by making the sphincter less competent)


Fever    (may be increased through anticholinergic suppression of sweat gland activity )


Glaucoma, angle-closure, or predisposition to    (although the effect is unlikely with usual doses of these combinations, anticholinergics may increase intraocular pressure and precipitate an acute attack of angle-closure glaucoma {01})


» Hemorrhage, acute, with unstable cardiovascular status     (increase in heart rate may be undesirable {28})


Hepatic function impairment    (decreased metabolism of anticholinergic {28})


Hypertension    (vasoconstrictive properties of sympathomimetic amines may exacerbate condition {01})


» Hypertension, severe    (pressor effect of sympathomimetic amines may precipitate a hypertensive crisis {01})


» Hyperthyroidism    (characterized by tachycardia, which may be increased due to cardiac stimulant properties of sympathomimetic amines and anticholinergics {01} {46})


Intestinal atony or
Paralytic ileus    (although this effect is unlikely with usual doses of these combinations, anticholinergic use may result in obstruction {28})


Lung disease, chronic, especially in infants, small children, and debilitated patients    (reduction in bronchial secretion can lead to inspissation and formation of bronchial plugs {01} {30})


» Myasthenia gravis {28}    (anticholinergics may aggravate condition because of inhibition of acetylcholine action)


Neuropathy, autonomic {28}    (urinary retention and cycloplegia may be aggravated)


» Pyloric obstruction    (may be aggravated)


Renal function impairment, severe {28} {47}    (decreased excretion may increase the risk of side effects; increased risk of adverse renal effects, especially with prolonged use of high doses)


Spastic paralysis, in children    (response to anticholinergics may be increased)


» Tachycardia {28}    (may be increased)


Toxemia of pregnancy    (hypertension may be aggravated)


Ulcerative colitis {28}    (although this effect is unlikely with usual doses of these combinations, large anticholinergic doses may suppress intestinal motility, possibly causing paralytic ileus; also, use may precipitate or aggravate the serious complication toxic megacolon)


» Xerostomia {28}    (prolonged use may further reduce limited salivary flow)




Side/Adverse Effects
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 reactions (hives; itching; skin rash)
    
blood dyscrasias (sore throat; fever; unusual bleeding or bruising; unusual tiredness or weakness)
    
psychotic episodes (mood or mental changes)—usually associated with previous history of psychiatric illness
    
tightness in chest {01}{40}
For pseudoephedrine—more frequent with high doses {49} {51} {52}
    
Convulsions
    
hallucinations
    
irregular or slow heartbeat
    
shortness of breath or troubled breathing




Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Drowsiness
    
nervousness
    
restlessness
    
thickening of mucus {01}
    
trouble in sleeping

Incidence less frequent
—more frequent with high doses    
Blurred vision
    
confusion
    
difficult or painful urination
    
dizziness
    
dryness of mouth, nose, or throat
    
fast or pounding heartbeat {46}
    
headache
    
increased sweating
    
loss of appetite
    
nausea or vomiting
    
paradoxical reaction (nightmares; unusual excitement, nervousness, restlessness, or irritability)
    
ringing or buzzing in ears
    
skin rash {01}
    
trembling
    
unusual paleness
    
weakness{01}





Overdose
For specific information on the agents used in the management of antihistamine, decongestant, and anticholinergic combination overdose, see:
   • Neostigmine in Antimyasthenics (Systemic) monograph; or
   • Physostigmine (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:
Acute and chronic
    
Anticholinergic effects (clumsiness or unsteadiness; severe dryness of mouth, nose, or throat; flushing or redness of face; shortness of breath or troubled breathing)
    
CNS stimulation (hallucinations ; seizures; trouble in sleeping)
    
drowsiness, severe
    
hypertension {01}{40}{46}(continuing headache; fast heartbeat)

For pseudoephedrine
    
Convulsions
    
fast breathing
    
hallucinations
    
increase in blood pressure
    
irregular heartbeat, continuing
    
shortness of breath or troubled breathing, severe or continuing
    
slow or fast heartbeat, severe or continuing
    
unusual nervousness, restlessness, or excitement


Treatment of overdose
There is no specific antidote for overdose with antihistamine, decongestant, and anticholinergic combinations. Treatment is symptomatic and supportive.


To decrease absorption:
Induction of emesis (syrup of ipecac recommended); however, precaution against aspiration necessary, especially in infants and children.

Gastric lavage (isotonic or 0.45% sodium chloride solution) if patient unable to vomit within 3 hours of ingestion.



To enhance elimination:
Saline cathartics (milk of magnesia) sometimes used.



Specific treatment:
To reverse severe anticholinergic symptoms, slow intravenous administration of physostigmine in doses of 0.5 to 2 mg (0.5 to 1 mg in children, up to a total dose of 2 mg), at a rate not to exceed l mg per minute; may be given in repeated doses of 1 to 4 mg as needed, up to a total dose of 5 mg in adults. Or, neostigmine methylsulfate administered intramuscularly in doses of 0.5 to 1 mg, repeated every 2 to 3 hours; or intravenously in doses of 0.5 to 2 mg, repeated as needed.

Vasopressors to treat hypotension; however, epinephrine should not be used since it may further lower blood pressure.

Precaution against use of stimulants (analeptic agents) because they may cause seizures.



Supportive care:
Oxygen and intravenous fluids.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Antihistamines, Decongestants, and Anticholinergics (Systemic).

Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.


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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to any of the medications in the combination being taken

Pregnancy— In animal studies, pseudoephedrine caused reduced average weight, length, and rate of skeletal ossification in the fetus





Breast-feeding—Antihistamines may cause excitement or irritability in nursing infant; high risk to infants from sympathomimetic amines; possible inhibition of lactation





Use in children—Increased susceptibility to anticholinergic effects and to vasopressor effects; hyperexcitability (paradoxical reaction) may occur; increased response to anticholinergics in infants and children with spastic paralysis or brain damage; caution should be used in infants, especially newborn and premature infants, because of higher-than-usual risk of side/adverse effects of pseudoephedrine






Use in the elderly—Anticholinergic and CNS stimulant effects more likely to occur in older patients; danger of precipitating undiagnosed glaucoma; possible impairment of memory





Dental—Possible development of dental problems because of decreased salivary flow
Other medications, especially alcohol, other anticholinergics, beta-adrenergic blocking agents, CNS depressants or stimulants, cocaine, digitalis glycosides, medicine for high blood pressure or depression, monoamine oxidase (MAO) inhibitors, and potassium chloride
Other medical problems, especially cardiovascular disease, diabetes mellitus, hemorrhage, severe hypertension, hyperthyroidism, myasthenia gravis, obstruction in gastrointestinal or urinary tract, prostatic hypertrophy, tachycardia, urinary retention, and xerostomia

Proper use of this medication
» Importance of not taking more medication than the amount recommended

Taking with food, water, or milk to minimize gastric irritation

Swallowing extended-release dosage form whole

» 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
Checking with physician if symptoms persist or become worse, or if high fever is present

Caution if skin tests using allergens required; possible interference with test results

» Caution during exercise or hot weather; overheating may result in heat stroke

» Possible increased sensitivity of eyes to light

» Caution if blurred vision occurs

» Caution if drowsiness or dizziness occurs

» Possible insomnia; taking the medication a few hours before bedtime

» Caution if taking appetite suppressants

Need to inform physician or dentist of use of medication if any kind of surgery (including dental surgery or emergency treatment) is required

Possible dryness of mouth; using sugarless gum or candy, ice, or saliva substitute for relief; checking with dentist if dry mouth continues for more than 2 weeks

» Suspected overdose: Getting emergency help at once


Side/adverse effects
Signs of potential side effects, especially allergic reactions, severe anticholinergic effects, blood dyscrasias, CNS stimulation, severe drowsiness, hypertension, psychotic episodes, tightness in chest, convulsions, irregular or slow heartbeat, and shortness of breath or troubled breathing


General Dosing Information
This medication may be taken with food, water, or milk to lessen gastric irritation.

ANTIHISTAMINES, DECONGESTANTS, AND ANTICHOLINERGICS


Oral Dosage Forms

Note: Products containing phenylpropanolamine were removed from the U.S. and Canadian Markets in November 2000.{53}

Table 1. Oral Dosage Forms


Note: Content per capsule, tablet, or 5 mL, unless otherwise stated.



Brand or
generic name
[availability]
Antihistamines
Decongestants
Anticholinergics
Other
information
Usual adult and
adolescent
dose *
(prn)
Usual
pediatric
dose (prn)
Packaging,
storage,
and
auxiliary
labeling
AH-chew Chewable
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 2 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
1.25 mg
Scored
1–2 tabs
q 4 hr
6–12 yrs:
1 tab
q 4 hr
a, c, d
 
D.A. Chewable Chewable
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 2 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
1.25 mg
Scored
1–2 tabs
q 4 hr
6–12 yrs:
1 tab
q 4 hr
a, c, d
 
Dallergy Syrup (Rx)
[U.S.]
Chlorpheniramine
maleate 2 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
0.625 mg
  10 mL
q 4–6 hr
6–12 yrs:
5 mL
q 4–6 hr
a, b, d
 
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 4 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
1.25 mg
Scored
1 tab
q 4–6 hr
6–12 yrs:
1/2 tab
q 4–6 hr
a, d
 
Dura-Vent/DA Extended-release
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 8 mg
Phenylephrine
HCl 20 mg
Methscopolamine
nitrate
2.5 mg
Scored
1 tab
q 12 hr
6–12 yrs:
1/2tab
q 12 hr
a, d
 
Extendryl Syrup (Rx)
[U.S.]
Chlorpheniramine
maleate 2 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
1.25 mg
  10 mL
q 4 hr
6–12 yrs:
5 mL
q 4 hr
a, b, d
 
Chewable
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 2 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
1.25 mg
  2 tabs
q 4 hr
6–12 yrs:
1 tab
q 4 hr
a, c, d
 
Extendryl JR Extended-release
Capsules (Rx)
[U.S.]
Chlorpheniramine
maleate 4 mg
Phenylephrine
HCl 10 mg
Methscopolamine
nitrate
1.25 mg
  Intended for
pediatric
patients
6–12 yrs:
1 cap
q 12 hr
a, d
 
Extendryl SR Extended-release
Capsules (Rx)
[U.S.]
Chlorpheniramine
maleate 8 mg
Phenylephrine
HCl 20 mg
Methscopolamine
nitrate
2.5 mg
  1 cap
q 12 hr
  a, d
 
Mescolor Extended-release
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 8 mg
Pseudoephedrine
HCl 120 mg
Methscopolamine
nitrate
2.5 mg
Scored
Dye free
1 tab
q 12 hr
(max 2 tabs/
day)
6–12 yrs:
1/2 tab
q 12 hr
(max 1 tab/
day)
a,d
 
OMNIhist L.A. Extended-release
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 8 mg
Phenylephrine
HCl 20 mg
Methscopolamine
nitrate
2.5 mg
Scored
1 tab
q 12 hr
6–12 yrs:
1/2 tab
q 12 hr
a, d
 
Stahist Extended-release
Tablets (Rx)
[U.S.]
Chlorpheniramine
maleate 8 mg
Phenylephrine
HCl 25 mg
Pseudoephedrine
HCl 40 mg
Atropine sulfate
0.04 mg,
Hyoscyamine
sulfate
0.19 mg,
Scopolamine
HBr 0.01 mg
Scored
Dye free
  a, d
 
{55} * Geriatric patients may be more sensitive to the effects of usual adult dose.
 For appropriate Packaging and storage and Auxiliary labeling information refer to designated letters as follows:

• a—Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a tight container, unless otherwise specified by manufacturer.


• b—Protect from freezing.


• c—May be chewed.


• d—Auxiliary labeling: o May cause drowsiness. o Avoid alcoholic beverages.





Strength(s) usually available
U.S.—
See above table.



Revised: 08/27/2002



References
  1. Ru-Tuss package insert (Boots—US), Rev 1/92.
  1. Horowitz JD, Howes LG, Christophidis N, et al. Hypertensive responses induced by phenylpropanolamine in anorectic and decongestant preparations. Lancet 1980; 1: 60-1.
  1. Lake CR, Zaloga G, Clymier R, Quirk RM, Chernow B. A double dose of phenylpropanolamine causes transient hypertension. Am J Med 1988 Sept; 85: 339-43.
  1. Lake CR, et al. Psychiatric side effects attributed to phenylpropanolamine. Pharmacopsychiatry 1988; 21: 171-81.
  1. Schlemmer RF, et al. Caffeine potentiates phenylpropanolamine lethality but not motor behavior [abstract]. Fed Proc 1984; 43: 572.
  1. Mueller SM. Neurologic complications of phenylpropanolamine use. Neurology 1983; 33: 650-2.
  1. Bain J. Visual hallucinations in children receiving decongestants. Br Med J 1984 June; 288: 1688.
  1. Logie AW. Phenylpropanolamine overdose. Br Med J 1984 Sept; 289: 591.
  1. Fallis RJ. Phenylpropanolamine—Cerebral hemorrhage and vasculitis. Reactions 1985 Apr: 9.
  1. Tatro DS, editor. Drug interaction facts. St. Louis: Facts and Comparisons, Mar 1987: 298-300b.
  1. Atropine sulfate injection package insert (BW—US), Rev 5/85, Rec 10/88.
  1. Levsin product information (Schwarz Pharma—US), Rev 8/88, Rec 1/89.
  1. Quarzan (Roche). In: PDR Physicians' desk reference. 44th ed. 1990. Oradell, NJ: Medical Economics Company, 1990: 1827.
  1. Darbid package insert (SKF—US), Rev 4/88, Rec 5/89.
  1. Aust J Hosp Pharm 1988; 18(2): 162.
  1. Miller P, et al. Association of low serum anticholinergic levels and cognitive impairment in elderly presurgical patients. Am J Psychiatry 1988; 145: 342-5.
  1. Rozzini R, et al. Delirium from transdermal scopolamine in an elderly woman. JAMA 1988; 260: 478.
  1. Rovner BW, et al. Self-care capacity and anticholinergic drug levels in nursing home patients. Am J Psychiatry 1988; 145: 107-9.
  1. Drug Information Facts, 1990.
  1. Can J Anaesth 1989; 36(4): 412-7.
  1. J R Soc Med; 79[1]: 19-21.
  1. Atropine sulfate injection package insert (BW—US), Rev 5/85, Rec 10/88.
  1. Dicyclomine package insert (Lederle—US), Rev 1/86, Rec 12/88.
  1. USP Analgesics Panel consensus.
  1. Portenoy R. Causes and treatment of constipation. Syllabus of postgraduate course, Sloan-Kettering Cancer Center, 1985.
  1. K+ 10 package insert (Alra—US), Rev 9/87.
  1. Patterson D. Endoscopic comparison of solid and liquid potassium chloride supplements. Lancet 1983 Nov 5; 1077-8.
  1. Valpin 50 package insert (DuPont—US), Rev 8/85, Rec 10/88.
  1. Hladik WB, Saha GB, Study KT. Essentials of nuclear medicine science. Baltimore: Williams & Wilkins, 1987: 216.
  1. Atropine sulfate injection package insert (LyphoMed—US), Rev 2/90.
  1. Histalet package insert (Solvay—US).
  1. AMA Drug evaluations. 5th ed. Chicago: American Medical Association, April 1983: 1327.
  1. Trinalin package insert (Schering—US).
  1. Pamine package insert (Upjohn—US), Rev 11/91.
  1. Transderm Scop package insert (Ciba—US), Rev 2/88.
  1. Scopolamine hydrobromide injection product information (LyphoMed—US), Rev 3/91.
  1. Marplan product information (Hoffman-LaRoche—Canada), Rev 11/84.
  1. Cantril (Merrell Dow). In: PDR Physicians' desk reference. 46th ed. 1992. Montvale, NJ: Medical Economics Data, 1992.
  1. Brockington IF, et al. Puerperal psychosis: phenomena and diagnosis. Arch Gen Psychiatry 1981; 38: 829-33.
  1. Lake CR, Gallant S, Masson E, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 1990; 89: 195-208.
  1. Wyngarden JB, Smith LH. Cecil textbook of medicine. 18th ed. Philadelphia: W.B. Saunders, 1988: 1951-3.
  1. Reviewers' comments per monograph revision of 12/02/92.
  1. West S, Brandon B, Stolley P, et al. A review of antihistamines and the common cold. Pediatrics 1975; 56: 100-7.
  1. Fireman P. Pathophysiology and pharmacotherapy of common upper respiratory diseases. Pharmacotherapy 1993; 13(6): 101S-109S.
  1. Hendeles L. Selecting a decongestant. Pharmacotherapy 1993; 13(6): 129S-134S.
  1. Johnson DA, Hricik JG. The pharmacology of alpha-adrenergic decongestants. Pharmacotherapy 1993; 13(6): 110S-115S.
  1. Kanfer I, Dowse R, Vusumuzi V. Pharmacokinetics of oral decongestants. Pharmacotherapy 1993; 13(6): 116S-128S.
  1. Rauwolfia package insert (Raudixin-Princeton). In: PDR Physicians' desk reference. 46th ed. 1992. Montvale, NJ: Medical Economics Data, 1992: 1803.
  1. Novafed package insert (Lakeside/Merrell Dow—US), Rev 5/86.
  1. Cocaine package insert (Lilly—US), Rec 7/84.
  1. Novafed (Lakeside/Merrell Dow). In: PDR Physicians' desk reference. 42nd ed. 1988. Oradell, NJ: Medical Economics Company, 1988: 1124.
  1. Novafed extended-release capsules (Marion Merrell Dow). In: PDR Physicians' desk reference. 47th ed. 1993. Montvale, NJ: Medical Economics Company, 1993: 1391.
  1. FDA Talk Paper: FDA issues public health warning on phenylpropanolamine. United States Food and Drug Administration, U.S. Department of Health and Human Services, Rockville, MD 11/2000.
  1. Horwitz, RI, Brass LM, Kernan WN, et al. Phenylpropanolamine and risk of hemorrhagic stroke: Final report of The Hemorrhagic Stroke Project (HSP). Yale University School of Medicine, New Haven, CT, 5/10/2000.
  1. Red book 2002 Online. Montvale, NJ: Medical Economics Data; 5/13/2002.
Hide
(web3)