Antidyskinetics (Systemic)

This monograph includes information on the following:

1) Benztropine
2) Biperiden
3) Ethopropazine
4) Procyclidine
5) Trihexyphenidyl


INN:
{03} Benztropine—Benzatropine
Ethopropazine—Profenamine

BAN:
{03}Benztropine—Benzatropine
Trihexyphenidyl—Benzhexol

VA CLASSIFICATION
Primary: AU305

Commonly used brand name(s): Akineton2; Apo-Benztropine1; Apo-Trihex5; Artane5; Artane Sequels5; Cogentin1; Kemadrin4; PMS Benztropine1; PMS Procyclidine4; PMS Trihexyphenidyl5; Parsidol3; Parsitan3; Procyclid4; Trihexane5; Trihexy5.

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



Category:


Antidyskinetic—

Indications

Note: Bracketed information in the Indications section refers to uses that are not included in U.S. product labeling.

Accepted

Parkinsonism (treatment){06}{07}{08}{09}{10}{11}{12}{13}{15}{17}{21}—Antidyskinetics are indicated in the treatment of mild cases of postencephalitic, arteriosclerotic, or idiopathic parkinsonism(paralysis agitans) {08} {11} {12} {13} {17} {21} in patients in whom anticholinergic therapy is not contraindicated. Antidyskinetics also are indicated as adjuncts to more potent medications to maximize improvement of symptoms. {06} {07} {09} {10} {13} {15} {16} {19} {21} Procyclidine usually produces a more beneficial effect in conditions of rigidity than in those of tremor. {12} {13}

Extrapyramidal reactions, drug-induced (treatment)—Antidyskinetics are indicated in the control of extrapyramidal disorders(except tardive dyskinesia) due to central nervous system (CNS) drugs such as reserpine, phenothiazines, dibenzoxazepines, thioxanthenes, and butyrophenones. {06} {07} {08} {09} {10} {11} {12} {13} {14} {15} {16} {17} {21} However, concomitant therapy with antipsychotics is not recommended beyond 3 months because extrapyramidal symptoms resulting from antipsychotic therapy usually resolve in 3 to 6 months {19} {26} and because prolonged, routine use of antidyskinetics with antipsychotics may predispose patients to the more serious neurological condition, tardive dyskinesia.

[Athetosis, congenital (treatment)]1or
[Degeneration, hepatolenticular (treatment)]1—Ethopropazine is used for the symptomatic treatment of hepatolenticular degeneration and congenital athetosis.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Benztropine mesylate: 403.54
    Biperiden hydrochloride: 347.93
    Biperiden lactate: 401.54
    Ethopropazine hydrochloride: 348.93
    Procyclidine hydrochloride: 323.91
    Trihexyphenidyl hydrochloride: 337.93

Mechanism of action/Effect:

Specific mode of action is unknown, but it is thought that these agents partially block central (striatal) cholinergic receptors, thereby helping to balance cholinergic and dopaminergic activity {09} in the basal ganglia; salivation may be decreased {10} {12} {20}, and smooth muscle may be relaxed. {12} {20} Drug-induced extrapyramidal symptoms and those due to parkinsonism may be relieved {06} {07} {08} {10} {20}, but tardive dyskinesia is not alleviated {06} {07} {08} {20} and may be aggravated by anticholinergic effects.


Other actions/effects:

Benztropine {06} {07} {21} and ethopropazine {21} also have a slight antihistaminic and local anesthetic effect. Biperiden may have a slight effect on the cardiovascular and respiratory systems. {21} Procyclidine {12} and trihexyphenidyl {14} {15} {16} {21} have a direct antispasmodic effect on smooth muscle. In small doses trihexyphenidyl depresses the CNS, but larger doses may cause cerebral excitation. {21}

Absorption:

Well-absorbed from gastrointestinal tract. {10} {20} {21}

Onset of action:


Benztropine:

Oral: 1 to 2 hours.

Intramuscular or intravenous: Within a few minutes. {06}



Biperiden:

Intramuscular: Average of 10 to 30 minutes. {10}

Intravenous: Within a few minutes. {10}



Trihexyphenidyl:

Oral: 1 hour. {20} {21}


Duration of action:

Benztropine—Oral, intramuscular, or intravenous: 24 hours.

Biperiden—Intravenous: 1 to 8 hours. {10}

Ethopropazine—Oral: 4 hours. {21}

Procyclidine—Oral: 4 hours. {20}

Trihexyphenidyl—Oral: 6 to 12 hours. {21}


Precautions to Consider

Pregnancy/Reproduction

Pregnancy—
Problems in humans have not been documented with benztropine, ethopropazine, procyclidine, or trihexyphenidyl.

For biperiden—Studies have not been done with biperiden in humans. {09}

Studies have not been done in animals. {09}

FDA Pregnancy Category C. {09}

Breast-feeding

It is not known whether antidyskinetics are distributed into breast milk. {09} However, antidyskinetics may inhibit lactation. {30}

Pediatrics

No information is available on the relationship of age to the effects of antidyskinetics in pediatric patients. However, it is known that pediatric patients exhibit increased sensitivity to other medications with anticholinergic properties. {30}


Geriatrics

{04}{05}
Chronic use of antidyskinetics may predispose geriatric patients to glaucoma. {14} {15} {16} {17}

Geriatric patients, especially those with arteriosclerotic changes, may respond to the usual doses of antidyskinetics, ethopropazine and procyclidine in particular, with mental confusion, disorientation, agitation, hallucinations, and psychotic-like symptoms. {18}

Memory may become severely impaired in geriatric patients {20}, especially those who already have memory problems, with the continued use of antidyskinetics since these drugs block the action of acetylcholine, which is responsible for many functions of the brain, including memory functions. {30}


Dental

Prolonged use of antidyskinetics may decrease or inhibit salivary flow {06} {07} {08} {09} {10} {11} {12} {14} {15} {16} {17} {20}, 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{09} or
» CNS depression–producing medications{06}{08}{18} (See Appendix II )    (concurrent use with antidyskinetics may cause increased sedative effects)


Amantadine{18} or
» Anticholinergics or other medications with anticholinergic action{06}{07}{09}{18}{19} (See Appendix II ) or
Monoamine oxidase (MAO) inhibitors, including furazolidone, procarbazine, and selegiline    (concurrent use may intensify anticholinergic effects of antidyskinetics because of the secondary anticholinergic activities of these medications; patients should be advised to report occurrence of gastrointestinal problems {06} {07} {08} {21}, fever {06}, or heat intolerance {06} promptly since paralytic ileus {06} {07} {08} {21}, hyperthermia {06}, or heat stroke {06} may occur with concurrent therapy)


Antidiarrheals, adsorbent    (simultaneous administration may reduce therapeutic effects of antidyskinetics because of particle adsorption; to avoid this effect, patients should be advised to allow at least 1 or 2 hours between doses of the different medications)


Carbidopa and levodopa or
Levodopa{18}    (concurrent use of these medications with benztropine {06} {07} {08}, procyclidine {12}, or trihexyphenidyl {14} {16} may result in increased efficacy of levodopa; however, concurrent use is not recommended if there is a history of psychosis {12})


Chlorpromazine{06}{07}{08}    (concurrent use of chlorpromazine with antidyskinetics may increase metabolism of chlorpromazine, resulting in decreased plasma concentration because of reduction in gastrointestinal motility)


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
Cardiac arrhythmias{09}{10}    (increased risk of tachycardia {06} {07} {08} {12} {13} {19})


» Cardiovascular instability{11}{14}{15}{16}{17}    (increased risk of cardiac arrhythmias)


» Dyskinesia, tardive{06}    (may be aggravated)


Extrapyramidal reactions, such as those resulting from phenothiazines or reserpine, in patients with mental disorders    (mental symptoms may be intensified, precipitating toxic psychosis {06} {12})


» Glaucoma, angle-closure, or predisposition to{06}{07}{08}{09}{11}{12}{13}{14}{15}{16}{17}{19}    (mydriatic effect resulting in increased intraocular pressure may precipitate an acute attack of angle-closure glaucoma)


» Glaucoma, open-angle    (mydriatic effect may cause a slight increase in intraocular pressure; glaucoma therapy may need to be adjusted {22})


Hepatic function impairment{14}{15}{16}{17}    (metabolism may be altered)


Hypertension{14}{15}{16}{17}    (may be aggravated)


» Intestinal obstruction, complete, partial or history of{09}{11}{14}{15}{16}{17}{19}    (decreased motility and tone may aggravate or precipitate obstruction)


» Myasthenia gravis{13}    (condition may be aggravated because of inhibition of acetylcholine action)


Prostatic hypertrophy, moderate to severe{06}{07}{08}{09}{10}{11}{12}{13}{14}{15}{16}{17}{19} or
» Urinary retention{12}{13}{14}{15}{16}{17}    (anticholinergic effect of antidyskinetics may precipitate or aggravate urinary retention {06})


Renal function impairment{14}{15}{16}{17}    (decreased elimination may increase risk of side effects)


Sensitivity to antidyskinetics (history of){06}{07}{09}{10}{16}

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Intraocular pressure determinations{14}{15}{16}{17}    (recommended at periodic intervals during therapy, especially in patients with angle-closure and open-angle glaucoma)




Side/Adverse Effects

Note: Anticholinergic side effects that may occur with antidyskinetics are rarely severe and either disappear as therapy is continued, or diminish when the dose is reduced. {19}
Anhidrosis and subsequent hyperthermia may occur with antidyskinetics when patients {06} {07} {08}, especially geriatric, chronically ill, and alcoholic, {06} {08} are exposed to high environmental temperatures.
Ethopropazine is a phenothiazine derivative. {11} {21} Although the likelihood of ethopropazine causing such side effects as changes in vision, jaundice, rare hematologic reactions, and electrocardiogram(ECG) abnormalities associated with phenothiazines seems to be minimal, the possibility exists. {18} {21}

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{06}{07}{08}{12}{13}{14}{15}{16}{17}{19} (skin rash)
    
confusion{06}{07}{08}{09}{10}{11}{12}{13}{19} —more frequent in the elderly{12}{13}{19} or with high doses
    
increased intraocular pressure{14}{15}{16} (eye pain)



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Anticholinergic effects{09} , mild (blurred vision{06}{07}{08}{09}{10}{11}{12}{13}{14}{15}{16}{17}; constipation{06}{07}{08}{09}{12}{13}{14}{15}{16}{17}{19}; decreased sweating{06}{07}{08}; difficult or painful urination{06}{07}{08}{09}{10}{14}{15}{16}{17}{19} , especially in older men; drowsiness{09}{10}{11}{14}{15}{16}{17}{19}; dryness of mouth{06}{07}{08}{09}{10}{11}{12}{13}{14}{15}{16}{17}{19} , nose, or throat; increased sensitivity of eyes to light{06}{07}{08}; nausea or vomiting{06}{07}{08}{12}{13}{14}{15}{16}{17}{19})

Incidence less frequent or rare
    
False sense of well-being{09}{10}{14}{15}{16}{17}{19} —especially in the elderly or with high doses
    
headache{11}{14}{15}{16}{17}{19}
    
loss of memory{06} —especially in the elderly{19}{20}
    
muscle cramps{19}
    
nervousness{14}{15}{16}{17}
    
numbness or weakness in hands or feet{06}{07}{08}{11}{19}
    
orthostatic hypotension{09}{10}{12}{13}{15}{16}{19} (dizziness or lightheadedness when getting up from a lying or sitting position)
    
soreness of mouth and tongue
    
stomach upset or pain{14}{19}
    
unusual excitement{06}{07}{08}{09}{10}{12}{13}{14} —more frequent with high doses of trihexyphenidyl



Those indicating possible withdrawal symptoms and the need for medical attention if they occur after discontinuation of long-term therapy
    
Anxiety{23}{24}{27}
    
extrapyramidal symptoms, recurrence or worsening of{23}{24}{25}{26}{27} (difficulty in speaking or swallowing; loss of balance control; mask-like face; muscle spasms, especially of face, neck, and back; restlessness or desire to keep moving; shuffling walk; stiffness of arms or legs; trembling and shaking of hands and fingers; twisting movements of body)—especially after abrupt withdrawal of antidyskinetic medication; may require reinstatement of the antidyskinetic
    
fast heartbeat{23}
    
orthostatic hypotension{23} (dizziness or lightheadedness when getting up from a lying or sitting position)
    
trouble in sleeping{23}




Overdose
For specific information on the agents used in the management of antidyskinetics, see:


Barbiturates (Systemic) monograph;


Diazepam in Benzodiazepines (Systemic) monograph;


Physostigmine Salicylate (Systemic) monograph; and/or


Pilocarpine (Ophthalmic) 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:

Anticholinergic effects,{07}{08}{09}{10} severe (clumsiness or unsteadiness{06}{07}{08}{09}; severe drowsiness; severe dryness of mouth{06}{07}{08}{09}{10}{13} , nose{09} , or throat{09}; fast heartbeat{06}{07}{08}{09}{10}; shortness of breath or troubled breathing{06}{07}{08}{09}{10}; warmth, dryness, and flushing of skin{06}{07}{08}{09})

CNS depression{06}{07}{08}{13} (severe drowsiness)

CNS stimulation (hallucinations{06}{07}{08}{09}{10} , seizures{09}{13} , trouble in sleeping)

toxic psychoses{06}{07}{08} (mood or mental changes)—especially in patients with mental illness being treated with neuroleptic drugs

Treatment of overdose
Recommended treatment for overdose with antidyskinetics includes the following:


To decrease absorption:
Emesis or gastric lavage, except in precomatose, convulsive, or psychotic states. {06} {07} {08} {09} {13} {18}



Specific treatment:
Intramuscular or slow intravenous administration of 1 to 2 mg of physostigmine salicylate {06} {07} {08} {09} {10} {18}, repeated after 2 hours if needed {06} {07} {08} {09} (0.5 mg initially in children {09} {18}, repeated at five-minute intervals, up to a maximum of 2 mg) {18}, to reverse the cardiovascular and CNS toxic effects.

Administration of small doses of diazepam {09} {18} or a short-acting barbiturate {06} {07} {08} {09} {18} to manage excitement.

Administration of pilocarpine {18} 0.5%, to counteract mydriasis.



Supportive care:
Respiratory assistance {06} {07} {08} {18} and symptomatic support {06} {07} {08} {09} {13} {18}.

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, Antidyskinetics (Systemic)

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

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to antidyskinetics (history of)





Breast-feeding—May inhibit lactation




Use in children——Increased susceptibility to anticholinergic effects






Use in the elderly—Predisposition to glaucoma with chronic use; increased risk of mental confusion and other psychotic-like symptoms; impairment of memory





Dental—Decrease or inhibition of salivary flow
Other medications, especially other anticholinergics and CNS depressants
Other medical problems, especially cardiovascular instability, tardive dyskinesia, glaucoma, intestinal obstruction, myasthenia gravis, or urinary retention

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

Taking with food to relieve gastric irritation

» Proper dosing
Missed dose: Taking as soon as possible; not taking if within 2 hours of next dose; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress during prolonged therapy; eye examination may also be needed

» Checking with physician before discontinuing medication; gradual dosage reduction may be necessary

» Avoiding use of alcohol or other CNS depressants

Avoiding use of antidiarrheal medications within 1 or 2 hours of taking this medication

Suspected overdose: Getting emergency help at once

Possible increased eye sensitivity to bright light

» Caution if drowsiness or blurred vision occurs

Caution when getting up suddenly from a lying or sitting position

» Caution during exercise and hot weather

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


Side/adverse effects
Signs of potential side effects, especially allergic reaction, confusion, increased intraocular pressure, anticholinergic effects, or CNS depression or stimulation


General Dosing Information

For oral dosage forms only
Therapy should be initiated with a low dose because of cumulative action, and dosage should be increased gradually at 5- or 6-day intervals. {06} {07} {08}

Titrated dosage is necessary to achieve the individual required therapeutic level, especially for geriatric patients, who tend to be more sensitive to anticholinergic effects {14} {15} {16}, and patients receiving other medications.

During therapy, necessary dosage adjustments of antidyskinetic or other medication used concurrently should be made gradually to maintain proper control of the patient's condition.

Postencephalitic and younger parkinsonism patients often require and tolerate higher dosages than idiopathic, arteriosclerotic, or geriatric parkinsonism patients. {12} {19} {20} {21}

A drug-abuse potential exists with these medications as they may cause euphoria and hallucinations at higher dosages. {28}

When an antidyskinetic is to be discontinued, dosage should be reduced gradually to prevent a sudden increase in adverse symptoms. {10} {14} {15} {16} {19} {20} {21} {28}

Diet/Nutrition
Antidyskinetics may be taken with or immediately after meals to lessen gastric irritation. {09} {10} {12} {13} {14} {15} {16} {17}

BENZTROPINE

Summary of Differences


Pharmacology/pharmacokinetics:


Other actions/effects—
Has slight antihistaminic and local anesthetic effect.



Onset of action—
Oral: 1 to 2 hours.

Intramuscular or intravenous: Within a few minutes.



Duration of action—
Oral, intramuscular, or intravenous: 24 hours.




Precautions:


Drug interactions and/or related problems—
May increase efficacy of levodopa if used concurrently; however, concurrent use not recommended if there is history of psychosis.




Additional Dosing Information
A single daily oral dose of benztropine at bedtime often provides maximum benefit for the patient because of the long duration of effect. {06} {07} {08}


Oral Dosage Forms

BENZTROPINE MESYLATE TABLETS USP

Usual adult and adolescent dose
Parkinsonism
Oral, 1 to 2 mg a day, the dosage being adjusted as needed and tolerated. {06} {07} {08}

Note: Idiopathic parkinsonism—Therapy may be initiated in some patients with a single oral daily dose of 500 mcg (0.5 mg) to 1 mg at bedtime. {06} {07} {08} {19}
Postencephalitic parkinsonism—Therapy may be initiated in most patients with 2 mg a day, given once a day or in divided doses. {07} {08}


Drug-induced extrapyramidal reactions
Oral, 1 to 4 mg one or two times a day. {06} {07} {08} {19} Or, 1 to 2 mg two or three times a day if drug-induced extrapyramidal reactions develop soon after initiation of treatment with neuroleptic drugs. {07}


Usual adult prescribing limits
Up to 6 mg daily. {06} {07} {08}

Usual pediatric dose
Parkinsonism or drug-induced extrapyramidal reactions
Children up to 3 years of age: Use is not recommended. {06} {07} {08}

Children 3 years of age and over: Dosage must be individualized by physician. {06} {07} {08}


Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose. {06} {07}


Strength(s) usually available
U.S.—


500 mcg (0.5 mg) (Rx) [Cogentin (scored)][Generic]


1 mg (Rx) [Cogentin (scored)][Generic]


2 mg (Rx) [Cogentin (scored)][Generic]

Canada—


500 mcg (0.5 mg) (Rx) [PMS Benztropine]


1 mg (Rx) [PMS Benztropine (scored)]


2 mg (Rx) [Apo-Benztropine (double-scored)] [Cogentin (scored) (lactose)] [PMS Benztropine (scored)][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), in a well-closed container, unless otherwise specified by manufacturer.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.



Parenteral Dosage Forms

BENZTROPINE MESYLATE INJECTION USP

Usual adult and adolescent dose
Parkinsonism
Intramuscular or intravenous, 1 to 2 mg a day, the dosage being adjusted as needed and tolerated.

Drug-induced extrapyramidal reactions
Intramuscular or intravenous, 1 to 4 mg one or two times a day.


Usual adult prescribing limits
Up to 6 mg daily.

Usual pediatric dose
Parkinsonism or drug-induced extrapyramidal reactions
Children up to 3 years of age: Use is not recommended. {06} {07} {08}

Children 3 years of age and over: Dosage must be individualized by physician. {06} {07} {08}


Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose. {06} {07}


Strength(s) usually available
U.S.—


1 mg per mL (Rx) [Cogentin (sodium chloride 9 mg/mL)]

Canada—


1 mg per mL (Rx) [Cogentin (sodium chloride 9 mg/mL)][Generic]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from freezing. {08}


BIPERIDEN

Summary of Differences


Pharmacology/pharmacokinetics:


Other actions/effects—
Slight cardiovascular and respiratory effects.




Side/adverse effects:
Has slight effect on cardiovascular and respiratory systems.



Oral Dosage Forms

BIPERIDEN HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Parkinsonism
Oral, 2 mg three or four times a day, the dosage being adjusted as needed and tolerated. {09} {10} {19}

Drug-induced extrapyramidal reactions
Oral, 2 mg one to three times a day. {09} {10} {19}


Usual adult prescribing limits
Parkinsonism
Up to 16 mg daily. {01} {09}


Usual pediatric dose
Safety and efficacy have not been established.

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.—


2 mg (Rx) [Akineton (scored) (corn syrup) (lactose) (magnesium stearate) (potato starch) ( talc)]

Canada—


2 mg (Rx) [Akineton]

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 container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.



Parenteral Dosage Forms

BIPERIDEN LACTATE INJECTION USP

Usual adult and adolescent dose
Drug-induced extrapyramidal reactions
Intramuscular or slow intravenous, 2 mg repeated at half-hour intervals as needed and tolerated up to a total of four doses a day. {09} {10}


Usual pediatric dose
Drug-induced extrapyramidal reactions
Intramuscular, initially 40 mcg (0.04 mg) per kg of body weight {19} {29}, or 1.2 mg per square meter of body surface {29}; dose may be repeated at half-hour intervals if necessary, up to four doses a day. {19} {29}


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.—


5 mg per mL (Rx) [Akineton (1.4% sodium lactate)]

Canada—
Not commercially available.

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


ETHOPROPAZINE

Summary of Differences


Indications:
Also used for the symptomatic treatment of hepatolenticular degeneration and congenital athetosis.



Pharmacology/pharmacokinetics:


Other actions/effects—
Has slight antihistaminic and local anesthetic effect.



Duration of action—
Oral: 4 hours.




Side/adverse effects:
May possess phenothiazine side effects, especially in high dosages.



Oral Dosage Forms

ETHOPROPAZINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Parkinsonism and
Drug-induced extrapyramidal reactions
Oral, 50 mg one or two times a day, the dosage being increased as needed and tolerated. In severe cases, the dose may be increased gradually to a total of 500 to 600 mg a day. {01} {19} {21}


Usual pediatric dose
Dosage has not been established.

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.—


10 mg (Rx) [Parsidol]


50 mg (Rx) [Parsidol (scored)]

Canada—


50 mg (Rx) [Parsitan (scored)]

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

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


PROCYCLIDINE

Summary of Differences


Pharmacology/pharmacokinetics:


Other actions/effects—
Direct antispasmodic effect on smooth muscle. {12}



Duration of action—
Oral: 4 hours.




Precautions:


Drug interactions and/or related problems—
May increase efficacy of levodopa if used concurrently; however, concurrent use not recommended if there is history of psychosis. {12}




General dosing information:
Provides more beneficial effect in conditions of rigidity than in those of tremor. {12}



Oral Dosage Forms

PROCYCLIDINE HYDROCHLORIDE ELIXIR

Usual adult and adolescent dose
Parkinsonism
Oral, initially 2.5 mg three times a day after meals. If tolerated, the dosage may be gradually increased to 5 mg three times a day and, occasionally, 5 mg at bedtime. {01} {13}

Note: For patients being transferred from other therapy, 2.5 mg three times a day may be substituted for all or part of the original medication. The dose of procyclidine may be increased while the original medication is decreased until a level of maximum benefit is reached. {01} {13}


Drug-induced extrapyramidal reactions
Oral, initially 2.5 mg three times a day, the dosage being increased in 2.5-mg increments per day as needed and tolerated. {13}


Usual pediatric dose
Dosage has not been established.

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—


2.5 mg per 5 mL (Rx) [Kemadrin (alcohol 10%)] [PMS Procyclidine (spearmint-flavored )] [Procyclid]

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 container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.


PROCYCLIDINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Procyclidine Hydrochloride Elixir .

Usual pediatric dose
See Procyclidine Hydrochloride Elixir .

Usual geriatric dose
See Procyclidine Hydrochloride Elixir .

Strength(s) usually available
U.S.—


5 mg (Rx) [Kemadrin (scored)]

Canada—


2.5 mg (Rx) [PMS Procyclidine (scored)]


5 mg (Rx) [Kemadrin (scored)] [PMS Procyclidine ( scored)] [Procyclid (scored)]

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 container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.


TRIHEXYPHENIDYL

Summary of Differences


Pharmacology/pharmacokinetics:


Other actions/effects—
Direct antispasmodic effect on smooth muscle; small doses depress CNS; larger doses may cause cerebral excitation.



Onset of action—
Oral: 1 hour.



Duration of action—
Oral: 6 to 12 hours.




Precautions:


Drug interactions and/or related problems—
May increase efficacy of levodopa if used concurrently; however, concurrent use not recommended if there is history of psychosis.




Side/adverse effects:
Unusual excitement (with high doses).



Oral Dosage Forms

TRIHEXYPHENIDYL HYDROCHLORIDE EXTENDED-RELEASE CAPSULES USP

Usual adult and adolescent dose
Parkinsonism
Oral, 5 mg a day after breakfast with an additional 5 mg taken twelve hours later as needed. {14}


Note: This dosage form is usually utilized only after the patient has been stabilized on the conventional dosage forms. {14}


Usual adult prescribing limits
Up to 15 mg daily. {14}

Usual pediatric dose
Dosage has not been established.

Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose. {14}


Strength(s) usually available
U.S.—


5 mg (Rx) [Artane Sequels{14}]

Canada—


5 mg (Rx) [Artane Sequels]

Packaging and storage:
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.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.


TRIHEXYPHENIDYL HYDROCHLORIDE ELIXIR USP

Usual adult and adolescent dose
Parkinsonism
Oral, 1 to 2 mg the first day, the dosage being increased by an additional 2 mg at three- to five-day intervals until the desired response is obtained or until the total dose per day reaches 6 to 10 mg, usually divided into three doses taken at mealtimes. {01} {14}

Note: Postencephalitic parkinsonism—A total dose of 12 to 15 mg per day may be required. {01} {14}


Drug-induced extrapyramidal reactions
Oral, initially 1 mg a day, the dosage being increased as needed and tolerated or until the total daily dose reaches 5 to 15 mg. {14} {19}


Usual adult prescribing limits
Up to 15 mg daily. {14}

Usual pediatric dose
Dosage has not been established.

Usual geriatric dose
See Usual adult and adolescent dose.

Note: Geriatric patients may be more sensitive to the effects of the usual adult dose. {14}


Strength(s) usually available
U.S.—


2 mg per 5 mL (Rx) [Artane (lime-mint flavored)][Generic]

Canada—


2 mg per 5 mL (Rx) [Artane (lime flavored)] [PMS Trihexyphenidyl]

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 container. Protect from freezing.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.


TRIHEXYPHENIDYL HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
See Trihexyphenidyl Hydrochloride Elixir USP .

Usual adult prescribing limits
See Trihexyphenidyl Hydrochloride Elixir USP .

Usual pediatric dose
See Trihexyphenidyl Hydrochloride Elixir USP .

Usual geriatric dose
See Trihexyphenidyl Hydrochloride Elixir USP .

Strength(s) usually available
U.S.—


2 mg (Rx) [Artane (scored)] [Trihexane] [Trihexy][Generic]


5 mg (Rx) [Artane (scored)] [Trihexane] [Trihexy][Generic]

Canada—


2 mg (Rx) [Apo-Trihex (scored) ( sodium <1 mmol (0.113 mg)/2 mg)] [Artane (scored)] [PMS Trihexyphenidyl (sodium <1 mmol (0.113 mg)/2 mg)]


5 mg (Rx) [Apo-Trihex (scored) ( sodium <1 mmol (0.188 mg)/5 mg)] [Artane (scored)] [PMS Trihexyphenidyl (sodium <1 mmol (0.188 mg)/5 mg)]

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 container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.
   • Keep container tightly closed.



Revised: 05/11/93



References
  1. Package inserts(Cogentin 7/85; Akineton 6/87; Kemadrin 6/85; Procyclid 3/84; Aparkane 9/87; Bensylate 4/78), received on 1/11/88.
  1. The United States pharmacopeia. The national formulary. USP 21st revision (January 1, 1985). NF 16th ed (January 1, 1985). Rockville, MD: The United States Pharmacopeial Convention, Inc., 1985.
  1. Fleeger CA, editor. USAN 1993. USAN and the USP dictionary of drug names. Rockville, MD: The United States Pharmacopeial Convention, Inc., 1992.
  1. Rovner B, et al. Self-care capacity and anticholinergic drug levels in nursing home patients. Am J Psychiatry 1988 Jan; 145: 107-9.
  1. Pullen G, et al. Br Med J 1984 Sep; 289: 612.
  1. Benztropine Mesylate package insert (Cogentin, MSD—US), Rev 5/89, Rec 9/89.
  1. Benztropine Mesylate package insert (Lederle—US), Rev 4/86, Rec 12/88.
  1. Benztropine Mesylate product monograph (Cogentin, MSD—Canada), CPS 1989: 220.
  1. Biperiden package insert (Akineton, Knoll—US), Rev 6/87, Rec 1/89.
  1. Biperiden package insert (Akineton, Knoll—Canada), Rev 2/78, Rec 4/90.
  1. Ethopropazine Hydrochloride product monograph (Parsitan—Canada), CPS 1989: 778.
  1. Procyclidine Hydrochloride package insert (Kemadrin, Wellcome—US), Rev 6/85, Rec 11/88.
  1. Procyclidine Hydrochloride product monograph (Kemadrin, Wellcome—Canada), CPS 1989: 518 (Rev 1988).
  1. Trihexyphenidyl Hydrochloride package insert (Artane, Lederle—US), Rev 4/87, Rec 12/88.
  1. Trihexyphenidyl Hydrochloride package insert (Bolar—US), Rev 1/88, Rec 11/88.
  1. Trihexyphenidyl Hydrochloride package insert (Danbury—US), Rev 10/86, Rec 1/89.
  1. Trihexyphenidyl Hydrochloride product monograph (Artane, Lederle—Canada), CPS 1989: 97.
  1. Olin BR, editor. Drug facts and comparisons. St. Louis: Facts and Comparisons Inc., l990: 289b-90.
  1. AMA Drug Evaluations. 5th ed. Chicago: American Medical Association, April 1983: 329-37.
  1. Reynolds JEF, editor. Martindale, the extra pharmacopeia. 29th ed. London: The Pharmaceutical Press, 1989: 527-9, 532, 542.
  1. AHFS 1984: 307-313.
  1. Paven-Langston D, editor. Manual of ocular diagnosis and therapy. 1st ed. l980: 221.
  1. McInnis M, Petursson H. Withdrawal of trihexyphenidyl. Acta Psychiatr Scand 1985; 71: 297-303.
  1. Jellinek T, Gardos G, Cole JO. Adverse effects of antiparkinson drug withdrawal. Am J Psychiatry 1981 Dec; 138(12): 1567-71.
  1. Klett CJ, Caffey E Jr. Evaluating the long-term need for antiparkinson drugs by chronic schizophrenics. Arch Gen Psychiatry 1972 Apr; 26: 374-9.
  1. Orlov P, et al. Withdrawal of antiparkinson drugs. Arch Gen Psychiatry 1971 Nov; 25: 410-2.
  1. McClelland HA, et al. The abrupt withdrawal of antiparkinson drugs in schizophrenic patients. Br J Psychiatry 1974; 124: 151-9.
  1. Pullen GP, et al. Br Med J 1984 Sep 8; 289: 612.
  1. Shirkey, 5th ed. l975: 1258.
  1. USP DI: Anticholinergics/Antispasmodics(Systemic) monograph.
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