Drug class: Anticholinergic Agents
VA class: AU350
CAS number: 52-49-3

Medically reviewed by Drugs.com on Feb 27, 2024. Written by ASHP.

Introduction

Antimuscarinic antiparkinsonian agent.^{157 200 201 b}

Uses for Trihexyphenidyl

Parkinsonian Syndrome

Symptomatic management of all forms of parkinsonian syndrome, including idiopathic parkinson disease and parkinsonism resulting from encephalitis (postencephalitic parkinsonism) or cerebral arteriosclerosis.^{123 157 200 201}

Has been used as monotherapy or as adjunctive therapy in the treatment of parkinson disease.^{123 157 158}

Levodopa is currently the most effective drug for relieving motor symptoms of parkinson disease; however, long-term use associated with motor complications.^{101 115 123 157} To avoid these complications, may initiate treatment with other antiparkinsonian agents first and postpone use of levodopa.^{115 123 157} Some clinicians state that anticholinergic agents (e.g., trihexyphenidyl, benztropine) may be particularly useful for initial therapy in patients <60 years of age with resting tremors as their only or most prominent symptom.^{115 123}

Although main use of anticholinergic agents in parkinson disease is to control tremors, evidence of a benefit largely anecdotal.^{123 157 158}

Drug-induced Extrapyramidal Reactions

Control of extrapyramidal symptoms (EPS) induced by antipsychotic agents (e.g., phenothiazines, thioxanthenes).^{200 201}

Anticholinergic agents (e.g., trihexyphenidyl, benztropine) are used traditionally to restore acetylcholine and dopamine imbalance in patients with antipsychotic-induced EPS; however, evidence supporting a benefit is lacking or inconsistent and the drugs are associated with a variety of adverse effects.^{160 161 162}

In general, use cautiously and for minimum duration necessary to control EPS.^{160 162}

Trihexyphenidyl Dosage and Administration

Administration

Oral Administration

Administer orally (as tablets or oral solution) before or after meals, depending on patient reaction.^{200 201} May be preferable to administer before meals in patients with excessive xerostomia (unless nausea is a problem) and after meals in patients prone to excessive salivation.^{200 201}

Tolerability may be increased if total daily dosage is administered in divided doses 3 times daily with meals; if a fourth dose is required (such as with dosages >10 mg daily), administer at bedtime.^{200 201}

Mint candies, chewing gum, water, or a saliva substitute may be used to relieve xerostomia that may accompany administration after meals.^{200 201 b}

Dosage

Available as trihexyphenidyl hydrochloride; dosage expressed in terms of the salt.^{200 201}

Adjust dosage carefully according to individual requirements and response.^{200 201} Initiate with low dosage and increase gradually to desired effect.^{200 201}

Adults

Parkinsonian Syndrome

Oral

Initially, 1 mg on first day.^{200 201} Dosage may be increased in 2-mg increments at 3- to 5-day intervals up to a maximum of 6–10 mg daily.^{200 201}

Parkinson disease: Usual maintenance dosage is 2 mg 3 times daily.¹²³

Postencephalitic patients: Dosages up to 12–15 mg daily may be required.^{200 201}

When used as an adjunct to levodopa, consider reducing dosage of both drugs.^{200 201} Generally, a dosage of 3–6 mg daily of trihexyphenidyl hydrochloride given in divided doses is adequate.^{200 201}

When transitioning from another antimuscarinic agent to trihexyphenidyl, increase trihexyphenidyl dosage as needed while decreasing dosage of other drug until complete replacement is achieved.^{200 201}

Drug-Induced Extrapyramidal Reactions

Oral

Usual total daily dosage: 2–15 mg.^{160 200 201}

Initially, 1 mg; if EPS not controlled within a few hours, progressively increase dose until control is achieved.^{200 201}

Alternatively, to achieve more rapid control, reduce dosage of the drug causing the reaction, then adjust dosage of both drugs to attain the desired drug effect without EPS.^{200 201} Once control of EPS has been maintained for several days, dosage of trihexyphenidyl may be reduced or discontinued.^{200 201}

Prescribing Limits

Adults

Parkinsonian Syndrome

Oral

Maximum of 6–10 mg daily in most patients; postencephalitic patients may require 12–15 mg daily.^{200 201}

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.^{200 201}

Renal Impairment

No specific dosage recommendations at this time.^{200 201}

Geriatric Patients

Patients ≥60 years of age: Manufacturer states to initiate with low dosage; titrate dosage gradually.^{200 201} (See Geriatric Use under Cautions.)

Cautions for Trihexyphenidyl

Contraindications

• Known hypersensitivity to trihexyphenidyl or any ingredient in the formulation.²⁰¹

• Some manufacturers state drug is contraindicated in patients with narrow angle glaucoma.²⁰¹ Blindness after long-term use due to narrow angle glaucoma has been reported.²⁰¹

Warnings/Precautions

Warnings

Ophthalmic Effects

Possible increased ocular tension.^{200 201} Possible precipitation of glaucoma in patients receiving prolonged therapy.^{200 201 c}

Use with caution in patients with glaucoma.^{200 201 c}

Periodic gonioscopic evaluation and intraocular pressure monitoring recommended.^{200 201}

General Precautions

Tardive Dyskinesia

Antiparkinsonian agents do not alleviate symptoms of tardive dyskinesia and may aggravate these symptoms.^{200 201}

Cardiovascular Effects

Possible tachycardia; use with caution and carefully monitor patients with cardiac disease or hypertension.^{200 201 c}

GU Effects

Possible urinary hesitancy and retention; use with caution and carefully monitor patients with prostatic hypertrophy or obstructive disease of the GU tract.^{200 201 c}

CNS Effects

Possible mental confusion, disorientation, behavioral disturbances, agitation, hallucinations, and psychotic-like symptoms.^{200 201}

GI Effects

Possible decreased intestinal mobility, paralytic ileus, and constipation; use with caution in patients with obstructive diseases of the GI tract.^{200 201}

Specific Populations

Geriatric Use

Possibility exists of greater sensitivity to the drug in some geriatric individuals.^{200 201} Careful dosage selection necessary.^{200 201} Some experts state to avoid use in geriatric patients because of unfavorable balance of benefits and risks compared with alternative treatments.^{157 159}

Hepatic Impairment

Careful monitoring recommended.^{200 201}

Renal Impairment

Careful monitoring recommended.^{200 201}

Common Adverse Effects

Dry mouth, blurred vision, dizziness, nausea, nervousness.^{200 201}

Drug Interactions

Specific Drugs

Trihexyphenidyl Pharmacokinetics

Absorption

Rapidly absorbed from the GI tract following oral administration.^b

Onset

Following oral administration, onset of action occurs within 1 hour.^b

Duration

6–12 hours.^b

Elimination

Elimination Route

Excreted principally in urine, probably as unchanged drug.^b

Stability

Storage

Oral

Oral Solution

20–25°C.²⁰¹

Tablets

20–25°C.²⁰⁰

Actions

• Exhibits atropine-like action and exerts antispasmodic effects on parasympathetic-innervated peripheral structures, including smooth muscle.^{200 201 b}

• Exact mechanism of action in parkinsonian syndrome not understood; may result from blockade of efferent impulses and from central inhibition of cerebral motor centers.^b

• Competitively inhibits acetylcholine or other cholinergic stimuli at autonomic effectors innervated by postganglionic nerves.^c

• Exhibits weak mydriatic, antisialagogue, and cardiovagal blocking effects.^b

Advice to Patients

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as concomitant illnesses.^{200 201}

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{200 201}

• Importance of informing patients of other important precautionary information.^{200 201} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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