Trihexyphenidyl (Monograph)
Drug class: Anticholinergic Agents
VA class: AU350
CAS number: 52-49-3
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
Drug |
Interaction |
|
---|---|---|
Anticholinergic agents |
Increased risk of adverse anticholinergic effectsc |
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
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Solution |
2 mg/5 mL* |
Trihexyphenidyl Hydrochloride Oral Solution |
|
Tablets |
2 mg* |
Trihexyphenidyl Hydrochloride Tablets |
||
5 mg* |
Trihexyphenidyl Hydrochloride Tablets |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions March 8, 2022. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
References
101. Olanow CW, Watts RL, Koller WC. An algorithm (decision tree) for the management of Parkinson’s disease (2001): treatment guidelines. Neurology. 2001; 56:S1-S88.
115. Lewitt PA. Levodopa for the treatment of Parkinson's disease. N Engl J Med. 2008; 359:2468-76. http://www.ncbi.nlm.nih.gov/pubmed/19052127?dopt=AbstractPlus
123. Connolly BS, Lang AE. Pharmacological treatment of Parkinson disease: a review. JAMA. 2014 Apr 23-30; 311:1670-83. http://www.ncbi.nlm.nih.gov/pubmed/24756517?dopt=AbstractPlus
157. . Drugs for Parkinson's disease. Med Lett Drugs Ther. 2017; 59:187-194. http://www.ncbi.nlm.nih.gov/pubmed/29136401?dopt=AbstractPlus
158. Katzenschlager R, Sampaio C, Costa J et al. Anticholinergics for symptomatic management of Parkinson's disease. Cochrane Database Syst Rev. 2003; :CD003735. http://www.ncbi.nlm.nih.gov/pubmed/12804486?dopt=AbstractPlus
159. By the 2019 American Geriatrics Society Beers Criteria Update Expert Panel. American Geriatrics Society 2019 Updated AGS Beers Criteria for Potentially Inappropriate Medication Use in Older Adults. J Am Geriatr Soc. 2019; 67:674-694. http://www.ncbi.nlm.nih.gov/pubmed/30693946?dopt=AbstractPlus
160. Salem H, Nagpal C, Pigott T et al. Revisiting Antipsychotic-induced Akathisia: Current Issues and Prospective Challenges. Curr Neuropharmacol. 2017; 15:789-798. http://www.ncbi.nlm.nih.gov/pubmed/27928948?dopt=AbstractPlus
161. Rathbone J, Soares-Weiser K. Anticholinergics for neuroleptic-induced acute akathisia. Cochrane Database Syst Rev. 2006; :CD003727. http://www.ncbi.nlm.nih.gov/pubmed/17054182?dopt=AbstractPlus
162. Ogino S, Miyamoto S, Miyake N et al. Benefits and limits of anticholinergic use in schizophrenia: focusing on its effect on cognitive function. Psychiatry Clin Neurosci. 2014; 68:37-49. http://www.ncbi.nlm.nih.gov/pubmed/24102938?dopt=AbstractPlus
200. Actavis. Trihexyphenidyl hydrochloride tablets prescribing information. Parsippany, NJ; 2015 Jun.
201. Mikart. Trihexyphenidyl hydrochloride oral solution prescribing information. Atlanta, GA; 2019 July.
b. AHFS drug information 2021. Snow EK, ed. Trihexyphenidyl. Bethesda, MD: American Society of Health-System Pharmacists; 2021.
c. AHFS drug information 2021. Snow EK, ed. Antimuscarinics/Antispasmodics General Statement. Bethesda, MD: American Society of Health-System Pharmacists; 2021.
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