Dystonia in cerebral palsy: Limited data available: Children and Adolescents: Oral: Initial: 0.1 to 0.2 mg/kg/day in 2 to 3 divided doses; after the first week, titrate weekly or every 2 weeks as tolerated (eg, increase by 0.15 mg/kg/day or increase by 10% to 20%) (Ref). Usual maximum daily dose: 0.75 mg/kg/day in 3 divided doses (Ref). Doses as high as 2.6 mg/kg/day in 3 divided doses have been described (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
There are no dosage adjustments provided in the manufacturer's labeling; use with caution.
(For additional information see "Trihexyphenidyl: Drug information")
Extrapyramidal symptoms (eg, dystonia and parkinsonism), medication-induced (treatment):
Note: Anticholinergic agents are not recommended for the treatment of akathisia or tardive dyskinesia (Ref). Duration of therapy is based on the severity of EPS reaction, pharmacologic profile of the causative agent (eg, half-life, adverse effects), and patient risk factors (Ref). Some experts recommend attempting taper and discontinuation after several weeks to months (Ref).
Oral: Initial: 1 mg/day; increase as necessary to usual range: 5 to 15 mg/day in 3 to 4 divided doses.
Parkinsonism: Oral: Initial: 1 mg/day, increase by 2 mg increments at intervals of 3 to 5 days; usual dose: 6 to 10 mg/day in 3 to 4 divided doses; doses of 12 to 15 mg/day may be required. Consider dosage reduction when used concomitantly with levodopa, the usual dose of each may need to be reduced. Usual range: 3 to 6 mg/day in divided doses.
Discontinuation of therapy: Dose reduction or discontinuation of trihexyphenidyl has been associated with neuroleptic malignant syndrome, exacerbation of parkinsonism, and withdrawal symptoms (eg, palpitations, headache, insomnia, fainting, and nausea (Ref)). According to the manufacturer's labeling, withdraw trihexyphenidyl gradually; abrupt or rapid discontinuation may result in acute exacerbation of symptoms or side effects (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Gastrointestinal: Nausea (30% to 50%), xerostomia (30% to 50%)
Nervous system: Dizziness (30% to 50%), nervousness (30% to 50%)
Ophthalmic: Blurred vision (30% to 50%)
Postmarketing:
Cardiovascular: Paradoxical bradycardia (sinus bradycardia) (Blumensohn 1986), tachycardia
Dermatologic: Erythema of skin (Zhao 2022), hypohidrosis (Zhao 2022), skin rash, xeroderma
Endocrine & metabolic: SIADH (Zhao 2022)
Gastrointestinal: Constipation (Zhao 2022), paralytic ileus, toxic megacolon, vomiting (Zhao 2022)
Genitourinary: Urinary hesitancy, urinary retention (Zhao 2022)
Nervous system: Anxiety (Zhao 2022), asthenia, choreiform movements (Warne 1979, cognitive dysfunction (including confusion and memory impairment) (Zhao 2022), delusion, drowsiness, euphoria (Jellinek 1977), hallucination (Zhao 2022), headache, myasthenia gravis (Ueno 1987), neuroleptic malignant syndrome (with abrupt withdrawal), paranoid ideation
Neuromuscular & skeletal: Dyskinesia (including tardive dyskinesia [orobuccal] (Hauser 1993, Zhao 2022)
Ophthalmic: Angle-closure glaucoma (including blindness), cycloplegia, increased intraocular pressure, mydriasis
Miscellaneous: High fever (Zhao 2022), malignant hyperthermia (Zhao 2022)
Hypersensitivity to trihexyphenidyl or any component of the formulation; narrow angle glaucoma.
Concerns related to adverse effects:
• Anhidrosis/hyperthermia: May cause anhidrosis and hyperthermia. Severe anhidrosis and fatal hyperthermia have occurred; use with caution in hot weather or during exercise, especially when administered concomitantly with other anticholinergic drugs to chronically ill patients, patients with alcohol use disorder, patients with CNS disease, or persons doing manual labor in a hot environment.
• Anticholinergic effects: May cause anticholinergic effects (constipation, xerostomia, blurred vision, urinary retention); monitor patients requiring long-term use.
• CNS depression: May impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery, driving).
• Ocular effects: May precipitate angle closure with an increase in intraocular pressure. If blurring of vision occurs, consider the possibility of narrow angle glaucoma; blindness because of aggravation of narrow angle glaucoma has been reported.
Disease-related concerns:
• Cardiovascular disease: Use with caution in patients with cardiovascular disease, including hypertension.
• GI obstruction: Use with caution in patients with obstructive disease of the GI tract.
• Glaucoma: Use with caution in patients with glaucoma; blindness after long-term use due to narrow angle glaucoma has been reported.
• Hepatic impairment: Use with caution in patients with hepatic impairment.
• Prostatic hyperplasia/urinary stricture: Use with caution in patients with prostatic hyperplasia and/or urinary stricture or retention.
• Psychiatric effects: May impair memory and further exacerbate cognitive deficits in elderly patients; in high doses may cause confusion, delirium, and hallucinations (Holloman 1997; Tonda 1994).
• Renal impairment: Use with caution in patients with renal impairment.
• Tardive dyskinesia: Not recommended for use in patients with tardive dyskinesia unless concomitant Parkinson disease or tardive dystonia exists (Kang 1986); trihexyphenidyl does not relieve symptoms of tardive dyskinesia and may potentially exacerbate symptoms.
Other warnings/precautions:
• Discontinuation of therapy: Dose reduction or discontinuation of trihexyphenidyl has been associated with neuroleptic malignant syndrome (NMS), exacerbation of Parkinsonism, and withdrawal symptoms including tension, irritability, perspiration, palpitations, headache, insomnia, abdominal distress, anorexia, faint or choking feelings, nausea, and photophobia (McInnis 1985). According to the manufacturer's labeling, withdraw trihexyphenidyl gradually; abrupt or rapid discontinuation may result in acute exacerbation of symptoms or side effects (Manos 1981a; Manos 1981b).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Oral:
Generic: 0.4 mg/mL (473 mL)
Tablet, Oral, as hydrochloride:
Generic: 2 mg, 5 mg
Yes
Solution (Trihexyphenidyl HCl Oral)
0.4 mg/mL (per mL): $0.11
Tablets (Trihexyphenidyl HCl Oral)
2 mg (per each): $0.18 - $0.55
5 mg (per each): $0.36 - $1.10
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral, as hydrochloride:
Generic: 2 mg, 5 mg
Oral: May be taken before or after meals (if excessive dry mouth develops, consider administering before meals unless it causes nausea); tolerated best if administered in 3 daily doses and with food. High doses (>10 mg/day) may be divided into 4 doses, at meal times and at bedtime.
Oral: May be administered before or after meals (if excessive dry mouth develops, consider administering before meals unless it causes nausea; postencephalitic patients who are prone to excessive salivation may prefer to take after meals); tolerated best if given in 3 daily doses and with food. High doses (>10 mg/day) may be divided into 4 doses (at each meal and at bedtime).
Store at 20°C to 25°C (68°F to 77°F).
Adjunctive treatment of Parkinson's disease and treatment of drug-induced extrapyramidal symptoms (EPS) (FDA approved in adults); has also been used for treatment of dystonia in cerebral palsy
Trihexyphenidyl may be confused with trifluoperazine
Beers Criteria: Trihexyphenidyl is identified in the Beers Criteria as a potentially inappropriate medication to be avoided in patients 65 years and older due to its highly anticholinergic properties. It is not recommended for the prevention or treatment of extrapyramidal symptoms with antipsychotics. In the treatment of Parkinson disease, more effective agents are available (Beers Criteria [AGS 2023]).
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy
Chlorprothixene: Anticholinergic Agents may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Lisuride: Trihexyphenidyl may enhance the adverse/toxic effect of Lisuride. Risk X: Avoid combination
Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy
Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Opioid Agonists: Anticholinergic Agents may enhance the adverse/toxic effect of Opioid Agonists. Specifically, the risk for constipation and urinary retention may be increased with this combination. Risk C: Monitor therapy
Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk X: Avoid combination
Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
Rivastigmine: Anticholinergic Agents may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Anticholinergic Agents. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination
May be taken before or after meals; tolerated best if given with food.
Animal reproduction studies have not been conducted. One case report did not show evidence of adverse events after trihexyphenidyl administration during pregnancy (Robottom 2011).
Intraocular pressure monitoring and gonioscopic evaluations (baseline and at regular intervals), anticholinergic adverse reactions (patients on long-term therapy)
Exerts a direct inhibitory effect on the parasympathetic nervous system. It also has a relaxing effect on smooth musculature; exerted both directly on the muscle itself and indirectly through parasympathetic nervous system (inhibitory effect)
Metabolism: Hydroxylation of the alicyclic groups (Brocks 1999)
Half-life elimination: 33 hours (Brocks 1999)
Time to peak, serum: 1.3 hours (Brocks 1999)
Excretion: Urine and bile (Brocks 1999)
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