Antihistamines (first Generation) (e.g., Diphenhydramine, Chlorpheniramine)Severe
Database
Significantly increased risk of severe anticholinergic side effects, including profound sedation, confusion, delirium, urinary retention, severe constipation, blurred vision, and dry mouth.
Avoid concomitant use. If an antihistamine is required, choose a second-generation antihistamine with minimal anticholinergic activity (e.g., loratadine, fexofenadine). If co-administration is unavoidable, use extreme caution and monitor closely for anticholinergic toxicity.
Potassium ChlorideSevere
Database
Clinical effect not specified
Source: DDInter
Potassium CitrateSevere
Database
Clinical effect not specified
Source: DDInter
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Source: DDInter
Tricyclic Antidepressants (tcas) (e.g., Amitriptyline, Imipramine)Severe
Database
Significantly increased risk of severe anticholinergic side effects, including paralytic ileus, urinary retention, severe constipation, blurred vision, dry mouth, confusion, delirium, and heatstroke (due to impaired sweating).
Avoid concomitant use if possible. If co-administration is unavoidable, use the lowest effective doses of both drugs and monitor closely for signs of anticholinergic toxicity. Educate patients on symptoms of anticholinergic excess and advise them to seek immediate medical attention if they occur.
Other AnticholinergicsSevere
Database
Additive anticholinergic toxicity; high risk of confusion, constipation, urinary retention, heat stroke
Avoid multiple anticholinergics; monitor for anticholinergic toxicity
Source: Kimi deep-research + Cla
Clinical effect not specified
Source: DDInter
Increased sedation, dizziness, confusion, and impairment of cognitive and motor skills. Increased risk of anticholinergic side effects.
Advise patients to avoid or limit alcohol consumption while taking trihexyphenidyl. Warn about impaired ability to drive or operate machinery.
Antipsychotics (e.g., Chlorpromazine, Haloperidol)Moderate
Database
Reduced efficacy of antipsychotics (due to anticholinergic effects counteracting dopamine blockade) and increased risk of anticholinergic side effects (e.g., dry mouth, constipation, blurred vision, urinary retention, confusion). May worsen tardive dyskinesia in some cases.
Monitor for reduced antipsychotic efficacy and increased anticholinergic side effects. Consider dose adjustment of either drug or using an alternative agent if possible. Avoid routine prophylactic use of trihexyphenidyl with antipsychotics unless absolutely necessary for severe extrapyramidal symptoms.
Increased risk of digoxin toxicity (e.g., nausea, vomiting, arrhythmias, visual disturbances).
Monitor digoxin serum concentrations closely when initiating or discontinuing trihexyphenidyl. Adjust digoxin dose as needed. Monitor for signs and symptoms of digoxin toxicity.
Source: DDInter
MetoclopramideModerate
Database
Reduced efficacy of metoclopramide in promoting gastrointestinal motility. May worsen extrapyramidal symptoms if metoclopramide is used for its antiemetic effects.
Avoid concomitant use if possible. If both are necessary, monitor for reduced efficacy of metoclopramide. Consider alternative antiemetics or prokinetics if appropriate.
Source: DDInter
Monoamine Oxidase Inhibitors (maois) (e.g., Phenelzine, Selegiline)Moderate
Database
Increased risk of anticholinergic side effects (e.g., dry mouth, constipation, blurred vision, urinary retention, confusion). MAOIs can also increase the risk of CNS excitation and delirium when combined with anticholinergics.
Use with caution. Monitor closely for anticholinergic side effects and CNS toxicity. Consider dose reduction of trihexyphenidyl. Avoid if possible, especially in elderly or susceptible patients.
