What is the substitution dose and frequency of Cogentin (Benztropine) for Artane (Trihexyphenidyl) 5mg three times a day (TID)?

Cogentin Substitution for Artane 5mg TID

For a patient taking Artane (trihexyphenidyl) 5mg three times daily (15mg total daily), substitute with Cogentin (benztropine) 1-2mg twice daily, starting at 1mg twice daily and titrating up to 2mg twice daily if needed for symptom control. 1

Dosing Rationale

The conversion from trihexyphenidyl to benztropine is not a direct milligram-to-milligram substitution due to differences in potency and duration of action between these anticholinergic agents. 2

Key Conversion Principles:

• Benztropine has a longer duration of action than trihexyphenidyl, allowing for less frequent dosing (typically once or twice daily versus three times daily). 1

• The FDA-approved dosing range for benztropine in drug-induced extrapyramidal disorders is 1-4mg once or twice daily, with most patients requiring 1-2mg twice daily. 1

• For Artane 15mg daily total dose, the equivalent benztropine dose typically falls in the range of 2-4mg total daily, divided into 1-2 doses. 1

Recommended Substitution Protocol:

Initial Conversion:

• Start benztropine at 1mg twice daily (2mg total daily). 1
• Do not abruptly discontinue trihexyphenidyl; instead, gradually taper it over 3-5 days while initiating benztropine. 1, 3

Titration Strategy:

• If symptoms are not adequately controlled after 5-6 days, increase benztropine by 0.5mg increments to a maximum of 6mg daily (though most patients respond to 2-4mg daily). 1
• The usual effective dose range is 1-2mg twice daily for most patients with drug-induced parkinsonism. 1

Alternative Dosing:

• Some patients may achieve adequate control with a single daily dose of 2mg at bedtime, taking advantage of benztropine's long duration of action. 1

Critical Warnings and Monitoring:

Avoid in Alzheimer's Disease:

• Guidelines explicitly recommend avoiding both benztropine and trihexyphenidyl in elderly patients with Alzheimer's disease due to significant anticholinergic side effects and risk of cognitive worsening. 4

Anticholinergic Toxicity Risk:

• Both medications have potent anticholinergic effects, with benztropine showing 5-10 times lower affinity in peripheral tissues compared to brain tissue. 2
• When combined with antipsychotics (especially olanzapine or clozapine), there is increased risk of severe constipation and potentially ischemic colitis. 5

Monitoring Parameters:

• Assess for anticholinergic side effects: dry mouth, urinary retention, constipation, blurred vision, confusion. 1
• Monitor for adequate control of extrapyramidal symptoms (tremor, rigidity, bradykinesia). 1
• In patients over 60 years, start with lower doses and titrate more cautiously. 1

Common Pitfalls to Avoid:

• Do not use 1:1 dose conversion - benztropine is more potent and longer-acting than trihexyphenidyl. 1, 3
• Do not abruptly discontinue trihexyphenidyl - this may cause acute exacerbation of parkinsonian symptoms or neuroleptic malignant syndrome. 3
• Do not exceed 6mg daily of benztropine without clear clinical justification, as higher doses increase anticholinergic side effects without proportional benefit. 1
• Reassess need for continued therapy after 1-2 weeks, as some drug-induced extrapyramidal reactions are transient and may not require long-term anticholinergic therapy. 1