Should pramipexole, amitriptyline, and trihexyphenidyl be continued in a patient with Parkinson's disease (PD) and new onset atrial fibrillation (AFib) who has been started on Cordarone (amiodarone)?

Medication Management in Parkinson's Disease Patient with New-Onset Atrial Fibrillation on Amiodarone

Amitriptyline should be discontinued immediately due to dangerous drug interactions with amiodarone, while pramipexole and trihexyphenidyl can be continued with close monitoring for bradycardia and QT prolongation. 1

Critical Drug Interaction: Amitriptyline and Amiodarone

Amitriptyline must be stopped because amiodarone is a potent inhibitor of CYP2D6, the primary enzyme responsible for metabolizing tricyclic antidepressants like amitriptyline. 1 This interaction can lead to:

• Unexpectedly high plasma levels of amitriptyline 1
• Increased risk of QT prolongation and torsades de pointes (both drugs independently prolong QT interval) 2
• Enhanced anticholinergic effects that could worsen cognitive function in a stroke patient
• Additive bradycardic effects in combination with amiodarone's AV nodal blocking properties 1

The FDA label explicitly warns that amiodarone inhibits CYP2D6 and can result in "unexpectedly high plasma levels of other drugs which are metabolized by those CYP450 enzymes," specifically mentioning this concern with medications like tricyclic antidepressants. 1

Pramipexole: Continue with Monitoring

Pramipexole can be safely continued as there are no significant pharmacokinetic interactions with amiodarone. 3, 4

• Pramipexole is effective for Parkinson's disease motor symptoms and may provide additional benefit for depression, which could be relevant given the patient's complex neurological status 3
• Monitor for additive bradycardic effects, as both amiodarone and dopamine agonists can occasionally cause bradycardia 1
• Watch for orthostatic hypotension, which could be problematic in a patient with hemiplegia/hemiparesis 3
• Pramipexole does not undergo significant CYP450 metabolism, avoiding the major interaction pathway with amiodarone 3

Trihexyphenidyl: Continue with Caution

Trihexyphenidyl can be continued but requires careful monitoring due to its anticholinergic properties in a stroke patient with aphasia. 1

• No direct pharmacokinetic interaction with amiodarone is documented 1
• However, anticholinergic medications can worsen cognitive function and may complicate recovery from stroke-related aphasia
• The anticholinergic effects could theoretically interact with amiodarone's effects on cardiac conduction 1
• Consider dose reduction if confusion, urinary retention, or worsening cognitive symptoms develop

Amiodarone Monitoring Requirements

Given this complex medication regimen, enhanced monitoring is essential:

• QT interval monitoring: Baseline and serial ECGs to detect excessive QT prolongation, especially after removing amitriptyline 2
• Heart rate monitoring: Watch for excessive bradycardia or AV block, particularly with the combination of amiodarone and Parkinson's medications 1
• Thyroid function: Amiodarone commonly causes thyroid dysfunction 2
• Pulmonary function: Monitor for pulmonary toxicity, a serious adverse effect of amiodarone 2
• Hepatic function: Regular liver enzyme monitoring 2

Alternative Antidepressant Consideration

If antidepressant therapy is needed after discontinuing amitriptyline:

• Avoid SSRIs like fluoxetine, which is also a potent CYP2D6 inhibitor 5
• Consider sertraline or citalopram at low doses, which have less CYP450 interaction potential
• Non-pharmacological approaches for depression in Parkinson's disease should be maximized 3

Common Pitfalls to Avoid

• Do not continue amitriptyline even at reduced doses—the interaction risk is too significant 1
• Do not abruptly stop amitriptyline—taper over 1-2 weeks to avoid withdrawal symptoms
• Do not add additional QT-prolonging medications without cardiology consultation 2
• Do not assume hemodynamic stability means drug interactions are absent—toxicity can develop gradually with amiodarone's long half-life 1

2, 1, 3