PACE Case: Improving Parkinson’s Symptom Control

An 85 y/o male with a history of Parkinson’s disease, neuropathy, CVD, and atrial fibrillation (AFib) is currently being treated for tremors with carbidopa/levodopa CR 25/100mg ER three times daily.

Other medications include:
• aspirin 81mg daily
• pravastatin 40mg daily
• duloxetine 30mg daily
• dronedarone 400mg every 12 hours
• carvedilol 3.125mg twice daily
• furosemide 40mg daily
• isosorbide ER 30mg daily
• diltiazem 360mg ER daily, and
• tramadol 50mg prn.

The physician contacted his CareKinesis pharmacist, inquiring about adding either rasagiline or primidone to this regimen for better Parkinson’s symptom control.

CK INTERVENTION
The CK clinical pharmacist indicated that rasagiline had to be ruled out as an option due to drug interactions with both duloxetine and tramadol. Rasagiline is an MAO inhibitor which inhibits serotonin metabolism; when combined with other serotonergic agents such as SNRIs and tramadol, rasagiline increases patient risk for serotonin syndrome. Adverse events associated with combined use include irritability, confusion, palpitations, excess sweating, BP changes, nausea/vomiting/diarrhea, tremor, rigidity, etc. A significant washout period of at least 14 days is recommended when switching from one agent to another, and concomitant use is considered contraindicated. In addition, rasagiline will cause a pharmacokinetic drug interaction with duloxetine as both drugs are substrates of the same CYP450 isozyme, namely CYP1A2.

Primidone was also deemed to be an inappropriate choice for this patient, as, through the formation of its active metabolite phenobarbital, it is a potent CYP3A4, CYP2B6, CYP2C8, CYP2C9, and CYP2C19 inducer. These conditions may lead to multiple drug interactions. Of most concern, primidone significantly decreases dronedarone plasma concentrations by inducing its metabolism, leading to a decrease in its clinical effectiveness. Additionally, primidone may also induce the metabolism of diltiazem and pravastatin, also resulting in decreased plasma concentrations and clinical effectiveness. In order to not compromise the participant’s AFib treatment through ventricular rate control (AV block), the CK clinical pharmacist recommended against primidone use.

The CK clinical pharmacist presented to the physician alternative therapies, which included increasing the participant’s carbidopa/levodopa dose and/or frequency, or adding a low dose dopamine agonist such as ropinerole or pramipexole. Long-term use of carbidopa/levodopa is associated with a weaning off effect as the disease progresses, which can be managed by increasing dosing frequency or by adding another agent. Dopamine agonists, when given concomitantly with carbidopa/levodopa, can prevent the weaning effects and prolong the duration of clinical effectiveness, and, for this participant, did not pose an issue with drug/drug or drug/disease interactions.

RESULTS
Ultimately, the physician and CK clinical pharmacist chose to add a low-dose dopamine agonist, ropinerole 0.25mg BID, to help control the participant’s Parkinson’s symptoms. The physician was asked to counsel the participant and watch for possible adverse events including dyskinesias, orthostatic hypotension, dizziness, somnolence, and GI effects, and to titrate the dose according to patient response and tolerability. The participant has since been stabilized and maintained on this regimen.

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