Is it reasonable to try pramipexole (Dopamine Agonist) in the elderly population with Impaired renal function or other comorbidities?

From the Guidelines

Pramipexole can be used cautiously in elderly patients, but requires special consideration due to increased risk of side effects. When prescribing pramipexole for elderly patients, start with a lower dose than typically used in younger adults, such as 0.125 mg three times daily, and titrate slowly based on response and tolerability 1. Elderly patients are more susceptible to orthostatic hypotension, hallucinations, confusion, and impulse control disorders with pramipexole. Close monitoring is essential, particularly during the initiation and dose adjustment periods. Renal function assessment is crucial before starting therapy, as pramipexole is primarily excreted unchanged by the kidneys, and dose adjustments are necessary for patients with reduced renal function. For elderly patients with creatinine clearance between 30-50 mL/min, consider extending the dosing interval to twice daily rather than three times daily. Nighttime administration may be preferred if daytime sedation occurs. Pramipexole should be discontinued gradually over 7-14 days to avoid withdrawal symptoms. The benefit-risk profile should be carefully evaluated, particularly in patients with cognitive impairment or a history of psychosis, as dopamine agonists can worsen these conditions. It is also important to consider the patient's overall health status, including the presence of comorbidities, polypharmacy, and functional impairment, when making decisions about pramipexole use in elderly patients 1. In general, the principles of prescribing in older adults with cardiovascular disease, including careful consideration of the benefits and risks of therapy, as well as the potential for drug interactions and adverse effects, should be applied when using pramipexole in this population 1.

From the FDA Drug Label

Pramipexole total oral clearance was approximately 30% lower in subjects older than 65 years compared with younger subjects, because of a decline in pramipexole renal clearance due to an age-related reduction in renal function. In clinical studies with Parkinson’s disease patients, 38.7% of patients were older than 65 years. There were no apparent differences in efficacy or safety between older and younger patients, except that the relative risk of hallucination associated with the use of pramipexole dihydrochloride tablets was increased in the elderly.

Key Points:

• The clearance of pramipexole is lower in elderly patients due to reduced renal function.
• Clinical studies included a significant proportion of patients older than 65 years.
• Efficacy and safety were similar between older and younger patients, except for an increased risk of hallucinations in the elderly.

Answer: It may be reasonable to try pramipexole in the elderly, but caution is advised due to the increased risk of hallucinations and the need to consider age-related reductions in renal function, which may affect dosing 2.

From the Research

Efficacy and Safety of Pramipexole in the Elderly

• Pramipexole is a nonergolinic dopamine agonist used for the treatment of early Parkinson's disease and restless legs syndrome 3, 4.
• The efficacy of pramipexole in improving motor symptoms and activities of daily living in patients with early Parkinson's disease has been demonstrated in several studies 3, 4.
• However, the use of pramipexole is not devoid of tolerability problems, including neuropsychiatric events such as excessive daytime somnolence, impulse-control disorders, hallucinations, and delusions 3, 4.

Adverse Events Associated with Pramipexole

• Common adverse events associated with pramipexole include nausea, dizziness, somnolence, insomnia, constipation, asthenia, and hallucinations 4, 5.
• Pramipexole has been associated with a higher risk of hallucinations compared to ropinirole, another dopamine agonist 5.
• The risk of hypotension and somnolence is higher with ropinirole compared to pramipexole 5.

Use of Pramipexole in Psychiatric Populations

• Pramipexole has been shown to have a large effect size in the treatment of both bipolar and unipolar depression, with a low short-term rate of manic switching in bipolar patients 6.
• However, pramipexole is associated with rare but serious side effects, including sleep attacks, compulsive behaviors, pathologic gambling, and psychosis 6.

Considerations for Use in the Elderly

• While there is limited information on the use of pramipexole in the elderly, the available evidence suggests that it can be effective in improving motor symptoms and activities of daily living in patients with early Parkinson's disease 3, 4.
• However, the risk of adverse events, particularly neuropsychiatric events, should be carefully considered when prescribing pramipexole to elderly patients 3, 4, 5, 6.