Mirapex (Pramipexole) Dosing and Administration
For Parkinson's Disease, Mirapex (pramipexole) should be initiated at 0.125 mg three times daily (0.375 mg/day) in patients with normal renal function, with gradual titration every 5-7 days to achieve maximum therapeutic effect while minimizing side effects. 1
Initial Dosing Schedule for Parkinson's Disease
The FDA-approved titration schedule for patients with normal renal function is:
| Week | Dose (mg) | Total Daily Dose (mg) |
|---|---|---|
| 1 | 0.125 tid | 0.375 |
| 2 | 0.25 tid | 0.75 |
| 3 | 0.5 tid | 1.50 |
| 4 | 0.75 tid | 2.25 |
| 5 | 1.0 tid | 3.0 |
| 6 | 1.25 tid | 3.75 |
| 7 | 1.5 tid | 4.50 |
Maintenance Dosing
- Effective dose range: 1.5 to 4.5 mg/day administered in equally divided doses three times per day
- Optimal therapeutic dose: 1.5 mg/day has been shown to provide significant benefit in early Parkinson's disease
- Higher doses: Doses above 3 mg/day are associated with increased adverse effects without providing additional clinical benefit 1
Dosing in Renal Impairment
Pramipexole requires dose adjustment in renal impairment:
| Renal Status | Starting Dose | Maximum Dose |
|---|---|---|
| Normal to mild impairment (CrCl >60 mL/min) | 0.125 mg tid | 1.5 mg tid |
| Moderate impairment (CrCl 35-59 mL/min) | 0.125 mg bid | 1.5 mg bid |
| Severe impairment (CrCl 15-34 mL/min) | 0.125 mg qd | 1.5 mg qd |
| Very severe impairment (CrCl <15 mL/min) | Not adequately studied | Not recommended |
Extended-Release Formulation
Pramipexole extended-release (ER) is available as a once-daily formulation that is bioequivalent to the immediate-release (IR) formulation. Over 80% of patients can be switched overnight from IR to ER without dosage adjustment 2.
Discontinuation
- Pramipexole should be discontinued gradually over a period of 1 week to avoid withdrawal symptoms 1
- Abrupt discontinuation may lead to withdrawal symptoms or worsening of Parkinson's symptoms
Special Considerations
Combination with Levodopa
When pramipexole is used in combination with levodopa in advanced Parkinson's disease, consider reducing the levodopa dosage (average reduction of 27% from baseline in controlled studies) 1.
Restless Legs Syndrome
Although not specifically addressed in the FDA label provided, clinical studies show:
- Initial doses are typically lower than for Parkinson's disease
- Long-term use may lead to augmentation (earlier symptom onset during the day) in 32-42% of patients
- Tolerance requiring dose increases occurs in 46% of patients 3, 4
Monitoring
- Monitor for common side effects: postural hypotension, nausea, constipation, somnolence, and amnesia
- Watch for impulse control disorders, which can develop in approximately 10% of patients on long-term therapy 4
- Daytime sleepiness occurs in up to 74% of patients on long-term therapy, with 10% reporting sleep attacks while driving 4
Common Pitfalls to Avoid
- Starting with too high a dose: Always begin with the lowest recommended dose to minimize adverse effects and orthostatic hypotension
- Rapid titration: Increase dose no more frequently than every 5-7 days
- Inadequate monitoring: Watch for development of impulse control disorders and excessive daytime sleepiness
- Abrupt discontinuation: Always taper gradually over at least one week
- Failure to adjust for renal function: Pramipexole is primarily eliminated by renal excretion and requires dose adjustment in renal impairment
By following these dosing guidelines, clinicians can optimize the therapeutic benefits of pramipexole while minimizing adverse effects in patients with Parkinson's disease.