Recommended Dosing and Treatment Plan for Mirapex (Pramipexole)
For Parkinson's disease patients, Mirapex (pramipexole) should be initiated at 0.125 mg three times daily (0.375 mg/day) and gradually titrated to an effective maintenance dose of 1.5 to 4.5 mg/day divided into three doses. 1
Dosing for Parkinson's Disease
Initial Titration Schedule
- Week 1: 0.125 mg three times daily (0.375 mg/day)
- Week 2: 0.25 mg three times daily (0.75 mg/day)
- Week 3: 0.5 mg three times daily (1.5 mg/day)
- Week 4: 0.75 mg three times daily (2.25 mg/day)
- Week 5: 1 mg three times daily (3 mg/day)
- Week 6: 1.25 mg three times daily (3.75 mg/day)
- Week 7: 1.5 mg three times daily (4.5 mg/day) 1
Maintenance Dosing
- Effective dose range: 1.5 to 4.5 mg/day in three divided doses
- Important note: Doses above 3 mg/day provide no additional benefit but increase adverse effects (postural hypotension, nausea, constipation, somnolence, amnesia) 1
- Optimal dose is typically 1.5 mg/day, which provides therapeutic benefit with somnolence rates comparable to placebo 1
Combination Therapy
- When used with levodopa, consider reducing levodopa dosage
- In controlled studies, levodopa was reduced by an average of 27% from baseline 1
Dosing for Restless Legs Syndrome (RLS)
- Recommended dosage: 0.125-0.75 mg taken as a single dose 2-3 hours before bedtime 2
- Typical effective dose: 0.25-0.5 mg for most patients 3
- For severe RLS: Mean effective dose is approximately 0.3 mg 4
- Important note: Alpha-2-delta ligands (pregabalin, gabapentin) are now strongly recommended as first-line therapy for RLS due to more favorable long-term safety profile compared to dopaminergic agents like pramipexole 4
Dosing Adjustments for 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 |
Administration Considerations
- Can be taken with or without food
- Initiate at subtherapeutic doses to avoid intolerable adverse effects and orthostatic hypotension 1
- Gradual titration is essential to minimize side effects
- Extended-release formulation is available to improve compliance and provide more continuous therapeutic effect over 24 hours 5
Discontinuation Protocol
- Recommended to taper off over a period of 1 week to avoid withdrawal symptoms 1
- Abrupt discontinuation has been uneventful in some studies but is not recommended 1
Monitoring and Side Effects
- Monitor for dopaminergic adverse effects (more common than with levodopa): somnolence, hallucinations, dyskinesia, dry mouth 1, 5
- Watch for augmentation (paradoxical worsening of symptoms) with long-term use in RLS patients 4
- If augmentation occurs, gradually taper and discontinue pramipexole and transition to alpha-2-delta ligands or opioids 4
Clinical Pearls
- For RLS, a single bedtime dose can provide 24-hour symptom relief 3
- Even low doses (0.125 mg) can provide acute relief of RLS symptoms 6
- Pramipexole has D3-preferring properties that may explain its efficacy in both motor and psychiatric symptoms of Parkinson's disease 7
- Consider iron therapy first for RLS patients with ferritin ≤75 ng/mL or transferrin saturation <20% 4