Usual Adult Dose for Parkinson's Disease

Immediate-release:
Initial dose: 0.125 mg orally three times a day
Titration: Increase gradually in small dose increments no more frequently than ever 5 to 7 days
Maintenance dose: 1.5 to 4.5 mg per day based on efficacy and tolerability
Maximum dose: 4.5 mg per day

Comment: The following dose titration was used in clinical trials:
Week 2, 0.25 mg 3 times a day
Week 3, 0.5 mg 3 times a day
Week 4, 0.75 mg 3 times a day
Week 5, 1 mg 3 times a day
Week 6, 1.25 mg 3 times a day
Week 7, 1.5 mg 3 times a day.

• When used in combination with levodopa, the levodopa dose was reduced by an average of 27% from baseline providing a concomitant dose of approximately 800 mg per day.

Extended-release:
Initial dose: 0.375 mg orally once a day
Titration: Increase gradually no more frequently than every 5 to 7 days, first dose increase should be to 0.75 mg once a day followed by incremental increases of 0.75 mg; assess therapeutic response and tolerability at a minimum of 5 days after each dose increase.
Maximum dose: 4.5 mg per day

SWITCHING FROM IMMEDIATE-RELEASE TO EXTENDED-RELEASE:

• Patients may be switched overnight from immediate-release tablets to extended-release tablets at the same daily dose; monitor closely to determine if dose adjustments may be necessary.

Comments:

• If a significant interruption in therapy occurs, re-titration may be necessary; upon discontinuation, doses should be tapered.

Use: Treatment of Parkinson's disease

Usual Adult Dose for Restless Legs Syndrome

Immediate-release:
Initial dose: 0.125 mg orally once a day 2 to 3 hours before bedtime
Titration: If needed, dose may be titrated upwards by increments of 0.125 mg every 4 to 7 days.
Maximum dose: 0.5 mg orally once a day

Comments:

• Extended-release tablets are not indicated for Restless Legs Syndrome.
• Doses of 0.75 mg once a day were used in clinical trials, but were not found to provide additional benefit as compared to the 0.5 mg dose.

Use: For the treatment of moderate to severe primary Restless Legs Syndrome.

Renal Dose Adjustments

Parkinson's Disease:
Immediate-release:

• Very severe renal impairment (CrCl less than 15 mL/min): Not recommended
• Severe renal impairment (CrCl 15 to less than 30 mL/min): Initial dose: 0.125 mg orally once a day; titrate gradually at intervals of no more frequently than every 5 to 7 days to a maximum dose of 1.5 mg once a day; Maximum dose: 1.5 mg once per day
• Moderate renal impairment (CrCl 30 to 50 mL/min): Initial dose: 0.125 mg orally twice a day; titrate gradually at intervals of no more frequently than every 5 to 7 days to a maximum dose of 0.75 mg 3 times a day; Maximum dose: 2.25 mg per day
• Normal to mild renal impairment (CrCl greater than 50 mL/min): No adjustment recommended

Extended-release:
Severe renal impairment: Not recommended
Moderate renal impairment (CrCl 30 to 50 mL/min): Initial dose: 0.375 mg orally every other day; after 1 week, may increase to once a day dosing based on therapeutic response and tolerability; subsequent dose titrations should be in increments of 0.375 mg no more frequently every 7 days; Maximum dose: 2.25 mg per day
Mild renal impairment (CrCl greater than 50 mL/min): No adjustment recommended

Restless Legs Syndrome:
Immediate-release:
Moderate to severe renal impairment (CrCl 20 to 60 mL/min): Initial dose: 0.125 mg orally once a day 2 to 3 hours before bedtime
Titration: If needed, dose may be titrated upwards by increments of 0.125 mg every 14 days; Maximum dose: 0.5 mg orally once a day

Liver Dose Adjustments

No adjustment recommended.

Dose Adjustments

If the patient is receiving levodopa, a reduction in the dosage of levodopa should be considered.

Patients may be switched overnight from pramipexole immediate-release to pramipexole extended-release at the same daily dose. Dose adjustment may be needed in some patients.

Discontinuation of Treatment:

• Parkinson's Disease: Taper off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg, then reduce by 0.375 mg per day.

• Restless Legs Syndrome: Taper is not needed

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions

Dialysis

Hemodialysis: Not recommended
Peritoneal dialysis: Data not available

Other Comments

Administration advice:
Immediate-release:

• Take orally with or without food
• If a dose is missed, advise patients not to double their next dose

Extended-release:

• Take orally with or without food
• Tablets should be swallowed whole; do not chew, crush, or divide
• If a dose is missed, take as soon as possible, but no later than 12 hours after the regularly scheduled time; after 12 hours, the missed dose should be skipped and dosing resumed on regular schedule

Storage requirements:

• Protect from light and high humidity

General:

• If a significant interruption in therapy occurs during treatment of Parkinson's disease, retitration may be necessary
• In a fixed dose study in early Parkinson's disease patients, no significant benefit was observed with daily doses of 3 mg, 4.5 mg, or 6 mg compared with 1.5 mg/day; however, the following adverse events increased with increasing dose: postural hypotension, nausea, constipation, somnolence, and amnesia.
• Upon discontinuation, this drug should be gradually tapered; during clinical trials, this drug was not tapered when used to treat restless legs syndrome.

Monitoring:

• Cardiovascular: Monitor for signs and symptoms of orthostatic hypotension, particularly during dose escalation
• Musculoskeletal: Monitor for posture changes, including neck bending forward, bending forward at the waist, tilting sideways when sitting, standing, or walking
• Nervous System: Monitor for somnolence and drowsiness
• Psychiatric: Question patients about new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges.

Patient advice:

• This drug frequently causes drowsiness; patients should not drive a car or operate machinery or other potentially dangerous activities until it is determined how this drug affects their mental and/or motor performance.
• Patients should be instructed to report episodes of sudden onset of sleep, new or worsening dyskinesia, new or worsening compulsive behaviors and/or unusual urges.
• Patients should be instructed to report posture changes that they are unable to control such as neck bending forward, bending forward at the waist, tilting sideways when sitting, standing, or walking
• Patients should be aware that this drug may cause orthostatic blood pressure changes including fainting and dizziness and advised to avoid standing rapidly after sitting or lying down.
• Patients should speak to their physician or health care provider if they become pregnant, intend to become pregnant, or are breastfeeding