Pramipexole

Pramipexole dihydrochloride is a non-ergot dopamine agonist indicated for the treatment of: Parkinson's disease (PD). Moderate-to-severe primary Restless Legs Syndrome (RLS)

Pramipexole is a non-ergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D 2 subfamily of dopamine receptors, binding with higher affinity to D 3 than to D 2 or D 4 receptor subtypes. Parkinson's Disease The precise mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that pramipexole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum. The relevance of D 3 receptor binding in Parkinson's disease is unknown.

Parkinson's Disease-Normal Renal Function*. Week Dosage (mg) Total Daily Dose (mg) 1 0.125 TID 0.375 2 TID 0.75 3 TID 1.5 4 TID 2.25 5 1 TID 3 6 TID 3.75 7 TID 4.5 * Doses should not be increased more frequently than every 5 to 7 days. Titrate to effective dose. If used with levodopa, may need to reduce levodopa dose. Parkinson's Disease-Impaired Renal Function. Creatinine Clearance Starting Dose (mg) Maximum Dose (mg) > 50 mL/min 0.125 TID TID 30 to 50 mL/min 0.125 BID TID 15 to 30 mL/min 0.125 QD QD < 15 mL/min and hemodialysis patients Data not available Restless Legs Syndrome*. Titration Step Dose (mg) 2 to 3 hours before bedtime 1 0.125 2 (if needed) 0.25 3 (if needed) 0.5 * Dosing interval is 4 to 7 days (14 days in patients with CrCl 20 to 60 mL/min) General Dosing Considerations Pramipexole dihydrochloride tablets are taken orally, with or without food.

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Falling Asleep During Activities of Daily Living: Sudden onset of sleep may occur without warning, advise patients to report symptoms. Symptomatic Orthostatic Hypotension: Monitor during dose escalation. Impulse Control/Compulsive Behaviors: Patients may experience compulsive behaviors and other intense urges. Hallucinations and Psychotic-like Behavior: May occur, risk increases with age. Dyskinesia: May be caused or exacerbated by pramipexole dihydrochloride tablets. Postural Deformity: Consider reducing the dose or discontinuing pramipexole dihydrochloride tablets if postural deformity occurs

Most common adverse reactions (incidence >5% and greater than placebo): Early PD without levodopa: nausea, dizziness, somnolence, insomnia, constipation, asthenia, and hallucinations. Advanced PD with levodopa: postural (orthostatic) hypotension, dyskinesia, extrapyramidal syndrome, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia, and urinary frequency. RLS: nausea, somnolence, fatigue, and headache or www.fda.gov/medwatc h. The following adverse reactions are discussed in greater detail in other sections of the labeling: Falling Asleep During Activities of Daily Living and Somnolence. Symptomatic Orthostatic Hypotension. Impulse Control/Compulsive Behaviors. Hallucinations and Psychotic-like Behavior. Dyskinesia. Postural Deformity. Rhabdomyolysis.

Dopamine antagonists: May diminish the effectiveness of pramipexole Dopamine Antagonists Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of pramipexole dihydrochloride tablets.

Store at 20° to 25°C (68° to 77°F), excursions permitted to 15° and 30°C (59° and 86°F). Protect from light. Store in a safe place out of the reach of children.