Pramipexol

Indications

Pramipexol is used for: Parkinson's disease, Restless leg syndrome

Adult Dose

Parkinson Disease Immediate-release: 0.125 mg PO q8hr initially; gradually titrated upward at weekly intervals to target range of 1.5-4.5 mg/day PO divided q8hr Restless Legs Syndrome 0.125 mg/day PO 2-3 hr before bedtime initially; may be increased every 4-7 days up to 0.5 mg/day (every 14 days if CrCl 20-60 mL/min)

Child Dose

Renal Dose

Parkinson disease Immediate release CrCl >50 mL/min: Dosage adjustment not necessary CrCl 30-50 mL/min: 0.125 mg twice daily initially; not to exceed 0.75 mg TID CrCl 15-29 mL/min: 0.125 mg qDay; not to exceed 1.5 mg qDay CrCl <15 mL/min: Dosage adjustment not provided in manufacturer's labeling; not studied ESRD requiring hemodialysis: Dosage adjustment not provided in manufacturer's labeling; not studied Restless legs syndrome Immediate release CrCl >60 mL/min: Dosasge adjustment not necessary CrCl 20-60 mL/min: Dosage adjustment not necessary but duration between titration should be increased to 14 days CrCl<20 mL/min: Dosage adjustment not provided by manufacturer's labeling; not studied

Administration

May be taken with or without food. May be taken w/ meals to minimise GI side effects such as nausea.

Contra Indications

Hypersensitivity. Lactation.

Precautions

Psychotic disorder, severe CV disease, augmentation (earlier onset, increase and spread of symptoms). Risk of neuroleptic malignant syndrome w/ abrupt withdrawal. Taper dose at 750 mcg/day for a wk, then reduce by 375 mcg/day thereafter. Renal impairment. Pregnancy and lactation. Patient Counselling Patients should be informed to refrain from activities involving mental alertness and physical coordination after drug intake. Monitoring Parameters Monitor BP, signs and symptoms of fibrosis and orthostatic hypotension, development of impulse control disorder, behavioural changes. Perform periodic skin examinations. Regular ophthalmological testing due to risk of visual disorders.

Pregnancy-Lactation

There are no adequate data on the developmental risk associated with therapy in pregnant women; no adverse developmental effects reported in animal studies in which pramipexole was administered to rabbits during pregnancy; effects on embryofetal development could not be adequately assessed in pregnant rats; however, postnatal growth was inhibited at clinically relevant exposures In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively; background risk of major birth defects and miscarriage for the indicated population is unknown Lactation: Not known if drug secreted in breast milk; may inhibit milk production; discontinue drug, or do not nurse

Interactions

Inhibits active tubular secretion of basic cationic drugs eg, cimetidine. Reduced clearance w/ drugs eliminated by active renal tubular secretion eg, amantadine. Alcohol & other sedatives.

Adverse Effects

Side effects of Pramipexol : >10% Somnolence, Dyskinesia, Hallucinations, Insomnia, Dizziness, Postural hypotension, Nausea, Constipation 1-10% (partial list) Abnormal dreams, thoughts, or vision, Amnesia, Confusion, Paranoia or delusion, Akathisia, Asthenia, Dry mouth

Mechanism of Action

Pramipexole is a nonergot-derivative dopamine receptor agonist which alleviates Parkinsonian motor deficits by directly stimulating postsynaptic dopamine activity on the striatum and substantia nigra It is used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome in patients w/ advanced disease. It is also used as monotherapy for the initial symptomatic management of parkinsonian syndrome.