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pramipexole (Mirapex)

Indications: 1) symptomatic treatment of Parkinson's disease* in patients who are L-dopa naive or with advanced disease - parkinsonism 2) should probably NOT be used in combination with other dopaminergic agonists 3) treatment of restless legs syndrome [8] 4) treatment of fibromyalgia [5] * of particular benefit for patients with depression &/or poorly-controlled tremor [4] Dosage: 1) take with food 2) titrate dosage gradually 3) may need to decrease L-dopa by 20-30% over 2-3 days when pramipexole is started 4) start: 0.125 mg PO TID 5) week 2: 0.25 mg PO TID 6) week 3: 0.5 mg PO TID 7) week 4: 0.75 mg PO TID 8) week 5: 1 mg PO TID 9) week 6: 1.25 mg PO TID 10) week 7: 1.5 mg PO TID 11) restless legs syndrome - start: 0.125 mg PO evenings 2-3 hours before bedtime - week 2: 0.25 mg PO evenings 2-3 hours before bedtime - maintenance: 0.5 mg PO evenings 2-3 hours before bedtime [7] 12) max daily dose: 4.5 mg QD Tablets: 0.125 mg, 0.25 mg, 1 mg, 1.5 mg. Dosage adjustment with renal failure: creatinine clearance initial dose max dose 35-59 mL/min 0.125 mg BID 1.5 mg BID 15-34 mL/min 0.125 mg QD 1.5 mg QD < 15 mL/min ?* ?* * use not adequately studied < 15 mL/min Pharmacokinetics: 1) oral bioavailability is approximately 90% 2) 15% of the drug is protein-bound 3) 90% excreted unchanged into the urine 4) elminated both by glomerular filtration & cationic transport system 5) elimination 1/2life is 8-12 hours Adverse effects: 1) common (> 10%) - nausea, somnolence, constipation, dizziness, dyskinesia, hallucinations, insomnia, asthenia 2) less common (1-10%) - edema, malaise, fever, anorexia, dysphagia, weight loss, confusion, amnesia, hypesthesia, dystonia, akathisia, thought disorder, decreased libido, myoclonus, visual disturbance, impotence, dry mouth, twitching, bursitis, delusions, myasthenia, paranoid reaction, urinary frequency, urinary incontinence 3) other - drowsiness - sudden sleep attack may occur without warning - more common with administered in combination with alcohol or other CNS depressant - orthostatic hypotension - transient sedation frequent; less common with maintenance therapy - potential risk of heart failure [6] Drug interactions: 1) alcohol or other CNS depressant increase the likelihood of sleep attack 2) drugs that are secreted by the cationic transport system: cimetidine, triamterene (Dyazide, Maxzide), ranitidine, diltiazem, verapamil, quinidine & quinine increase pramipexole serum levels 3) pramiprexol increases L-dopa clearance 4) effect antagonized by dopamine antagonists: phenothiazines, butyrophenones, thiothixene, metoclopramide Mechanism of action: 1) non-ergot dopaminergic D3 > D2 agonist 2) stimulates dopamine receptors in the striatum 3) selective agonist at D2, D3, D4 receptor subtypes 4) may have neuroprotective effects

Interactions

drug adverse effects (more general classes)

General

dopaminergic receptor agonist pharmacologic agents for treatment of Parkinson's disease

Properties

AGONIST-FOR: adrenergic receptor MISC-INFO: elimination route KIDNEY 1/2life 8-12 HOURS

Database Correlations

PUBCHEM correlations

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary - restricted to neurology
  2. Prescriber's Letter 6(10):57, Oct, 1999
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
  5. Prescriber's Letter 12(9): 2005 Special Report on Drugs and Natural Products for Fibromyalgia Detail-Document#: 211008 (subscription needed) http://www.prescribersletter.com
  6. FDA MedWatch, 9/19/2012 Mirapex (pramipexole): Drug Safety Communication - Ongoing Safety Review, Possible Risk of Heart Failure http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm320054.htm
  7. Allen RP et al. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med 2014 Feb 13; 370:621 PMID: 24521108 http://www.nejm.org/doi/full/10.1056/NEJMoa1303646 - Chokroverty S Therapeutic Dilemma for Restless Legs Syndrome. N Engl J Med 2014; 370:667-668February 13, 2014 PMID: 24521115 http://www.nejm.org/doi/full/10.1056/NEJMe1313155
  8. Winkelman JW, Sethi KD, Kushida CA et al Efficacy and safety of pramipexole in restless legs syndrome. Neurology. 2006 Sep 26;67(6):1034-9. Epub 2006 Aug 23. PMID: 16931507