pramipexole (Mirapex)
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Indications
- symptomatic treatment of Parkinson's disease* in patients who are L-dopa naive or with advanced disease
- should probably NOT be used in combination with other dopaminergic agonists
- treatment of restless legs syndrome[8]
- treatment of fibromyalgia[5]
* of particular benefit for patients with depression &/or poorly-controlled tremor[4]
Dosage
- take with food
- titrate dosage gradually
- may need to decrease L-dopa by 20-30% over 2-3 days when pramipexole is started
- start: 0.125 mg PO TID
- week 2: 0.25 mg PO TID
- week 3: 0.5 mg PO TID
- week 4: 0.75 mg PO TID
- week 5: 1 mg PO TID
- week 6: 1.25 mg PO TID
- week 7: 1.5 mg PO TID
- restless legs syndrome
- 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
- oral bioavailability is approximately 90%
- 15% of the drug is protein-bound
- 90% excreted unchanged into the urine
- elminated both by glomerular filtration & cationic transport system
- elimination 1/2life is 8-12 hours
elimination via kidney
1/2life = 8-12 hours
Adverse effects
- common (> 10%)
- 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
- other
- drowsiness
- sudden sleep attack may occur without warning
- orthostatic hypotension
- transient sedation frequent; less common with maintenance therapy
- potential risk of heart failure[6]
- drug adverse effects of adrenergic receptor agonists
- drug adverse effects of dopaminergic receptor agonists
- drug adverse effects of sympathomimetic(s)
Drug interactions
- alcohol or other CNS depressant increase the likelihood of sleep attack
- drugs that are secreted by the cationic transport system: cimetidine, triamterene (Dyazide, Maxzide), ranitidine, diltiazem, verapamil, quinidine & quinine increase pramipexole serum levels
- pramiprexol increases L-dopa clearance
- effect antagonized by dopamine antagonists: phenothiazines, butyrophenones, thiothixene, metoclopramide
Mechanism of action
- non-ergot dopaminergic D3 > D2 agonist
- stimulates dopamine receptors in the striatum
- selective agonist at D2, D3, D4 receptor subtypes
- may have neuroprotective effects
More general terms
References
- ↑ 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 - ↑ Prescriber's Letter 6(10):57, Oct, 1999
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 4.0 4.1 Bronstein J, In: Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- ↑ 5.0 5.1 Prescriber's Letter 12(9): 2005 Special Report on Drugs and Natural Products for Fibromyalgia Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=211008&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 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
- ↑ 7.0 7.1 Allen RP et al. Comparison of pregabalin with pramipexole for restless legs syndrome. N Engl J Med 2014 Feb 13; 370:621 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24521108 <Internet> 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24521115 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMe1313155 - ↑ 8.0 8.1 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: https://www.ncbi.nlm.nih.gov/pubmed/16931507
Database
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=59868
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=166589
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=4885
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=119570
- PubChem: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=11959