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pergolide (Permax, pergolidum)
Withdrawn from US Market 2007
Tradename: Permax.
Indications:
1) symptomatic treatment of Parkinson's disease
- parkinsonism
2) adjunctive treatment to L-dopa/carbidopa
3) used to permit a reduction in dosage of Sinemet with improvement of side-effect profile
Dosage:
1) start 0.05 mg PO QD
2) increase by 0.1-0.15 mg every 3rd day over 12 days to 1 mg PO TID
3) max 5 mg/day (no added benefit of higher doses)
Tabs: 0.05, 0.25, 1 mg
Pharmacokinetics:
1) 90% of drug is protein-bound
2) at least 10 metabolites are known; it is not known if any of them are active
3) eliminated in the urine
Adverse effects:
1) high incidence of syncope & orthostatic hypotension upon initiation of therapy
2) common (> 10%)
- dyskinesias, dizziness, hallucinations, dystonia, confusion, somnolence, nausea, constipation, rhinitis
3) less common (1-10%)
- diarrhea, abdominal pain, asthenia, chest pain, flu-like syndrome, chills, vasodilation, palpitations, arrhythmias, vomiting, dry mouth, anorexia, dyspnea, peripheral edema, weight gain, insomnia, abnormal vision
4) valvular heart disease
- mitral regurgitation (RR = 6.3)
- aortic regurgitation (RR = 4.2) [6]
- withdrawn from US Market 2007 [7]
Drug interactions:
1) dopamine antagonists, methyldopa, reserpine, metoclopramide may diminish the effectiveness of pergolide
2) meperidine in combination may cause lethal seizures
Mechanism of action:
1) mixed dopamine D1 & D2 receptor agonist
2) directly stimulate post-synaptic dopamine receptors in the nigrostriatal system
3) 5-HT2B receptor agonist
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
pregnancy-category B
safety in lactation ?
Database Correlations
PUBCHEM correlations
References
- The Pharmacological Basis of Therapeutics, 9th ed.
Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- Saunders Manual of Medical Practice, Rakel (ed),
WB Saunders, Philadelphia, 1996, pg 1051
- Drug Information & Medication Formulary, Veterans Affairs,
Central California Health Care System, 1st ed., Ravnan et al
eds, 1998
- Kaiser Permanente Northern California Regional Drug
Formulary, 1998
- Bronstein J, In: Intensive Course in Geriatric Medicine &
Board Review, Marina Del Ray, CA, Sept 29-Oct 2, 2004
- Schade R et al,
Dopamine agonists and the risk of cardiac-valve regurgitation.
N Engl J Med 2007 Jan 4; 356:29-38
- Zanettini R et al,
Valvular heart disease during treatment with dopamine agonists
for Parkinson's disease.
N Engl J Med 2007 Jan 4; 356:39-46
PMID: 17202454
- Roth BL.
Drugs and valvular heart disease.
N Engl J Med 2007 Jan 4; 356:6-9
PMID: 17202450
- Prescriber's Letter 14(2): 2007
Drug-induced heart valve dysfunction
Detail-Document#: 230206
(subscription needed) http://www.prescribersletter.com
- FDA MedWatch
http://www.fda.gov/medwatch/safety/2007/safety07.htm#Pergolide