Pramipexole dosing

Pramipexole is initiated at a dose of 0.125 mg three times daily and increased every 5 to 7 days as tolerated. It is primarily renally excreted, and the initial dose must be adjusted in renal insufficiency. 

L-DOPA can be initiated at 50 mg taken at bedtime and increased stepwise over a few weeks until the symptoms are relieved. Bromocriptine can be initiated at 7.5 mg at bedtime, pramipexole is often dosed at 0.125-0.375 mg at night, and ropinirole, which has an indication for RLS, is typically administered at 0.25-3 mg at bedtime. These medications are not without side effects. They may cause nausea and, over time, insomnia. Less commonly, these medications can cause hallucinations or involuntary movements called dyskinesias. These side effects usually resolve rapidly upon discontinuing the medication. 

Maintenance treatment - Pramipexole is effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses 3 times/day with or without concomitant levodopa ( 800 mg/day). When pramipexole is used in combination with levodopa, consider a reduction of the levodopa dosage. 

Because of these adverse effects, the drugs are generally first administered at low doses and then the dose is gradually increased over weeks or months as tolerance to the adverse effects develops. These symptoms are generally less frequent and less severe with pramipexole and ropinirole, which allows for a more rapid achievement of therapeutic response. Also, because pramipexole and ropinirole are better tolerated, they are increasingly used as monotherapy. 

Pramipexole is not an ergot derivative, but it has preferential affinity for the D3 family of receptors. It is effective as monotherapy for mild parkinsonism and is also helpful in patients with advanced disease, permitting the dose of levodopa to be reduced and smoothing out response fluctuations. Pramipexole may ameliorate affective symptoms. A possible neuroprotective effect has been suggested by its ability to scavenge hydrogen peroxide and enhance neurotrophic activity in mesencephalic dopaminergic cell cultures. 

Pramipexole is rapidly absorbed after oral administration, reaching peak plasma concentrations in approximately 2 hours, and is excreted largely unchanged in the urine. It is started at a dosage of 0.125 mg three times daily, doubled after 1 week, and again after another week. Further increments in the daily dose are by 0.75 mg at weekly intervals, depending on response and tolerance. Most patients require between 0.5 and 1.5 mg three times daily. Renal insufficiency may necessitate dosage adjustment. 

FIGURE 7—48. Heroic combo 4 High-dose venlafaxine plus stimulant. Here, 5HT and NE are single-boosted and DA is double-boosted. The stimulants could include (/-amphetamine, methylphen-idate, phentermine, or diethylpropion. It could also include direct-acting dopamine agonists such as pramipexole. 

This patient had taken ecstasy 10 times during the year before, the last time about 3 months before the onset of symptoms. Apart from marijuana, he denied using other substances. He was treated with maximal tolerable doses of levodopa and pramipexole, without improvement. The authors reported that they had no explanation for this patient s symptoms, other than the use of ecstasy. They felt that the parkinsonian symptoms most closely resembled MPTP-induced parkinsonism. They further postulated that this could be a delayed neurotoxic effect of ecstasy in the substantia nigra and striatum and could have occurred as a result of neuronal damage by free radicals. 

DOPAMINERGICS PARACETAMOL Amantadine, bromocriptine, levodopa, pergolide, pramipexole and selegiline may slow the onset of action of intermittent-dose paracetamol Anticholinergic effects delay gastric emptying and absorption Warn patients that the action of paracetamol may be delayed. This will not be the case when paracetamol is taken regularly... 

PRAMIPEXOLE, ROPINIROLE H2-RECEPTOR BLOCKER-CIMETIDINE T efficacy and adverse effects of pramipexole 1 renal excretion of pramipexole by inhibition of cation transport system. Inhibition of CYP1A2-mediated metabolism of ropinirole Monitor closely i dose of pramipexole may be required. Adjust dose of ropinirole as necessaiy or use alternative acid suppression, e.g. H2 antagonist proton pump inhibitor (not omeprazole or lansoprazole)... 

Parkinson Study Group (1997) Safety and efficacy of pramipexole in early Parkuison s disease A randomized dose ranging study. JAMA 278 125-130. 

Eight men aged 54-83 years, who had taken pramipexole 1-4.5 mg/day for Parkinson s disease for an average of 7 months, all fell asleep while driving, resulting in accidents but no injuries (5). They described sudden irresistible sleepiness, with virtually no warning, and four had had similar episodes during other activities. In six patients pramipexole was withdrawn, and in the other two the dose was reduced. 

Pramipexole is initiated at a dose of 0.125 mg three times a day and increased every 5 to 7 days as tolerated. In a fixed-dose study, daily doses of 3, 4.5, and 6 mg were not more effective than 1.5 mg/day, and the higher doses were associated with a higher frequency of adverse effects. When switching from bromocriptine or pergolide to pramipexole, a 10 1 and 1 1 dosage substitution is recommended, respectively. Ropinirole is initiated at 0.25 mg three times a day and increased by 0.25 mg three times a day on a weekly basis to a maximum of 24 mg/day. The dose of dopaminergic agonists is best determined by slow titration to enhance tolerance and to find the least dose that provides optimal benefit. 

Muscarinic receptor blockers may improve muscle rigidity and tremor in Parkinsons disease but result in very little improvement in bradykinesia thus, they are mainly considered as adjunctive to the use of drugs that improve dopaminergic function. Selegiline is the inhibitor of MAO type B, and pramipexole is a non-ergot DA receptor agonist. Carbidopa inhibits peripheral AAAD (dopa decarboxylase) tolcapone is an inhibitor of COMT. Levodopa causes a high incidence of dose-dependent dyskinesias that are not slow in onset, like tardive dyskinesia that results from chronic administration of DA receptor blockers. 

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