Pergolide dosing

Pergolide is usually administered in divided doses 3 times/day. During dosage titration, the dosage of concurrent levodopa/carbidopa may be cautiously decreased. In clinical studies, the mean therapeutic daily dosage of pergolide was 3 mg/day. 

The average concurrent daily dosage of levodopa/carbidopa (expressed as levodopa) was approximately 650 mg/day. The efficacy of pergolide at doses above 5 mg/day has not been systematically evaluated. 

Pharmacokinetics Following oral administration, approximately 55% of the dose can be recovered from the urine. Pergolide is approximately 90% bound to plasma proteins. The major route of excretion is via the kidney. 

Neuroleptic malignant syndrome fA//WSj A symptom complex resembling the NMS (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy, including pergolide. 

More potent with longer half-life than bromocriptine or pergolide, allowing for less frequent dosing... 

Pergolide is a mixed D2-D1 agonist used to increase dopaminergic activity in Parkinson s disease. In lower doses, it is believed to have greater effect on presynap-tic D2 autoreceptors than on postsynaptic receptors, which, ultimately, reduces dopaminergic transmission. In a 6-week open-label trial of pergolide in 32 patients (ages 7-19 years) with TS, three-quarters of subjects reported an improvement of at least 50% in tic severity, at a mean dose of 177 61 j,g in three divided doses. 

The involvement of dopaminergic neurotransmission in AD has led to the use of agonists such as bromocriptine, lisuride, and pergolide, with poor results. A selective monoamine oxidase B inhibitor (MAO-B) such as deprenyl has also been employed. Little solid information exists on the effects of deprenyl on AD. Unfortunately, all information available comes from small studies. In a double-blind study, Tariot et al. (1987) observed that, with a daily dose of 10 mg in 17 patients with AD, a significant reduction in the scores for anxiety, depression, tension, and excitement was achieved. Burke et al. (1993), in a study of more than 20 patients with AD during a period of 15 months, found no behavioral changes in the progression of the illness nor in its scores. 

Postural hypotension may occur, particularly at the initiation of therapy. Painless digital vasospasm is a dose-related complication of long-term treatment with the ergot derivatives (bromocriptine or pergolide). When cardiac arrhythmias occur, they are an indication for discontinuing treatment. Peripheral edema is sometimes problematic. Cardiac valvulopathy may occur with pergolide. 

Later, the disease does not respond to the drug and doses are required to be given in combination with carbidopa. Levodopa is effective in relieving bradykinesia and other disorderly voluntary movements. Parkinson s disease is not a hereditary disease. Drugs such as levodopa, carbidopa, benserazide, bromocriptine, pergolide, selegiline, and amantadine are used as therapeutic agents.61... 

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... 

A 36-year-old woman with a 4-year history of Parkinson s disease, who had been taking pergolide 3 mg/day and levodopa 200 mg/day continued to take it during pregnancy. The end-of-dose wearing-off effect completely disappeared, and reappeared at their previous intensity after delivery. There were no adverse effects in the mother. The baby was healthy at birth and remained so at the time of the report, at the age of 13 months. 

In 41 patients with Parkinson s disease who took pergolide, confusion and hallucinations were the adverse effects that were most likely to result in withdrawal of pergolide (2). Symptoms suggestive of dose-related angina pectoris occurred in four patients in the open phase and two patients in the earlier double-blind phase these symptoms were easily controlled by dosage reduction or withdrawal of pergolide without sequelae. There was leukopenia in one patient. 

A 57-year-old woman and a 61-year-old man taking pergolide 4.5 mg/day and 5 mg/day respectively both suffered sleep disorders the woman did not suffer from sleepiness but had abrupt sleep episodes, while the man was sleepy for much of the day (6). These were high doses and a reduction to 3 mg/day led to cessation of sleepiness in both patients. 

Supraventricular extra beats have rarely been reported after low doses of ropinirole and have also been reported after pergolide and levodopa (1). Symptomatic postural hypotension has occurred after even low oral doses of ropinirole (2-5), related to peripheral dopaminergic activity. Hypotensive effects occur within 3 minutes of standing, usually between 2 and 4 hours after an oral dose, associated with nonspecific malaise (2). Dizziness occurred in up to 40% of patients in clinical trials. Related symptoms include faintness, malaise, and yawning (2). Bradycardia has occasionally accompanied postural hypotension (4). Syncope has been reported. 

A recommended initial dose of pergolide (which is about 13 times more potent than bromocriptine) is 0.05 mg/day for 2 days, gradually increasing the dose by approximately 0.1-0.15 mg/day every 3 days over a 12-day period. Should more drug be needed, the dose then may be increased by 0.25 mg every 3 days until symptoms are eliminated or adverse effects occur. The mean therapeutic dose in most clinical trials was approximately 3 mg/day. 

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. 

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