No

Anti-Parkinson's Agent (Dopamine Agonist)

Treatment of the signs and symptoms of idiopathic Parkinson's disease

C

Patients with known hypersensitivity to pramipexole or any of the product's ingredients

Caution should be taken in patients with renal insufficiency and in patients with pre-existing dyskinesias. May cause orthostatic hypotension; Parkinson's disease patients appear to have an impaired capacity to respond to a postural challenge. Use with caution in patients at risk of hypotension (such as those receiving antihypertensive drugs) or where transient hypotensive episodes would be poorly tolerated (cardiovascular disease or cerebrovascular disease). Parkinson's patients being treated with dopaminergic agonists ordinarily require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and should be informed of this risk. May cause hallucinations, particularly in older patients. Pathologic degenerative changes were observed in the retinas of albino rats during studies with this agent, but were not observed in the retinas of pigmented rats or in other species. The significance of these data for humans remains uncertain.

Pramipexole has been associated with somnolence, particularly at higher dosages (> 1.5 mg/day). In addition, patients have been reported to fall asleep during activities of daily living, including driving, while taking this medication. Whether these patients exhibited somnolence prior to these events is not clear. Patients should be advised of this issue and factors which may increase risk (sleep disorders, other sedating medications, or concomitant medications which increase pramipexole concentrations) and instructed to report daytime somnolence or sleepiness to the prescriber. Patients should use caution in performing activities which require alertness (driving or operating machinery), and to avoid other medications which may cause CNS depression, including ethanol.

>10%:

Cardiovascular: Postural hypotension

Central nervous system: Asthenia, dizziness, somnolence, insomnia, hallucinations, abnormal dreams

Gastrointestinal: Nausea, constipation

Neuromuscular & skeletal: Weakness, dyskinesia, EPS

1% to 10%:

Cardiovascular: Edema, postural hypotension, syncope, tachycardia, chest pain

Central nervous system: Malaise, confusion, amnesia, dystonias, akathisia, thinking abnormalities, myoclonus, hyperesthesia, gait abnormalities, hypertonia, paranoia

Endocrine & metabolic: Decreased libido

Gastrointestinal: Anorexia, weight loss, xerostomia

Genitourinary: Urinary frequency (up to 6%), impotence

Neuromuscular & skeletal: Muscle twitching, leg cramps, arthritis, bursitis

Ocular: Vision abnormalities (3%)

Respiratory: Dyspnea, rhinitis

<1%: Elevated liver transaminase levels

Cimetidine in combination with pramipexole produced a 50% increase in AUC and a 40% increase in half-life

Drugs secreted by the cationic transport system (diltiazem, triamterene, verapamil, quinidine, quinine, ranitidine) decrease the clearance of pramipexole by ~20%

Dopamine antagonists (antipsychotics, metoclopramide) may decrease the efficiency of pramipexole

Pramipexole is a nonergot dopamine agonist with specificity for the D₂ subfamily dopamine receptor, and has also been shown to bind to D₃ and D₄ receptors. By binding to these receptors, it is thought that pramipexole can stimulate dopamine activity on the nerves of the striatum and substantia nigra.

Protein binding: 15%

Bioavailability: 90%

Half-life: ~8 hours (12-14 hours in the elderly)

Time to peak serum concentration: Within 2 hours

Elimination: Urine, 90% recovered as unmetabolized drug

Adults: Oral: Initial: 0.375 mg/day given in 3 divided doses, increase gradually by 0.125 mg/dose every 5-7 days; range: 1.5-4.5 mg/day

Food intake does not affect the extent of drug absorption, although the time to maximal plasma concentration is delayed by 60 minutes when taken with a meal

Monitor for improvement in symptoms of Parkinson's disease (eg, mentation, behavior, daily living activities, motor examinations), blood pressure, body weight changes, and heart rate

No information available to require special precautions

No effects or complications reported

Do not take other medications, including over-the-counter products without consulting prescriber (especially important are other medicines that could make you sleepy such as sleeping pills, tranquilizers, some cold and allergy medicines, narcotic pain killers, or medicines that relax muscles). Avoid alcohol as this may increase the potential for drowsiness or sedation. Report daytime somnolence or sleepiness to the prescriber. Use caution in performing activities which require alertness (such as driving or operating machinery). Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Tablet: 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, 1.25 mg, 1.5 mg

Guttman M, "Double-Blind Comparison of Pramipexole and Bromocriptine Treatment With Placebo in Advanced Parkinson's Disease," International Pramipexole-Bromocriptine Study Group, Neurology, 1997, 49(4):1060-5.

Lieberman A, Ranhosky A, and Korts D, "Clinical Evaluation of Pramipexole in Advanced Parkinson's Disease: Results of a Double-Blind, Placebo-Controlled, Parallel-Group Study," Neurology, 1997, 49(1):162-8.

Molho ES, Factor SA, Weiner WJ, et al, "The Use of Pramipexole, a Novel Dopamine (DA) Agonist, in Advanced Parkinson's Disease," J Neural Trans, 195, 45(Suppl):225-30.

Piercey MF, Hoffman WE, Smith MW, et al, "Inhibition of Dopamine Neuron Firing by Pramipexole, a Dopamine D(3) Receptor-Preferring Agonist: Comparison to Other Dopamine Receptor Agonists," Eur J Pharmacol, 1996, 312:35-44.

"Safety and Efficacy of Pramipexole in Early Parkinson Disease. Parkinson Study Group," JAMA, 1997, 278(2):125-30.

Shannon KM, Bennet JP Jr, and Friedman JH, "Efficacy of Pramipexole, A Novel Dopamine Agonist, as Monotherapy in Mild to Moderate Parkinson's Disease," The Pramipexole Study Group, Neurology, 1997, 49(3):724-8.

Stern MB, "Contemporary Approaches to the Pharmacotherapeutic Management of Parkinson's Disease: An Overview," Neurology, 1997, 49(1 Suppl 1):S2-9.

Szegedi A, Wetzel H, Hillert A, et al, "Pramipexole, A Novel Selective Dopamine Agonist, in Major Depression," Mov Disorders, 1996, 11(Suppl):266.

Ting RM and Force RW, "Pramipexole for Parkinson's Disease," J Fam Prac, 1998, 46(1):19-20.

Watts RL, "The Role of Dopamine Agonists in Early Parkinson's Disease," Neurology, 1997, 49(1 Suppl 1):S34-48.