Mirapex (pramipexole) - Confusion/disorientation

Fever, altered consciousness, autonomic dysfunction and muscle rigidity are the hallmarks of the neuroleptic malignant syndrome (NMS). NMS is associated with a case fatality rate of about 20%.

The sedative effects of pramipexole may affect mental and/or motor performance. Some patients on pramipexole were reported to have fallen asleep while driving, resulting in accidents. Some of these patients exhibited no warning signs such as excessive drowsiness and believed they were alert immediately prior to the event. The risk of drowsiness may be increased when pramipexole is taken with other CNS depressants or in patients with sleep disorders. Some of these events have been reported as late as one year after therapy was initiated. Somnolence is a common occurrence in patients receiving pramipexole at doses above 1.5 mg/day. Many clinicians believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not exhibit such a history. Therefore, patients should continually be reassessed for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Physicians should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation, pramipexole should be discontinued. If a decision is made to continue pramipexole therapy, patients should be advised to not drive and to avoid other potentially dangerous activities. While dose reduction clearly reduces the degree of somnolence, there is insufficient information to determine that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

Dopaminergic therapy in general should not be discontinued abruptly. Sudden discontinuation may result in a worsening of Parkinsonism or, less frequently, a symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability). The manufacturer of pramipexole recommends withdrawal of medication over a one- week period.

Ocular side effects have included accommodation abnormalities (4%), vision abnormalities (3%), and diplopia (1%).

Nervous system side effects have been reported frequently during clinical trials and were cited as the primary reason for discontinuation of therapy. Dizziness (25%), somnolence (6% to 22%), insomnia (17%), and hallucinations (9%) have been reported in patients on pramipexole monotherapy. Dyskinesia and extrapyramidal syndrome were most often observed in patients with advanced Parkinson's disease treated concomitantly with levodopa, occurring in 47% and 28% of these patients, respectively. Confusion (4%), amnesia (4%), hypesthesia (3%), dystonia (2%), akathisia (2%), thinking abnormalities (2%), decreased libido (1%), myoclonus (1%), sudden sleep attacks, and headache have also been reported. Syncope and libido disorders (including increased libido and hypersexuality) have been reported during postmarketing experience.

Psychiatric side effects including at least one case of mania have been reported. Abnormal behavior, abnormal dreams, hallucinations (all kinds), increased eating (including binge eating, compulsive eating, and hyperphagia), and pathological gambling have been reported during postmarketing experience.

A 41-year-old female with a history of bipolar II disorder experienced mania coincident with pramipexole therapy. Pramipexole was added to her regimen of valproic acid 750 mg twice daily. The starting dose of 0.125 mg was titrated over a 3-week period to 1.5 mg a day, to which there was a partial response. As the dosage was increased to 2 mg, the patient developed mania characterized by symptoms of euphoria, paranoia, irritability, decreased requirement of sleep, poor judgment, increased libido, and excessive spending of money. The manic symptoms lasted 2 months, but subsided within a week of pramipexole discontinuation.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Stop taking pramipexole and call your doctor at once if you have any of these serious side effects: extreme drowsiness, falling asleep suddenly, even after feeling alert; hallucinations; fever, stiff muscles, confusion, sweating, fast or uneven heartbeats; nausea, sweating, feeling light-headed, fainting; or restless muscle movements in your eyes, tongue, jaw, or neck. Less serious side effects may include: constipation, upset stomach, loss of appetite; dry mouth, trouble swallowing; urinating more often than usual; mild drowsiness or sleepiness; sleep problems (insomnia), unusual dreams; amnesia, forgetfulness, thinking problems; headache, confusion, weakness; blurred vision; joint pain, muscle weakness; swelling in your hands or feet; runny or stuffy nose; weight loss; or impotence, loss of interest in sex, or trouble having an orgasm. This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. You may report side effects to FDA at 1-800-FDA-1088.

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