Mirapex Er

Falling Asleep During Activities of Daily Living and Somnolence

• Patients on pramipexole have reported falling asleep while engaged in activities, some had no warning signs and believed they were alert prior to the event.
• Some of these events have been reported as late as 1 year after initiating treatment.
• In clinical trials, sudden onset of sleep/sleep attacks occurred in 2% of patients treated with Mirapex ER and 1% of patients who received placebo.
• Advise patients of the potential to develop drowsiness.
• If significant daytime sleepiness or episodes of falling asleep during activities occur, Mirapex ER should generally be discontinued.
• If Mirapex ER is continued, advise patients not to drive or avoid other potentially dangerous activities.
• Dose reduction may not eliminate episodes of falling asleep.

Symptomatic Orthostatic Hypotension

• Dopamine agonists may impair the systemic regulation of blood pressure, resulting in orthostatic hypotension, esp during dose escalation.
• Monitor carefully for signs/symptoms of orthostatic hypotension, esp during dose escalation.
• In clinical trials, symptomatic orthostatic hypotension was reported in 3% of patients treated with Mirapex ER and 1% of placebo patients.

Impulse Control/Compulsive Behaviors

• There have been reports of patients experiencing intense urges and the inability to control them while on medications that increase central dopaminergic tone.
• Discuss new or increased urges with patients being treated with Mirapex ER.
• Consider dose reduction or discontinuing medication if urges develop.
• Urges reported in clinical trials included pathological gambling, hypersexuality, and/or compulsive buying.

Hallucinations and Psychotic-like Behavior 

• In clinical trials, hallucinations were reported in 6% of patients treated with Mirapex ER and 2% of patients who received placebo.
• Increased risk of hallucinations with age.
• Postmarketing reports indicate that some patients may experience new or worsening mental status and behavioral changes; may be severe (eg, psychotic-like behavior).
• Patients with major psychotic disorders generally should not receive dopamine agonists; may exacerbate psychosis.
• Drugs that treat psychosis may exacerbate symptoms of Parkinson disease and may decrease the effectiveness of Mirapex ER.

Dyskinesia

• Treatment with Mirapex ER may cause or exacerbate dyskinesia.

Postural Deformity

• Postural deformities (eg, antecollis, camptocormia, pleurothotonus) have been reported with Mirapex ER use.
• May occur several months after starting treatment or increasing dose.
• Reducing dosing or discontinuing treatment has resulted in improvement in some patients.

Rhabdomyolysis

• In clinical trials of immediate-release pramipexole tablets, there was a single case of rhabdomyolysis, where the patient was hospitalized with CPK of 10,631 IU/L; symptoms resolved after discontinuing the drug.
• Unexplained muscle pain, tenderness, or weakness should be reported and may be symptoms of rhabdomyolysis.

Retinal Pathology

• Two-year, randomized safety study of retinal deterioration and vision compared immediate-release pramipexole (n=115) and immediate-release ropinirole (n=119). 
• 196 patients treated for 2 years; 29 judged to have developed clinical abnormalities that were meaningful.
• No statistical difference in retinal deterioration between the treatment arms.
• Unknown whether findings were related to drug or ageing population as there was no placebo arm.

Dopaminergic Therapy-Related Events

• Hyperpyrexia and confusion: Avoid sudden discontinuation or rapid dose reduction; taper to reduce risk.
• Fibrotic complications: Cases have been reported in the postmarketing period with immediate-release pramipexole tablets.

Withdrawal Symptoms

• Symptoms include apathy, anxiety, depression, fatigue, insomnia, sweating, pain.
• Symptoms generally do not respond to levodopa.
• Severe withdrawal symptoms: Consider trial re-administration of a dopamine agonist at the lowest effective dose.