Does Mirapex (pramipexole) cause side effects?

Mirapex (pramipexole) is a dopamine agonist used to treat Parkinson's disease (PD) and restless leg syndrome (RLS).

Mirapex stimulates dopamine receptors in the brain. The exact mechanism of action of Mirapex in Parkinson's disease is unknown. However, treatment benefits are thought to be related to the stimulation of dopamine receptors in the area of the brain known as the striatum.

Mirapex may improve movement performance and activities of daily living in patients usually within 2-3 weeks of starting treatment. The exact mechanism of action of Mirapex for the treatment of RLS is unknown. Benefits of treatment are thought to be associated with stimulating dopamine receptors in the brain.

Common side effects of Mirapex include

Serious side effects of Mirapex include

  • significant daytime sleepiness or falling asleep while engaged in activities of daily living, including the operation of motor vehicles which may result in accidents. 

Drug interactions of Mirapex include dopamine antagonists, which are drugs with the opposite pharmacological effects, from Mirapex, such as

Mirapex has not been adequately evaluated in pregnant women. Due to the lack of conclusive safety data, Mirapex should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

It is unknown if Mirapex is excreted in breast milk. Due to the lack of conclusive safety data, Mirapex should be used cautiously in females who are breastfeeding.

What are the important side effects of Mirapex (pramipexole)?

WARNING

Falling Asleep During Activities of Daily Living

  • Patients treated with Mirapex (pramipexole dihydrochloride) tablets have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents.
  • Although many of these patients reported somnolence while on Mirapex tablets, some perceived that they had no warning signs such as excessive drowsiness, and believed that they were alert immediately prior to the event.
  • Some of these events had been reported as late as one year after the initiation of treatment.
  • Before initiating treatment with Mirapex tablets, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with Mirapex tablets such as
    • concomitant sedating medications,
    • the presence of sleep disorders, and
    • concomitant medications that increase pramipexole plasma levels.
  • If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), Mirapex tablets should ordinarily be discontinued.
  • If a decision is made to continue Mirapex tablets, 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 establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

Common side effects

The most common side effects reported are:

Mirapex (pramipexole) side effects list for healthcare professionals

The following adverse reactions are discussed in greater detail in other sections of the labeling:

  • Falling Asleep During Activities of Daily Living and Somnolence.
  • Symptomatic Orthostatic Hypotension.
  • Impulse Control/Compulsive Behaviors.
  • Hallucinations and Psychotic-like Behavior.
  • Dyskinesia.
  • Postural Deformity.
  • Rhabdomyolysis.
  • Retinal Pathology.
  • Events Reported with Dopaminergic Therapy.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

Parkinson's Disease

During the premarketing development of pramipexole, patients with either early or advanced Parkinson's disease were enrolled in clinical trials. Apart from the severity and duration of their disease, the two populations differed in their use of concomitant levodopa therapy.

Patients with early disease did not receive concomitant levodopa therapy during treatment with pramipexole; those with advanced Parkinson's disease all received concomitant levodopa treatment. Because these two populations may have differential risks for various adverse reactions, this section will, in general, present adverse-reaction data for these two populations separately.

Because the controlled trials performed during premarketing development all used a titration design, with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse reactions.

Early Parkinson's Disease

In the three double-blind, placebo-controlled trials of patients with early Parkinson's disease, the most common adverse reactions (>5%) that were numerically more frequent in the group treated with Mirapex tablets were

Approximately 12% of 388 patients with early Parkinson's disease and treated with Mirapex tablets who participated in the double-blind, placebo-controlled trials discontinued treatment due to adverse reactions compared with 11% of 235 patients who received placebo. The adverse reactions most commonly causing discontinuation of treatment were

  • related to the nervous system (hallucinations [3.1% on Mirapex tablets vs 0.4% on placebo];
  • dizziness [2.1% on Mirapex tablets vs 1% on placebo];
  • somnolence [1.6% on Mirapex tablets vs 0% on placebo];
  • headache and confusion [1.3% and 1.0%, respectively, on Mirapex tablets vs 0% on placebo]) and
  • gastrointestinal system (nausea [2.1% on Mirapex tablets vs 0.4% on placebo]).
Adverse-reaction Incidence in Controlled Clinical Studies in Early Parkinson's Disease

Table 4 lists adverse reactions that occurred in the double-blind, placebo-controlled studies in early Parkinson's disease that were reported by ≥1% of patients treated with Mirapex tablets and were numerically more frequent than in the placebo group. In these studies, patients did not receive concomitant levodopa.

Table 4 Adverse-Reactions in Pooled Double-Blind, Placebo-Controlled Trials with Mirapex in Early Parkinson's Disease

Body System/Adverse ReactionMirapex
(N=388)
%
Placebo
(N=235)
%
Nervous System
  Dizziness2524
  Somnolence229
  Insomnia1712
  Hallucinations93
  Confusion41
  Amnesia42
  Hypesthesia31
  Dystonia21
  Akathisia20
  Thinking abnormalities20
  Decreased libido10
  Myoclonus10
Digestive System
  Nausea2818
  Constipation146
  Anorexia42
  Dysphagia20
Body as a Whole
  Asthenia1412
  General edema53
  Malaise21
  Reaction unevaluable21
  Fever10
Metabolic & Nutritional System
  Peripheral edema54
  Decreased weight20
Special Senses
  Vision abnormalities30
Urogenital System
  Impotence21

In a fixed-dose study in early Parkinson's disease, occurrence of the following reactions increased in frequency as the dose increased over the range from 1.5 mg/day to 6 mg/day:

The frequency of these reactions was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence with pramipexole at a dose of 1.5 mg/day was comparable to that reported for placebo.

Advanced Parkinson's Disease

In the four double-blind, placebo-controlled trials of patients with advanced Parkinson's disease, the most common adverse reactions (>5%) that were numerically more frequent in the group treated with Mirapex tablets and concomitant levodopa were

  • postural (orthostatic) hypotension,
  • dyskinesia, extrapyramidal syndrome,
  • insomnia,
  • dizziness,
  • hallucinations,
  • accidental injury,
  • dream abnormalities,
  • confusion,
  • constipation,
  • asthenia,
  • somnolence,
  • dystonia,
  • gait abnormality,
  • hypertonia,
  • dry mouth,
  • amnesia, and
  • urinary frequency.

Approximately 12% of 260 patients with advanced Parkinson's disease who received Mirapex tablets and concomitant levodopa in the double-blind, placebo-controlled trials discontinued treatment due to adverse reactions compared with 16% of 264 patients who received placebo and concomitant levodopa.

The reactions most commonly causing discontinuation of treatment were

  • related to the nervous system (hallucinations [2.7% on Mirapex tablets vs 0.4% on placebo];
  • dyskinesia [1.9% on Mirapex tablets vs 0.8% on placebo]) and
  • cardiovascular system (postural [orthostatic] hypotension [2.3% on Mirapex tablets vs 1.1% on placebo]).

Adverse-reaction Incidence in Controlled Clinical Studies in Advanced Parkinson's Disease

Table 5 lists adverse reactions that occurred in the double-blind, placebo-controlled studies in advanced Parkinson's disease that were reported by ≥1% of patients treated with Mirapex tablets and were numerically more frequent than in the placebo group. In these studies, Mirapex tablets or placebo was administered to patients who were also receiving concomitant levodopa.

Table 5 Adverse-Reactions in Pooled Double-Blind, Placebo-Controlled Trials with Mirapex in Advanced Parkinson's Disease

Body System/Adverse ReactionMirapex
(N=260)
%
Placebo
(N=264)
%
Nervous System
  Dyskinesia4731
  Extrapyramidal syndrome2826
  Insomnia2722
  Dizziness2625
  Hallucinations174
  Dream abnormalities1110
  Confusion107
  Somnolence96
  Dystonia87
  Gait abnormalities75
  Hypertonia76
  Amnesia64
  Akathisia32
  Thinking abnormalities32
  Paranoid reaction20
  Delusions10
  Sleep disorders10
Cardiovascular System
  Postural hypotension5348
Body as a Whole
  Accidental injury1715
  Asthenia108
  General edema43
  Chest pain32
  Malaise32
Digestive System
  Constipation109
  Dry mouth73
Urogenital System
  Urinary frequency63
  Urinary tract infection43
  Urinary incontinence21
Respiratory System
  Dyspnea43
  Rhinitis31
  Pneumonia20
Special Senses
  Accommodation abnormalities42
  Vision abnormalities31
  Diplopia10
Musculoskeletal System
  Arthritis31
  Twitching20
  Bursitis20
  Myasthenia10
Metabolic & Nutritional System
  Peripheral edema21
   Increased creatine PK10
Skin & Appendages
  Skin disorders21

Restless Legs Syndrome

Mirapex tablets for treatment of RLS have been evaluated for safety in 889 patients, including 427 treated for over six months and 75 for over one year.

The overall safety assessment focuses on the results of three double-blind, placebo-controlled trials, in which 575 patients with RLS were treated with Mirapex tablets for up to 12 weeks.

The most common adverse reactions with Mirapex tablets in the treatment of RLS (observed in >5% of pramipexole-treated patients and at a rate at least twice that observed in placebo-treated patients) were nausea and somnolence. Occurrences of nausea and somnolence in clinical trials were generally mild and transient.

Approximately 7% of 575 patients treated with Mirapex tablets during the double-blind periods of three placebo-controlled trials discontinued treatment due to adverse reactions compared to 5% of 223 patients who received placebo. The adverse reaction most commonly causing discontinuation of treatment was nausea (1%).

Table 6 lists reactions that occurred in three double-blind, placebo-controlled studies in RLS patients that were reported by ≥2% of patients treated with Mirapex tablets and were numerically more frequent than in the placebo group.

Table 6 Adverse-Reactions in Pooled Double-Blind, Placebo-Controlled Trials with Mirapex in Restless Legs Syndrome

Body System/Adverse ReactionMirapex
0.125 – 0.75 mg/day
(N=575)
%
Placebo
(N=223)
%
Gastrointestinal disorders
  Nausea165
  Constipation41
  Diarrhea31
  Dry mouth31
Nervous system disorders
  Headache1615
  Somnolence63
General disorders and administration site conditions
  Fatigue97
Infections and infestations
  Influenza31

Table 7 summarizes data for adverse reactions that appeared to be dose related in the 12-week fixed dose study.

Table 7 Dose-Related Adverse Reactions in a 12-Week Double-Blind, Placebo-Controlled Fixed Dose Study in Restless Legs Syndrome (Occurring in ≥5% of all Patients in the Treatment Phase)

Body System/Adverse ReactionMirapex
0.25 mg
(N=88)
%
Mirapex
0.5 mg
(N=80)
%
Mirapex
0.75 mg
(N=90)
%
Placebo
(N=86)
%
Gastrointestinal disorders
  Nausea1119275
  Diarrhea3170
  Dyspepsia3147
Psychiatric disorders
  Insomnia99139
  Abnormal dreams2182
General disorders and administration site conditions
  Fatigue3575
Musculoskeletal and connective tissue disorders
  Pain in extremity3371
Infections and infestations
  Influenza1471
Respiratory, thoracic and mediastinal disorders
  Nasal congestion0361

Adverse Reactions

Relationship to Age, Gender, and Race

Among the adverse reactions in patients treated with Mirapex tablets, hallucination appeared to exhibit a positive relationship to age in patients with Parkinson’s disease. Although no gender-related differences were observed in Parkinson’s disease patients, nausea and fatigue, both generally transient, were more frequently reported by female than male RLS patients. Less than 4% of patients enrolled were non-Caucasian: therefore, an evaluation of adverse reactions related to race is not possible.

Laboratory Tests

During the development of Mirapex tablets, no systematic abnormalities on routine laboratory testing were noted.

Post Marketing Experience

In addition to the adverse events reported during clinical trials, the following adverse reactions have been identified during post-approval use of Mirapex tablets, primarily in Parkinson’s disease patients. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Decisions to include these reactions in labeling are typically based on one or more of the following factors:

  • (1) seriousness of the reaction,
  • (2) frequency of reporting, or
  • (3) strength of causal connection to pramipexole tablets.

Cardiac Disorders: cardiac failure

Gastrointestinal Disorders: vomiting

Metabolism and Nutrition Disorders: syndrome of inappropriate antidiuretic hormone secretion (SIADH), weight increase

Musculoskeletal and Connective Tissue Disorders: postural deformity

Nervous System Disorders: syncope

Skin and Subcutaneous Tissue Disorders: skin reactions (including erythema, rash, pruritus, urticaria)

What drugs interact with Mirapex (pramipexole)?

Dopamine Antagonists

Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of Mirapex tablets.

Summary

Mirapex (pramipexole) is a dopamine agonist used to treat Parkinson's disease (PD) and restless leg syndrome (RLS). Common side effects of Mirapex include nausea, dizziness, sleepiness, difficulty sleeping, constipation, weakness, dizziness on standing, movement disorder (extrapyramidal syndrome), dry mouth, amnesia (memory impairment), and urinary frequency. Mirapex has not been adequately evaluated in pregnant women. Due to the lack of conclusive safety data, Mirapex should be used cautiously in females who are breastfeeding.

Treatment & Diagnosis

Medications & Supplements

FDA Logo

Report Problems to the Food and Drug Administration

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 7/6/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
CONTINUE SCROLLING FOR RELATED SLIDESHOW