Pramipexole
The following side effects are listed when using pramipexole: abnormal dreams, amnesia, behavioral disorders (symptoms of impulsive and compulsive actions) - such as compulsive overeating (hyperphagia), obsessive shopping (pathological shopping), pathological gambling, hypersexuality; libido disorders, anxiety, paranoia, hallucinations, delirium, heart failure, confusion, constipation, dizziness, tachycardia, dyskinesia, asthenia, headache, dyspnea, weakness, hyperkinesia, hiccups, decreased blood pressure, insomnia, psychosis, extrapyramidal syndrome, nausea , peripheral edema; pneumonia; bursitis, myasthenia gravis, muscle twitching, itching, rash, dry mouth, impaired secretion of antidiuretic hormone, respiratory and urinary tract infections, frequent urination, drowsiness, sudden falling asleep, fainting; visual impairment including diplopia, decreased visual acuity and clarity; vomiting, change in body weight, loss of appetite.
Based on an analysis of pooled placebo-controlled studies including 1923 patients treated with pramipexole and 1354 patients treated with placebo, drug-related adverse effects were reported in both groups. 63% of patients in the pramipexole group and 52% of patients in the placebo group experienced at least one drug reaction. Tables 1 and 2 show the incidence of side effects in placebo-controlled studies in patients with Parkinson's disease and restless legs syndrome. The tables provide information about effects that occurred in 1% or more of patients taking pramipexole if the effect was considered clinically significant.
Typically, side effects appear at the beginning of the course of therapy and disappear with long-term use of the drug.
The frequency and manifestations of side effects are dose-dependent and reversible.
Expected side effects - may be related to the pharmacodynamic profile of the dopamine antagonist and the doses used. These include nausea, vomiting, hyperkinesia, hallucinations, agitation and orthostatic hypotension. A decrease in blood pressure may occur in some patients early in treatment, especially if pramipexole doses are titrated too quickly.
A sharp dose reduction or discontinuation of the drug in patients with Parkinson's disease can cause the emergence and development of neuroleptic malignant syndrome. Dyskinesia was reported as a side effect when taken simultaneously with levodopa. The frequency of side effects is dose-dependent.
Drowsiness
Pramipexole is often associated with drowsiness and, infrequently, excessive drowsiness.
Sudden falling asleep
Episodes of sudden falling asleep during daytime activities, including driving, have been recorded. While some patients did not report the presence of alarming signs, such as drowsiness, often observed in patients while taking pramipexole in doses above 1.5 mg/day, which always lead to sudden sleep onset. A clear relationship with duration of therapy was not observed. However, some patients were also taking other medications with potentially sedative properties. After dose reduction or discontinuation of the drug, there were no reports of such side effects in these patients.
Sexual desire disorders
While taking pramipexole, libido disturbances may rarely be observed (increase (0.1%) or decrease (0.4%)).
Symptoms of impulsive and compulsive actions
Patients receiving dopamine agonist therapy, including pramipexole, may experience pathological gambling, hypersexuality, pathological shopping, and compulsive overeating.
In a cross-sectional retrospective case-control screening study of 3090 patients with Parkinson's disease, 13.6% of all patients receiving dopaminergic or nondopaminergic therapy reported symptoms of impulse control disorders in the past six months. Observed manifestations included pathological gambling, compulsive shopping, compulsive overeating and compulsive sexual behavior (hypersexuality). Possible independent risk factors for the development of impulse control disorders included dopaminergic therapy and high dose of dopaminergic medications.
Heart failure
In clinical studies and during post-marketing surveillance, an increased risk of primary heart failure associated with the use of pramipexole by patients was recorded. Two pharmacoepidemiological studies using pramipexole also reported an increased risk of heart failure compared with placebo.
Laboratory indicators:
increased activity of creatine phosphokinase (CPK), decreased secretion of prolactin.
For systemic organ classes according to the frequency of side effects, the following classification is used (WHO): very often >1/10, often from >1/100 to <1/10, infrequently from >1/1000 to <1/100, rarely from >1/10000 to <1/1000, very rarely <1/10000, including isolated reports.
Parkinson's disease, most common side effects
Table 1. Frequency of side effects in patients with Parkinson's disease
| Organ system | frequency | By-effect |
| Nervous system | Often | dizziness, dyskinesia, drowsiness |
| infrequently | amnesia, hyperkinesia, sudden sleep onset, fainting | |
| Endocrine system | infrequently | impaired secretion of antidiuretic hormone* |
| The cardiovascular system | often | lowering blood pressure |
| infrequently | heart failure* | |
| Gastrointestinal tract | Often | nausea |
| often | constipation, vomiting | |
| Mental disorders | often | abnormal dreams, amnesia, behavioral disturbances (symptoms of impulsive and compulsive actions), confusion, hallucinations, insomnia |
| infrequently | compulsive overeating, obsessive shopping (pathological shopping), pathological gambling, delusions, hypersexuality; libido disturbance, paranoia, anxiety | |
| Respiratory system | infrequently | dyspnea, hiccups |
| Organs of vision | often | visual impairment, including diplopia, decreased visual acuity and clarity of perception |
| Skin and subcutaneous tissue | infrequently | itching, rash |
| Infections and infestations | infrequently | Pneumonia and other upper and lower respiratory tract infections |
| General violations | often | fatigue, peripheral edema |
| Violations identified during special studies | often | loss of appetite, weight loss |
| infrequently | weight gain |
*Side effects recorded in post-registration observations. With a 95% probability, the frequency category does not exceed “infrequently”, but may be lower. An accurate estimate of the frequency category is not possible because the side effect was not recorded in the clinical trials database containing information on 2762 patients with Parkinson's disease who took pramipexole.
Idiopathic restless legs syndrome, most common side effects
In patients with restless legs syndrome taking pramipexole, the most frequently reported side effects (≥5%) are nausea, headache, dizziness, and fatigue. Nausea and fatigue were more frequently reported in female patients taking pramipexole (20.8% and 10.5%, respectively) compared to male patients (6.7% and 7.3%, respectively).
Table 2. Frequency of side effects in patients with restless legs syndrome
| Organ system | frequency | by-effect |
| Nervous system | often | dizziness, headache, drowsiness, fatigue |
| infrequently | amnesia, dyskinesia, hyperkinesia, sudden sleep onset, fainting | |
| Endocrine system | infrequently | impaired secretion of antidiuretic hormone* |
| The cardiovascular system | infrequently | lowering blood pressure |
| infrequently | heart failure* | |
| Mental disorders | often | abnormal dreams, insomnia |
| infrequently | behavioral disorders (symptoms of impulsive and compulsive actions), such as binge eating, compulsive shopping, delusions*, hyperphagia*, hypersexuality, confusion, hallucinations, libido disorders, paranoia*, anxiety, pathological gambling*, restlessness | |
| Infections and infestations | infrequently | pneumonia and other upper and lower respiratory tract infections |
| Organs of vision | infrequently | visual impairment, including diplopia, decreased visual acuity and clarity of perception |
| Respiratory system | infrequently | dyspnea, hiccups |
| Gastrointestinal tract | Often | nausea |
| often | constipation, vomiting | |
| Skin and subcutaneous tissue | infrequently | itching, rash and other symptoms of hypersensitivity |
| General violations | often | fatigue |
| infrequently | peripheral edema | |
| Violations identified during special studies | infrequently | weight loss, loss of appetite, weight gain |
* Side effects recorded in post-registration observations. With a 95% probability, the frequency category does not exceed “infrequently”, but may be lower.
Material and methods
The dynamics of emotional and cognitive disorders during therapy were assessed in 36 patients (group 1), sleep disorders - in 30 patients (group 2) diagnosed with PD. The study included PD patients without dementia. Basic demographic and anamnestic data are shown in the table.
| Table 1. Basic demographic and anamnestic data of patients included in the study |
Mirapex was prescribed in addition to levodopa and other antiparkinsonian drugs in accordance with the standard drug regimen until the optimal dose was achieved in terms of effectiveness and tolerability. The average daily dose was 3.5±1.1 mg in group 1 and 2.90±0.96 mg in group 2.
To assess the dynamics of motor disorders, the Unified Rating Scale for PD (UUSBP) and the Scale for Rating the Severity of Motor Fluctuations and Dyskinesias 17 were used. To study the effect of treatment on emotional disorders, the Beck Depression Inventory and the Spielberger Anxiety Rating Scale were used. The dynamics of integrative indicators of cognitive functions were assessed using the Mattis Comprehensive Assessment of Cognitive Functions Scale; neurodynamic indicators of mental activity - methods for assessing short-term auditory-verbal memory - patients memorizing 10 unrelated words from five presentations (A.R. Luria method), associative test (assessing the number of grammatically and semantically mediated associations in 1 minute), Schulte test. To study the effect of therapy on regulatory (frontal) functions, the Wisconsin Card Sorting Test (VTSC) and computer tests (developed by A. Kurgansky) were used to assess selective visual and auditory attention. Computer tests included a simple reaction time measurement when the task did not contain a choice element, as well as a complex reaction time measurement that assessed switching attention, i.e., the choice reaction. Analysis of the dynamics of cognitive activity indicators was initially carried out in the general sample, and then in selected groups of patients with varying degrees of severity of PD. Sleep disturbances were assessed using the PD Sleep Rating Scale 16 and a questionnaire we developed for patients, aimed at clarifying the severity of disturbances in falling asleep and maintaining sleep in PD, as well as identifying the main (secondary) causes of their occurrence. Methods for examining patients with motor fluctuations were used in the “on” phase.
The reliability of the dynamics of the scale indicators was assessed by statistical analysis of the differences between the initial indicators and indicators after 2 months of therapy using the Marginal Homogeneity Test. To identify the relationship between the dynamics of motor and non-motor disorders, the Spearman correlation coefficient was used.
