Description of the drug PRAMIPEXOLE-NAN

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

*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

* Side effects recorded in post-registration observations. With a 95% probability, the frequency category does not exceed “infrequently”, but may be lower.

Pramipexole, 0.25 mg, tablets, 30 pcs.

When prescribing Pramipexole to patients with Parkinson's disease and renal failure, a reduced dose is recommended.

Hallucinations and confusion are known adverse reactions during treatment with dopamine receptor agonists and levodopa. When using the drug Pramipexole in combination with levodopa in the late stages of the disease, hallucinations were observed more often than when using pramipexole monotherapy in patients at an early stage of the disease. Patients should be informed about the possibility of hallucinations (mainly visual), which may affect the ability to drive a car.

In advanced Parkinson's disease, dyskinesia may occur during the initial titration of Pramipexole in combination with levodopa treatment. If this occurs, the dose of levodopa should be reduced.

Patients and those caring for them should be aware that in connection with the treatment of patients with dopaminergic drugs, signs of manic behavior (symptoms of impulsive and compulsive actions), such as a tendency to overeat (hyperphagia), compulsive shopping (pathological shopping), hypersexuality and pathological gambling. In such cases, a decision should be made to reduce the dose/gradually discontinue treatment.

Patients and those caring for them should be aware that mania may occur in patients taking pramipexole and should be closely monitored for its development. In such cases, the issue of reducing the dose of the drug or discontinuing it should be decided.

In patients with mental disorders, the prescription of dopamine receptor agonists in combination with pramipexole is possible only after a preliminary assessment of the ratio of possible risks and expected benefits of therapy. Concomitant use of pramipexole with antipsychotics should be avoided.

It is recommended to monitor vision at certain intervals or immediately after prescribing the drug in the presence of such disorders.

Caution must be exercised if the patient has severe cardiovascular disease. Due to the risk of developing orthostatic hypotension during therapy with dopaminergic drugs, it is recommended to monitor blood pressure, especially at the beginning of treatment. Patients should be warned about the possible sedative effect of the drug. It has been reported that cases of drowsiness and sudden falling asleep during daily activities (including when driving a car or operating complex machinery) may occur at any time during the treatment period, and patients should be informed about this.

When using pramipexole, rhabdomyolysis was observed in a single case, the symptoms of which disappeared after discontinuation of the drug.

In the treatment of Parkinson's disease, with abrupt cessation of therapy, a symptom complex resembling neuroleptic malignant syndrome was observed.