Mirapex, tablets 1 mg 30 pcs

Pramipexole is a dopaminergic, antiparkinsonian.

Pharmacodynamics

Pramipexole is a dopamine receptor agonist and binds with high selectivity and specificity to dopamine receptors of subgroup D₂ group, of which it has the most pronounced affinity for D₃ receptors. Reduces motor deficits in Parkinson’s disease by stimulating dopamine receptors in the striatum. Pramipexole inhibits dopamine synthesis, release, and metabolism. In vitro, pramipexole protects dopamine neurons from degeneration in response to ischemia or methamphetamine neurotoxicity.

The drug’s exact mechanism of action in the treatment of restless legs syndrome is currently unknown. Although the pathophysiology of restless legs syndrome is not fully understood, there is neuropharmacological evidence of primary involvement of the dopaminergic system. Studies using positron emission tomography (PET) have shown that moderate presynaptic dopaminergic dysfunction in the striatum may be involved in the pathogenesis of restless legs syndrome.

Pramipexole in vitro protects neurons from levodopa neurotoxicity.

Decreases prolactin secretion (dose-dependent).

In long-term use (>3 years) of pramipexole in patients with Parkinson’s disease, there was no evidence of decreased efficacy.

When pramipexole was used for 1 year in patients with restless legs syndrome, efficacy was maintained.

Pharmacokinetics

Pramipexole is rapidly and completely absorbed after oral administration. Absolute bioavailability is more than 90% and C_max in plasma is observed after 1-3 hours. Absorption rate is reduced with food, but total absorption is not affected by food intake. Pramipexole is characterized by linear kinetics and relatively little variability in concentrations between patients.

Pramipexole binds very little to proteins (d(400L). It is metabolized to a negligible extent. About 90% of the dose is excreted through the kidneys (80% unchanged) and less than 2% is found in the feces. Total clearance of pramipexole is about 500 ml/min, renal clearance is about 400 ml/min.T_1/2 ranges from 8 h in the young to 12 h in the elderly.

Indications

Parkinson’s disease

Symptomatic treatment of idiopathic Parkinson’s disease (monotherapy or in combination with levodopa) and idiopathic restless legs syndrome.

Active ingredient

Pramipexole

Composition

Active ingredient:

pramipexole dihydrochloride monohydrate 1 mg;

Auxiliary substances:

Mannitol;

Corn starch;

Colloidal silica;

povidone;

magnesium stearate;

How to take, the dosage

Overly, regardless of the meal, with water.

The daily dose is divided evenly into 3 doses.

The symptomatic treatment of Parkinson’s disease

Initial therapy. As described below, the initial daily dose of 0.375 mg is increased every 5 to 7 days. To reduce side effects, the dose should be adjusted gradually until maximum therapeutic effect is achieved.

If further increases in the daily dose are necessary, add 0.75 mg weekly up to a maximum dose of 4.5 mg/day.

Supportive therapy. The individual dose should be between 0.375 mg and 4.5 mg/day. In both early and late stages of the disease, the drug was effective starting with a daily dose of 1.5 mg. However, it is possible that doses higher than 1.5 mg/day may have additional therapeutic benefit in some patients, especially in the late stage of disease when a reduction in levodopa dose is indicated.

Cessation of treatment. Pramipexole should be withdrawn gradually over several days.

Doses for patients receiving concomitant therapy with levodopa. When concomitant therapy with levodopa, it is recommended that the dose of levodopa be reduced as the dose is increased and also during maintenance therapy with pramipexole. This is to avoid excessive dopaminergic stimulation.

Doses for patients with renal insufficiency. For initial therapy: in patients with a Cslcreatinine greater than 50 ml/min, there is no need to reduce the daily dose or frequency of administration. In patients with HDL 20-50 mg/ml the initial daily dose of the preparation is administered in 2 intakes, starting from 0.125 mg 2 times per day (0.25 mg/day). The maximum daily dose of 2.25 mg of pramipexole should not be exceeded. In Cl creatinine

If renal function decreases during maintenance therapy, the daily dose of the drug should be reduced by the same percentage by which creatinine clearance decreases, i.e., if creatinine clearance decreases by 30%, the daily dose of the drug should be reduced by 30%. The daily dose may be divided into two doses if creatinine Cl is within 20-50 ml/min, and taken once daily if creatinine Cl is less than 20 ml/min.

Doses for patients with hepatic impairment. There is no need to reduce the dose in patients with hepatic impairment.

The symptomatic treatment of idiopathic restless legs syndrome:

Initial therapy. The recommended initial daily dose is 0.125 mg, 2-3 hours before bedtime. If patients require additional symptom reduction, the dose may be increased every 4 to 7 days to a maximum dose of 0.75 mg daily

Supportive therapy. The individual dose should be between 0.125 and 0.75 mg/day.

The discontinuation of treatment. Treatment can be discontinued without gradually decreasing the dose. In clinical studies, only 10% of patients showed evidence of worsening symptoms after abrupt discontinuation of treatment; this effect was seen at any dosage.

Doses for patients with renal impairment. Excretion of the drug depends on renal function and is directly related to creatinine clearance. On the basis of pharmacokinetic studies in patients with renal insufficiency, for patients with creatinine clearance more than 20 ml/min a daily dose decrease is not required. The use of Mirapex^® in patients with restless legs syndrome with renal impairment has not been studied.

Doses for patients with hepatic impairment. The need to reduce the dose in patients with hepatic impairment is not considered because approximately 90% of the absorbed drug is excreted through the kidneys.

Dose for children and adolescents. The safety and effectiveness of Mirapex^® in children and adolescents under 18 years of age has not been established.

Interaction

Pramipexole to a small extent (

Drugs that inhibit active secretion of cationic drugs through the renal tubules (e.g. cimetidine), or are themselves excreted by active secretion through the renal tubules, may interact with pramipexole, which is reflected in decreased clearance of one or both medications. In case of concomitant use of such drugs (including amantadine) and pramipexole, it is necessary to pay attention to such signs of excessive dopamine stimulation as dyskinesia, agitation or hallucinations. In such cases, the dose should be reduced.

Selegyline and levodopa do not affect the pharmacokinetics of pramipexole. Paramipexole does not affect the overall absorption or elimination of levodopa. Interaction with anticholinergic drugs and amantadine has not been studied. However, interaction with amantadine is possible because the drugs have a similar elimination mechanism. Anticholinergic drugs are mostly metabolized, so interactions with pramipexole are unlikely.

When the dose of pramipexole is increased, it is recommended to decrease the dose of levodopa, and the dose of other antiparkinsonian medications should be kept constant.

Because of possible cumulative effects, patients should be advised to exercise caution when taking other sedative medications or alcohol in combination with Mirapex^® and also when taking concomitant medications that increase plasma concentrations of pramipexole (e.g. cimetidine).

The concomitant administration of pramipexole with antipsychotic drugs should be avoided (e.g., if antagonism is expected).

Special Instructions

Hallucinations and confusion are known side effects of treatment with dopamine agonists and levodopa. When used in combination with levodopa in the later stages of the disease, hallucinations were observed more frequently than when used with pramipexole monotherapy in patients in the early stages of the disease. Patients should be informed about the possibility of hallucinations (mostly visual) that may affect driving ability.

Patients and their caregivers should be aware that treatment of patients with dopaminergic medications may cause signs of abnormal behavior (symptoms of impulsive and compulsive behaviors), such as 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.

In patients with psychotic disorders, administration of dopamine agonists in combination with pramipexole is possible only after prior assessment of the possible risk-benefit. Concomitant administration of pramipexole with antipsychotics should be avoided.

It is recommended to check vision at intervals or immediately after prescribing the drug in the presence of such abnormalities.

Caution should be exercised if the patient has severe cardiovascular disease. Because of the risk of orthostatic hypotension with dopaminergic therapy, blood pressure should be monitored, especially at the start 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 driving or operating complex machinery) may occur at any time during treatment, and patients should be informed.

Epidemiologic studies have shown that patients with Parkinson’s disease have a high risk (2 to approximately 6 times higher) of developing melanoma than the general population. Whether this increased risk is due to Parkinson’s disease, or to other factors, such as taking medications used for Parkinson’s, is not known.

Because of the reasons given above, patients and their caregivers should be informed to be alert to the possible development of melanoma while taking pramipexole or other dopaminergic drugs.

Parkinson’s disease

It has been reported that a symptom complex resembling malignant neuroleptic syndrome has been observed when therapy is stopped abruptly.

A worsening of restless legs syndrome

Reports in the literature suggest that treatment of restless legs syndrome with dopaminergic drugs can lead to a worsening of it.

This worsening represented an earlier onset of symptoms in the evening (or even in the afternoon), a worsening of these symptoms, and a spread of symptoms to other limbs. However, in a 26-week controlled clinical trial specifically examining this effect, no significant difference in clinical symptom enhancement was found between the pramipexole and placebo groups.

The effect on the ability to drive and operate machinery. Patients should be informed of the likelihood of hallucinations (mostly visual) that may affect driving ability.

Sedation effects, including drowsiness and falling asleep during daily activities, may occur with use of the drug. Because drowsiness is a frequent adverse event with potentially serious consequences, patients should not drive or operate other complex machinery until they have had sufficient experience with treatment with Mirapex^® to evaluate whether or not it adversely affects their mental and/or motor activities. If patients experience increased drowsiness or episodes of falling asleep during daily activities (i.e., talking, eating, etc.) during treatment, they should discontinue driving, operating machinery, and see their physician.

Contraindications

• high sensitivity to pramipexole or to any drug component
• children (under 18 years).

With caution: renal failure, decreased blood pressure.

Side effects

• anomalous behavior (symptoms of impulsive and compulsive behaviors), such as tendency to overeating (hyperphagia), compulsive shopping (pathological shopping), hypersexuality and pathological gambling;
• pneumonia;
• rash, rash, and other hypersensitivity reactions;
• anxiety, drowsiness, sudden falling asleep, fainting, visual disturbances, including decreased visual acuity and clarity, vomiting, weight changes.

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Similarities

Mirapex, Mirapex PD, Pramipexole