Mirapex, tablets 0.25 mg 30 pcs

Phramipexole 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 occurring in response to ischemia or methamphetamine neurotoxicity.

The drug’s exact mechanism of action in the treatment of restless legs syndrome is not currently known. Although the pathophysiology of restless legs syndrome is not fully understood, there is neuropharmacological evidence of primary involvement of the dopaminergic system.

Positron emission tomography (PET) studies 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. The rate of absorption 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.

The 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

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

Active ingredient

Composition

Active ingredient:

pramipexole dihydrochloride monohydrate 0.25 mg;

Excipients:

Mannitol;

Corn starch;

Colloidal silicon dioxide;

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, no reduction in the daily dose or frequency of administration is required.

In creatinine Cl 20-50 mg/ml, the initial daily dose of the drug is administered in 2 doses, starting with 0.125 mg twice daily (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 is 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 between 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 reduction 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

There is no pharmacokinetic interaction between pramipexole and selegiline.

In concomitant use with cimetidine there is an increase in plasma concentrations of pramipexole.

Other drugs that are secreted by the system of transport of organic cations in the kidneys may also contribute to increased plasma concentrations of pramipexole.

Special Instructions

Since treatment with pramipexole, episodes of sudden falling asleep while awake during the day have been reported. Sleepiness usually develops when using Mirapex in doses greater than 1.5 mg/day.

Episodes of falling asleep suddenly during daytime wakefulness occur against a background of already developed somnolence. Factors that increase the risk of drowsiness include: concomitant use of sedatives, sleep disorders, concomitant use of drugs that increase plasma levels of pramipexole (e.g., cimetidine).

Before prescribing Mirapex, the physician must determine the presence of these risk factors. During therapy, the patient’s condition should be monitored to determine if there is a tendency to drowsiness.

If pronounced somnolence develops during daytime or episodes of sudden falling asleep during daytime wakefulness that require active intervention, Mirapex should be discontinued. If continuation of therapy is necessary, the drug dose should be reduced and the patient should be advised to refrain from driving and other potentially dangerous activities.

The incidence of arterial hypotension has generally not increased with therapy with Mirapex compared to placebo.

Patients of advanced age (65 years and older) require dose adjustment of Mirapex.

Because pramipexole is excreted by the kidneys, patients with kidney disease may need to adjust the dose of the drug.

Impact on driving and operating machinery

The patient should refrain from driving and other potentially hazardous activities until the effect of the drug on the ability to concentrate and the speed of psychomotor reactions has been determined.

Paediatric use

The safety and effectiveness of Mirapex in children has not been established.

Contraindications

With caution: renal failure, decreased blood pressure.

Side effects

CNS and peripheral nervous system disorders: somnolence, dyskinesia, hallucinations; in some cases – insomnia. Malignant neuroleptic syndrome has been observed with rapid reduction of the pramipexolepsol dose, as well as with abrupt withdrawal of the drug.

Digestive system disorders: nausea, constipation.

Cardiovascular system disorders: in some cases at the beginning of treatment – arterial hypotension (especially if the dose is gradually increased for too short a time).

Others: in some cases – peripheral edema.

Overdose

Symptoms: not established. There is no clinical experience with a significant overdose of Mirapex. One patient with a 10-year history of schizophrenia took 11 mg/d of pramipexole for 2 days; this was 2-3 times the daily dose recommended by the protocol.

There were no adverse effects associated with the increased dose. BP remained stable, although HR increased to 100-120 bpm.

Treatment: The antidote for pramipexole is unknown. Neuroleptics – phenothiazine or butyrophenone derivatives – may be used if symptoms of CNS stimulation occur, but the effectiveness of these drugs in reversing the effects of Mirapex overdose has not been evaluated.

The treatment of overdose may require supportive therapy, gastric lavage, use of rehydration and detoxification means, ECG monitoring.

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