Mirapex PD – antiparkinsonian drug – dopamine receptor agonist. With high selectivity and specificity associated with dopamine receptor subgroups D2, most of which has a pronounced affinity for D3 receptors. It reduces the deficit of motor activity in Parkinson’s disease by stimulating dopamine receptors in the striatum. Pramipexole inhibit the synthesis, release and metabolism of dopamine. Pramipexole in vitro protects neurons from degeneration of dopamine that occurs in response to ischemia or methamphetamine neurotoxicity.
Pramipexole in vitro protects neurons from levodopa neurotoxicity.
Reduces the secretion of prolactin (dose-dependent).
In clinical studies in healthy human volunteers who have increased doses of the drug PD mirapex performed faster than it should (every 3 days), up to 4.5 mg / day, there was an increase in blood pressure and heart rate. In studies on patients, this effect was not observed.
Absorption and distribution
Pramipexole after ingestion rapidly and completely absorbed. The absolute bioavailability is greater than 90% and Cmax in plasma attained after approximately 6 hours. Typically, the food intake does not affect the bioavailability of pramipexole. After a fatty meal there was a slight increase of about 20%, Cmax and deceleration, approximately 2 hours, the time to reach Cmax, having no clinical significance.
Pramipexole shows linear kinetics and a relatively small variation in plasma levels between patients regardless of the pharmaceutical form. Pramipexole binds to plasma proteins to a very small extent (
Metabolism and excretion
It is metabolized to a small extent.
About 90% of the dose is excreted via the kidneys (80% in unmodified form) 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. T1 / 2kolebletsya from 8 hours in the young to 12 hours in the elderly.
Boehringer Ingelheim Austria
The active ingredient is:
Pramipexole dihydrochloride monohydrate, 3 mg;
From the nervous system and sensory organs: fatigue, drowsiness / insomnia, hallucinations, delirium, amnesia, confusion, dizziness, anxiety, depression, dysphagia, dystonia, akathisia, thought disorders, suicidal tendencies, extrapyramidal syndrome, dyskinesia, tremor, gipostezii, hypokinesia, myoclonus, ataxia, impaired motor coordination, double vision, paralysis of accommodation, conjunctivitis, impaired hearing; in a few cases (with the rapid reduction of the dose or abrupt withdrawal) – neuroleptic malignant syndrome (hyperthermia, muscle rigidity, disturbance of consciousness, autonomic lability).
Cardio-vascular system and blood (blood, hemostasis): orthostatic hypotension, tachycardia, arrhythmia.
From the respiratory system: dyspnea, rhinitis, pharyngitis, sinusitis, flu-like symptoms, increased cough.
From the digestive tract: nausea, vomiting, dyspepsia, flatulence, diarrhea, dry mouth, anorexia, constipation.
On the part of the musculoskeletal system: muscle hypertonicity, cramps in the leg muscles, muscle twitching, myasthenia gravis, arthritis, bursitis.
Other: fever; peripheral edema, sweating, increased intraocular pressure, decreased libido, impotence, reduction in body weight; frequent urination, urinary tract infections; pain, including chest pain, abdominal pain, pain in the lumbosacral spine, neck pain; change of voice; increasing the activity of CK; allergic reactions.
How to accept, acceptance rate and dosage
The tablets of the prolonged action should be taken one time a day, at about the same time of the day. Swallow whole tablets, drinking water, the tablets should not be chewed, crush or grind. Tablets can be taken regardless of the meal.
If the time of the next dose was missed, the case since the conventional reception timing is not more than 12 hours, the drug should be taken in a daily dose. If it has been more than 12 hours, the drug should not be taken, the next reception will take place the next day at the usual time.
Patients who are already taking pills mirapex can translate pills prolonged action mirapex PD during the day, at the same dose.
As shown below, the dose should be gradually increased from the starting dose of 0.375 mg / day and then increased every 5-7 days. To prevent undesirable side-effects, the dosage should be selected to achieve a maximal therapeutic effect.
In a dry place at a temperature not higher than 25 ° C
Pramipexole slightly (
Drugs that inhibit the secretion of active cationic drugs through the renal tubules (e.g., cimetidine) or which themselves are derived due to active secretion by the renal tubules, may interact with pramipexole, resulting in reduction of clearance of one or both drugs. In the case of simultaneous use of these drugs (including amantadine) and pramipexole is necessary to pay attention to features such excessive dopamine stimulation as dyskinesia, agitation or hallucinations. In such cases it is necessary to reduce the dose.
Selegiline and levodopa do not influence the pharmacokinetics of pramipexole. Pramipexole has no effect on the overall amount of absorption or elimination of levodopa. Interaction with anticholinergic drugs and amantadine was not studied. However, the interaction with amantadine possible because drugs have a similar inference engine. Anticholinergic drugs are mainly derived pathway, therefore the interaction with pramipexole unlikely.
With increasing doses of the drug in patients with Parkinson’s disease is recommended lowering the dose of levodopa, the dose of other antiparkinsonian medicinal products should be maintained at a constant level.
Due to the possible cumulative effects, patients should be encouraged to exercise caution when receiving other sedating drugs or alcohol in combination with a preparation mirapex PD, but also while receiving drugs that increase the concentration in plasma pramipexole (e.g., cimetidine).
During treatment with pramipexole observed episodes of sudden sleep on the background of daily wakefulness. Drowsiness usually develops in applying mirapex at doses above 1.5 mg / day. Sudden episodes of falling asleep on the background of daily wakefulness arise against the background of already developed sleepiness.
Factors that increase the risk of drowsiness include: simultaneous reception of sedatives, sleep disorders, concomitant use of medications that increase pramipexole plasma (eg, cimetidine). Before the appointment mirapex physician should determine the presence of these risk factors. In the course of treatment is necessary to monitor the patient’s condition to identify the tendency to drowsiness.
If severe daytime sleepiness or episodes of falling asleep suddenly appears against the background of daily wakefulness, which require the active intervention mirapex should be abolished. In the case of the need for continued therapy should be to reduce the dose of the drug and to recommend to the patient to refrain from driving and other potentially hazardous activities.
The therapy mirapex incidence of hypotension, as a rule, did not increase as compared to placebo.
Elderly patients (65 years and older) Dosage adjustment mirapex.
Since pramipexole excreted by the kidneys, patients with kidney disease may require adjustment of the dose.
Effects on ability to drive vehicles and management mechanisms
The patient should refrain from driving and other potentially hazardous activities until such time as there is no established character of the influence of the drug on the ability to focus and speed of psychomotor reactions.
Use in Pediatrics
Safety and effectiveness of mirapex in children has not been established.
Pregnancy and lactation
Perhaps if the effect of therapy outweighs the potential risk to the fetus (adequate and well-controlled studies on the use during pregnancy has not been performed).
Category effects on the fetus by FDA – C.
At the time of treatment should stop breastfeeding (data on the penetration of breast milk in humans are not available).
Symptoms have not been established. Clinical experience with large overdose mirapex absent. One patient with a 10 year history of schizophrenia received 11 mg / day of pramipexole over 2 days; it is 2-3 times more than the recommended daily dose protocol.
Adverse effects due to the increased dose was noted. Blood pressure remained stable, although the heart rate increased to 100-120 beats / min.
Treatment: Antidote pramipexole unknown.
When the symptoms of CNS stimulation may be used neuroleptics – phenothiazine derivatives or butyrophenone, but the effectiveness of these drugs in the elimination of effects mirapex overdose was not evaluated.
In the treatment of an overdose may require maintenance therapy, gastric lavage, application means for rehydration and detoxification, monitoring ECG.