Мирапекс®

General characteristics. Structure:

Active ingredient: 0,25 mg or 1 mg of a pramipeksol of dihydrochloride of monohydrate (equivalent 0,18; 0,7 mg of a pramipeksol of the basis).

Excipients: Mannitolum, starch corn, silicon dioxide colloid, povidone, magnesium stearate.

Pharmacological properties:

Pharmacodynamics. Pramipeksol - an agonist of dopamine receptors, with high selectivity and specificity contacts dopamine receptors of subgroup of D2, has the expressed affinity to D3 to receptors. Reduces deficit of a physical activity at Parkinson's disease due to stimulation of dopamine receptors in a striate body. Pramipeksol inhibits synthesis, release and metabolism of dopamine, protects dopamine neurons from the degeneration arising in response to ischemia or a metamfetaminovy neurotoxicity. Reduces prolactin secretion (дозозависимо).
At prolonged use (more than 3 years) of signs of decrease in efficiency it is not established.

Pharmacokinetics. Pramipeksol after intake is quickly and completely soaked up. Absolute bioavailability makes more than 90%, and the maximum concentration in plasma are observed in 1-3 hours. Speed of absorption decreases at meal, however meal does not influence the total amount of absorption. The linear kinetics and rather small variability of concentration between certain patients is characteristic of a pramipeksol. Pramipeksol contacts proteins in very insignificant degree (<20%), and has the large volume of distribution (400 l). Is exposed to metabolism in slightly degree. About 90% of a dose are removed through kidneys (80% in not changed look) and less than 2%

it is found in Calais. The general clearance of a pramipeksol makes about 500 ml/min., the renal clearance makes about 400 ml/min. The elimination half-life (shopping center) fluctuates from the 8th hour at young people and to the 12th hour at elderly people.

Indications to use:

Treatment of symptoms of a disease of Parkinson (monotherapy, or in a combination with a levodopa).

Route of administration and doses:

Inside, regardless of meal, washing down with water. The daily dose is evenly divided into 3 receptions.

Initial therapy. As shown below, the initial daily dose of 0.375 mg is increased by each 5-7 days. For reduction of side effects, the dose needs to be selected gradually before achievement of the maximum therapeutic effect.

Scheme of increase in a dose of drug MIRAPEKS
week	dose (mg)	full daily dose (mg)
1	3 x 0.125	0.375
2	3 x 0.25	0.75
3	3 x 0.5	1.50

In need of further increase in a daily dose, add 0.75 mg a week to the maximum dose of 4.5 mg a day.

Maintenance therapy. The individual dose has to be ranging from 0.375 mg to 4.5 mg a day. Both on early, and at a late stage of a disease drug was effective, since a daily dose of 1.5 mg. At the same time it is not excluded that at certain patients of a dose higher than 1.5 mg a day can give additional therapeutic effect, especially at a late stage of a disease when the levodopa dose decline is shown.

Pramipeksol it is necessary to cancel gradually within several days. Doses for the patients receiving at the same time therapy by a levodopa. At simultaneous therapy with a levodopa, it is recommended in process of increase in a dose, and also during a maintenance therapy pramipeksoly    to reduce  a levodopa dose. It is necessary in order to avoid excessive dofaminergichesky stimulation.

Doses for patients with a renal failure. For initial therapy: with clearance of creatinine higher than 50 ml/min. are not required from patients decrease in a daily dose. At clearance of creatinine of 20 - 50 mg/ml the initial daily dose of drug is appointed in two steps, since 0.125 mg by 2 times a day (0.25 mg a day). At clearance of creatinine less than 20 ml/min. appoint a daily dose of drug once a day, since 0.125 mg.

If during a maintenance therapy function of kidneys decreases, the daily dose of drug is lowered by the same percent on which the clearance of creatinine decreases i.e. if the clearance of creatinine decreases by 30%, the daily dose of drug needs to be lowered by 30%. The daily dose can be divided into two receptions if the clearance of creatinine is in limits of 20 - 50 ml/min., or to accept once a day if the clearance of creatinine is less than 20 ml/min.

Doses for patients with a liver failure: there is no need to reduce a dose at patients with a liver failure.

Features of use:

Hallucinations and confusion of consciousness - the known side effects at treatment by dopamine agonists and a levodopa. At use of drug of Mirapeks in a combination with a levodopa at late stages of a disease of a hallucination were observed more often than at monotherapy pramipeksoly at patients at an early stage of a disease. Patients have to be informed on possibility of hallucinations (generally visual) which can influence ability to driving of the car. It is necessary to show care in the presence at a sick serious serdechnoksosudisty illness. Due to the risk of development of orthostatic hypotension when performing dofaminergichesky therapy it is recommended to control arterial pressure, in particular in an initiation of treatment.

Patients should be warned about possible sedation of drug. It was reported about backfilling cases during daily activity, (including when driving the car) that sometimes led to accidents. In certain cases backfilling was not preceded by a condition of drowsiness which is often observed at the patients accepting прамипексол in doses it is higher than 1.5 mg/days and which, according to modern knowledge in the field of dream physiology, always precedes to backfilling. The accurate interrelation between expressiveness of drowsiness and duration of treatment was not traced. Some patients accepted at the same time other medicines with potentially sedative properties. In most cases (according to the available data) after a dose decline or the termination of treatment further episodes of backfilling were not observed.

It was reported that at the sharp termination of therapy the symptom complex allowing to assume a malignant antipsychotic syndrome was observed.

Influence on ability to drive the car and the equipment. Patients have to be informed on possibility of hallucinations (generally visual) which can influence ability to driving of the car.

At use of drug development of sedations, including drowsiness and backfilling is possible during daily activity. As drowsiness is the frequent undesirable phenomenon with potentially serious effects, patients should not drive the car or work with other difficult mechanisms until they do not gain sufficient experience of treatment by drug of Mirapeks whether to estimate it influences negatively or not their intellectual and/or physical activity. It has to be recommended to patients that if during treatment they test the increased drowsiness or episodes of backfilling during daily activity (i.e. during the conversation, food etc.), then they have to refuse driving, work with the equipment, and will see a doctor.

Pregnancy and lactation. Influence on pregnancy and a lactation at the person is not investigated. During pregnancy it is necessary to appoint drug only if the potential advantage for mother surpasses potential risk for a fruit. Removal of drug with breast milk was not studied. As прамипексол inhibits prolactin secretion, it is possible to assume that it also suppresses a lactation. Therefore drug should not be accepted during feeding by a breast.

Side effects:

At an early stage of a disease of more frequent undesirable reactions there were a drowsiness and a lock, and at later stage of a disease at treatment in a combination with a levodopa dyskinesia and hallucinations were more often observed. These undesirable phenomena decreased at therapy continuation; the lock, nausea and dyskinesia tended to disappearance. From a nervous system: confusion of consciousness, malignant antipsychotic syndrome (hyperthermia, muscular rigidity, consciousness disturbance, akathisia, vegetative lability, disturbances of thinking), sleeplessness, extrapyramidal syndrome, dizzinesses, adynamy, amnesia, hypesthesia, dystonia, myoclonus, tremor, depression, uneasiness, ataxy, hypokinesia, nonsense, suicide mood.

From a musculoskeletal system: a hyper tone of muscles, spasms in muscles of legs, muscular twitchings, arthritis, a bursitis, a myasthenia, pains in poyasnichn-sacral department of a backbone, thorax pain, neck pain.

From the alimentary system: a loss of appetite, a dysphagy, dyspepsia, an abdominal pain, a meteorism, diarrhea, dryness in a mouth, vomiting.

From respiratory system: pharyngitis, sinusitis, rhinitis, grippopodobny syndrome, asthma, strengthening of cough, change of a voice.

From urinogenital system: infection of urinary tract, increase of an urination.

From cardiovascular system: orthostatic hypotension, tachycardia, increase in activity of a kreatinfosfokinaza, stenocardia, arrhythmias.

From sense bodys: conjunctivitis, accommodation paralysis, diplopia, cataract, increase in intraocular pressure, hearing easing.

Allergic reactions. Other: hyperthermia, retroperitoneal fibrosis, pulmonary infiltration, pleural exudate, decrease in body weight. the increased sweating. Arterial hypotension at treatment by drug MIRAPEKS developed not more often than at placebo reception. At certain patients arterial hypotension can arise in an initiation of treatment, in particular, if the dose of drug is increased too quickly. Cases of sleeplessness and peripheral hypostases were noted.

It was reported about backfilling cases during daily activity, (including when driving the car) that sometimes led to accidents.

Use of drug of Mirapeks can cause change (reduction or increase) of a libido.

In literature cases of pathological thirst for gamblings against the background of reception of a pramipeksol (especially in high doses) which stopped after drug withdrawal are described.

Interaction with other medicines:

Pramipeksol in insignificant degree (<20%) contacts proteins of plasma and is exposed to biotransformation. Therefore interactions with other drugs influencing linkng with proteins of plasma, or removal at the expense of biotransformation are improbable.

Drugs which inhibit active secretion of cationic drugs through renal tubules (for example, Cimetidinum) or which are removed due to active secretion through renal tubules, can interact with pramipeksoly that is expressed in decrease in clearance of one or both drugs.

In case of simultaneous use of such drugs (including an amantadina) and a pramipeksola it is necessary to pay attention to such signs of dopamine excess stimulation as dyskinesia, excitement or hallucinations. In similar cases it is necessary to lower a dose.

Diltiazem, Triamterenum, verapamil, quinidine, quinine, reduce clearance by 20%.

Selegelin and levodopa do not influence pharmacokinetics of a pramipeksol. Pramipeksol increases concentration of a levodopa and reduces TCmax from 2,5 to 0,5 h.

Interaction with anticholinergic medicines and amantadiny was not studied. However, interaction with amantadiny is possible since drugs have the similar mechanism of removal.

Anticholinergic medicines are generally removed in the metabolic way therefore interaction with pramipeksoly is improbable. At increase in a dose of a pramipeksol the levodopa dose decline is recommended, at the same time the dose of other protivoparkinsonichesky medicines needs to be supported at the constant level.

Antagonists of dopamine (derivatives of a fenotiazin, phenyl propyl ketone, thioxanthene, Metoclopramidum) reduce efficiency of treatment.

Because of possible cumulative effects, patients should recommend to show care at reception of other sedative medicines or alcohol in combination with drug of Mirapeks, as well as at a concomitant use of the medicines increasing concentration of a pramipeksol in plasma (for example, Cimetidinum).

Contraindications:

Hypersensitivity to a pramipeksol or to any component of drug.

With care. Renal failure, arterial hypotension.

At a carcinogenicity research on animals the degeneration and loss of photoreceptor cells in a retina of rats of albinos were observed. Potential value of this effect at the person is not established, but it should be considered because of possible disturbance of the mechanism (washing out of a disk), universal for all vertebrata.

Overdose:

Cases of the expressed overdose are not described. Estimated symptoms: nausea, vomiting, hyperkinesia, hallucinations, excitement and lowering of arterial pressure.

Therapy: gastric lavage, symptomatic therapy. The established antidote does not exist. In the presence of signs of stimulation of a nervous system, neuroleptics can be recommended. Efficiency of carrying out a hemodialysis is not established.

Storage conditions:

To store at a temperature not above 30 °C in protected from light and the place, unavailable to children. Period of validity 3 years. Not to use drug after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

10 tablets in the blister of Pas/aluminium/PVC. On 3 blisters in a cardboard pack with the application instruction.