Mirapex

Active material: Pramipexole
When ATH: N04BC05
CCF: Of anti-drug – stimulant of dopaminergic transmission in the CNS
ICD-10 codes (testimony): G20, G21
When CSF: 02.06.01.02
Manufacturer: BOEHRINGER INGELHEIM INTERNATIONAL GmbH (Germany)

Pharmaceutical form, composition and packaging

Pills white, Oval, with a beveled edge, flat on both sides, on one side of a deep risk with marking “P7” on both sides of the risks; on the other side – risk and company logo on both sides of the risks.

Excipients: mannitol, corn starch, colloidal silicon dioxide, povidone, magnesium stearate.

10 PC. – blisters (3) – packs cardboard.

Pills white, round, with a beveled edge, flat on both sides, on one side of a deep risk with marking “P9” on both sides of the risks; on the other side – risk and company logo on both sides of the risks.

Excipients: mannitol, corn starch, colloidal silicon dioxide, povidone, magnesium stearate.

10 PC. – blisters (3) – packs cardboard.

Pharmacological action

Of anti-drug. Pramipexole – dopamine receptor agonist, with high selectivity and specificity is associated with dopaminovymi (D)₂-receptors, possesses strong affinity to dopaminovym (D)₃-Receptor. Reduces motor activity deficiency with Parkinson's disease by stimulating the dopaminovykh receptors in the striatum. Pramipexol ingibiruet synthesis, release and metabolism of dopamine, protect dopamine neurons from degeneration, arising in response to ischemia or metamfetaminovuû neurotoxicity.

Dozozawisimo reduces the secretion of prolactin.

With prolonged use (more 3 years) signs of reducing the effectiveness of the drug has not been established.

Pharmacokinetics

Absorption

Pramipexol after intake of rapidly and completely absorbed, reaching C_max approximately 1-3 no. The absolute bioavailability of pramipexole exceeds 90%. The rate of absorption is reduced when food intake, However, the total amount of suction eating no effect. For pramipexole is characterized by linear kinetics and relatively small concentration variability between individual patients.

Distribution

V_d is 400 l. Plasma protein binding – less 20%.

Metabolism and excretion

Slight metabolised in the body.

About 90% the dose is excreted in the urine (80% – unchanged) less 2% – with feces. The total klirens pramipexole is about 500 ml / min, renal clearance – about 400 ml / min.

The value of a finite T_1/2 is 8 h young healthy volunteers and about 12 no – elderly.

Testimony

— the treatment of the symptoms of Parkinson's disease (in the form alone or in combination with levodopa).

Dosage regimen

The drug is taken orally, regardless of the meal, drinking water. Daily dose should be evenly divided into 3 admission.

The initial daily dose 375 mcg should be increased every 5-7 days. To reduce the side effects dose should pick up gradually to achieve maximum therapeutic effect.

Scheme of improving dose Mirapeksa^®

If necessary, further increasing the daily dose of added 750 mcg per week up to a maximum daily dose of 4.5 mg.

Individual supporting daily intake ranges from 375 micrograms to 4.5 mg. As in the early, and at a late stage of the disease the drug was effective, starting with a daily dose of 1.5 mg. This does not prevent the, that individual patients doses above 1.5 mg/day may provide additional therapeutic effect, especially at a late stage of the disease, When shown to reduce levodopa dose.

While it is recommended that therapy with levodopa dose increases, as well as during maintenance therapy Mirapeksom^® reduce the dose of levodopa. This is necessary to avoid excessive stimulation dopaminergičeskoj.

For initial therapy with patients QC more 50 ml / min you are not required to reduce the daily dose. In of patients with CC 20 to 50 ml / min the initial daily dose should be divided into 2 reception and start with a dose of 125 g 2 times / day (daily dose – 250 g). In patients with KK less 20 ml / min shows a single entire daily dose, starting dose 125 mg / day.

If a maintenance therapy kidney function decreases, the daily dose of the drug reduced by the same percentage, what CC declined (eg, If KK decreased by 30%, daily dose should be reduced by 30%). The daily dose should be divided into 2 admission, If the value CC is 20-50 ml / min. The drug should be taken 1 time / day, If creatinine clearance is less than 20 ml / min.

In Patients with liver failure There is no need to reduce the dose.

Mirapex^® should be lifted gradually over several days.

Side effect

At the early stage of the disease more frequent undesirable reactions were drowsiness and constipation, and at a later stage of the disease when treatment in combination with levodopa more common dyskinesia and hallucinations. These adverse events decreased with continued therapy; constipation, nausea and dyskinesia tended to disappear.

From the nervous system: confusion, neuroleptic malignant syndrome (hyperthermia, muscle rigidity, disturbance of consciousness, akathisia, vegetative lability, thought disorders), insomnia, extrapyramidal syndrome, dizziness, asthenia, amnesia, gipesteziya, dystonia, myoclonus, tremor, depression, anxiety, ataxia, gipokineziya, delirium, suicidal thoughts.

On the part of the musculoskeletal system: hypertonus muscles, cramping of the leg muscles, vellication, arthritis, ʙursit, myasthenia, pain in the lumbosacral spine, chest pain, neck pain.

From the digestive system: decreased appetite, dysphagia, dyspepsia, abdominal pain, flatulence, diarrhea, dry mouth, vomiting.

The respiratory system: pharyngitis, sinusitis, rhinitis, flu-like symptoms, breathlessness, increased cough, voice alteration, pulmonary infiltration, pleural effusion.

With the genitourinary system: urinary tract infection, increased urination.

Cardio-vascular system: orthostatic hypotension, tachycardia, Increase CPK activity, angina, Arrhythmia. Arterial gipotenzia when treated with Mirapex^® developed no more, than when receiving the placebo. Individual patients have hypotension may occur at the beginning of treatment, especially, If the dose is increased too fast.

From the senses: conjunctivitis, cycloplegia, diplopia, Cataract, increased intraocular pressure, impaired hearing.

Other: allergic reactions, hyperthermia, ryetropyeritonyealinyi fibrosis, weight loss, increased perspiration. There have been cases of peripheral edema.

Cases were reported of sleep during daily activities, (incl. while driving), that sometimes led to accidents.

The drug Mirapex^® can cause change (decrease or increase the) libido.

The literature describes cases of pathological craving for gambling against the backdrop of the admission of pramipexole (especially in high doses), that stopped after drug withdrawal.

Contraindications

-hypersensitivity to pramipeksolu or other components of the drug.

FROM caution should be prescribed in patients with renal insufficiency, hypotension.

Pregnancy and lactation

Influence on pregnancy and lactation in humans should be studied.

During pregnancy drug appoint only, If the potential benefits for a mother than the potential risk to the fetus.

Drug excretion in breast milk was not investigated. As pramipexol inhibits the secretion of prolactin, We can assume, that it also suppresses lactation. Therefore, the drug should not be taken during breastfeeding.

Cautions

Hallucinations and confusion – known side effects in the treatment of dopaminovymi and agonists levodopa. In applying the drug Mirapex^® in combination with levodopa in the later stages of the disease more frequently experienced hallucinations, than with monotherapy in patients pramipeksolom at the early stage of the disease. Patients should be informed about the possibility of hallucinations (primarily Visual), that may affect the ability to drive a car.

Caution If the patient of severe cardiovascular disease. Because of the risk of orthostatic hypotension in conducting dopaminergičeskoj therapy to monitor ad, especially at the beginning of treatment.

Patients must be warned of the possible effect of sedativnom drug. Cases were reported of sleep during daily activities (incl. while driving), that sometimes led to accidents. In certain cases, falling asleep is not preceded by a State of sleepiness, which is often observed in patients, receiving pramipexol dose above 1.5 mg / day, and which, in accordance with the latest knowledge in Physiology of sleep, always preceded by falling asleep. A clear relationship between manifestation of sleepiness and the duration of treatment is not intended. Some patients were taking other medicines with potential sedative properties. In most cases (According to the information) After dose reduction or discontinuation of treatment in future episodes of sleep was not observed.

It has been reported, that sudden cessation of therapy observed symptom, allowing assume neirolepticeski Malignant Syndrome.

In the study of animal carcinogenicity degeneration and loss of photoreceptor cells in the retina of albino rats. The potential significance of this effect in humans has not been established, but it cannot be due to possible violation of mechanism (blur disk), Universal for all vertebrates.

Effects on ability to drive vehicles and management mechanisms

Patients should be informed about the possibility of hallucinations (primarily,. Visual), that may affect the ability to drive a car.

In applying the drug may develop sedative effects, including drowsiness and sleep during daily activities. Since drowsiness is a frequent undesirable phenomenon with potentially serious consequences, patients should not drive a car or work with other complex mechanisms so far, until they gain sufficient experience treating drug Mirapex^®, to evaluate, whether it is negative or is not on their mental and/or motor activity. Patients should be advised when available during treatment increased sleepiness or episodes of sleep during daily activities (ie. during the conversation, Food), unsubscribe from driving, work with technology and consult a physician.

Overdose

Cases pronounced overdose not described. Alleged symptoms: nausea, vomiting, giperkineziya, hallucinations, arousal and decrease ad.

Treatment: gastric lavage, simptomaticheskaya therapy. There is no specific antidote. If there are signs of stimulation of the nervous system may be recommended to antipsychotics. The efficiency of hemodialysis is not installed.

Drug Interactions

Pramipexol marginally (<20%) associated with the plasma protein and biotransformation. Therefore, interactions with other drugs, influence on plasma protein binding, or excretion through biotransformation is unlikely.

Preparations, that inhibit active secretion of cationic drugs through the renal tubules (eg, cimetidine), or who themselves are displayed through the active secretion via the renal tubules, may interact with pramipeksolom, that translates into a decrease in clearance of one or both of the drugs. In the case of simultaneous use of these drugs (incl. amantadina) and pramipexole should pay attention to such signs of dopaminovoj of excess stimulation, how dyskinesia, arousal or hallucinations. In such cases, it is necessary to reduce the dose.

Diltiazem, triamterene, verapamil, quinidine, quinones, reduce clearance pramipexole on 20%.

Selegelin and levodopa will not affect the farmakokinetiku pramipexole. Pramipexol levodopa increases the concentration and reduces the time to C_max from 2.5 to 0.5 no.

Interact with anticholinergic drugs and amantadine was not investigated. However, interaction with amantadine may, tk. drugs have a similar inference mechanism. Anticholinergic drugs mainly excreted by metabolic, Therefore, interaction with pramipeksolom it is unlikely.

When increasing doses of levodopa dose reduction is recommended pramipexole, When the dose of other drugs protivoparkinsoničeskih must be maintained at a constant level.

Dopamine antagonists (phenothiazines, butyrofenona, thioxanthen, metoclopramide) reduce the effectiveness of pramipexole.

Due to the potential for cumulative effects, patients should be advised to exercise caution when taking other sedative drugs or ethanol (alcohol) in combination with the drug Mirapex^®, and while admission of medicines, increases concentration in plasma pramipexole (eg, cimetidine).

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored in the dark, inaccessible to children at temperature not exceeding 30 ° C. Shelf life – 3 year. Do not use the medication after the expiration date, on the package.