Азилект®

General characteristics. Structure:

Active agent: a razagilina мезилат 1,56 mg (it is equivalent to 1 mg of a razagilin of the basis)
excipients: Mannitolum, silicon dioxide colloid, starch corn, starch corn prezhelatizirovanny, stearic acid, talc

Description: White or almost white color round, ploskotsilindrichesky tablets with a facet. On one party of a tablet an engraving of "GIL 1"

Pharmacological properties:

Pharmacodynamics. Razagilin is selective irreversible inhibitor of a monoaminooxidase like B (MAO-B), enzyme, for 80% defining activity of a monoaminooxidase in a brain and dopamine metabolism. It at 30-80 times is more active concerning MAO-B, than to other type of this enzyme - MAO-A. As a result of an inhibiting effect of drug on MAO-B in the central nervous system dopamine level increases, education of toxic free radicals whose excess education is observed at patients with Parkinson's disease decreases. Razagilin possesses also neurotyre-tread action. Unlike the MAO not selective inhibitors, drug in therapeutic doses does not block metabolism of the biogenic amines arriving with food (for example, tyramine) in this connection does not cause tyramine - the caused hypertensive syndrome ("cheese effect").

Pharmacokinetics. Razagilin is quickly soaked up after intake; its maximum concentration in a blood plasma (Cmax) is reached in 0.5 hours. Absolute bioavailability of drug after single introduction makes about 36%. Food does not influence time of achievement of the maximum concentration of a razagilin in blood, however, at consumption of Cmax greasy food and the area under a curve of concentration of drug (AUC) decrease by 60% and 20%, respectively. The pharmacokinetics of drug has linear character in the range of doses of 0,5-2 mg. Communication with proteins of a blood plasma fluctuates from 60 to 70%.
Razagilin is almost completely metabolized in a liver. Biotransformation is carried out by N-dealkylation and/or a hydroxylation with formation of the main biologically low-active metabolite - 1 aminoindan, and also 2 other metabolites - 3-hydroxy-N-propargyl-1 of aminoindan and Z-gidroksi-1-aminoindana. Metabolism of drug is carried out with the participation of the CYP 1A2 isoform of system of R-450 cytochrome. Razagilin is brought preferential by kidneys (more than 60%) and to a lesser extent through intestines (more than 20%). Less than 1% of the entered dose of drug are allocated in an invariable look. The elimination half-life makes 0,6-2 hours. Parameters of pharmacokinetics of a razagilin practically do not change at patients with a slight and moderate renal failure. At a slight liver failure increase in values of the AUC and Cmax parameters for 80% and 38% can be observed, and at patients with moderate abnormal liver functions these parameters reach more than 500% and 80%, respectively.

Indications to use:

Monotherapy or combination therapy of a disease of Parkinson (with levodopa drugs).

Route of administration and doses:

Razagilin apply inside in a dose 1 mg both in monotherapy, and against the background of use of a levodopa once a day, it is long. Administration of drug does not depend on meal.

Features of use:

Use of a razagilin in the recommended therapeutic dose does not cause "a tiraminovy syndrome" ("cheese effect") that allows patients to use without restrictions in food the products containing significant amounts of tyramine (cheeses, chocolate, etc.). Studying of influence of a razagilin on driving of the car and control of other mechanisms was not carried out.

Side effects:

The listed side effects met frequency more than 1/100, the side effects meeting with frequency of 1/100 - 1/1000 are specified as seldom meeting.
At monotherapy razagiliny:
From a nervous system: headaches, a depression, dizziness, anorexia, spasms, it is rare: disturbance of cerebral circulation.
From digestive tract: loss of appetite, dispepsichesky phenomena.
From a musculoskeletal system: an arthralgia, arthritis, pain in a neck.
From integuments: vezikulobullezny rash, contact dermatitis; seldom: skin carcinoma.
From cardiovascular system: stenocardia, it is rare: myocardial infarction.
Others: fippopodobny syndrome, fever, leukopenia, rhinitis, general weakness, conjunctivitis, acute disorders of an urinary system, allergic reactions.
At use together with a levodopa:
From a nervous system: dyskinesia, a muscular allotopia, anorexia, unusual dreams, an ataxy, it is rare: disturbance of cerebral circulation.
From bodies of digestive tract: a lock, vomiting, an abdominal pain, dryness in a mouth.
From a musculoskeletal system: the arthralgia, pain in a neck, tendosinoviit.
From integuments: rash, it is rare: mslanoma of skin.
From cardiovascular system: postural hypotension, it is rare: stenocardia.
Others: accidental falling, decrease in body weight, allergic reactions.
There are two messages on development of a rabdomioliz and disturbance of secretion of antidiuretic hormone. Both cases are recorded when carrying out post-registration researches without control placebo, developed against the background of falling and the subsequent long immobilization. The interrelation between these complications and reception of a razagilin cannot be defined.

Interaction with other medicines:

Because the mechanism of action of a razagilin is connected with MAO inhibition as in a case with other medicines of the similar mechanism of action, it is impossible to appoint it along with other inhibitors of this enzyme because of risk of development of hypertensive crisis. It is necessary to avoid the combined use of a razagilin with medicines which mechanism of action includes braking of the return neyronalny serotonin reuptake (fluoxetine, флувоксамин, etc.), tricyclic and tetracyclic antidepressants, MAO inhibitors as at the same time development of the "serotonergic syndrome" which is shown in confusion of consciousness, a hypomaniacal state, motive concern, a fever, a tremor, diarrhea is possible. In need of use by the patients receiving разагилин, similar drugs - they are applied with care.
Also combined use of a razagilin with the sympathomimetic medicines including ephedrine, pseudoephedrine, which are contained in drugs for treatment of rhinitises or cold (decongestants) is not recommended. Besides, purpose of a razagilin with analgetic/antibechic drug dextromethorphan and the combined means supporting him is not recommended. Because the enzyme isoform P450 1A2 cytochrome (CYP1A2) participates in metabolism of a razagilin, active inhibitors of this enzyme (for example, ciprofloxacin) can increase concentration of drug in a blood plasma that defines care at a combination of such medicines with razagiliny.
At patients with Parkinson's disease use of drugs of a levodopa does not exert impact on clearance of a razagilin.

Contraindications:

- hypersensitivity to a razagilin or any of drug components;
- the accompanying therapy by pethidine or other MAO inhibitors, fluoxetine and fluvoksaminy. The break between cancellation of a razagilin and the beginning of therapy by these drugs has to be not less than 14 days;
- a moderate or heavy liver failure (on Chayld-Pyyu);
- joint therapy with decongestants, sympathomimetics (including with means them containing), dextromethorphan.
- pheochromocytoma;
- the age is younger than 18 years;
- pregnancy;
- the lactation period (risk of oppression of products of milk against the background of braking of formation of prolactin).

With care
Easy form of a liver failure; joint reception with selective inhibitors of the return serotonin reuptake, tricyclic and tetracyclic antidepressants, active CYP1A2 inhibitors.

Overdose:

Symptoms of overdose of drug are similar to the MAO not selective inhibitors, those at overdose (arterial hypertension, postural hypotension, etc.).
Treatment: There is no specific antidote. Gastric lavage, reception of absorbent carbon, symptomatic therapy.

Storage conditions:

Period of validity 3 years. Not to use after the expiry date specified on packaging. At a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of 1 mg. On 10 tablets in the blister. On 1, 3, 10 blisters with the application instruction in a cardboard pack.