Expiration date: 11/2022
The composition and form of issue:
Tablets. 1 tablet contains active substance:
rasagiline mesylate of 1.56 mg (corresponding to 1 mg rasagiline base)
excipients: corn starch 20 mg corn starch pregelatinization 20 mg mannitol — 159,24 mg silica colloidal anhydrous — 1.2 mg stearic acid 4 mg talc 4 mg
blistere in 10 PCs in a pack a cardboard 1, 3 or 10 blisters.
Description pharmaceutical form:
Tablets white or almost white, round, ploskotsylindriceskie, chamfered and engraving "GIL 1" on one side.
Rasagiline is rapidly absorbed after oral administration, Cmax in plasma achieved through 0.5 h. the Absolute bioavailability of the drug after a single injection of about 36%. Food does not affect the time to reach Cmax rasagiline in the blood, however, eat fatty food Cmax and AUC are reduced by 60 and 20%, respectively.
The pharmacokinetics of the drug is linear in the dose range of 0.5–2 mg. Linking blood plasma proteins ranges from 60% to 70%.
Rasagiline almost completely metabolized in the liver. Biotransformation is carried out by N-dealkilirovanie and/or hydroxylation with the formation of biologically less active metabolite — 1-aminoindan, as well as two other metabolites — 3-hydroxy-N-propargyl-1-aminoindan and 3-hydroxy-1-aminoindan. The metabolism of the drug is carried out with the participation of isoenzyme 1A2 of cytochrome P450.
Rasagiline excreted by the kidney (>60%) and to a lesser extent through the intestines (>20%). Less than 1% of the administered dose is excreted unchanged. T1/2 — 0,6–2 h
Pharmacokinetics in special clinical cases
Pharmacokinetics parameters rasagiline virtually unchanged in patients with renal insufficiency mild to moderate.
When liver failure mild can be observed increased values of the parameters AUC and Cmax by 80 and 38%, and in patients with mild impairment of liver function, these parameters reach more than 500 and 80%, respectively.
Description pharmacological action:
Selective irreversible inhibitor of MAO type b enzyme, 80% of which determines the activity of MAO in the brain and metabolism of dopamine. Rasagiline in 30-80 times more active against MAO-b compared to MAO-A.
The result of inhibitory drug action on MAO-b in CNS increases dopamine levels, decreases the formation of toxic free radicals, excessive formation of which is observed in Parkinson's disease. Rasagiline also has a neuroprotective effect.
Unlike nonselective MAO inhibitors, the drug in therapeutic doses does not block the metabolism of dietary biogenic amines (e.g. tyramine), therefore does not cause tyramine - induced hypertensive syndrome ("cheese effect").
Parkinson's disease (as monotherapy or combination therapy with levodopa).
- hypersensitivity to rasagiline or any component of the drug
- concomitant treatment with pethidine or other MAO inhibitors (a break between the cancellation rasagiline and starting therapy with these drugs should be not less than 14 days)
- moderate or severe hepatic impairment (class B and C child-Pugh)
- joint therapy with the sympathomimetics (ephedrine, pseudoephedrine), other decongestants, dextromethorphan, and medications containing them
- childhood and adolescence to 18 years
- lactation (risk of suppression of production of milk on the background of inhibition of the formation of prolactin).
- easy liver failure
- joint reception with SSRIs (fluoxetine and fluvoxamine), tricyclic and tetracyclic antidepressants, active inhibitors of the isoforms 1A2 of cytochrome P450.
Application of pregnancy and breast-feeding:
The drug is contraindicated during pregnancy and lactation.
Listed side effects occurred at a frequency 1/100 of the side effects encountered with a frequency of 1/100–1/1000 is listed as rare.
CNS: headaches, depression, dizziness, anorexia, convulsions, rarely — violation of cerebral circulation.
From the digestive system: decreased appetite, diarrhoea phenomenon.
From the side of musculoskeletal system: arthralgia, arthritis, pain in the neck.
Dermatological reactions: vesiculobullous rash, contact dermatitis rarely, carcinoma.
From the side of cardiovascular system: angina, rarely myocardial infarction.
Other: grippopodobnyy syndrome, fever, leukopenia, rhinitis, General weakness, conjunctivitis, dysuria, allergic reactions.
When combined with levodopa
CNS and peripheral nervous system: dyskinesia, muscle dystonia, anorexia, unusual dreams, ataxia, rarely — violation of cerebral circulation.
From the digestive system: constipation, vomiting, abdominal pain, dry mouth.
From the side of musculoskeletal system: artralgia, pain in the neck, tendosynovit.
Dermatological reactions: rash, rarely — melanoma of the skin.
From the side of cardiovascular system: postural hypotension is rarely angina.
Other: accidental falls, reducing body weight, allergic reactions.
Due to the fact that the mechanism of action rasagiline is associated with inhibition of MAO, it cannot be administered concurrently with other inhibitors of this enzyme because of the risk of development of hypertensive crisis.
While the use of rasagiline with inhibitors of serotonin reuptake (fluoxetine, fluvoxamine), tricyclic and tetracyclic antidepressants may develop "serotonin syndrome", which manifests itself in confusion, hypomania, physical restlessness, shivering, tremor, diarrhea. If possible, avoid combined use rasagiline of such drugs and, if necessary, their simultaneous application should provide increased precautions.
Due to the fact that the isoforms 1A2 of cytochrome P450 (CYP1A2) is involved in the metabolism rasagiline, active inhibitors of this enzyme (e.g. ciprofloxacin) can increase the concentration of drug in plasma that determines caution when combining these drugs with rasagiline.
In patients with Parkinson's disease applying levodopa has no effect on the clearance rasagiline.
Method of application and dose:
Inside, in the dose 1 mg 1 times a day as monotherapy or on a background of levodopa long-term. The drug is not depends of food intake.
Symptoms of drug overdose Azilect the same as for overdose of non-selective MAO inhibitors (including hypertension, postural hypotension).
Treatment: gastric lavage, reception activated carbon, symptomatic therapy. There is no specific antidote.
The use of Azilect at the recommended therapeutic dose does not cause "tyramine syndrome" ("cheese effect") that allows patients to unrestricted use in food products containing significant amounts of tyramine (cheese, chocolate).
Effects on ability to drive vehicles and management mechanisms
The study of the influence rasagiline on driving and operating other mechanisms was conducted.