AZILEKT

Active material: rasagiline
When ATH: N04BD02
CCF: Of anti-drug – MAO-B selective inhibitor
ICD-10 codes (testimony): G20
Manufacturer: TEVA Pharmaceutical Industries Ltd. (Israel)

Pharmaceutical form, composition and packaging

Pills white or nearly white, round, Valium, bevelled and engraved “GIL 1” on one side.

Excipients: mannitol, colloidal silicon dioxide, corn starch, pregelatinized corn starch, stearic acid, talc.

10 PC. – blisters (1) – packs cardboard.
10 PC. – blisters (3) – packs cardboard.
10 PC. – blisters (10) – packs cardboard.

Pharmacological action

Of anti-drug. Selective irreversible MAO type B, enzyme, on 80% determining the activity of MAO in the brain and metabolism of dopamine. rasagiline 30-80 times more active against MAO type B, compared to the type A MAO.

As a result of the inhibitory effect of the drug on the MAO-B in the central nervous system increases the level of dopamine, decreases the formation of toxic free radicals, excessive formation is observed in Parkinson's disease. Rasagiline has also neuroprotective effect.

In contrast, non-selective MAO inhibitors, the drug at therapeutic doses, does not block the metabolism of dietary biogenic amines (eg, tyramine), and therefore does not cause tyramine-induced hypertensive syndrome (“cheesy” effect).

Pharmacokinetics

Absorption

Rasagiline is rapidly absorbed after oral administration, C_max plasma levels achieved after 0.5 no. Absolute bioavailability following a single administration is approximately 36%. Food has no effect on the time to reach C_max rasagiline in Resurrection, but when consumed fatty foods C_max and AUC are reduced by 60% and 20% respectively.

Distribution

Pharmacokinetics is linear in a range of doses 0.5-2 mg. The binding to plasma proteins ranged from 60% to 70%.

Metabolism

Rasagiline almost completely metabolized in the liver. The biotransformation is carried out by N-dealkylation and / or hydroxylation to form the main biologically less active metabolite - 1-aminoindan, as well as two other metabolites - 3-hydroxy-N-propargyl-1-aminoindan and 3-hydroxy-1-aminoindan. Metabolism preparation is produced with the assistance of isoenzyme CYP1A2.

Deduction

Rasagiline excreted mainly by the kidneys (more 60%) and to a lesser extent through the gut (more 20%). Less 1% administered dose of the drug is released in unaltered form. T_1/2 is 0.6-2 no.

Pharmacokinetics in special clinical situations

Pharmacokinetic parameters of rasagiline virtually unchanged in patients with renal insufficiency, mild to moderate.

In mild hepatic impairment can be observed increase in AUC values ​​of parameters and C_max on 80% and 38%, and in patients with moderate impairment of liver function, these parameters reach more 500% and 80% respectively.

Testimony

- the treatment of Parkinson's disease (as monotherapy or combination therapy with levodopa).

Dosage regimen

Assign 1 mg 1 time / day as monotherapy, and during treatment with levodopa, protractedly.

Tablets are taken orally without food.

Side effect

These side effects occurred at a frequency more 1/100, side effects, occurs with a frequency 1/100-1/1000 listed as rare.

Rasagiline monotherapy:

CNS: headache, depression, dizziness, anorexia, convulsions; rarely – cerebrovascular accident.

From the digestive system: decreased appetite, dyspepsia.

On the part of the musculoskeletal system: arthralgia, arthritis, neck pain.

Dermatological reactions: vesiculobullous rash, contact dermatitis; rarely – skin cancer.

Cardio-vascular system: angina; rarely – myocardial infarction.

Other: flu-like symptoms, fever, leukopenia, rhinitis, generalized weakness, conjunctivitis, dizurija, allergic reactions.

When applied together with levodopa:

From the central and peripheral nervous system: dyskinesia, muscular dystonia, anorexia, unusual dreams, ataxia; rarely – cerebrovascular accident.

From the digestive system: constipation, vomiting, abdominal pain, dry mouth.

On the part of the musculoskeletal system: arthralgia, neck pain, tendosynovyt.

Dermatological reactions: rash; rarely – melanoma skin.

Cardio-vascular system: postural hypotension; rarely – angina.

Other: accidental falls, weight loss, allergic reactions.

Contraindications

- pethidine or concomitant therapy with other MAO inhibitors (the interval between the abolition of rasagiline and initiation of therapy with these drugs should not be less than 14 days);

- moderate or severe liver failure (Class B and C on the Child-Pugh);

- co-therapy with sympathomimetics (ephedrine, Pseudoephedrine), other decongestants, dextromethorphan, and also to medicines containing them;

- Pheochromocytoma;

- Childhood and adolescence up 18 years;

- Pregnancy;

- Lactation (the risk of oppression milk production against the background of the formation of inhibition of prolactin);

- increased sensitivity of rasagiline or any of the components.

FROM caution prescribers with mild hepatic insufficiency, when co-administered with a selective serotonin reuptake inhibitor (fluoksetinom and fluvoksaminom), tritsiklicheskimi and tetratsiklicheskimi antidepressantami, active inhibitors of CYP1A2 isoenzyme.

Pregnancy and lactation

The drug is contraindicated in pregnancy and lactation.

Cautions

Application Azilekta at the recommended therapeutic dose does not cause the tyramine syndrome (“cheesy” effect), allowing patients to freely used in food products, containing significant amounts of tyramine (cheeses, chocolate).

Effects on ability to drive vehicles and management mechanisms

Study of the effect of rasagiline on the driving and control of other mechanisms has not been.

Overdose

Symptoms drug overdose Azilekt similar to those of non-selective MAO inhibitor overdose (incl. arterial hypertension, postural hypotension).

Treatment: gastric lavage, administration of activated charcoal, simptomaticheskaya therapy. No specific antidote.

Drug Interactions

Because, that rasagiline mechanism of action is associated with inhibition of MAO, it should not be administered concomitantly with other inhibitors of the enzyme due to risk of hypertensive crisis.
With simultaneous application of rasagiline with serotonin reuptake inhibitors (fluoxetine, fluvoxamine), tricyclic and tetracyclic antidepressants may develop serotonin syndrome, manifested in the confusion, elated state, restlessness, oznobe, tremors, diarrhea. Possibly, combined use should be avoided with such preparations rasagiline, and if necessary, their simultaneous application should provide increased safety precautions.

Because, that the isoenzyme CYP1A2 involved in the metabolism of rasagiline, active inhibitors of this enzyme (eg, Ciprofloxacin) may increase the plasma concentration of the drug, that defines caution when combining these drugs with rasagiline.

In patients with Parkinson's disease levodopa use does not affect the clearance of rasagiline.

Conditions of supply of pharmacies

The drug is released under the prescription.

Conditions and terms

The drug should be stored out of reach of children at or above 25 ° C. Shelf life – 3 year.