Universal reference book for medicines
Product name: AZILECT (AZILECT)

Active substance: rasagiline
Type: An antiparkinsonian drug is a selective MAO inhibitor of type B
Manufacturer: Teva Pharmaceutical Industries (Israel)
Composition, form of production and packaging
Tablets white or almost white, round, flat-cylindrical, with a facet, with engraving "GIL 1" on one side of the tablet.
1 tab.
rasagiline mesylate 1.56 mg,
is equivalent to rasagiline (base) 1 mg
Excipients: mannitol - 159.24 mg, silicon dioxide colloid - 1.2 mg, corn starch - 20 mg, corn pregelatinized corn starch - 20 mg, stearic acid - 4 mg, talc - 4 mg.
10 pieces. - blisters (3) - packs of cardboard.
10 pieces. - blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2016.
PHARMACHOLOGIC EFFECT
An antiparkinsonian preparation. Azilekt is a selective irreversible inhibitor of MAO type B, an enzyme that determines 80% of the activity of MAO in the brain and the metabolism of dopamine. Razagilin is 30-80 times more active against MAO type B, in comparison with MAO type A.
As a result of the inhibitory effect of the drug on MAO type B in the central nervous system, the level of dopamine increases, the formation of toxic free radicals, excessive formation of which is observed in Parkinson's disease, decreases. Razagilin also has a neuroprotective effect.
Unlike non-selective MAO inhibitors, the drug does not block the metabolism of nutrient-derived biogenic amines (eg, tyramine) in therapeutic doses, and therefore does not cause a tyramine-mediated hypertensive syndrome ("cheese" effect).
PHARMACOKINETICS
Suction
Razagilin is rapidly absorbed after ingestion, C max in blood plasma is reached after 0.5 h. Absolute bioavailability of the drug after a single administration is about 36%. Food does not affect the time to reach C max rasagiline in the blood, but when consumed fatty foods C max and AUC are reduced by 60% and 20%, respectively.
Pharmacokinetics of the drug is linear in the dose range of 0.5-2 mg.
Distribution
Binding to plasma proteins varies from 60% to 70%.
Metabolism
Rasagiline is almost completely metabolized in the liver. Biotransformation is carried out by N-dealkylation and / or hydroxylation to form the main biologically inactive metabolite - 1-aminoindane, as well as two other metabolites - 3-hydroxy-N-propargyl-1-aminoindane and 3-hydroxy-1-aminoindane. The drug is metabolized with the participation of the CYP1A2 isoenzyme.
Excretion
Razagiline is excreted mainly by the kidneys (more than 60%) and to a lesser extent through the intestine (more than 20%). Less than 1% of the administered dose of the drug is released unchanged. T 1/2 is 0.6-2 hours.
Pharmacokinetics in special clinical cases
The parameters of rasagiline pharmacokinetics practically do not change in patients with mild and moderate renal insufficiency.
In mild liver failure, an increase in the values ​​of AUC and C max parameters by 80% and 38% can be observed, and in patients with moderate violations of liver function these parameters reach more than 500% and 80%, respectively.
INDICATIONS
- treatment of Parkinson's disease (in the form of monotherapy or combination therapy with drugs of levodopa).
DOSING MODE
Assign 1 mg 1 time / day as a monotherapy, and against the background of the use of levodopa, for a long time.
Tablets are taken orally regardless of food intake.
SIDE EFFECT
Overall, 1361 patients participated in the rasagiline clinical trial program, which was 3,076.4 patient-years. In double-blind, placebo-controlled trials, 529 patients took rasagiline at a dose of 1 mg / day, which was 212 patient-years, and 539 patients received placebo, which was 213 patient-years.
Monotherapy
The following list describes unwanted reactions reported with an increased incidence in placebo-controlled studies in patients receiving rasagiline at a dose of 1 mg / day (rasagiline group - n = 149, placebo group - n = 151).
Undesirable reactions with differences greater than 2% compared with the placebo group are indicated in italics .
The frequency of adverse reactions (% of patients) is indicated in parentheses: rasagiline / placebo.
Undesired reactions are distributed according to the following frequency: very often (? 1/10), often (? 1/100 to <1/10), infrequently (? 1/1000 to <1/100), rarely (? 1/10 000 to <1/1000), very rarely (<1/10 000).
Infectious and parasitic diseases: often - influenza (4.7% / 0.7%).
Benign, malignant and unspecified neoplasms (including cysts and polyps): often - skin cancer (1.3% / 0.7%).
On the part of the hematopoiesis system: often - leukopenia (1.3% / 0%).
On the part of the immune system: often - allergic reactions (1.3% / 0.7%).
From the side of metabolism and nutrition: infrequently - a decrease in appetite (0.7% / 0%).
Mental disorders: often - depression (5.4% / 2%), hallucinations (1.3% / 0.7%).
From the nervous system: very often - headache (4.1% / 11.9%); infrequently - a disorder of cerebral circulation (0.7% / 0%).
From the side of the organ of vision: often - conjunctivitis (2.7% / 0.7%).
From the side of the hearing organ and labyrinthine disturbances: often - vertigo (2.7% / 1.3%).
From the cardiovascular system: often - angina (1.3% / 0%); infrequently, myocardial infarction (0.7% / 0%).
From the digestive system: bloating (1.3% / 0%).
On the part of the respiratory system: often - rhinitis (3.4% / 0.7%).
From the skin and subcutaneous tissues: often - dermatitis (2% / 0%); infrequently - a vesiculo-bullous rash (0.7% / 0%).
From the musculoskeletal system: often - musculoskeletal pain (6.7% / 2.6%), neck pain (2.7% / 0%), arthritis (1.3% / 0.7%).
From the urinary system: often - the urge to urinate (1.3% / 0.7%).
Other: often - fever (2.7% / 1.3%), malaise (2% / 0%) .
When used as an auxiliary therapy
The list below includes unwanted reactions reported with an increased incidence in placebo-controlled studies in patients receiving rasagiline at a dose of 1 mg / day (rasagiline group - n = 380, placebo group - n = 388). The frequency of adverse reactions (% of patients) is indicated in parentheses: rasagiline / placebo.
Undesirable reactions with differences greater than 2% compared with the placebo group are indicated in italics .
The frequency of adverse reactions (% of patients) is indicated in parentheses: rasagiline / placebo.
Undesired reactions are distributed according to the following frequency: very often (? 1/10), often (? 1/100 to <1/10), infrequently (? 1/1000 to <1/100), rarely (? 1/10 000 to <1/1000), very rarely (<1/10 000).
Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequently - skin melanoma (0.5% / 0.3%).
From the side of metabolism and nutrition: often - a decrease in appetite (2.4% / 0.8%).
Mental disorders: often - hallucinations (2.9% / 2.1%), nightmarish dreams (2.1% / 0.8%); infrequently - confusion (0.8% / 0.5%).
From the nervous system: very often - dyskinesia (10.5% / 6.2%) , often - dystonia (2.4% / 0.8%), carpal tunnel syndrome (1.3% / 0%), imbalance (1.6% / 0.3%); infrequently - a disorder of cerebral circulation (0.5% / 0.3%).
From the cardiovascular system: infrequently - angina (0.5% / 0%); often - orthostatic hypotension (3.9% / 0.8%) .
From the digestive system: often - abdominal pain (4.2% / 1.3%), constipation (4.2% / 2.1%), nausea and vomiting (8.4% / 6.2%) , dry mouth (3.4% / 1.8%).
From the skin and subcutaneous tissues: often - a rash (1.1% / 0.3%).
From the musculoskeletal system: often - arthralgia (2.4% / 2.1%), pain in the neck (1.3% / 0.5%).
Other: often - weight loss (4.5% / 1.5%) , falls (4.7% / 3.4%).
With Parkinson's disease, hallucinations and confusion arise. According to the post-experience experience, these symptoms were noted in patients with Parkinson's disease who received rasagiline.
Serious adverse reactions that occur with the simultaneous use of SSRIs, SSRIs, tricyclic / tetracyclic antidepressants and MAO inhibitors are well known. In the post-marketing period, cases of development of serotonin syndrome, manifested in agitation, confusion, rigidity, fever and myoclonus, in patients taking antidepressants / SSRIs and rasagiline simultaneously were reported.
In clinical studies of rasagiline, simultaneous use of it with fluoxetine or fluvoxamine was not allowed. However, the following antidepressants were allowed in the indicated doses: amitriptyline not more than 50 mg / day, trazodone not more than 100 mg / day, citalopram not more than 20 mg / day, sertraline not more than 100 mg / day and paroxetine not more than 30 mg / day. In a clinical trial in which rasagiline was simultaneously used with tricyclic antidepressants (115 patients) and SSRIs / SSRIs (141 patients), no cases of serotonin syndrome were noted.
When rasagiline was used during the postgrade period, there was a reported increase in blood pressure, including rare cases of hypertensive crises, in patients using an unlimited number of products rich in tyramine in the diet.
There are cases of drug interaction with the simultaneous use of MAO inhibitors with sympathomimetic drugs.
In the post-marketing period, a case of increased blood pressure was reported in a patient who used an ophthalmic vasoconstrictor tetrahydrozoline and simultaneously received rasagiline treatment.
Impulsive personality disorder
There have been reports of increased libido, hypersexuality, gambling, compulsive need to buy or acquire, overeating and compulsive overeating in patients treated with dopamine receptor agonists and / or other dopaminomimetics. A similar pattern of impulsive personality disorder was observed in the post-marketing period in patients taking rasagiline, and was characterized by compulsive and impulsive behavior, obsessive ideas.
CONTRAINDICATIONS
- hypersensitivity to rasagiline or any of the components of the drug;
- simultaneous use with other MAO inhibitors (including drugs and food additives containing St. John's wort), pethidine. The break between the cancellation of rasagiline and the initiation of therapy with these drugs should be at least 14 days;
- hepatic insufficiency of moderate and severe degree (classes B and C on the Child-Pugh scale);
- Children and adolescence under 18 years (no data on effectiveness and safety).
Carefully
- Lung insufficiency of mild degree (class A on the Child-Pugh scale);
- simultaneous use with selective serotonin reuptake inhibitors (SSRIs) (including fluoxetine, fluvoxamine), selective serotonin and noradrenaline reuptake inhibitors (SSRIs), tricyclic and tetracyclic antidepressants, potent inhibitors of the CYP1A2 isoenzyme.
PREGNANCY AND LACTATION
Data on the use of rasagiline in pregnant women are absent. The results of animal studies do not indicate the presence of direct or indirect undesirable effects on pregnancy, embryo-fetal development, childbirth and postnatal development. If it is necessary to use rasagiline in pregnant women, it is necessary to correlate the expected benefit to the mother and the risk to the fetus.
According to experimental data, rasagiline inhibits the secretion of prolactin and, thus, can suppress lactation. Information on the penetration of rasagiline in breast milk is not available. If it is necessary to use rasagiline during breastfeeding, it is necessary to correlate the expected benefit to the mother and child.
APPLICATION FOR FUNCTIONS OF THE LIVER
The parameters of rasagiline pharmacokinetics practically do not change in patients with mild and moderate renal insufficiency.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindicated in moderate or severe hepatic insufficiency (class B and C on the Child-Pugh scale).
APPLICATION FOR CHILDREN
Contraindicated: children and adolescence under 18 years.
SPECIAL INSTRUCTIONS
Avoid simultaneous use of the drug Azilect and fluoxetine or fluvoxamine. The interval between the abolition of fluoxetine and the initiation of Azilect treatment should be 5 weeks, and between the cancellation of Azilect and the onset of fluoxetine or fluvoxamine 14 days.
Cases of impulsive personality disorder have been reported in patients treated with dopamine receptor agonists and / or other dopaminomimetics. The same disorders were observed in the post-marketing period in patients taking the drug Azilect. It is necessary to observe patients, in connection with the possibility of developing an impulsive personality disorder. Patients and carers should be informed of the potential for behavioral disorders in patients taking Azilekt, including compulsive behavior, obsessions, gambling, increased libido, hypersexuality, impulsive behavior, and compulsive needs to buy or purchase.
Simultaneous use of the drug Azilekt with dextromethorphan, with sympathomimetics or complex anti-cold medications for oral administration or for nasal use, containing ephedrine or pseudoephedrine, is not recommended.
There is evidence that Parkinson's disease, rather than the use of any drug, incl. drug Azilekt, is a risk factor for the development of skin cancer, in particular melanoma. It is necessary to warn
patient about the need to consult a doctor if any pathological changes in the skin occur.
It must be borne in mind that such symptoms as hallucinations and confusion that appear against the background of Azilect treatment can be considered both as a manifestation of Parkinson's disease and as undesirable reactions of the drug Azilect.
It is necessary to use with caution the drug Azilect in patients with mild hepatic insufficiency. The use of Azilekt in patients with moderate impairment of liver function is not recommended. In case of a change in the severity of liver failure from mild to moderate, the use of Azilect should be discontinued.
Impact on the ability to drive vehicles and manage mechanisms
The study of the influence of rasagiline on the ability to control vehicles and mechanisms was not carried out. However, given the possibility of significant side effects from the CNS, during the treatment with Azilect, patients should be informed of the need to exercise caution when driving vehicles and engage in potentially dangerous activities that require a high concentration of attention and speed of psychomotor reactions until they are certified , that the drug does not have a negative effect.
OVERDOSE
Symptoms of drug overdose Azilect are similar to those in overdose with non-selective MAO inhibitors (including arterial hypertension, postural hypotension).
Treatment: gastric lavage, reception of activated charcoal, symptomatic therapy. There is no specific antidote.
DRUG INTERACTION
Simultaneous use of rasagiline with other MAO inhibitors, incl. with medicinal preparations and food additives containing St. John's wort, is contraindicated, since there is a risk of developing a severe hypertensive crisis due to nonselective MAO inhibition.
The development of serious adverse reactions with the concomitant use of pethidine and MAO inhibitors has been reported, among others. selective MAO-B inhibitors. The simultaneous use of rasagiline and pethidine is contraindicated.
It was reported on the interaction of MAO inhibitors and sympathomimetic drugs in their simultaneous application. Due to the rasagiline property of MAO inhibition, the simultaneous use of rasagiline with sympathomimetics, such as decongestants or complex anti-cold medications for oral or nasal administration, containing ephedrine or pseudoephedrine is not recommended.
It was reported on the interaction of dextromethorphan and indiscriminate MAO inhibitors during their simultaneous application. Due to the property of rasagiline to inhibit MAO, the simultaneous use of rasagiline with dextromethorphan and the combined drugs containing it is not recommended.
The simultaneous use of rasagiline with fluoxetine or fluvoxamine should be avoided. The break between the cancellation of rasagiline and the initiation of therapy with these drugs should be at least 14 days. After discontinuation of treatment with fluoxetine or fluvoxamine (long half-life) and treatment with rasagiline should be at least 5 weeks.
Information on the simultaneous use of SSRIs / SSRIs and rasagiline in clinical trials is presented in the "Side effect" section.
The development of serious adverse reactions with the simultaneous use of SSRIs, SSRIs, tricyclics and tetracyclic antidepressants with MAO inhibitors has been reported.
In view of the property of rasagiline to inhibit MAO, care must be taken when it is used simultaneously with SSRIs, SSRIs, tricyclics and tetracyclic antidepressants.
In patients with Parkinson's disease, long-term receiving levodopa, as an auxiliary therapy, levodopa had no significant effect on the clearance of rasagiline.
In vitro studies have shown that the main enzyme involved in the metabolism of rasagiline is the isoenzyme CYP1A2. Simultaneous use of ciprofloxacin and rasagiline increases the AUC of the latter by 83%.
The simultaneous use of rasagiline and theophylline (the substrate of the isoenzyme CYP1A2) did not affect the pharmacokinetics of either of them. Thus, potent inhibitors of the CYP1A2 isoenzyme can alter the plasma concentration of rasagiline and require careful simultaneous application.
There is a risk that, in connection with the CYP1A2 isoenzyme induction in smokers may decrease rasagiline plasma concentration.
Studies in vitro have shown that rasagiline at a concentration of 1 .mu.g / ml (equivalent to a concentration greater than 160 times the average C max (5.9-8.5 ng / ml) after repeated administration of 1 mg rasagiline patients with Parkinson's disease) does not inhibit isozymes CYP1A2, CYP2A6 , CYP2C9, CYP2C19, CYP2D6, CYP2E1 , CYP3A4 and CYP4A. This suggests that therapeutic concentrations of rasagiline is likely not affected by clinically significant effect substrates of these isoenzymes.
With simultaneous application of rasagiline with entacapone increased clearance at the last 28%.
Clinical studies of the interaction of tyramine and rasagiline volunteers and patients with Parkinson's disease (0.5-1 mg / day rasagiline or placebo as adjunctive therapy to levodopa for 6 months without receiving restrictions tyramine) have shown that any interaction between rasagiline and tyramine absent, and rasagiline can be used safely without tyramine restrictions in the diet.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
AZIL-RU-NP-00001-DOC-PHARM-19082016
TERMS AND CONDITIONS OF STORAGE
The drug should be stored in reach of children at a temperature not higher than 25 ° C. Shelf life - 3 years.
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