Active substanceRazagilinRazagilin
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  • Razagilin Mediabsor
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    MEDISORB, CJSC     Russia
  • Dosage form: & nbsppills
    Composition:

    Composition per one tablet:

    active substance: rasagiline mesylate 1.56 mg (in terms of rasagiline 1.00 mg); Excipients: Mannitol, potato starch, starch pregelatinized, talc, magnesium stearate.

    Description:Round flat cylindrical tablets white or almost white with a bevel on both sides.
    Pharmacotherapeutic group:An antiparkinsonian drug is a selective monoamine oxidase (MAO) inhibitor of type B
    ATX: & nbsp

    N.04.B.D   Inhibitors of monoamine oxidase type B

    N.04.B.D.02   Razagilin

    Pharmacodynamics:

    An antiparkinsonian agent, an inhibitor of monoamine oxidase (MAO). Razagilin - selective irreversible inhibitor of MAO type B, an enzyme responsible for 80% of MAO activity in the brain and dopamine metabolism. Razagilin 30-80 times more active in relation to MAO type B. than to MAO type A.

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

    In contrast to non-selective MAO inhibitors, the drug in therapeutic doses does not block the metabolism of nutrient biogenic amines (for example, tyramine), and therefore does not cause a tyramine-mediated hypertensive syndrome ("cheese effect").

    Pharmacokinetics:

    Suction

    Razagilin is rapidly absorbed after oral administration, the maximum concentration (Cmah) in blood plasma is achieved after 0.5 h. Absolute bioavailability of the drug after a single administration is about 36%. Food does not affect the time to reach CmRasagiline in the blood, but when consuming fatty foods Cmand the value of the area under the curve "concentration - time" (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 Ndealkylation and / or hydroxylation to form the main biologically inactive metabolite, 1-aminoindane, as well as two other metabolites of 3-hydroxy-1-propargyl-1-aminoindane and 3-hydroxy-1-aminoindane. The drug is metabolized with the participation of the isoenzyme CYP1A2.

    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. The half-life period (T1 / 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.

    With mild liver failure, an increase in the values ​​of the parameters can be observed AUC and Cm80% and 38%, and in patients with moderate impairment 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).

    Contraindications:

    - Hypersensitivity to rasagiline and / or any other component of the drug;

    - simultaneous application 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 under 18 years of age (no data on effectiveness and safety).

    Carefully:Hepatic 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 isoenzyme CYP1A2.
    Pregnancy and lactation:

    There are no data on rasagiline in pregnant women. The results of the study on animals 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 estimated risk for the fetus.

    According to the experimental data rasagiline inhibits 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.

    Dosing and Administration:

    Take inside, regardless of food intake, at a dose of 1 mg 1 time per day, either with monotherapy or in combination with levodopa.

    Elderly patients

    Dose adjustments in elderly patients are not required.

    Patients with impaired hepatic function

    The use of rasagiline in patients with moderate or severe hepatic insufficiency is contraindicated.

    Care should be taken when using rasagiline in patients with mild hepatic insufficiency. If the progress of treatment with rasagiline marked progression of liver failure to an average degree, the drug should be discontinued.

    Patients with renal insufficiency

    Correction of the dose is not required.

    Side effects:

    The incidence of adverse reactions is classified according to the recommendations of the World Health Organization: very often (≥1 / 10); often (≥1 / 100, <1/10); infrequently (≥1 / 1000, <1/100); rarely (≥1 / 10000, <1/1000); very rarely (<1/10000), the frequency is unknown (the frequency of undesired reactions can not be estimated based on the available data).

    Monotherapy

    Infections and infestations: often - the flu.

    Benign, malignant and unspecified neoplasms (including cysts and polyps): often - skin cancer.

    Violations from the blood and lymphatic system: often - leukopenia.

    Immune system disorders: often - allergies.

    Metabolic and nutritional disorders: infrequent - a decrease in appetite.

    Mental disorders: often - depression, hallucinations.

    Impaired nervous system: very often - a headache, infrequently - a violation of cerebral circulation.

    Disorders from the side of the organ of vision: often - conjunctivitis.

    Violations from the organ of hearing and labyrinth: often - vertigo.

    Heart Disease: often - angina, infrequently - myocardial infarction.

    Disturbances from the respiratory system, chest and mediastinal organs: often - rhinitis

    Gastrointestinal disorders: often - bloating.

    Disorders from the rut and subcutaneous tissues: often - dermatitis, infrequently - a vesiculo-bullous rash.

    Disturbances from muscular, skeletal and connective tissue: often - musculoskeletal disease, neck pain, arthritis.

    Disorders from the kidneys and urinary tract: often - the urge to urinate. Common disorders and reactions at the site of administration: often - fever, malaise.

    When used as an auxiliary therapy:

    Benign, malignant and unspecified neoplasms (including cysts and polyps): infrequently - skin melanoma.

    Metabolic and nutritional disorders: often - a decrease in appetite.

    Mental disorders: often - hallucinations, nightmarish dreams, infrequently - confusion.

    Impaired nervous system: very often - dyskinesia, often - dystonia, carpal tunnel syndrome, imbalance, infrequently - impaired cerebral circulation.

    Heart Disease: infrequently - angina.

    Vascular disorders: often - orthostatic hypotension.

    Gastrointestinal disorders: often - abdominal pain, constipation, nausea and vomiting, dry mouth.

    Disturbances from the skin and subcutaneous tissues: often - a rash.

    Disturbances from muscular, skeletal and connective tissue: often - arthralgia, pain in the neck.

    Common disorders and reactions at the site of administration: often - weight loss.

    Injuries, intoxications and complications of procedures: often - falls.

    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.

    There is evidence of clinical trials of rasagiline, in which simultaneous use with fluoxetine or fluvoxamine was not allowed. However, the following antidepressants were allowed in these doses: amitriptyline no 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 research program in which rasagiline was simultaneously used with tricyclic antidepressants (115 patients) and SSRIs / SSRIs (141 patients), cases of serotonin syndrome were not observed.

    When rasagiline was used during the postgistribution period, it was reported that blood pressure (BP) increased, including rare cases of hypertensive crises, in patients using an undefined 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 and purchase, overeating and compulsive overeating in patients treated with dopamine receptor agonists and / or other dopaminomimetics. A similar picture of impulsive personality disorder was observed in the post-marketing period in patients taking rasagiline, which was characterized by compulsive and impulsive behavior, obsessive ideas.

    It is important to report suspected adverse reactions with a view to ensuring continuous monitoring of the relationship between the benefits and risks of the drug. If you experience any undesirable reactions, contact your doctor, a pharmacy worker or a manufacturer. Medical workers are advised to report any suspected adverse drug reactions through national systems reporting unwanted reactions.

    Overdose:

    Symptoms rasagiline overdoses are similar to those in overdose with nonselective MAO inhibitors (including arterial hypertension, postural hypotension).

    Treatment: gastric lavage, reception of activated charcoal, symptomatic therapy. There is no specific antidote.

    Interaction:

    The simultaneous use of rasagiline with other MAO inhibitors, including drugs 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.

    There have been reports of the development of serious adverse reactions with simultaneous use of pethidine and MAO inhibitors,including selective MAO inhibitors of type B. 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, simultaneous use of rasagiline with sympathomimetics, such as decongestants or complex anti-cold medications for oral or nasal use, 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 studies in vitro It is shown that the main enzyme involved in the metabolism of rasagiline is isoenzyme CYP1A2. Simultaneous use of ciprofloxacin and rasagiline increases AUC the latter by 83%. The simultaneous use of rasagiline and theophylline (substrate isoenzyme CYP1A2) did not affect the pharmacokinetics of any of them. Thus, potent inhibitors of the isoenzyme CYP1A2 can change the plasma concentration of rasagiline and require careful simultaneous application.

    There is a risk that, due to induction of the isoenzyme CYP1A2 in smokers, the concentration of rasagiline in the blood plasma may decrease.

    Research in vitro showed that rasagiline in a concentration of 1 μg / ml (which is equivalent to a concentration exceeding 160 times the average Cmah (5.9-8.5 ng / ml) after repeated administration of 1 mg rasagiline in patients with Parkinson's disease) does not inhibit isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2A19, CYP2D6, CYP2E1, CYP3A4, CYP4A. This shows that. that the therapeutic concentrations of rasagiline are most likely not affected by the clinically significant effect of the substrates of these isoenzymes.

    With the simultaneous use of entacapone with rasagiline, the clearance of the latter increases by 28%.

    Clinical studies of the interaction of tyramine and rasagiline in volunteers and patients with Parkinson's disease (0.5-1 mg / day rasagiline or placebo as an additional therapy for levodopa for 6 months without restriction of tyramine intake) have shown that any interaction of rasagiline can be safely apply without limitation of tyramine in the diet.

    Special instructions:

    Avoid simultaneous use of rasagiline and fluoxetine or fluvoxamine (see section "Interaction with other drugs"). The interval between the elimination of fluoxetine and the initiation of rasagiline treatment should be 5 weeks, and between the withdrawal of rasagiline 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 rasagiline. 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 possibility of developing behavioral disorders in patients taking rasagiline. including compulsive behavior, obsessions, gambling, increased libido, hypersexuality, impulsive behavior, or compulsive needs to buy or acquire.

    The simultaneous use of rasagiline with dextromethorphan, with sympathomimetics or complex anti-cold medications for oral or nasal administration, containing ephedrine or pseudoephedrine, is not recommended (see section "Interaction with other medicinal products").

    There is evidence that Parkinson's disease, and not the use of any drug, including rasagiline, is a risk factor for skin cancer, in particular melanoma (see "Side effect" section). It is necessary to warn the patient about the need to consult a doctor if any pathological changes in the skin occur.

    It should be borne in mind that such symptoms as hallucinations and confusion that appear on the background of rasagiline treatment can be considered both as a manifestation of Parkinson's disease and as undesirable reactions of rasagiline (see "Side effect" section).

    It is necessary to use caution rasagiline in patients with mild hepatic insufficiency. The use of rasagiline in patients with moderate impairment of liver function is not recommended. In the case of a change in the severity of liver failure from mild to moderate, rasagiline should be discontinued (see section "Pharmacological properties" ("Pharmacokinetics")).
    Effect on the ability to drive transp. cf. and fur:

    The study of the influence of rasagiline on the ability to manage vehicles and mechanisms was not carried out.

    However, taking into account the possibility of significant side effects from the central nervous system, during the treatment with the drug should inform patients about the need to take care when driving vehicles and engage in potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions until they make sure that the drug does not have a negative effect.

    Form release / dosage:Tablets 1 mg.
    Packaging:

    For 7, 10 or 14 tablets in a contour mesh package.

    For 30, 50 or 100 tablets in cans of polymer with a lid.

    Each jar or 1, 2, 3, 4 contour squares, together with instructions for use, are placed in a pack of cardboard boxes.

    Storage conditions:

    At a temperature of no higher than 25 ° C

    Keep out of the reach of children.
    Shelf life:3 years.
    Terms of leave from pharmacies:On prescription
    Registration number:LP-004820
    Date of registration:23.04.2018
    Expiration Date:23.04.2023
    The owner of the registration certificate:MEDISORB, CJSC MEDISORB, CJSC Russia
    Manufacturer: & nbsp
    Information update date: & nbsp05.06.2018
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