Razagilin (Rasagilinum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Dopaminomimetics

Anti-Parkinsonics

Included in the formulation
  • Azilect®
    pills inwards 
    Teva Pharmaceutical Enterprises Co., Ltd.     Israel
  • Razagilin Mediabsor
    pills inwards 
    MEDISORB, CJSC     Russia
    • АТХ:

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

    N.04.B.D.02   Razagilin

    Pharmacodynamics:Antiparkinsona selective irreversible inhibitor of MAO type B, which determines the activity of MAO in the brain and the metabolism of dopamine by 80%. Increases the concentration of dopamine, reduces the formation of toxic free radicals, excessive formation of which is observed in Parkinson's disease. Razagilin possesses neuroprotectivem action in therapeutic doses does not block the metabolism of biogenic amines fed from food (including tyramine), and therefore does not cause tyramine-dependenthypertensive syndrome.
    Pharmacokinetics:Absorption rapid, absolute bioavailability after a single application - 36%. The maximum concentration is achieved after 0.5 h. The food does not affect the maximum concentration, however, with the intake of fatty foods, the maximum concentration and AUC decrease by 60% and 20%, respectively. Pharmacokinetics is linear in the dose range of 0.5-2 mg. The connection with proteins is 60-70%. Metabolized in the liver by N-dealkylatedand / or hydroxylationI with the formation of the main biologically inactive metabolite - 1-aminoindane, as well as 2 other metabolites - 3-hydroxy-M-propargyl-1-aminoinand Z-hydroxy-1-abutindan. Metabolism is carried out with the participation of the isoenzyme CYP1A2. The half-life is 0.6-2 hours. It is excreted by the kidneys (more than 60%), by the intestine (more than 20%). Less than 1% of the administered dose is excreted unchanged. With mild hepatic insufficiency, the AUC and maximum concentration values ​​can increase by 80% and 38%, respectively; with moderate hepatic impairment - more than 500% and 80%, respectively.
    Indications:Parkinson's disease (monotherapy or as part of combination therapy with levodopa).
    ICD-10

    VI.G20-G26.G20   Parkinson's disease

    Contraindications:Hypersensitivitymoderate or severe hepatic insufficiency (on the Child-Pugh scale), pheochromocytoma.
    Concomitant therapy with pethidine or other MAO inhibitors, fluoxetine and fluvoxamine (a break between the withdrawal of rasagiline and the initiation of therapy with these drugs should be at least 14 days), with decongestants, sympathomimetics    and (including with drugs containing them), dextromethorphanm.
    Pregnancy, lactation (risk of suppression of lactation against the background of inhibition of prolactin formation), children and adolescence (up to 18 years).
    Carefully:Hepatic insufficiency of mild degree, joint administration with tricyclic and tetracyclicand antidepressantsand, by powerful inhibitors of CYP1A2.
    Pregnancy and lactation:Recommendations for FDA - Category C. Contraindicated in pregnancy and lactation (breastfeeding).
    Dosing and Administration:Accepted inwards, regardless of food intake in a dose of 1 mg once a day, for a long time.
    Side effects:

    With rasagiline monotherapy

    From the side nervous system: headaches, depression, dizziness, anorexia, convulsions, hallucinations; rarely - cerebrovascular accident.

    From the side digestive system: decreased appetite, dyspeptic phenomena.

    From the side musculoskeletal system: arthralgia, arthritis, pain in the neck.

    Dermatological reactions: vesicle-bulbous rash, contact dermatitis; rarely - skin carcinoma.

    From the side of cardio-vascular system: angina pectoris; rarely - myocardial infarction.

    Other: flu-like syndrome, fever, leukopenia, rhinitis, general weakness, conjunctivitis, acute disorders of the urinary system, allergic reactions.

    When combined with levodopa

    From the side nervous system: dyskinesia, muscular dystonia, anorexia, unusual dreams, ataxia, hallucinations; rarely - a violation of cerebral circulation, confusion.

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

    From the side musculoskeletal system: arthralgia, pain in the neck, tenosynovitis.

    Dermatological reactions: rash; rarely - skin melanoma.

    From the side of cardio-vascular system: postural hypotension; rarely - angina.

    Other: accidental falls, weight loss, allergic reactions.

    Overdose:

    Symptoms: are similar to those in overdose of indiscriminate MAO inhibitors (including arterial hypertension, postural hypotension).

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

    Interaction:

    Levodopa + Benserazide. A combination is possible; it is recommended that the dose of levodopa be adjusted depending on efficacy and tolerability.

    Fluvoxamine, Fluoxetine. With the simultaneous use of rasagiline with serotonin reuptake inhibitors (including fluoxetine, fluvoxamine), tricyclic and tetracyclic antidepressants, MAO inhibitors possibly the development of serotonin syndrome, manifested in confusion, hypomanic state, motor anxiety, chills, tremors, diarrhea. Wherever possible, combined use should be avoided and, if necessary, simultaneous application, increased precautions should be envisaged.

    Ciprofloxacin. Due to the fact that the cytochrome P450 isoenzyme CYP1A2 is involved in the metabolism of rasagiline, ciprofloxacin (active inhibitor of CYP1A2) can increase the concentration of rasagiline in the blood plasma, which requires caution when combining ciprofloxacin with rasagiline. Rclaim of hypertensive crisis development.

    It is also not recommended that the combined use of rasagiline with sympathomimetic drugs, including ephedrine, pseudoephedrine, contained in preparations for the treatment of rhinitis or the common cold. In addition, the use of rasagiline with dextromethorphan and its combined agents is not recommended.

    Special instructions:

    The use of rasagiline in the recommended therapeutic dose does not cause a tyramine syndrome ("cheese" effect), which allows patients without restrictions to use in food products containing significant amounts of tyramine (cheeses, chocolate).

    There is evidence that Parkinson's disease, and not the use of any drug, including rasagiline, is a risk factor for the development of skin cancer, in particular melanoma. It is necessary to warn the patient about the need to consult a doctor at occurrence of any pathological changes of integuments.

    It should be borne in mind that symptoms such as hallucinations and confusion that appear on the background of rasagiline treatment, can be regarded as a manifestation of Parkinson's disease, and as side effects of rasagiline.

    Impact on the ability to drive vehicles and manage mechanisms

    Given the possibility of significant side effects from the central nervous system, during treatment with rasagiline, care must be taken when driving vehicles and engaging in potentially dangerous activities requiring increased concentration and speed of psychomotor reactions.

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