Composition, structure and packing
Tablets are white or nearly white, round, ploskotsilindricheskie, with beveled and etched "GIL 1" on one side.
1 tab. razagilina mesilate 1.56 mg, which corresponds to the content razagilina 1 mg.
Excipients: mannitol, colloidal silicon dioxide, corn starch, corn starch pregelatinized, stearic acid, talc.
Clinico-pharmacological group: antiparkinsonian drug - a selective MAO inhibitors of type B.
Pharmacological action
Antiparkinsonian medication. Selective irreversible MAO type B enzyme, 80% is determined by the activity of MAO in the brain and metabolism of dopamine. Razagilin in 30-80 times more active on MAO type B compared with MAO type A.
As a result of the inhibiting action of the drug on the type of MAO B in the central nervous system increases dopamine levels, decreases the formation of toxic free radicals, excessive formation of which occurs in Parkinson's disease. Razagilin also has a neuroprotective effect.
Unlike the nonselective MAO inhibitors, the drug at therapeutic doses does not block the metabolism of incoming dietary biogenic amines (eg tyramine), and therefore is not due to tyramine-hypertensive syndrome ("cheese effect").
Pharmacokinetics
Absorption
Razagilin rapidly absorbed after oral administration, Cmax plasma levels achieved after 0.5 h. The absolute bioavailability after a single administration is about 36%. Food does not affect the time to achieve Cmax razagilina in blood, however, when fat intake reduces Cmax and AUC of 60% and 20% respectively.
Distribution
Pharmacokinetics is linear within the dose range 0.5-2 mg. Relationship to plasma proteins ranges from 60% to 70%.
Metabolism
Razagilin almost completely metabolized in the liver. Biotransformation is carried out by N-dealkylation and / or hydroxylation with the formation of basic biological metabolite fallow period - 1-aminoindana, as well as two other metabolites - 3-hydroxy-N-propargyl-1-aminoindana and 3-hydroxy-1-aminoindana. The metabolism of the drug carried out with the participation of isoenzyme 1A2 of cytochrome P450.
Withdrawal
Razagilin derived primarily by the kidneys (60%) and to a lesser extent through the intestine (20%). Less than 1% of the administered dose of the drug is released in unchanged form. T1 / 2 was 0.6-2 h.
Pharmacokinetics in special clinical situations
Pharmacokinetic Parameters razagilina virtually unchanged in patients with renal insufficiency with mild and moderate.
When liver failure may occur mild increase in the parameters AUC and Cmax by 80% and 38%, while patients with moderate hepatic impairment, these parameters reach more than 500% and 80% respectively.
Statement
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, long time. The tablets are inside, regardless of the meal.
Side effect
These side effects occurred with a frequency of more than 1 / 100, side effects encountered with a frequency of 1 / 100 - 1 / 1000 are listed as rare.
Monotherapy razagilinom:
From the CNS: headaches, depression, dizziness, anorexia, convulsions, rarely - and cerebral blood flow.
On the part of the digestive system: loss of appetite, dyspeptic phenomena.
From the Musculoskeletal System: arthralgia, arthritis, pain around the neck. Dermatological reactions: vezikulobulleznaya rashes, contact dermatitis, rarely - carcinoma of the skin.
Since the cardiovascular system: angina pectoris; rarely - myocardial infarction.
Other: flu-like syndrome, fever, leukopenia, rhinitis, weakness, conjunctivitis, dysuria, allergic reactions.
In the application, together with levodopa:
From the central nervous system and peripheral nervous system: dyskinesia, muscle dystonia, anorexia, unusual dreams, ataxia, rarely - and cerebral blood flow.
On the part of the digestive system: constipation, vomiting, abdominal pain, dry mouth.
From the Musculoskeletal System: arthralgia, pain in the neck, peritendinitis.
Dermatological reactions: rash, rarely - melanoma of the skin.
Since the cardiovascular system: postural hypotension; rarely - angina.
Other: accidental falls, weight loss, allergic reactions.
Contraindications
concomitant therapy pethidine or other MAO inhibitors (a break between the lifting razagilina and the beginning of therapy these medicines should not be less than 14 days);
moderate or severe hepatic impairment (class B and C on the scale of Child-Pugh);
co-therapy with sympathomimetics (ephedrine, pseudoephedrine), other decongestants, dextromethorphan, and with drugs containing them;
pheochromocytoma;
childhood and adolescence to 18 years;
Pregnancy
Lactation (milk production risk of oppression against the background of inhibition of Education prolactin);
Hypersensitivity to razagilinu or to any of the components of the drug.
With care prescribers in mild hepatic insufficiency, with a joint reception with selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine), tricyclic and tetracyclic antidepressants, active inhibitors of cytochrome P450 1A2 isoform.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Application for violations of liver function
Contraindicated in moderate or severe hepatic insufficiency (Class B and C on the scale of Child-Pugh).
Application for violations of renal function
Pharmacokinetic Parameters razagilina virtually unchanged in patients with renal insufficiency with mild and moderate.
Cautions
Application
Azilekta at the recommended therapeutic dose does not cause "tiraminovogo syndrome" ("cheese effect") that allows patients to use without any restrictions in food products containing significant amount of tyramine (cheese, chocolate).
Effects on ability to drive vehicles and management mechanisms
The influence of razagilina on driving and managing other mechanisms was conducted.
Overdose
Symptoms of overdosing Azilekt similar to those of an overdose of non-selective MAO inhibitors (including hypertension, postural hypotension).
Treatment: gastric lavage, activated charcoal method, symptomatic therapy. No specific antidote.
Drug Interactions
Due to the fact that the mechanism of action razagilina associated with inhibition of MAO, it should not be prescribed concomitantly with other inhibitors of this enzyme because of the risk of hypertensive crisis.
With simultaneous application of razagilina with serotonin reuptake inhibitors (fluoxetine, fluvoxamine), tricyclic and tetracyclic antidepressants may develop "serotonin syndrome" when in confusion, hypomanic, restlessness, shivering, tremor, diarrhea. If possible, avoid combined use razagilina with similar drugs, and if necessary their simultaneous use should provide increased precautions.
Due to the fact that the isoform of the enzyme cytochrome P450 1A2 (CYP1A2) participates in the metabolism of razagilina, active inhibitors of this enzyme (eg, ciprofloxacin) can increase the concentration of drug in plasma that determines caution when combining these drugs with razagilinom. Patients with Parkinson's disease use of levodopa does not affect the clearance razagilina.
Terms and Conditions of storage
The drug should be stored out of reach of children at or above 25 ° C.
Shelf life - 3 years.
Tablets are white or nearly white, round, ploskotsilindricheskie, with beveled and etched "GIL 1" on one side.
1 tab. razagilina mesilate 1.56 mg, which corresponds to the content razagilina 1 mg.
Excipients: mannitol, colloidal silicon dioxide, corn starch, corn starch pregelatinized, stearic acid, talc.
Clinico-pharmacological group: antiparkinsonian drug - a selective MAO inhibitors of type B.
Pharmacological action
Antiparkinsonian medication. Selective irreversible MAO type B enzyme, 80% is determined by the activity of MAO in the brain and metabolism of dopamine. Razagilin in 30-80 times more active on MAO type B compared with MAO type A.
As a result of the inhibiting action of the drug on the type of MAO B in the central nervous system increases dopamine levels, decreases the formation of toxic free radicals, excessive formation of which occurs in Parkinson's disease. Razagilin also has a neuroprotective effect.
Unlike the nonselective MAO inhibitors, the drug at therapeutic doses does not block the metabolism of incoming dietary biogenic amines (eg tyramine), and therefore is not due to tyramine-hypertensive syndrome ("cheese effect").
Pharmacokinetics
Absorption
Razagilin rapidly absorbed after oral administration, Cmax plasma levels achieved after 0.5 h. The absolute bioavailability after a single administration is about 36%. Food does not affect the time to achieve Cmax razagilina in blood, however, when fat intake reduces Cmax and AUC of 60% and 20% respectively.
Distribution
Pharmacokinetics is linear within the dose range 0.5-2 mg. Relationship to plasma proteins ranges from 60% to 70%.
Metabolism
Razagilin almost completely metabolized in the liver. Biotransformation is carried out by N-dealkylation and / or hydroxylation with the formation of basic biological metabolite fallow period - 1-aminoindana, as well as two other metabolites - 3-hydroxy-N-propargyl-1-aminoindana and 3-hydroxy-1-aminoindana. The metabolism of the drug carried out with the participation of isoenzyme 1A2 of cytochrome P450.
Withdrawal
Razagilin derived primarily by the kidneys (60%) and to a lesser extent through the intestine (20%). Less than 1% of the administered dose of the drug is released in unchanged form. T1 / 2 was 0.6-2 h.
Pharmacokinetics in special clinical situations
Pharmacokinetic Parameters razagilina virtually unchanged in patients with renal insufficiency with mild and moderate.
When liver failure may occur mild increase in the parameters AUC and Cmax by 80% and 38%, while patients with moderate hepatic impairment, these parameters reach more than 500% and 80% respectively.
Statement
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, long time. The tablets are inside, regardless of the meal.
Side effect
These side effects occurred with a frequency of more than 1 / 100, side effects encountered with a frequency of 1 / 100 - 1 / 1000 are listed as rare.
Monotherapy razagilinom:
From the CNS: headaches, depression, dizziness, anorexia, convulsions, rarely - and cerebral blood flow.
On the part of the digestive system: loss of appetite, dyspeptic phenomena.
From the Musculoskeletal System: arthralgia, arthritis, pain around the neck. Dermatological reactions: vezikulobulleznaya rashes, contact dermatitis, rarely - carcinoma of the skin.
Since the cardiovascular system: angina pectoris; rarely - myocardial infarction.
Other: flu-like syndrome, fever, leukopenia, rhinitis, weakness, conjunctivitis, dysuria, allergic reactions.
In the application, together with levodopa:
From the central nervous system and peripheral nervous system: dyskinesia, muscle dystonia, anorexia, unusual dreams, ataxia, rarely - and cerebral blood flow.
On the part of the digestive system: constipation, vomiting, abdominal pain, dry mouth.
From the Musculoskeletal System: arthralgia, pain in the neck, peritendinitis.
Dermatological reactions: rash, rarely - melanoma of the skin.
Since the cardiovascular system: postural hypotension; rarely - angina.
Other: accidental falls, weight loss, allergic reactions.
Contraindications
concomitant therapy pethidine or other MAO inhibitors (a break between the lifting razagilina and the beginning of therapy these medicines should not be less than 14 days);
moderate or severe hepatic impairment (class B and C on the scale of Child-Pugh);
co-therapy with sympathomimetics (ephedrine, pseudoephedrine), other decongestants, dextromethorphan, and with drugs containing them;
pheochromocytoma;
childhood and adolescence to 18 years;
Pregnancy
Lactation (milk production risk of oppression against the background of inhibition of Education prolactin);
Hypersensitivity to razagilinu or to any of the components of the drug.
With care prescribers in mild hepatic insufficiency, with a joint reception with selective serotonin reuptake inhibitors (fluoxetine and fluvoxamine), tricyclic and tetracyclic antidepressants, active inhibitors of cytochrome P450 1A2 isoform.
Pregnancy and lactation
The drug is contraindicated during pregnancy and lactation.
Application for violations of liver function
Contraindicated in moderate or severe hepatic insufficiency (Class B and C on the scale of Child-Pugh).
Application for violations of renal function
Pharmacokinetic Parameters razagilina virtually unchanged in patients with renal insufficiency with mild and moderate.
Cautions
Application
Azilekta at the recommended therapeutic dose does not cause "tiraminovogo syndrome" ("cheese effect") that allows patients to use without any restrictions in food products containing significant amount of tyramine (cheese, chocolate).
Effects on ability to drive vehicles and management mechanisms
The influence of razagilina on driving and managing other mechanisms was conducted.
Overdose
Symptoms of overdosing Azilekt similar to those of an overdose of non-selective MAO inhibitors (including hypertension, postural hypotension).
Treatment: gastric lavage, activated charcoal method, symptomatic therapy. No specific antidote.
Drug Interactions
Due to the fact that the mechanism of action razagilina associated with inhibition of MAO, it should not be prescribed concomitantly with other inhibitors of this enzyme because of the risk of hypertensive crisis.
With simultaneous application of razagilina with serotonin reuptake inhibitors (fluoxetine, fluvoxamine), tricyclic and tetracyclic antidepressants may develop "serotonin syndrome" when in confusion, hypomanic, restlessness, shivering, tremor, diarrhea. If possible, avoid combined use razagilina with similar drugs, and if necessary their simultaneous use should provide increased precautions.
Due to the fact that the isoform of the enzyme cytochrome P450 1A2 (CYP1A2) participates in the metabolism of razagilina, active inhibitors of this enzyme (eg, ciprofloxacin) can increase the concentration of drug in plasma that determines caution when combining these drugs with razagilinom. Patients with Parkinson's disease use of levodopa does not affect the clearance razagilina.
Terms and Conditions of storage
The drug should be stored out of reach of children at or above 25 ° C.
Shelf life - 3 years.
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