Azilect pills 1mg, 100pcs

Composition

Tablets are white or almost white in color, round, flat-cylindrical, chamfered, with the inscription “GIL 1” on one side of the tablet.

1 tab. rasagiline mesylate 1.56 mg, which corresponds to the rasagiline content of 1 mg

Excipients:

mannitol-159.24 mg,

colloidal silicon dioxide-1.2 mg,

corn starch-20 mg,

pregelatinized corn starch-20 mg,

stearic acid-4 mg,

talc-4 mg

Pharmacological action

inhibitory MAO-B, antiparkinsonian.

Rasagiline is a selective irreversible inhibitor of MAO type B, an enzyme that controls 80% of MAO activity in the brain and dopamine metabolism. Rasagiline is 30-80 times more active against MAO-B, than to another type of this enzyme-MAO-A.

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

Unlike non-selective MAO inhibitors, the drug in therapeutic doses does not block the metabolism of biogenic amines (for example, tyramine) coming from food, and therefore does not cause tyramine-related hypertensive syndrome (“cheese effect”).

Indications

Monotherapy or combination therapy of Parkinson’s disease (with levodopa).

Use during pregnancy and lactation

There are no data on the use of rasagiline in pregnant women. The results of animal studies do not indicate the presence of direct or indirect undesirable effects on pregnancy, embryophetal development, childbirth and postnatal development. When using 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 prolactin secretion and, thus, can suppress lactation. There are no data on the penetration of rasagiline into breast milk.

If it is necessary to use rasagiline during breastfeeding, it is necessary to correlate the expected benefits for the mother and child.

Contraindications

hypersensitivity to rasagiline or any of the components of the drug;

simultaneous use with other MAO inhibitors (including medicines and food additives containing St. John’s wort), pethidine. The interval between the withdrawal of rasagiline and the start of therapy with these drugs should be at least 14 days;

moderate to severe hepatic insufficiency (Child-Pugh classes B and C);

children under 18 years of age (no data on efficacy and safety).

With caution:  mild hepatic insufficiency (Child-Pugh class A); concomitant use with SSRIs (including fluoxetine, fluvoxamine), SSRIs, tricyclic and tetracyclic antidepressants, powerful inhibitors of the isoenzyme CYP1A2.

Side effects

Monotherapy

The following list describes adverse reactions that were reported with increased frequency in placebo-controlled studies in patients receiving 1 mg/day of rasagiline (rasagiline group-n=149, placebo group-n=151).

Adverse reactions with differences of more than 2% compared to the placebo group are shown in italics. The frequency of adverse reactions (% of patients) to rasagiline/placebo is shown in parentheses.

Adverse reactions are distributed according to the following frequency: very often — not less than 10%; often — not less than 1%, but less than 10%; infrequently — not less than 0.1%, but less than 1%; rarely — not less than 0.01%, but less than 0.1%; very rarely — less than 0.01%.

Infections and infestations:  often — flu (4.7/0.7%).

Benign, malignant, and unspecified neoplasms (including cysts and polyps):  often — skin cancer (1.3/0.7%).

Blood and lymphatic system disorders:  often-leukopenia (1,3/0%).

From the immune system:  often-allergies (1,3/0,7%).

From the side of metabolism and nutrition:  infrequently-decreased appetite (0.7 / 0%).

Mental disorders:  often — depression (5.4 / 2%), hallucinations (1.3/0.7%).

Nervous system disorders:  very often — headache (14.1 / 11.9%); infrequently — cerebrovascular accident (0.7/ 0%).

From the side of the visual organ:  often — conjunctivitis (2.7/0.7%).

From the side of the organ of hearing and balance:  often — vertigo (2.7/1.3%).

From the side of the heart:  often-angina pectoris (1.3 / 0%); infrequently — myocardial infarction (0.7/0%).

Respiratory, thoracic and mediastinal disorders:  often-rhinitis (3,4/0,7%).

From the digestive system:  often — bloating (1,3 / 0%).

Skin and subcutaneous tissue disorders:  often-dermatitis (2/0%); infrequently — vesicular bullous rash (0.7/0%).

Musculoskeletal and connective tissue disorders:  often-musculoskeletal pain (6.7 / 2.6%), neck pain (2.7/0%), arthritis (1.3/0.7%).

From the side of the kidneys and urinary tract:  frequent urge to urinate (1.3/0.7%).

General disorders and disorders at the injection site:  often — fever (2.7 / 1.3%), malaise (2/0%).

When used as adjunctive therapy

The following list includes adverse reactions that were reported with increased frequency in placebo-controlled trials in patients receiving 1 mg/day of rasagiline (rasagiline group-n=380, placebo group-n=388). The frequency of adverse reactions (% of patients) to rasagiline/placebo is shown in parentheses.

Adverse reactions are distributed according to the following frequency: very often — not less than 10%; often — not less than 1%, but less than 10%; infrequently — not less than 0.1%, but less than 1%; rarely — not less than 0.01%, but less than 0.1%; very rarely — less than 0.01%.

Benign, malignant, and unspecified neoplasms (including cysts and polyps):  infrequently-skin melanoma (0.5/0.3%).

From the side of metabolism and nutrition:  often-decreased appetite (2.4/0.8%).

Mental disorders:  often-hallucinations (2.9 / 2.1%), dream disturbances (2.1/0.8%); infrequently — confusion (0.8/0.5%).

Nervous system disorders:  very often — dyskinesia (10.5/6.2%); often — dystonia (2.4/0.8%), carpal tunnel syndrome (1.3/0%), balance disorder (1.6/0.3%); infrequently — cerebrovascular accident (0.5/0.3%).

From the side of the heart:  infrequently-angina pectoris (0.5/0%).

From the side of blood vessels:  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%).

Skin and subcutaneous tissue disorders:  often-rash (1.1/0.3%).

Musculoskeletal and connective tissue disorders:  often-arthralgia (2.4/2.1%), neck pain (1.3/0.5%).

Research results:  often — weight loss (4.5 / 1.5%).

Injuries, poisoning and complications of procedures:  often-falls (4.7/3.4%).

Parkinson’s disease causes hallucinations and confusion. According to post-marketing experience, these symptoms were observed in patients with Parkinson’s disease treated with rasagiline.

About serious adverse reactions that occur with simultaneous use SSRIs, SSRIs, tricyclic / tetracyclic antidepressants and inhibitors MAO is well known. In the post-marketing period, cases of serotonin syndrome, manifested in agitation, confusion, rigidity, fever, and myoclonus, have been reported in patients taking concomitant antidepressants/SSRIs and rasagiline.

In clinical studies of rasagiline, concomitant use of it with fluoxetine or fluvoxamine was not allowed. However, the following antidepressants were allowed in the indicated doses: amitriptyline-no more than 50 mg / day, trazodone – no more than 100 mg/day, citalopram-no more than 20 mg / day, sertraline-no more than 100 mg / day and paroxetine-no more than 30 mg / day. In a clinical trial program in which rasagiline was co-administered with tricyclic antidepressants (115 patients) and SSRIs/SSRIs (141 patients), there were no cases of serotonin syndrome.

When using rasagiline in the post-marketing period, an increase in the use of rasagiline in the post-marketing period has been reported. Blood pressure, including rare cases of hypertensive crises, in patients who use an indefinite amount of tyramine-rich foods in their diet.

There are known 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. Blood pressure in a patient who used the ophthalmic vasoconstrictor tetrahydrozoline and simultaneously received treatment.

Interaction

Concomitant use of rasagiline with other MAO inhibitors, including medications and food additives containing St. John’s wort, is contraindicated, since there is a risk of developing a severe hypertensive crisis due to non-selective MAO inhibition.

Serious adverse reactions have been reported with concomitant use of pethidine and MAO inhibitors, including selective inhibitors MAO-V. Concomitant use of rasagiline and pethidine is contraindicated.

Inhibitor interactions have been reported MAO and sympathomimetic drugs with their simultaneous use. Due to the property of rasagiline to inhibit MAO, concomitant use of rasagiline with sympathomimetics, such as decongestants or complex antipruritic drugs for oral or nasal use containing ephedrine or pseudoephedrine, is not recommended.

Interactions between dextromethorphan and non-selective inhibitors have been reported MAO with their simultaneous use. Due to the property of rasagiline to inhibit MAO, concomitant use of rasagiline with dextromethorphan and combined drugs containing it is not recommended.

Concomitant use of rasagiline with fluoxetine or fluvoxamine should be avoided. The interval between the withdrawal of rasagiline and the start of therapy with these drugs should be at least 14 days. At least 5 weeks should elapse after discontinuation of fluoxetine or fluvoxamine (long-term T1/2) and initiation of rasagiline treatment.

Information about simultaneous use SSRIs/SSRIs and rasagiline in clinical trials are presented in the section “Side effects”. Serious adverse reactions have been reported with concomitant use SSRIs, SSRIs, tricyclic and tetracyclic antidepressants with MAO inhibitors. Due to rasagiline’s ability to inhibit MAO, caution should be exercised when using it concomitantly with SSRIs, SSRIs, tricyclic and tetracyclic antidepressants.

In patients with Parkinson’s disease receiving long-term levodopa as adjunctive therapy, levodopa did not significantly affect the clearance of rasagiline.

In vitro studies have shown that the main enzyme involved in rasagiline metabolism is the CYP1A2 isoenzyme. Simultaneous use of ciprofloxacin and rasagiline increases the AUC of the latter by 83%. Concomitant use of rasagiline and theophylline (a substrate of the CYP1A2 isoenzyme) did not affect the pharmacokinetics of either drug. Thus, potent inhibitors of the CYP1A2 isoenzyme can alter the plasma concentration of rasagiline and require careful concomitant use. There is a risk that due to the induction of the CYP1A2 isoenzyme in smoking patients, the concentration of rasagiline in blood plasma may decrease.

In vitro studies have shown that rasagiline at a concentration of 1 mcg / ml (equivalent to a concentration exceeding 160 times the average Cmax (5.9–8.5 ng/ml) after repeated use of 1 mg of rasagiline to patients with Parkinson’s disease) does not inhibit the isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4 and CYP4A. This indicates that the therapeutic concentrations of rasagiline are most likely not clinically affected by the substrates of these isoenzymes.

Concomitant use of entacapone with rasagiline increased the clearance of the latter by 28%.

Clinical studies of the interaction of tyramine and rasagiline in volunteers and patients with Parkinson’s disease (0.5-1 mg / day of rasagiline or placebo as adjunctive therapy to levodopa for 6 months without restriction of tyramine intake) have shown that there is no interaction of rasagiline and tyramine, and rasagiline can be safely used without restriction of tyramine in the diet.

How to take, course of use and dosage

Inside, regardless of food intake, at a dose of 1 mg once a day, both with monotherapy and in combination with levodopa.

Elderly patients

No dose adjustment is required in elderly patients.

Patients with impaired liver function

Rasagiline is contraindicated in patients with moderate to severe hepatic insufficiency.

Caution should be exercised when using rasagiline in patients with mild hepatic insufficiency. If hepatic insufficiency progresses to a moderate degree during treatment with rasagiline, the drug should be discontinued.

Patients with renal insufficiency

No dose adjustment is required.

Overdose

Symptoms of overdose of the drug are similar to those of overdose with non-selective MAO inhibitors (including arterial hypertension, postural hypotension).

Treatment: there is no specific antidote. Gastric lavage, taking activated charcoal, symptomatic therapy.

Special instructions

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

Influence on the ability to drive vehicles and work with equipment that requires increased concentration of attention. The effect of rasagiline on driving and controlling other mechanisms has not been studied.

However, given the possibility of significant side effects from the central nervous system, during treatment with Azilect, care should be taken when driving vehicles and engaging in potentially dangerous activities that require increased concentration of attention and speed of psychomotor reactions.

Storage conditions

At a temperature not exceeding 25 °C

Shelf life

3 years

Active ingredient

Rasagiline

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

Adults as prescribed by a doctor

Indications

Parkinson ‘s Disease