Parlin (Rasagiline) 1 Mg 30 Tablets

4. CLINICAL FEATURES

4.1. Therapeutic indications In theindicated

treatment of idiopathic Parkinson's disease, PARLIN isas monotherapy (without accompanying levodopa treatment) or as adjuvant therapy (with accompanying levodopa therapy) in patients with end-of-dose fluctuations.

4.2. Posology and mode of administration

Posology / administration frequency and duration:

Rasagiline is administered orally, at a dose of 1 mg once daily, without levodopa treatment.

Application: Can

be taken with or without food.

Additional information on specific populations:

Renal failure: No

change in dose is required for renal impairment.

Hepatic impairment:

Rasagilin is contraindicated in patients with severe hepatic impairment (Child-Pugh score C) (see section 4.3). In patients with moderate hepatic impairment (Child-Pugh score B), the use of rasagiline should be avoided. Care should be taken when starting treatment with rasagiline in patients with mild liver disorder (Child-Pugh score A). Rasagiline should be discontinued in patients with mild hepatic impairment who progress to moderate hepatic impairment (see section 4.4).

Pediatric population: Since

there is not enough data on its reliability and efficacy, it is not recommended to use rasaj in this age group.

Geriatric population: No

change in dosage is required for elderly patients.

4.3. Contraindications

POINTS are contraindicated in the following cases;

In the case of hypersensitivity to any of the active substance or excipients (see section 6.1).

Other monoaminoxidase (MAO) inhibitors (including over-the-counter medical and natural products, eg St. John's Wort) or concurrent treatment with petidine (see section 4.5). It should be at least 14 days between the discontinuation of rasagenin and initiation of MAO inhibitors or initiation of treatment with petidine.

In patients with severe liver disorder (Child-Pugh score C).

4.4. Special warnings and precautions for use use of

Along with the rasagiline, fluoxetine or fluvoxamine should be avoided (see section 4.5). At least five weeks must pass between the discontinuation of fluoxetine and the initiation of treatment with rasagenin. It should be at least 14 days between the discontinuation of rasagenin and the initiation of fluoxetine or fluvoxamine treatment.

It is not recommended to use rasagiline and dextromethorphan or sympathomimetics (eg nasal and oral decongestants with ephedrine or pseudoephedrine or cold medications) (see section 4.5).

The emergence of melanoma cases during the clinical development program led to the idea that there may be a connection between the cases of melanoma and rasagenin. The collected data indicate that Parkinson's disease is not associated with a high risk of skin cancer (not just melanoma), rather than a particular drug. Any suspected skin lesions should be evaluated by a qualified physician.

Care should be taken when starting rasaciline treatment in patients with mild hepatic impairment. The use of rasagiline should be avoided in patients with moderate hepatic impairment. Rasagiline should be discontinued in patients with mild hepatic impairment who progress to moderate hepatic impairment (see section 5.2).

This medicinal product contains mannitol. However, it does not require any warning due to its dose.

4.5. Interactions with other medicinal products and other forms of

interaction There are many known interactions between nonselective MAO inhibitors and other drugs and rasagenin.

Rasajilin should not be co-administered with other MAO inhibitors (including over-the-counter medical and natural products, including St. John's Wort), as there may be a risk of nonselective MAO inhibition that may lead to hypertensive crises (see section 4.3).

Serious adverse effects have been reported in the simultaneous use of MAO inhibitors and petidine, including other selective MAO-B inhibitors. Concomitant use of rasagiline and pethidine is contraindicated (see section 4.3).

There have been reports of drug interaction in the simultaneous use of sympathomimetic drugs with MAO inhibitors. Due to the MAO inhibitory effect of rasagiline,rasagiline and

it is not recommended to simultaneously administer sympathomimetics (such as ephedrine or pseudoephedrine-containing drugs and sympathomimetics in the content of nasal and oral decongestants) (see section 4.4).

There have been drug interaction notifications for the simultaneous use of dextromethorphan and non-selective MAO inhibitors. Due to the MAO inhibitory effect of rasagiline, simultaneous administration of rasacilin and dextromethorphan is not recommended (see section 4.4).

The simultaneous use of rasagiline and fluoxetine or fluvoxamine should be avoided

(see section 4.4).

For clinical studies, see section 4.8 for the simultaneous use of rasagenin and selective serotonin reuptake inhibitors (SSRriar) / selective serotonin-norepinephrine reuptake inhibitors (SNRIs).

Serious adverse effects have been reported in the simultaneous use of selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic, tetracyclic antidepressants, and MAO inhibitors. Due to the MAO inhibitory effect of rasagiline, antidepressants should be used with caution.

In patients with Parkinson's disease receiving chronic levodopa therapy as adjuvant therapy, no clinically significant effect of levodopa treatment on rasagenyl clearance was found.

In vitro metabolism studies have shown that the main enzyme responsible for the metabolism of rasajiline is P4501A2 (CYP1A2). Co-administration of rasagiline and ciprofloxacin (an inhibitor of CYP1A2) increased the AUC of rasagiline by 83%. Rasagiline and theophylline(cypla2,represents a substrate), the co-administration did not affect the pharmacokinetics of both products. Strong CYP1A2 inhibitors can alter the plasma levels of rasagiline and should therefore be administered with caution.

In smokers, there is a risk that rasagiline will decrease in plasma levels due to the induction of the metabolizing CYP1A2 enzyme.

In vitro studies on rasagiline of 1 pg / ml (mean Cmax value 160 added equals ~ after 1 mg multiple doses of rasagiline 5.9-8.5 in Parkinson's patients ng / ml) of cytochrome

P450 isoenzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 Showed that it does not inhibit CYP3A4 and CYP4A). These results indicate that the therapeutic concentrations of the racemate are not expected to cause a clinically significant interaction with the substrates of these enzymes.

Simultaneous administration of rasagiline and entacapone increased the oral clearance of rasagiline by 28%.

Thyramine / rasagiline interaction: Five studies of thyroid (in volunteers and Parkinson's patients) monitor the blood pressure at home after meals (without any tyramine restriction for six months, as adjuvant therapy to levodopia, 464 patients treated with rasagiline or placebo 0.5 or 1 mg daily) the absence of any reports of tyramine / rasagenin interaction in clinical trials without tyramine restriction; Rasajiline can be used safely without diet-dependent tyramine restrictions.

4.6. Pregnancy and lactation

General advice

Pregnancy category: C

Women with childbearing potential / Contraception No

clinical data on the use of rasagiline during pregnancy are available. Animal studies do not show any direct or indirect adverse effects related to pregnancy, embryonal / fetal development, birth or postnatal development. (see section 5.S) The potential risk to humans is unknown.

Pregnancy The

benefits of drug therapy during pregnancy should be assessed against possible risks to the fetus.

PARLI should not be used during pregnancy unless necessary.

Lactation

According to experimental data, rasagiline inhibits prolactin release and can therefore inhibit breastfeeding. It is not known whether Rasajiline is excreted in breast milk.

It should not be given during breastfeeding period.

Reproductive ability / Ferticte In

studies of pre-clinical reproductive toxicity, no effect on fertility / fertility has been determined.

4.7. Tools and Effects on use

machinesand there are no studies on the effects on the ability to drive and use machines.

Patients should be cautioned to be careful when using dangerous machines, including motor vehicles, until they are sufficiently certain that they do not adversely affect PARLI.

8.4. Undesirable effects

A total of 1361 patients in the Rasagiline clinical program were treated with rasagiline and 3076.4 patient years. In double-blind placebo-controlled studies, 529 patients were treated with 212 mg per year with rasagiline and 539 patients were treated with 213 patients years with placebo.

Monotherapy

The following list contains adverse events reported with a higher incidence in placebo-controlled trials with rasagiline (rasagiline group n = 149, placebo group n = 151) per day.

Adverse effects with at least 2% difference compared to placebo are indicated in italics.

The incidence of adverse events (% of patients) for rasagiline and placebo was given in brackets, respectively.

Adverse effects are given according to the following frequency sequence:

Very common (> 1/10), common (> 1/100 to <1/10), uncommon (> 1 / 1,000 to <1/100), infrequent (> 1 / 10,000 to <1 / 1,000, very rare (<1 / 10.000), unknown (unpredictable from available data).

Infection and infestations

Common: Influenza (4.7%; 0.7%)

Benign, malignant and unspecified neoplasms (including cysts and polyps)

Common: Skin carcinoma (1.3%, 0.7%)

Blood and lymphatic system disorders

Common: Leukopenia (1.3%; 0%)

Immune system disorders

Common: Allergy (1.3%; 0.7%)

Metabolism and malnutrition

Uncommon: Declining appetite (0.7%; 0%)

Psychiatric disorders

Common: Depression (5.4%; 2%), hallucinations (1.3%; 0.7%)

Nervous system disorders

Very common: Headache (14.%;% ii.9)

Uncommon: Cerebrovascular damage (0.7%; 0%)

Eye disorders

Common: Conjunctivitis (2.7%; 0.7%)

Ear and inner ear disorders

Common: Vertigo (2.7%; 1.3%)

Cardiac disorders

Common: Angina pectoris (1.3%; 0%)

Uncommon: Myocardial infarction (0.7%; 0%)

Respiratory, chest disorders and mediastinal disorders

Common: Rhinitis (3.4%; 0.7%)

Gastrointestinal disorders

Common: flatulence (1.3%, 0%)

skin and subcutaneous tissue disorders

Common: Dermatitis (2.0%; 0%)

Uncommon: Vesiculobulloz rash (0.7%; 0%)

Musculoskeletal and connective tissue disorders

Common: Musculoskeletal pain (6.7%; 2.6%), neck pain (2.7%; 0%), arthritis (1.3%; 0.7%)

Kidney and urinary tract disorders

Common: Sudden urinary urgency (1.3%; 0.7%)

General disorders and conditions of administration

Common: Fever (2.7%; 1.3%), malaise (2%; 0%)

Adjuvant Treatment

The following list shows patients with rasagiline taking 1 mg daily (380, placebo group n = 388) included adverse effects reported with a higher incidence in placebo-controlled trials. The incidence of adverse effects (for% of the patient) in rasagiline and placebo was given in parentheses, respectively. Adverse effects with at least 2% difference compared to placebo are indicated in italics.

Adverse effects are given according to the following frequency sequence:

Very common (> 1/10), common (> 1/100 to <1/10), uncommon (> 1 / 1,000 to <1/100), infrequent (> 1 / 10,000 to <1 / 1,000, very rare (<1 / 10.000), unknown (unpredictable from available data).

Benign, malignant and unspecified neoplasms

Uncommon: Skin melanoma (0.5%, 0.3%)

Metabolism and nutritional disorders

Common: Declining appetite (2.4%; 0.8%)

Psychiatric disorders

Common: Hallucinations (2.9%; 2.1%), abnormal dreams (2.1%; 0.8%)

Uncommon: Confusion (0.8%; 0.5%)

Nervous system disorders

Very common: Dyskinesia (% I0.5; 6.2%)

Common: Dystonia (2.4%; 0.8%), carpal tunnel syndrome (%) 1.3; 0%), balance disorders (1.6%; 0.3%)

Uncommon: Cerebrovascular damage (0.5%; 0.3%)

Cardiac disorders

Uncommon: Angina pectoris (0.5%; 0%)

Vascular disorders

Common: Postural hypotension (3.9%) , 0.8%)

Gastrointestinal disorders

Common: 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 skin subcutaneous tissue disorders:

Common: rash (1.1%; 0.3%)

Musculoskeletal and connective tissue disorders

common arthralgia (2.4%; 2.1%), neck pain (1.3%; 0.5%)

was Res r studies

Common: weight loss (4.5%; 1.5%)

Injury and poisoning

Common: fall (4.7%; 3.4%

Parkinson's disease has symptoms of hallucination and confusion. In post-marketing experience, these symptoms were also observed in patients with Parkinson's who were treated with rasacillin.

It is known that serious adverse effects occur in the simultaneous use of selective serotonin reuptake inhibitors (SSRTs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic, tetracyclic antidepressants and MAO inhibitors. In the post-marketing period, serotonin syndromes associated with agitation, confusion, rigidity, pyrexia and myoclonus have been reported in patients receiving antidepressant / SNRI therapy simultaneously with rasagiline.

In clinical trials with rasagiline, the use of fluoxetine or fluvoxamine in combination with rasagiline is not permitted, but the following antidepressants and doses have been allowed for use in the clinical trials of rasacillin: amitriptyline <50 mg / day, trazodone <100 mg / day, citalopram <20 mg / day , sertraline <100 mg / day and paroxetine <30 mg / day. There were no serotonin syndrome cases in the clinical program of rasagiline in which 115 patients were simultaneously exposed to rasacillin and tricyclines and 141 patients to rasacillin and SSRriar / SNRIs.

In the post-marketing period, increased blood pressure, including rare cases of hypertensive crises associated with the ingestion of unknown quantities of tiramine-rich foods, has been reported in patients using rasagiline.

There have been reports of drug interaction in the simultaneous use of sympathomimetic drugs with MAO inhibitors.

In a single case of post-marketing experience, an increase in blood pressure was reported in a patient using ophthalmic vasoconstrictor tetrahydrozoline hydrochloride while using rasagiline.