Azilect

1. NAME OF THE MEDICINAL PRODUCT

AZILECT 1 mg tablets

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains 1 mg rasagiline (as mesilate).

For a full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Tablet

White to off-white, round, flat, bevelled tablets, debossed with “GIL” and “1” underneath on one side and

plain on the other side.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

AZILECT is indicated for the treatment of idiopathic Parkinson’s disease (PD) as monotherapy (without

levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations.

4.2 Posology and method of administration

Posology

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

It may be taken with or without food.

Elderly

: No change in dose is required for elderly patients.

: AZILECT is not recommended for use in children and adolescents due to lack of

data on safety and efficacy.

: Rasagiline use in patients with severe hepatic impairment is

contraindicated (see section ) . Rasagiline use in patients with moderate hepatic impairment should be

avoided. Caution should be used when initiating treatment with rasagiline in patients with mild hepatic

impairment. In case patients progress from mild to moderate hepatic impairment rasagiline should be

stopped (see section 4.4) .

Patients with renal impairment

: No change in dose is required for renal impairment.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients (see section 6.1) .

Concomitant treatment with other monoamine oxidase (MAO) inhibitors (including medicinal and natural

products without prescription e.g. St. John's Wort) or pethidine (see section 4.5) . At least 14 days must

elapse between discontinuation of rasagiline and initiation of treatment with MAO inhibitors or pethidine.

Rasagiline is contraindicated in patients with severe hepatic impairment.

2

Paediatric population

Patients with hepatic impairment

4.3

4.4 Special warnings and precautions for use

The concomitant use of rasagiline and fluoxetine or fluvoxamine should be avoided (see section 4.5) . At

least five weeks should elapse between discontinuation of fluoxetine and initiation of treatment with

rasagiline. At least 14 days should elapse between discontinuation of rasagiline and initiation of treatment

with fluoxetine or fluvoxamine.

The concomitant use of rasagiline and dextromethorphan or sympathomimetics such as those present in

nasal and oral decongestants or cold medicinal product containing ephedrine or pseudoephedrine is not

recommended (see section 4.5) .

During the clinical development program, the occurrence of cases of melanoma prompted the

consideration of a possible association with rasagiline. The data collected suggests that Parkinson’s

disease, and not any medicinal products in particular, is associated with a higher risk of skin cancer (not

exclusively melanoma). Any suspicious skin lesion should be evaluated by a specialist.

Caution should be used when initiating treatment with rasagiline in patients with mild hepatic

impairment. Rasagiline use in patients with moderate hepatic impairment should be avoided. In case

patients progress from mild to moderate hepatic impairment, rasagiline should be stopped (see section

5.2) .

4.5 Interaction with other medicinal products and other forms of interaction

There are a number of known interactions between non selective MAO inhibitors and other medicinal

products.

Rasagiline must not be administered along with other MAO inhibitors (including medicinal and natural

products without prescription e.g. St. John's Wort) as there may be a risk of non-selective MAO inhibition

that may lead to hypertensive crises (see section 4.3) .

Serious adverse reactions have been reported with the concomitant use of pethidine and MAO inhibitors

including another selective MAO-B inhibitor. The concomitant administration of rasagiline and pethidine

is contraindicated (see section 4.3) .

With MAO inhibitors there have been reports of medicinal product interactions with the concomitant use

of sympathomimetic medicinal products. Therefore, in view of the MAO inhibitory activity of rasagiline,

concomitant administration of rasagiline and sympathomimetics such as those present in nasal and oral

decongestants or cold medicinal products, containing ephedrine or pseudoephedrine, is not recommended

(see section 4.4) .

There have been reports of medicinal product interactions with the concomitant use of dextromethorphan

and non selective MAO inhibitors. Therefore, in view of the MAO inhibitory activity of rasagiline, the

concomitant administration of rasagiline and dextromethorphan is not recommended (see section 4.4) .

The concomitant use of rasagiline and fluoxetine or fluvoxamine should be avoided (see section 4.4).

For concomitant use of rasagiline with selective serotonin reuptake inhibitors (SSRIs)/selective serotonin-

norepinephrine reuptake inhibitors (SNRIs) in clinical trials, see section 4.8.

Serious adverse reactions have been reported with the concomitant use of SSRIs, SNRIs, tricyclic/

tetracyclic antidepressants and MAO inhibitors. Therefore, in view of the MAO inhibitory activity of

rasagiline, antidepressants should be administered with caution.

In Parkinson's disease patients receiving chronic levodopa treatment as adjunct therapy, there was no

clinically significant effect of levodopa treatment on rasagiline clearance.

3

In vitro metabolism studies have indicated that cytochrome P450 1A2 (CYP1A2) is the major enzyme

responsible for the metabolism of rasagiline. Co-administration of rasagiline and ciprofloxacin (an

inhibitor of CYP1A2) increased the AUC of rasagiline by 83%. Co-administration of rasagiline and

theophylline (a substrate of CYP1A2) did not affect the pharmacokinetics of either product. Thus, potent

CYP1A2 inhibitors may alter rasagiline plasma levels and should be administered with caution.

There is a risk that the plasma levels of rasagiline in smoking patients could be decreased, due to

induction of the metabolising enzyme CYP1A2.

In vitro studies showed that rasagiline at a concentration of 1 µg/ml (equivalent to a level that is 160

times the average C max ~ 5.9-8.5 ng/ml in Parkinson’s disease patients after 1 mg rasagiline multiple

dosing), did not inhibit cytochrome P450 isoenzymes, CYP1A2, CYP2A6, CYP2C9, CYP2C19,

CYP2D6, CYP2E1, CYP3A4 and CYP4A. These results indicate that rasagiline’s therapeutic

concentrations are unlikely to cause any clinically significant interference with substrates of these

enzymes.

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

Tyramine/rasagiline interaction: Results of five tyramine challenge studies (in volunteers and PD

patients), together with results of home monitoring of blood pressure after meals (of 464 patients treated

with 0.5 or 1 mg/day of rasagiline or placebo as adjunct therapy to levodopa for six months without

tyramine restrictions), and the fact that there were no reports of tyramine/rasagiline interaction in clinical

studies conducted without tyramine restriction, indicate that rasagiline can be used safely without dietary

tyramine restrictions.

4.6 Fertility, pregnancy and lactation

For rasagiline no clinical data on exposed pregnancies is available. Animals studies do not indicate direct

or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or

postnatal development (see section 5.3) . Caution should be exercised when prescribing to pregnant

women.

Experimental data indicated that rasagiline inhibits prolactin secretion and thus, may inhibit lactation.

It is not known whether rasagiline is excreted in human milk. Caution should be exercised when

rasagiline is administered to a breast-feeding mother.

4.7 Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

Patients should be cautioned about operating hazardous machines, including motor vehicles, until they are

reasonably certain that AZILECT does not affect them adversely.

4.8 Undesirable effects

In the rasagiline clinical program overall, 1,361 patients were treated with rasagiline for 3,076.4 patient

years. In the double blind placebo controlled studies, 529 patients were treated with rasagiline 1 mg/day

for 212 patient years and 539 patients received placebo for 213 patient years.

4

Monotherapy

The list below includes adverse reactions which were reported with a higher incidence in placebo-

controlled studies, in patients receiving 1 mg/day rasagiline (rasagiline group n=149, placebo group

n=151).

Adverse reactions with at least 2% difference over placebo are marked in italics .

In parentheses is the adverse reaction incidence (% of patients) in rasagiline vs. placebo, respectively.

Adverse reactions are ranked under headings of frequency using the following conventions: very common

( ≥ 1/10), common ( ≥ 1/100 to <1/10), uncommon ( ≥ 1/1000 to <1/100), rare ( ≥ 1/10000 to <1/1000), very

rare (<1/10000).

Common: influenza (4.7% vs. 0.7%)

Neoplasms benign, malignant and unspecified (including cysts and polyps)

Common: skin carcinoma (1.3% vs. 0.7%)

Blood and lymphatic system disorders

Common: leucopenia (1.3% vs. 0%)

Immune system disorders

Common: allergy (1.3% vs. 0.7%)

Metabolism and nutrition disorders

Uncommon: decreased appetite (0.7% vs. 0%)

Psychiatric disorders

Common: depression (5.4% vs. 2%) , hallucinations (1.3% vs. 0.7%)

Nervous system disorders

Uncommon: cerebrovascular accident (0.7% vs. 0%)

Common: conjunctivitis (2.7% vs . 0.7%)

Ear and labyrinth disorders

Common: vertigo (2.7% vs. 1.3%)

Cardiac disorders

Common: angina pectoris (1.3% vs. 0%);

Uncommon: myocardial infarction (0.7% vs. 0%)

Respiratory, thoracic and mediastinal disorders

Gastrointestinal disorders

Common : flatulence (1.3% vs.0%)

Skin and subcutaneous tissue disorders

Common: dermatitis ( 2.0% vs. 0% )

Uncommon: vesiculobullous rash (0.7% vs. 0%)

Common: musculoskeletal pain (6.7% vs. 2.6%), neck pain (2.7% vs. 0%) , arthritis (1.3% vs.

0.7%)

Renal and urinary disorders

Common: urinary urgency (1.3% vs. 0.7%).

General disorders and administration site conditions

Common: fever (2.7% vs. 1.3%), malaise (2% vs. 0%)

5

Infections and infestations

Very common : headache (14.1% vs. 11.9%)

Eye disorders

Common: rhinitis ( 3.4% vs. 0.7 %)

Musculoskeletal and connective tissue disorders

Adjunct Therapy

The list below includes adverse reactions which were reported with a higher incidence in placebo-

controlled studies in patients receiving 1 mg/day rasagiline (rasagiline group n=380, placebo group

n=388). In parentheses is the adverse reaction incidence (% of patients) in rasagiline vs. placebo,

respectively.

Adverse reactions with at least 2% difference over placebo are in italics .

Adverse reactions are ranked under headings of frequency using the following conventions: very common

( ≥ 1/10), common ( ≥ 1/100, <1/10), uncommon ( ≥ 1/1000, <1/100), rare ( ≥ 1/10000, <1/1000), very rare

(<1/10000).

Neoplasms benign, malignant and unspecified

Metabolism and nutrition disorders

Common: decreased appetite (2.4% vs. 0.8%)

Psychiatric disorders

Common: hallucinations (2.9% vs. 2.1%), abnormal dreams (2.1% vs. 0.8%)

Uncommon: confusion (0.8% vs. 0.5%)

Very common : dyskinesia (10.5% vs. 6.2%)

Common: dystonia (2.4% vs. 0.8%), carpal tunnel syndrome (1.3% vs. 0%), balance disorder

(1.6% vs. 0.3%)

Uncommon: cerebrovascular accident (0.5% vs. 0.3%)

Cardiac disorders

Uncommon: angina pectoris (0.5% vs. 0%)

Vascular disorders

Common: orthostatic hypotension (3.9% vs. 0.8%)

Gastrointestinal disorders

Common: abdominal pain ( 4.2% vs. 1.3% ), constipation (4.2% vs. 2.1%) , nausea and vomiting

(8.4% vs. 6.2%) , dry mouth (3.4% vs. 1.8%)

Skin and subcutaneous tissue disorders

Common: rash (1.1% vs. 0.3%)

Musculoskeletal and connective tissue disorders

Common: arthralgia (2.4% vs. 2.1%), neck pain (1.3% vs. 0.5%)

Common: decreased weight (4.5% vs. 1.5%)

Injury, poisoning and procedural complications

Common: fall (4.7% vs. 3.4%)

Parkinson's disease is associated with symptoms of hallucinations and confusion. In post marketing

experience, these symptoms have also been observed in Parkinson's disease patients treated with

rasagiline.

Serious adverse reactions are known to occur with the concomitant use of SSRIs, SNRIs, tricyclic/

tetracyclic antidepressants and MAO inhibitors. In the post-marketing period, cases of serotonin

syndrome associated with agitation, confusion, rigidity, pyrexia and myoclonus have been reported by

patients treated with antidepressants/SNRI concomitantly with rasagiline.

Rasagiline clinical trials did not allow concomitant use of fluoxetine or fluvoxamine with rasagiline, but

the following antidepressants and doses were allowed in the rasagiline trials: amitriptyline ≤ 50 mg/daily,

trazodone ≤ 100 mg/daily, citalopram ≤ 20 mg/daily, sertraline ≤ 100 mg/daily, and paroxetine ≤ 30

mg/daily. There were no cases of serotonin syndrome in the rasagiline clinical program in which 115

patients were exposed concomitantly to rasagiline and tricyclics and 141 patients were exposed to

rasagiline and SSRIs/ SNRIs.

6

Uncommon: skin melanoma (0.5% vs. 0.3%)

Nervous system disorders

Investigations

In the post-marketing period, cases of elevated blood pressure, including rare cases of hypertensive crisis

associated with ingestion of unknown amounts of tyramine-rich foods, have been reported in patients

taking rasagiline.

With MAO inhibitors, there have been reports of drug interactions with the concomitant use of

sympathomimetic medicinal products.

In post marketing period, there was one case of elevated blood pressure in a patient using the ophthalmic

vasoconstrictor tetrahydrozoline hydrochloride while taking rasagiline.

4.9 Overdose

Overdosage: Symptoms reported following overdose of Azilect in doses ranging from 3 mg to 100 mg

included dysphoria, hypomania, hypertensive crisis and serotonin syndrome.

Overdose can be associated with significant inhibition of both MAO-A and MAO-B. In a single-dose

study healthy volunteers received 20 mg/day and in a ten-day study healthy volunteers received

10 mg/day. Adverse events were mild or moderate and not related to rasagiline treatment. In a dose

escalation study in patients on chronic levodopa therapy treated with 10 mg/day of rasagiline, there were

reports of cardiovascular undesirable reactions (including hypertension and postural hypotension) which

resolved following treatment discontinuation. These symptoms may resemble those observed with non-

selective MAO inhibitors.

There is no specific antidote. In case of overdose, patients should be monitored and the appropriate

symptomatic and supportive therapy instituted.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Anti-Parkinson-Drugs, Monoamine oxidase -B inhibitors, ATC code:

N04BD02

Mechanism of action :

Rasagiline was shown to be a potent, irreversible MAO-B selective inhibitor, which may cause an

increase in extracellular levels of dopamine in the striatum. The elevated dopamine level and subsequent

increased dopaminergic activity are likely to mediate rasagiline's beneficial effects seen in models of

dopaminergic motor dysfunction.

1-Aminoindan is an active major metabolite and it is not a MAO-B inhibitor.

Clinical studies:

The efficacy of rasagiline was established in three studies: as monotherapy treatment in study I and as

adjunct therapy to levodopa in the studies II and III.

Monotherapy:

In study I, 404 patients were randomly assigned to receive placebo (138 patients), rasagiline 1 mg/day

(134 patients) or rasagiline 2 mg/day (132 patients) and were treated for 26 weeks, there was no active

comparator.

In this study, the primary measure of efficacy was the change from baseline in the total score of the

Unified Parkinson’s Disease Rating Scale (UPDRS, parts I-III). The difference between the mean change

from baseline to week 26/termination (LOCF, Last Observation Carried Forward) was statistically

significant (UPDRS, parts I-III: for rasagiline 1 mg compared to placebo -4.2, 95% CI

[-5.7, -2.7]; p<0.0001; for rasagiline 2 mg compared to placebo -3.6, 95% CI [-5.0, -2.1]; p<0.0001,

UPDRS Motor, part II: for rasagiline 1 mg compared to placebo -2.7, 95% CI [-3.87, -1.55], p<0.0001;

for rasagiline 2 mg compared to placebo -1.68, 95% CI [-2.85, -0.51], p=0.0050). The effect was evident,

7

although its magnitude was modest in this patient population with mild disease. There was a significant

and beneficial effect in quality of life (as assessed by PD-QUALIF scale).

Adjunct therapy:

In study II, patients were randomly assigned to receive placebo (229 patients), or rasagiline 1 mg/day

(231 patients) or the catechol-O–methyl transferase (COMT) inhibitor, entacapone, 200 mg taken along

with scheduled doses of levodopa (LD)/decarboxylase inhibitor (227 patients), and were treated for 18

weeks. In study III, patients were randomly assigned to receive placebo (159 patients), rasagiline

0.5 mg/day (164 patients), or rasagiline 1 mg/day (149 patients), and were treated for 26 weeks.

In both studies, the primary measure of efficacy was the change from baseline to treatment period in the

mean number of hours that were spent in the “OFF” state during the day (determined from “24-hour”

home diaries completed for 3 days prior to each of the assessment visits).

In study II, the mean difference in the number of hours spent in the “OFF” state compared to placebo was

-0.78h, 95% CI [-1.18, -0.39], p=0.0001. The mean total daily decrease in the OFF time was similar in the

entacapone group (-0.80h, 95% CI [-1.20, -0.41], p<0.0001) to that observed in the rasagiline 1 mg group.

In study III, the mean difference compared to placebo was -0.94h, 95% CI [-1.36, -0.51], p<0.0001. There

was also a statistically significant improvement over placebo with the rasagiline 0.5 mg group, yet the

magnitude of improvement was lower. The robustness of the results for the primary efficacy endpoint,

was confirmed in a battery of additional statistical models and was demonstrated in three cohorts (ITT,

per protocol and completers).

The secondary measures of efficacy included global assessments of improvement by the examiner,

Activities of Daily Living (ADL) subscale scores when OFF and UPDRS motor while ON. Rasagiline

produced statistically significant benefit compared to placebo.

5.2 Pharmacokinetic properties

Absorption : Rasagiline is rapidly absorbed, reaching peak plasma concentration (C max ) in approximately

0.5 hours. The absolute bioavailability of a single rasagiline dose is about 36%.

Food does not affect the T max of rasagiline, although C max and exposure (AUC) are decreased by

approximately 60% and 20%, respectively, when the medicinal product is taken with a high fat meal.

Because AUC is not substantially affected, rasagiline can be administered with or without food.

Distribution : The mean volume of distribution following a single intravenous dose of rasagiline is 243 l.

Plasma protein binding following a single oral dose of 14 C-labelled rasagiline is approximately 60 to 70%.

Metabolism : Rasagiline undergoes almost complete biotransformation in the liver prior to excretion. The

metabolism of rasagiline proceeds through two main pathways: N-dealkylation and/or hydroxylation to

yield: 1-Aminoindan, 3-hydroxy-N-propargyl-1 aminoindan and 3-hydroxy-1-aminoindan. In vitro

experiments indicate that both routes of rasagiline metabolism are dependent on cytochrome P450

system, with CYP1A2 being the major iso-enzyme involved in rasagiline metabolism. Conjugation of

rasagiline and its metabolites was also found to be a major elimination pathway to yield glucuronides.

Excretion : After oral administration of 14 C-labelled rasagiline, elimination occurred primarily via urine

(62.6%) and secondarily via faeces (21.8%), with a total recovery of 84.4% of the dose over a period of

38 days. Less than 1% of rasagiline is excreted as unchanged product in urine.

Linearity/non-linearity: Rasagiline pharmacokinetics are linear with dose over the range of 0.5-2 mg. Its

terminal half-life is 0.6-2 hours.

Characteristics in patients

Patients with hepatic impairment : In subjects with mild hepatic impairment, AUC and C max were

increased by 80% and 38%, respectively. In subjects with moderate hepatic impairment, AUC and C max

were increased by 568% and 83%, respectively (see section 4.4) .

8

Patients with renal impairment : Rasagiline's pharmacokinetics characteristics in subjects with mild (CLcr

50-80 ml/min) and moderate (CLcr 30-49 ml/min) renal impairment were similar to healthy subjects.

5.3 Preclinical safety data

Preclinical data reveal no special hazard for humans based on conventional studies of safety

pharmacology, repeated-dose toxicity and reproduction toxicity.

Rasagiline did not present genotoxic potential in vivo and in several in vitro systems using bacteria or

hepatocytes. In the presence of metabolite activation rasagiline induced an increase of chromosomal

aberrations at concentrations with excessive cytotoxicity which are unattainable at the clinical conditions

of use.

Rasagiline was not carcinogenic in rats at systemic exposure, 84 – 339 times the expected plasma

exposures in humans at 1 mg/day. In mice, increased incidences of combined bronchiolar/alveolar

adenoma and/or carcinoma were observed at systemic exposures, 144 - 213 times the expected plasma

exposure in humans at 1 mg/day.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Mannitol

Maize starch

Pregelatinised maize starch

Colloidal anhydrous silica

Stearic acid

Talc

6.2 Incompatibilities

Not applicable

6.3 Shelf life

Blisters: 3 years

Bottles: 3 years

6.4 Special precautions for storage

Do not store above 25ºC.

6.5 Nature and contents of container

Blisters: Aluminium/aluminium blister packs of 7, 10, 28, 30, 100 or 112 tablets.

Bottles: White, high-density polyethylene bottle with or without a child-resistant cap containing

30 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal

No special requirements.

9

7. MARKETING AUTHORISATION HOLDER

Teva Pharma GmbH

Kandelstr 10

D-79199 Kirchzarten

Germany

8. MARKETING AUTHORISATION NUMBER(S)

EU/1/04/304/001-007

9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

Date of first authorisation:

21 February 2005

Date of latest renewal:

21 September 2009

10. DATE OF REVISION OF THE TEXT

Detailed information on this product is available on the website of the European Medicines Agency

http://www.ema.europa.eu

10

ANNEX II

A. MANUFACTURING AUTHORISATION HOLDER

RESPONSIBLE FOR BATCH RELEASE

B. CONDITIONS OF THE MARKETING AUTHORISATION

11

A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH

RELEASE

Name and address of the manufacturer responsible for batch release

Teva Pharmaceuticals Europe B.V.

Computerweg 10

3542 DR Utrecht

The Netherlands

B. CONDITIONS OF THE MARKETING AUTHORISATION

•

CONDITIONS OR RESTRICTIONS REGARDING SUPPLY AND USE IMPOSED ON

THE MARKETING AUTHORISATION HOLDER

Medicinal product subject to medical prescription.

•

CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND

EFFECTIVE USE OF THE MEDICINAL PRODUCT

Not applicable.

•

OTHER CONDITIONS

PSURs

The next PSUR will be submitted with a 3-year frequency (covering period 3 January 2010 to 2 January

2013).

12

ANNEX III

LABELLING AND PACKAGE LEAFLET

13

A. LABELLING

14

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

(CARTON FOR BLISTER PACK)

1.

NAME OF THE MEDICINAL PRODUCT

AZILECT 1 mg tablets

rasagiline

2.

STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 1 mg of rasagiline (as mesilate).

3.

LIST OF EXCIPIENTS

4.

PHARMACEUTICAL FORM AND CONTENTS

7 tablets

10 tablets

28 tablets

30 tablets

100 tablets

112 tablets

5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use.

Read the package leaflet before use.

6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7.

OTHER SPECIAL WARNING(S), IF NECESSARY

8.

EXPIRY DATE

EXP {MM/YYYY}

9.

SPECIAL STORAGE CONDITIONS

Do not store above 25°C.

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF

APPROPRIATE

15

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Teva Pharma GmbH

D-79199 Kirchzarten, Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/04/304/001

EU/1/04/304/002

EU/1/04/304/003

EU/1/04/304/004

EU/1/04/304/005

EU/1/04/304/006

13. BATCH NUMBER

Lot {number}

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

AZILECT

16

MINIMUM PARTICULARS TO APPEAR ON BLISTERS OR STRIPS

1.

NAME OF THE MEDICINAL PRODUCT

AZILECT 1 mg tablets

rasagiline

2.

NAME OF THE MARKETING AUTHORISATION HOLDER

Teva Pharma GmbH

3.

EXPIRY DATE

EXP {MM/YYYY}

4.

BATCH NUMBER

Lot {number}

5.

OTHER

17

PARTICULARS TO APPEAR ON THE OUTER PACKAGING

(CARTON FOR BOTTLE AND BOTTLE LABEL)

1.

NAME OF THE MEDICINAL PRODUCT

AZILECT 1 mg tablets

rasagiline

2.

STATEMENT OF ACTIVE SUBSTANCE(S)

Each tablet contains 1 mg of rasagiline (as mesilate).

3.

LIST OF EXCIPIENTS

4.

PHARMACEUTICAL FORM AND CONTENTS

30 tablets

5.

METHOD AND ROUTE(S) OF ADMINISTRATION

Oral use.

Read the package leaflet before use.

6.

SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT

OF THE REACH AND SIGHT OF CHILDREN

Keep out of the reach and sight of children.

7.

OTHER SPECIAL WARNING(S), IF NECESSARY

8.

EXPIRY DATE

EXP {MM/YYYY }

9.

SPECIAL STORAGE CONDITIONS

Do not store above 25°C.

18

10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS

OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF

APPROPRIATE

11. NAME AND ADDRESS OF THE MARKETING AUTHORISATION HOLDER

Teva Pharma GmbH

D-79199 Kirchzarten, Germany

12. MARKETING AUTHORISATION NUMBER(S)

EU/1/04/304/007

13. BATCH NUMBER

Lot {number}

14. GENERAL CLASSIFICATION FOR SUPPLY

Medicinal product subject to medical prescription.

15. INSTRUCTIONS ON USE

16. INFORMATION IN BRAILLE

AZILECT

19

B. PACKAGE LEAFLET

20

PACKAGE LEAFLET: INFORMATION FOR THE USER

AZILECT 1 mg tablets

Rasagiline

Read all of this leaflet carefully before you start taking this medicine.

-

Keep this leaflet. You may need to read it again.

-

This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if

their symptoms are the same as yours.

-

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,

please tell your doctor or pharmacist.

In this leaflet

1. What AZILECT is and what it is used for

:

2. Before you take AZILECT

3. How to take AZILECT

4. Possible side effects

5. How to store AZILECT

6. Further information

1. WHAT AZILECT IS AND WHAT IT IS USED FOR

AZILECT is used for the treatment of Parkinson’s disease. It can be used together with or without

Levodopa (another medicine that is used to treat Parkinson’s disease).

With Parkinson’s disease, there is a loss of cells that produce dopamine in the brain. Dopamine is a

chemical in the brain involved in movement control. AZILECT helps to increase and sustain levels of

dopamine in the brain.

2.

BEFORE YOU TAKE AZILECT

Do not

-

take AZILECT

-

if you are allergic (hypersensitive) to rasagiline or any of the other ingredients of AZILECT.

Do not

-

monoamine oxidase (MAO) inhibitors (e.g. for treatment of depression or Parkinson’s disease, or

used for any other indication), including medicinal and natural products without prescription e.g.

St. John's Wort.

take the following medicines while taking AZILECT:

- pethidine (a strong pain killer).

You must wait at least 14 days after stopping AZILECT treatment and starting treatment with MAO

inhibitors or pethidine.

Take special care with AZILECT

-

if you have mild to moderate liver problems

-

You should speak with your doctor about any suspicious skin changes.

Children

AZILECT is not recommended for use under the age of 18.

21

-

If you have any further questions, ask your doctor or pharmacist.

if you have severe liver problems.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,

including medicines obtained without prescription or if you are smoking or intend to stop smoking.

Ask your doctor

- Certain antidepressants (selective serotonin reuptake inhibitors, selective serotonin-norepinephrine

reuptake inhibitors, tricyclic or tetracyclic antidepressants)

for advice before taking any of the following medicines together with AZILECT:

- the antibiotic ciprofloxacin used against infections

- the cough suppressant dextromethorphan

- sympathomimetics such as those present in eye drops, nasal and oral decongestants and cold

medicine containing ephedrine or pseudoephedrine

The use of AZILECT together with the antidepressants containing fluoxetine or fluvoxamine should be

avoided.

If you are starting treatment with AZILECT, you should wait at least 5 weeks after stopping fluoxetine

treatment.

If you are starting treatment with fluoxetine or fluvoxamine, you should wait at least 14 days after

stopping AZILECT treatment.

Taking AZILECT with food and drink

AZILECT may be taken with or without food.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed. Ask

your doctor for advice prior to driving or using machines.

3.

HOW TO TAKE AZILECT

Always take AZILECT exactly as your doctor has told you. You should check with your doctor or

pharmacist if you are not sure.

The usual dose of AZILECT is 1 tablet of 1 mg taken by mouth once daily. AZILECT may be taken with

or without food.

If you take more AZILECT than you should

If you think that you may have taken too many AZILECT tablets, contact your doctor or pharmacist

immediately. Take the AZILECT carton/bottle with you to show the doctor or pharmacist.

If you forget to take AZILECT

Do not take a double dose to make up for a forgotten dose. Take the next dose normally, when it is time

to take it.

If you stop taking AZILECT

Do not stop taking AZILECT without first talking to your doctor.

If you have any further questions on the use of this product, ask your doctor or pharmacist.

4.

POSSIBLE SIDE EFFECTS

Like all medicines, AZILECT can cause side effects, although not everybody gets them.

The following side effects have been reported in placebo controlled clinical trials:

22

The frequency of possible side effects listed below is defined using the following convention:

 Very common (affects more than 1 user in 10)

 Common (affects 1 to 10 users in 100)

 Uncommon (affects 1 to 10 users in 1,000)

 Rare (affects 1 to 10 users in 10,000)

 Very rare (affects less than 1 user in 10,000)

 Not known (frequency cannot be estimated from the available data)

Very common

- abnormal movements (dyskinesia)

- headache

Common:

- abdominal pain

- fall

- allergy

- fever

- flu (influenza)

- general feeling of being unwell (malaise)

- neck pain

- chest pain (angina pectoris)

- low blood pressure when rising to a standing position with symptoms like dizziness/light-headedness

(orthostatic hypotension)

- Decreased appetite

- constipation

- dry mouth

- nausea and vomiting

- flatulence

- abnormal results of blood tests (leucopenia)

- joint pain (arthralgia)

- musculoskeletal pain

- joint inflammation (arthritis)

- numbness and muscle weakness of the hand (carpal tunnel syndrome )

- decreased weight

- abnormal dreams

- difficulty in muscular coordination (balance disorder)

- depression

- dizziness (vertigo)

- prolonged muscle contractions (dystonia)

- runny nose (rhinitis)

- irritation of the skin (dermatitis)

- rash

- bloodshot eyes (conjunctivitis)

- urinary urgency

Uncommon:

- stroke (cerebrovascular accident)

- heart attack (myocardial infarction)

- blistering rash (vesiculobullous rash)

In addition, skin cancer was reported in around 1% of patients in the placebo controlled clinical trials.

Nevertheless, scientific evidence suggests that Parkinson’s disease, and not any medicine in particular, is

associated with a higher risk of skin cancer (not exclusively melanoma). You should speak with your

doctor about any suspicious skin changes.

23

Parkinson's disease is associated with symptoms of hallucinations and confusion.

In post marketing experience these symptoms have also been observed in Parkinson's disease patients

treated with AZILECT.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell

your doctor or pharmacist.

5.

HOW TO STORE AZILECT

Keep out of the reach and sight of children.

Do not use AZILECT after the expiry date which is stated on the carton, bottle or blister. The

expiry date refers to the last day of that month.

Do not store above 25 o C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to

dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION

What AZILECT contains

-

The other ingredients are mannitol, colloidal anhydrous silica, maize starch, pregelatinised maize

starch, stearic acid, talc.

What AZILECT looks like and contents of the pack

AZILECT tablets are presented as white to off-white, round, flat, bevelled tablets, debossed with “GIL”

and “1” underneath on one side and plain on the other side.

The tablets are available in blister packs of 7, 10, 28, 30, 100 and 112 tablets or in a bottle containing 30

tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Manufacturer

Teva Pharma GmbH

Teva Pharmaceuticals Europe B.V.

D-79199 Kirchzarten

Computerweg 10

Germany

The Netherlands

24

-

The active substance is rasagiline. Each tablet contains 1 mg rasagiline (as mesilate).

Kandelstrasse 10

3542 DR Utrecht

For any information about this medicinal product, please contact the local representative of the Marketing

Authorisation Holder:

België/Belgique/Belgien

Lundbeck S.A./N.V.

Avenue Molière 225

B-1050 Bruxelles/Brussel/Brüssel

Tél/Tel: +32 2 340 2828

Luxembourg/Luxemburg

Lundbeck S.A.

Avenue Molière 225

B-1050 Bruxelles/Brüssel

Belgique/Belgien

Tél/Tel: +32 2 340 2828

България

Лундбек Експорт

Търговско представителство

ЕКСПО 2000

Бул. “Н. Вапцаров” №55

София 1407

Тел.: +359 2 962 46 96

Magyarország

Teva Magyarország Zrt.

Rákóczi út 70-72.

H-1074 Budapest

Tel.: +36 1 288 6400

Česká republika

Lundbeck Česká republika s.r.o.

Bozděchova 7

Malta

Charles di Giorgio Ltd

Triq il-Kanonku Karmenu

MT-1114 B’Kara BKR

Tel: +356 25600500

CZ-150 00 Praha 5

Tel: +420 225 275 600

Danmark

Lundbeck Pharma A/S

Dalbergstrøget 5

DK-2630 Taastrup

Tlf: +45 4371 4270

Nederland

Teva Pharma B.V.

Swensweg 5

NL-2003 RN Haarlem

Tel: +31 23 514 7147

Deutschland

Lundbeck GmbH

Karnapp 25

D-21079 Hamburg

Tel: +49 40 23649 0

Norge

H. Lundbeck AS

Postboks 361

N-1326 Lysaker

Tlf: +47 91300800

Eesti

Lundbeck Eesti AS

Weizenbergi 29

EE-10150 Tallinn

Tel: +372 605 9350

Österreich

Lundbeck Austria GmbH

Dresdner Straße 82

A-1200 Wien

Tel: +43 1 33107 0

Ελλάδα

Lundbeck Hellas S.A.

Λεωφόρος Κηφισίας 64

GR-151 25 Μαρούσι, Αθήνα

Τηλ: +30 210 610 5036

Polska

Lundbeck Poland Sp. z o. o.

ul. Krzywickiego 34

PL-02-078 Warszawa

Tel: +48 22 626 93 00

España

Lundbeck España S.A.

Av. Diagonal, 605, 9-1a

E-08028 Barcelona

Tel: +34 93 494 9620

Portugal

Lundbeck Portugal, Lda.

Quinta da Fonte

Edifício D. João I – Piso 0 Ala A

P-2770-203 Paço d’Arcos

Tel: +351 21 00 45 900

25

France

Lundbeck SAS

37-45, quai du Président Roosevelt

F-92445 Issy-les-Moulineaux Cedex

Tél: + 33 1 79 41 29 00

România

Lundbeck Export A/S Reprezentanţa din România

Str. Ghiocei no.7A, Sector 2

Bucureşti 020571 RO

Tel: +40 21 319 88 26

Ireland

Lundbeck (Ireland) Limited

7 Riverwalk

Citywest Business Campus

IRL - Dublin 24

Tel: +353 1 4689800

Slovenija

Lundbeck Pharma d.o.o.

Titova cesta 8

SI-2000 Maribor

Tel: +386 2 229 45 00

Ísland

Lundbeck Export A/S, útibú á Íslandi

Ármúla 1

IS-108 Reykjavik

Sími: +354 414 7070

Slovenská republika

Lundbeck Slovensko s.r.o.

Zvolenská 19

SK-821 09 Bratislava 2

Tel: +421 2 5341 4218

Italia

Lundbeck Italia S.p.A.

Via G. Fara 35

I-20124 Milano

Tel: +39 02 677 4171

Suomi/Finland

Oy H. Lundbeck Ab

Itäinen Pitkäkatu 4

FIN-20520 Turku (Åbo)

Puh/Tel: +358 2 276 5000

Κύπρος

Lundbeck Hellas A .E

Θεµ. ∆έρβη – Φλωρίνης

STADYL BUILDING

CY-1066 Λευκωσία

Τηλ: +357 22490305

Sverige

H. Lundbeck AB

Rundgången 30 B

Box 23

S-250 53 Helsingborg

Tel: +46 42 254300

Latvija

SIA Lundbeck Latvia

Kleistu iela 24

LV-1067 Riga

Tel: +371 7 067 884

United Kingdom

Lundbeck Limited

Lundbeck House

Caldecotte Lake Business Park

Caldecotte

Milton Keynes MK7 8LG - UK

Tel: +44 1908 64 9966

Lietuva

UAB Lundbeck Lietuva

L. Stuokos-Gucevičiaus 9-3

LT-01122 Vilnius

Tel: +370 5 231 4188

This leaflet was last approved in .

26

European Drugs Encyclopedia

European Drugs
Encyclopedia