Israel - English - Ministry of Health
PATIENT PACKAGE INSERT IN
ACCORDANCE WITH THE PHARMACISTS’
REGULATIONS (PREPARATIONS) - 1986
The medicine is dispensed with
a doctor’s prescription only.
Each tablet contains:
Rasagiline (as mesilate) 1 mg
For the list of inactive ingredients in the preparation, see
section 6 – “Further Information”.
Read this leaflet carefully in its entirety before using
the medicine. This leaflet contains concise information
about the medicine. If you have further questions, refer
to the doctor or pharmacist.
This medicine has been prescribed for the treatment
of your ailment. Do not pass it on to others. It may
harm them, even if it seems to you that their medical
condition is similar.
1. WHAT IS THE MEDICINE INTENDED FOR?
AZILECT is intended for the treatment of Parkinson’s in
adults, and can be used with or without taking levodopa.
Selective monoamine oxidase type B inhibitors.
With Parkinson’s disease, there is a loss of cells that
produce dopamine in the brain. Dopamine is a chemical
substance in the brain involved in movement control.
AZILECT helps increase and sustain levels of dopamine
in the brain.
2. BEFORE USING THE MEDICINE
Do not use the preparation if:
∙ You are sensitive (allergic) to the active ingredient
(rasagiline) or any of the additional ingredients
contained in the medicine (see section 6 – “Further
∙ You are suffering from severe liver insufficiency.
Do not use AZILECT concomitantly with the following
∙ Pethidine (a strong pain killer).
∙ Monoamine oxidase inhibitors (whether given as
medicines for depression, Parkinson’s disease, or
any other indication, including natural or medicinal
preparations given without a doctor’s prescription,
e.g. St. John’s Wort for depression).
You must wait at least 14 days between discontinuing
AZILECT and starting treatment with monoamine
oxidase inhibitors or with pethidine.
Special warnings regarding use of the medicine
Before beginning treatment with AZILECT, tell the
∙ you are suffering from a liver problem.
∙ if you noticed suspicious skin changes.
Notify the doctor if your family/caregiver notice that
you are developing unusual behaviors, where you fail
to resist an impulse, urge or desire to carry out actions
harmful or destructive to yourself or others. This
condition is defined as impulse control disorders. In
patients taking AZILECT together with other medicines
to treat Parkinson’s disease, behavior disorders, such
as compulsive behavior, obsessive thoughts, gambling
addiction, excessive spending, impulse to behave
abnormally, increased sexual drive or increased sexual
thoughts/excitement have been observed. Your doctor
will consider adjusting the dosage or stopping the
medicine (see section 4 – “Side effects”).
AZILECT may cause drowsiness and may cause you to
suddenly fall asleep during day time activities, especially
if you are taking other dopaminergic medicines (used to
treat Parkinson’s disease). For further information, see
“Driving and operating machinery” section.
Use in children and adolescents
The safety and effectiveness of AZILECT in children
and adolescents has not been tested; the medicine
has not been used to treat Parkinson’s in children and
adolescents. Therefore, AZILECT is not intended for use
under 18 years of age.
Inform the doctor or pharmacist if you smoke or plan to
stop smoking. Smoking can reduce the levels of AZILECT
in the blood.
If you are taking, have recently taken or plan to
take other medicines, including non-prescription
medicines and nutritional supplements, tell the doctor
In particular, inform the doctor if you are taking the
∙ Antidepressants (e.g., tricyclics, tetracyclics,
selective serotonin reuptake inhibitors [SSRIs],
serotonin-norepinephrine reuptake inhibitors [SNRIs]),
monoamine oxidase inhibitors.
∙ Ciprofloxacin (an antibiotic against infections).
∙ Dextromethorphan (cough suppressant).
∙ Sympathomimetics such as those present in eye drops,
oral or nasal decongestants or cold medicines that
contain ephedrine or pseudoephedrine.
Pethidine – see in section 2 “Do not use the preparation”.
Avoid using this medicine concomitantly with
antidepressants that contain fluoxetine or fluvoxamine.
Wait at least a period of 5 weeks between discontinuing
treatment with fluoxetine and starting treatment with
AZILECT. On the other hand, if you start treatment with
fluoxetine or fluvoxamine, do so at least 14 days after
discontinuing treatment with AZILECT.
Pregnancy and breastfeeding
If you are pregnant or breastfeeding, suspect that you are
pregnant or are considering becoming pregnant, consult
a doctor or pharmacist before using the medicine.
You must avoid taking AZILECT if you are pregnant, as
the effects of AZILECT on pregnancy and on the fetus
Driving and operating machinery
Consult with your doctor before you drive and operate
machinery, since Parkinson’s disease itself, as well as the
treatment with AZILECT, may influence your ability to do
so. AZILECT can cause dizziness or drowsiness and can
also cause episodes of sudden sleep onset.
The effect can be increased if you take other medicines
to treat the symptoms of your Parkinson’s disease, or if
you take medicines which can make you feel drowsy, or
if you drink alcohol while taking AZILECT.
If you have experienced drowsiness and/or episodes of
sudden sleep onset in the past or while taking AZILECT,
do not drive or operate machinery.
3. HOW SHOULD YOU USE THE MEDICINE?
Always use the medicine according to the doctor’s
instructions. Check with the doctor or pharmacist if you
are uncertain about the dosage and treatment regimen
of the preparation.
The dosage and treatment regimen will be determined
by the doctor only. The usual dosage is generally: one
1 mg tablet per day, with or without food.
Use this medicine at specified time intervals, as
determined by the attending doctor.
Do not exceed the recommended dosage
Do not crush/halve/chew! Swallow the tablet whole,
If you accidentally take a higher dosage
If you took an overdose, or if a child has accidentally
swallowed the medicine, refer immediately to a doctor
or proceed to a hospital emergency room and bring the
package of the medicine with you.
An AZILECT overdose can manifest in the following
symptoms: slightly euphoric mood (light form of mania),
very high blood pressure and serotonin syndrome (see
section 4 – “Side effects”).
If you forgot to take this medicine at the required time,
do not take two doses together to compensate for the
forgotten dose. Take the next dose at the usual time.
Adhere to the treatment regimen as recommended
by the doctor. Even if there is an improvement in your
health, do not stop treatment with AZILECT without
consulting the doctor.
Do not take medicines in the dark! Check the label and
dose each time you take medicine. Wear glasses if you
If you have further questions regarding use of the
medicine, consult the doctor or pharmacist.
4. SIDE EFFECTS
As with any medicine, use of this medicine may cause
side effects in some users. Do not be alarmed by the
list of side effects. You may not suffer from any of them.
Contact the doctor immediately if:
∙ you develop unusual behaviors such as compulsive
behavior, obsessive thoughts, gambling addiction,
excessive shopping or spending, impulsive behavior
and an abnormally high sex drive or an increase in
sexual thoughts (impulse control disorders) (see
section 2 – “Before using the medicine”).
∙ you see or hear things that do not exist (hallucinations).
∙ any combination of hallucinations, fever, restlessness,
tremor or sweating (serotonin syndrome).
∙ you notice any suspicious skin changes – consult a
specialist since there is a higher risk of skin cancer
(not exclusively melanoma) in patients with Parkinson’s
disease (see section 2 – “Before using the medicine”).
Additional side effects
Very common side effects – effects that occur in more
than 1 user in 10:
∙ involuntary movements (dyskinesia)
Common side effects – effects that occur in 1-10
in 100 users:
∙ abdominal pain
∙ allergic reactions
∙ general unwell feeling
∙ neck pain
∙ chest pain (angina pectoris)
∙ low blood pressure upon transitioning from sitting to
standing with symptoms such as dizziness
∙ anorexia (lack of appetite)
∙ dry mouth
∙ nausea and vomiting
∙ abdominal bloating
∙ abnormal blood test results (leucopenia - reduced
number of white blood cells)
∙ joint pain
∙ muscle pain
∙ numbness and weakness of the hand muscles (Carpal
∙ weight loss
∙ abnormal dreams
∙ dizziness (vertigo)
∙ prolonged muscle contractions (dystonia)
∙ runny nose (nasal inflammation)
∙ skin irritation (skin inflammation - dermatitis)
∙ red and swollen eyes (conjunctivitis)
∙ urinary urgency
Uncommon side effects – effects that occur in 1-10
in 1,000 users:
∙ heart attack (myocardial infarction)
∙ a rash that appears in the form of blisters
Side effects whose frequency is unknown (it is not
possible to know the frequency based on the existing
∙ rise in blood pressure
∙ excessive drowsiness
∙ sudden onset of sleep
If a side effect occurs, if one of the side effects worsens
or if you suffer from a side effect not mentioned in
this leaflet, consult with the doctor.
Side effects can be reported to the Ministry of Health
by clicking on the link “Report Side Effects of Drug
Treatment” found on the Ministry of Health homepage
(www.health.gov.il) that directs you to the online form for
reporting side effects, or by entering the link:
5. HOW SHOULD THE MEDICINE BE STORED?
∙ Avoid poisoning! This medicine and any other medicine
should be kept in a safe place out of the reach of
children and/or infants in order to avoid poisoning. Do
not induce vomiting unless explicitly instructed to do
so by the doctor.
∙ Do not use the medicine after the expiry date
(exp. date) that appears on the package. The expiry
date refers to the last day of that month.
∙ Store in a cool place, below 25°C. Store in the original
∙ Do not discard medicines in the wastewater or waste
bin. Ask the pharmacist how to dispose of medicines
that are not in use. These measures will help protect
6. FURTHER INFORMATION
In addition to the active ingredient, the medicine also
Mannitol, starch, pregelatinized starch, stearic acid, talc,
colloidal silicon dioxide.
What the medicine looks like and the contents of
A white to off-white, round tablet, debossed with “GIL”
and “1” underneath on one side and plain on the other
The package contains 10 or 30 tablets.
Not all package sizes may be marketed.
Name of Manufacturer and License Holder and its
Teva Pharmaceutical Industries Ltd.,
P.O.B. 3190, Petah-Tikva.
This leaflet was checked and approved by the Ministry of
Health in June 2014 and was updated in February 2018
in accordance with the Ministry of Health guidelines.
Registration number of the medicine in the National
Drug Registry of the Ministry of Health:
AZIL TAB PL SH 180718
AZIL TAB PL SH 180718
فقوتلا زوجي لا .بيبطلا ةيصوت بسح جلاعلا ىلع ةبظاوملا بجي نسحت أرط ولو ىتح بيبطلا ةراشتسإ نودب تكليزأ ـب جلاعلا نع .ةيحصلا كتلاح ىلع دكأتلاو ءاودلا عباط صيخشت بجي !ةمتعلا يف ةيودأ لوانت زوجي لا ةيبطلا تاراظنلا عض .ءاود اهيف لوانتت ةرم لك يف ةيئاودلا ةعرجلا نم .كلذ رملأا مزل اذإ بيبطلا رشتسإ ،ءاودلا اذه لامعتسإ لوح ةيفاضإ ةلئسأ كيدل ترفوت اذإ .يلديصلا وأ ةيبناجلا ضارعلأا )4 دنع ةيبناج
اضارعأ ببسي دق ءاودلا اذه لامعتسإ نإ ،ءاود لكب امك زئاجلا نم .ةيبناجلا ضارعلأا ةمئاق نم شهدنت لا .نيلمعتسملا ضعب .اهنم
ايأ يناعت لاأ :اذإ بيبطلل
لااح هجوتلا بجي ،ةيساوسو راكفأ ،يرسق كولس لثم ةذاش تايكولس كيدل تروطت ∙ مجان كولس ،هيف غلابم لكشب ءارشلا وأ قافنلإا ،رامقلا ىلع نامدلإا ةيسنج راكفأ وأ داتعملا نع ةدئاز ةيسنج ةبغرو )ةيعافدنإ( عفاد نع لبق« ـ 2 ةرقفلا رظنأ( )عفاودلا يف مكحتلا تابارطضإ( ةديازتم .)»ءاودلا لامعتسإ .)نايذه( ةدوجوم ريغ ءايشأ عمست وأ ىرت تنك ∙ قرعت وأ فاجترإ ،ةحار مدع ،ةنوخس ،نايذه نم جيزم يأ كيدل دجو ∙ .)نينوتوريسلا ةمزلاتم(
ارظن صتخم ةراشتسإ بجي ،كشلل ةريثم ةيدلج تاريغت تظحلا
)امونلايم طقف سيل( دلجلا ناطرس ثودحل ةدئاز ةروطخ دوجول .)»ءاودلا لامعتسإ لبق« ـ 2 ةرقفلا رظنأ( نوسنيكراپلا ىضرم ىدل ةيفاضإ ةيبناج ضارعأ لمعتسم نم رثكأ ىدل رهظت ضارعأ ـ
ادج ةعئاش ةيبناج ضارعأ :ةرشع نيب نم دحاو
( ةيدارإ لا تاكرح ∙ عادص ∙ نيلمعتسم 10-1 ىدل رهظت ضارعأ ـ ةعئاش ةيبناج ضارعأ :100 نيب نم نطبلا يف ملاآ
طوقس ∙ ةيسسحت لعف دودر ∙ ةنوخس ∙ ازنإولفنإ
ةكعوب ماع روعش ∙ ةبقرلا يف ملاآ
)ةيبلق ةحبذ( ردصلا يف ملأ
فوقولا ىلإ سولجلا ةيعضو نم لاقتنلإا دنع مدلا طغض ضافخنإ
راودلا لثم ضارعأ عم )ماعطلل ةيهشلا ةلق(
مفلا فافج ∙ ؤيقتو نايثغ ∙ نطبلا يف خافتنإ
مدلا ايلاخ ةلق ـ
( مدلا صوحف جئاتن ةملاس مدع ∙ )ءاضيبلا ةيلصفم ملاآ
( لصافملا باهتلإ
Carpal Tunnel syndrome
( ديلا ةحار تلاضع يف فعضو ردخ ∙ نزولا صقانت ∙ ةذاش ملاحأ
)نزاوتلا يف بارطضإ( تلاضعلا قسانت يف ةبوعص ∙ بائتكإ
)وغيتريﭬ( راود ∙
( تلاضعلل لصاوتم صلقت ∙ )فنلأا باهتلإ( حشر ∙
ـ دلجلا باهتلإ( دلجلا جيهت ∙ حفط ∙ )ةمحتلملا باهتلإ( نينيعلا خافتنإو رارمحإ
لوبتلا ىلع حاحللإا
نيلمعتسم 10-1 ىدل رهظت ضارعأ ـ ةعئاش ريغ ةيبناج ضارعأ :1000 نيب نم ةيغامد ةتكس ∙ )بلقلا ةلضع ءاشتحإ( ةيبلق ةبون ∙ تلاصيوح لكش ىلع رهظي يذلا حفط ∙ عويشلا ةفرعم نكمي لا( فورعم ريغ اهعويش ةيبناج ضارعأ )ةرفوتملا تامولعملا نم مدلا طغض عافترإ
طرفم ساعن ∙ ئجافملا مونلا
وأ ةيبناجلا ضارعلأا ىدحإ تمقافت اذإ ،يبناج ضرع رهظ اذإ كيلع ،ةرشنلا هذه يف ركذي مل يبناج ضرع نم يناعت امدنع .بيبطلا ةراشتسإ طغضلا ةطساوب ةحصلا ةرازول ةيبناج ضارعأ نع غيلبتلا ناكملإاب دوجوملا »يئاود جلاع بقع ةيبناج ضارعأ نع غيلبت« طبارلا ىلع
( ةحصلا ةرازو عقومل ةيسيئرلا ةحفصلا ىلع نع وأ ةيبناج ضارعأ نع غيلبتلل رشابملا جذومنلا ىلإ كهجوي يذلا :طبارلا حفصت قيرط
؟ءاودلا نيزخت ةيفيك )5 قلغم ناكم يف رخآ ءاود لكو ءاودلا اذه ظفح بجي !ممستلا بنجت ∙ مهتباصإ يدافتل كلذو عضرلا وأ/و لافطلأا يديأ لوانتم نع
اديعب .بيبطلا نم ةحيرص تاميلعت نودب ؤيقتلا ببست لا .ممستلاب
( ةيحلاصلا خيرات ءاضقنإ دعب ءاودلا لامعتسإ زوجي لا ∙ ريخلأا مويلا ىلإ ةيحلاصلا خيرات ريشي .ةبلعلا رهظ ىلع رهظي يذلا .رهشلا سفن نم ءاودلا ظفحي ،ةيوئم ةجرد 25 نود دراب ناكم يف نيزختلا بجي ∙ .ةيلصلأا ةبلعلا يف نع يلديصلا لأسإ .ةمامقلا يف وأ يراجملا يف ةيودلأا يمر زوجي لا ∙ دعاست لئاسولا هذه .لامعتسلإا ديق دعت مل ةيودأ نم صلختلا ةيفيك .ةئيبلا ىلع ظافحلا يف ةيفاضإ تامولعم )6
اضيأ ةلاعفلا ةداملل ةفاضلإاب ءاودلا يوتحي
Mannitol, starch, pregelatinized starch, stearic acid, talc,
colloidal silicon dioxide.
ةبلعلا ىوتحم وه امو ءاودلا ودبي فيك بناج يف »
« ةعابطلا عم ركع ضيبأ وأ ضيبأ هنول ريدتسم صرق .صرقلا نم يناثلا بناجلا يف ةعابط نودبو »
« هتحتو صرقلا نم دحاو
اصرق 30 وأ 10 ىلع ةبلعلا يوتحت .بلعلا ماجحأ ةفاك ق
وست لاأ زئاجلا نم هناونعو زايتملإا بحاصو جتنملا مسإ ،.ض.م ةيبطلا تارضحتسملاو ةيودلأل عڤيت .اڤكت ـ حتيپ ،3190 .ب.ص يف صخ
ف اهاوتحمو ةرشنلا هذه ةغيص ةحصلا ةرازو ترقأ ةحصلا ةرازو تاميلعت بجومب اهثيدحت متو 2014 ناريزح خيرات 2018 طابش خيراتب :ةحصلا ةرازو يف يموكحلا ةيودلأا لجس يف ءاودلا لجس مقر
.ركذملا ةغيصب ةرشنلا هذه ةغايص تمت ،ةءارقلا نيوهتو ةلوهس لجأ نم .نيسنجلا لاكل صصخم ءاودلا نإف ،كلذ نم مغرلا ىلع ةمتت
SUMMARY OF PRODUCT CHARACTERISTICS
NAME OF THE MEDICINAL PRODUCT
AZILECT 1 mg tablets
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains 1 mg rasagiline (as mesilate).
For the full list of excipients, see section
White to off-white, round, flat, bevelled tablets, debossed with “GIL” and “1” underneath on one side
and plain on the other side.
AZILECT is indicated for the treatment of idiopathic Parkinson’s disease as monotherapy (without
levodopa) or as adjunct therapy (with levodopa) in patients with end of dose fluctuations.
Posology and method of administration
The recommended dose of rasagiline is 1 mg (one tablet of AZILECT) once daily, to be taken with or
No change in dose is required for elderly patients (see section 5.2).
Rasagiline is contraindicated in patients with severe hepatic impairment (see section
4.3). 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 and 5.2).
No special precautions are required in patients with renal impairment.
The safety and efficacy of AZILECT in children and adolescents have not been established. There is no
relevant use of AZILECT in the paediatric population in the indication Parkinson’s disease.
Method of administration
For oral use.
AZILECT may be taken with or without food.
Hypersensitivity to the active substance or to any of the excipients listed in 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.
Severe hepatic impairment.
Special warnings and precautions for use
Concomitant use of rasagiline with other medicinal products
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).
Concomitant use of rasagiline and levodopa
Since rasagiline potentiates the effects of levodopa, the adverse reactions of levodopa may be increased
and pre-existing dyskinesia exacerbated. Decreasing the dose of levodopa may ameliorate this adverse
There have been reports of hypotensive effects when rasagiline is taken concomitantly with levodopa.
Patients with Parkinson’s disease are particularly vulnerable to the adverse reactions of hypotension due
to existing gait issues.
Excessive daytime sleepiness (EDS) and sudden sleep onset (SOS) episodes
Rasagiline may cause daytime drowsiness, somnolence, and, occasionally, especially if used with other
dopaminergic medicinal products - falling asleep during activities of daily living. Patients must be
informed of this and advised to exercise caution while driving or operating machines during treatment
with rasagiline. Patients who have experienced somnolence and/or an episode of sudden sleep onset must
refrain from driving or operating machines (see section 4.7).
Impulse control disorders (ICDs)
ICDs can occur in patients treated with dopamine agonists and/or dopaminergic treatments. Similar
reports of ICDs have also been received post-marketing with rasagiline. Patients should be regularly
monitored for the development of impulse control disorders. Patients and carers should be made aware of
the behavioural symptoms of impulse control disorders that were observed in patients treated with
rasagiline, including cases of compulsions, obsessive thoughts, pathological gambling, increased libido,
hypersexuality, impulsive behaviour and compulsive spending or buying.
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
Interaction with other medicinal products and other forms of interaction
Rasagiline is contraindicated 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).
SNRI/SSRI/tri- and tetracyclic antidepressants
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.
Agents that affect CYP1A2 activity
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.
Other cytochrome P450 isoenzymes
studies showed that rasagiline at a concentration of 1 µg/ml (equivalent to a level that is 160
times the average C
~ 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 (see section 5.3).
Levodopa and other Parkinson’s disease medicinal products
In Parkinson’s disease patients receiving rasagiline as adjunct therapy to chronic levodopa treatment,
there was no clinically significant effect of levodopa treatment on rasagiline clearance.
Concomitant administration of rasagiline and entacapone increased rasagiline oral clearance by 28%.
Results of five tyramine challenge studies (in volunteers and Parkinson’s disease 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.
Fertility, pregnancy and lactation
There are no data from the use of rasagiline in pregnant women. Animals studies do not indicate direct
or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary
measure, it is preferable to avoid the use of rasagiline during pregnancy.
Non-clinical data indicate 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.
No human data on the effect of rasagiline on fertility are available. Non-clinical data indicate that
rasagiline has no effect on fertility.
Effects on ability to drive and use machines
In patients experiencing somnolence/sudden sleep episodes, rasagiline may have major influence on the
ability to drive and use machines.
Patients should be cautioned about operating hazardous machines, including motor vehicles, until they
are reasonably certain that rasagiline does not affect them adversely.
Patients being treated with rasagiline and presenting with somnolence and/or sudden sleep episodes must
be informed to refrain from driving or engaging in activities where impaired alertness may put
themselves or others at risk of serious injury or death (e.g. operating machines) until they have gained
sufficient experience with rasagiline and other dopaminergic medications to gauge whether or not it
affects their mental and/or motor performance adversely.
If increased somnolence or new episodes of falling asleep during activities of daily living (e.g. watching
television, passenger in a car, etc.) are experienced at any time during treatment, the patients should not
drive or participate in potentially dangerous activities.
Patients should not drive, operate machinery, or work at heights during treatment if they have previously
experienced somnolence and/or have fallen asleep without warning prior to use of rasagiline.
Patients should be cautioned about possible additive effects of sedating medicinal products, alcohol, or
other central nervous system depressants (e.g. benzodiazepines, antipsychotics, antidepressants) in
combination with rasagiline, or when taking concomitant medications that increase plasma levels of
rasagiline (e.g. ciprofloxacin) (see section 4.4).
Summary of the safety profile
In clinical studies in Parkinson's disease patients the most commonly reported adverse reactions were:
headache, depression, vertigo, and flu (influenza and rhinitis) in monotherapy; dyskinesia, orthostatic
hypotension, fall, abdominal pain, nausea and vomiting, and dry mouth in adjunct to levodopa therapy;
musculoskeletal pain, as back and neck pain, and arthralgia in both regimens. These adverse reactions
were not associated with an elevated rate of drug discontinuation.
Tabulated list of adverse reactions
Adverse reactions are listed below in Tables 1 and 2 by system organ class and frequency using the
following conventions: very common (≥1/10), common (≥1/100 to <1/10), uncommon
(≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), not known (cannot be
estimated from the available data).
The tabulated list below includes adverse reactions which were reported with a higher incidence in
placebo-controlled studies, in patients receiving 1 mg/day rasagiline.
and sudden sleep
Ear and labyrinth
Renal and urinary
*See section description of selected adverse reactions
The tabulated list below includes adverse reactions which were reported with a higher incidence in
placebo-controlled studies in patients receiving 1 mg/day rasagiline.
and sudden sleep
*See section description of selected adverse reactions
Description of selected adverse reactions
In blinded placebo-controlled studies, severe orthostatic hypotension was reported in one subject (0.3%)
in the rasagiline arm (adjunct studies), none in the placebo arm. Clinical trial data further suggest that
orthostatic hypotension occurs most frequently in the first two months of rasagiline treatment and tends
to decrease over time.
Rasagiline selectively inhibits MAO-B and is not associated with increased tyramine sensitivity at the
indicated dose (1 mg/day). In blinded placebo-controlled studies (monotherapy and adjunct) severe
hypertension was not reported in any subjects in the rasagiline arm. In the post-marketing period, cases of
elevated blood pressure, including rare serious cases of hypertensive crisis associated with ingestion of
unknown amounts of tyramine-rich foods, have been reported in patients taking rasagiline. In post-
marketing period, there was one case of elevated blood pressure in a patient using the ophthalmic
vasoconstrictor tetrahydrozoline hydrochloride while taking rasagiline.
Impulse control disorders
One case of hypersexuality was reported in monotherapy placebo-controlled study. The following were
reported during post-marketing exposure with unknown frequency: compulsions, compulsive shopping,
dermatillomania, dopamine dysregulation syndrome, impulse-control disorder, impulsive behaviour,
kleptomania, theft, obsessive thoughts, obsessive-compulsive disorder, stereotypy, gambling,
pathological gambling, libido increased, hypersexuality, psychosexual disorder, sexually inappropriate
behaviour. Half of the reported ICD cases were assessed as serious. Only single cases of reported cases
had not recovered at the time they were reported.
Excessive daytime sleepiness (EDS) and sudden sleep onset (SOS) episodes
Excessive daily sleepiness (hypersomnia, lethargy, sedation, sleep attacks, somnolence, sudden onset of
sleep) can occur in patients treated with dopamine agonists and/or other dopaminergic treatments. A
similar pattern of excessive daily sleepiness has been reported post-marketing with rasagiline.
Cases of patients, treated with rasagiline and other dopaminergic medicinal products, falling asleep while
engaged in activities of daily living have been reported. Although many of these patients reported
somnolence while on rasagiline with other dopaminergic medicinal products, some perceived that they
had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior
to the event. Some of these events have been reported more than 1-year after initiation of treatment.
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 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 (see section 4.5).
In the post-marketing period, cases of potentially life-threating serotonin syndrome associated with
agitation, confusion, rigidity, pyrexia and myoclonus have been reported by patients treated with
antidepressants, meperidine, tramadol, methadone, or propoxyphene concomitantly with rasagiline.
Incidence of skin melanoma in placebo-controlled clinical studies was 2/380 (0.5%) in rasagiline 1 mg as
adjacent to levodopa therapy group vs. 1/388 (0.3%) incidence in placebo group. Additional cases of
malignant melanoma were reported during post-marketing period. These cases were considered serious in
Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows
continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events
should be reported to the Ministry of Health according to the National Regulation by using an online
Symptoms reported following overdose of rasagiline in doses ranging from 3 mg to 100 mg included
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 reactions 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 adverse 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.
Pharmacotherapeutic group: Anti-Parkinson-Drugs, monoamine oxidase -B inhibitors, ATC code:
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 efficacy and safety
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.
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
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, 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).
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
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.
Rasagiline is rapidly absorbed, reaching peak plasma concentration (C
) in approximately 0.5 hours.
The absolute bioavailability of a single rasagiline dose is about 36%.
Food does not affect the T
of rasagiline, although C
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.
The mean volume of distribution following a single intravenous dose of rasagiline is 243 l. Plasma
protein binding following a single oral dose of
C-labelled rasagiline is approximately 60 to 70%.
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.
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.
experiments demonstrate that rasagiline is neither inhibitor nor inducer of major CYP450 enzymes
(see section 4.5).
After oral administration of
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.
Rasagiline pharmacokinetics is linear with dose over the range of 0.5-2 mg in Parkinson’s disease
patients. Its terminal half-life is 0.6-2 hours.
In subjects with mild hepatic impairment, AUC and C
were increased by 80% and 38%, respectively.
In subjects with moderate hepatic impairment, AUC and C
were increased by 568% and 83%,
respectively (see section
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.
Age has little influence on rasagiline pharmacokinetics in the elderly (> 65 years) (see section 4.2)
Preclinical safety data
Non-clinical data reveal no special hazard for humans based on the standard studies of safety
pharmacology, repeated dose toxicity, genotoxicity, carcinogenicity, reproduction and development.
Rasagiline did not present genotoxic potential
and in several
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
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.
List of excipients
colloidal silicon dioxide
The expiry date of the product is indicated on the packaging materials
Special precautions for storage
Store in a cool place not above 25ºC.
Store in the original package.
Nature and contents of container
Aluminium/aluminium blister packs of 7, 10, 28, 30, 100 or 112 tablets.
Aluminium/aluminium perforated unit dose blister packs of 10 x 1, 30 x 1 and 100 x 1 tablets.
White, high-density polyethylene bottle with or without a child-resistant cap containing 30 tablets.
Not all pack sizes may be marketed.
Special precautions for disposal
No special requirements for disposal.
MARKETING AUTHORISATION HOLDER
Teva Pharmaceutical Industries Ltd.,
P. O. Box 3190,
Petach Tikva 49131.
132 17 31000
The content of this leaflet was approved by the Ministry of Health in 06.2014 and updated according to
the guidelines of the Ministry of Health in 02.2018
)תוחיטב )תוחיטב ןכדועמ( ןכדועמ(
January 7, 2014
AZILECT Tablets 1 mg
אפור אפור דבלב תורמחהה טורפל דעוימ הז ספוט
Posology, dosage & administration
Special Warnings and Special
Precautions for Use
Impulse control disorders (ICDs) can occur in patients
treated with dopamine agonists and/or dopaminergic
treatments. Similar reports of ICDs have also been
received post-marketing with rasagiline. Patients should
be regularly monitored for the development of impulse
control disorders. Patients and carers should be made
aware of the behavioural symptoms of impulse control
disorders that were observed in patients treated with
rasagiline, including cases of compulsions, obsessive
hypersexuality, impulsive behaviour and compulsive
spending or buying.
Since rasagiline potentiates the effects of levodopa, the
adverse effects of levodopa may be increased and pre-
existing dyskinesia exacerbated. Decreasing the dose of
levodopa may ameliorate this side effect.
There have been reports of hypotensive effects when
rasagiline is taken concomitantly with levodopa. Patients
with Parkinson’s disease are particularly vulnerable to
the adverse effects of hypotension due to existing gait
Interaction with Other
Medicaments and Other Forms of
Fertility, pregnancy and
Impulse control disorders
Pathological gambling, increased libido, hypersexuality,
compulsive spending or buying, binge eating and
compulsive eating can occur in patients treated with
rasagiline, which also included compulsions, obsessive
thoughts and impulsive behaviour (see section 4.4).
ןכרצל ןכרצל תורמחהה
שמתשהל ןיא יתמ
רועב ןיחבמ ךניהו הדימב לפטמה/אפורל חוודל שי ,ףחדב דמוע ךניא רשאכ תוגירח תוגהנתהב וא תוקיזמ תולועפ עצבל הקושת וא יוריג רדגומ הז בצמ .םירחאב וא ךמצעב תוינסרה םילפוטמב .םיפחד לע הטילש תוערפהכ תורחא תופורת םע דחי וז הפורת םילטונה תוערפה ופצנ ,ןוסניקרפה תלחמב לופיטל ,תויביססבוא תובשחמ ,הייפכ ןוגכ תוגהנתהב ףחד ,תומזגומ תואצוה ,םירומיהל תורכמתה ינימ
תוגהנתהל אפורה .םירבגומ םיינימ םישוגיר/תובשחמ/רבגומ .ןונימה תקספה וא המאתה לוקשי ךלש םע תינמז-וב וז הפורתב שומישמ ענמיהל שי וא ןיטסקואולפ תוליכמה ןואכיד ידגונ תופורת לש הפוקתל ןיתמהל שי .ןימסקובולפ
תועובש ןיטסקואולפב לופיטה תקספה רחאל תוחפל ךניהו הדימב ,ךדיאמ .טקליזאב לופיטה תליחתו שי ןימסקובולפ וא ןיטסקואולפב לופיט ליחתמ תוחפל ןיתמהל
לופיטה תקספה רחאל םימי .טקליזאב
תועגונה תודחוימ תורהזא
הפורתב שמתשהל ןיא
ינפל אפורב ץעוויהל ילבמ
תויתופורת ןיב תובוגת יאוול תועפותב הילע לש םיקרמ וחווד -הפודובל האצותכ םדה ץחלב הדירי םגו הפודובל לש .הפודובלו טקליזא לש בולישהמ
הפורתב שמתשת דציכ
יאוול תועפות וא הפורת ולטנש םילפוטמ םהב םירקמ ולגתנ דגנתהל םילוכי םניא ןוסניקרפב לופיטל רתוי וא תוקיזמ תולועפ עצבל יותיפ וא יוריג ,ףחדל רדגומ הז בצמ .םירחאל וא םמצעל תוינסרה םילטונה םילוחב .םיפחד לע הטילש תוערפהכ ,ןוסניקרפב לופיטל תורחא תופורת וא/ו טקליזא :תואבה תועפותה ופצנ .ףחד ךותמ תוגהנתה וא תויביססבוא תובשחמ תוכלשהה תורמל םימזגומ םירומיהל קזח ףחד .תורומחה תויתחפשמה וא תוישיאה םגיאדמ םיינימ תוגהנתהו ףחדב הרבגה וא יוניש .ינימה יוריגה תרבגה ןוגכ ,םירחאל וא ךל .תוטלשנ יתלבו תומזגומ תואצוהו תושיכר ל"נה תועפותהמ תחאב ןיחבמ ךניהו הדימב וא לרטנל דציכ לוקשי אוה .אפורל חוודל ךילע .ולא תועפות תיחפהל