EXELON 6 MG

Israel - English - Ministry of Health

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Active ingredient:
RIVASTIGMINE AS HYDROGEN TARTRATE
Available from:
NOVARTIS ISRAEL LTD
ATC code:
N06DA03
Pharmaceutical form:
CAPSULES
Composition:
RIVASTIGMINE AS HYDROGEN TARTRATE 6 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
NOVARTIS PHARMACEUTICA S.A.,SPAIN
Therapeutic group:
RIVASTIGMINE
Therapeutic area:
RIVASTIGMINE
Therapeutic indications:
Treatment of patients with mild to moderately severe dementia of the alzheimer type, also termed probable alzheimer's disease or alzheimer's disease.Symptomatic treatment of mild to moderately severe Alzheimer's dementia.Symptomatic treatment of mild to moderately severe dementia associated with Parkinson's disease.
Authorization number:
110 69 29192 00
Authorization date:
2013-04-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

24-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

08-09-2020

PATIENT PACKAGE INSERT IN ACCORDANCE

WITH THE PHARMACISTS’ REGULATIONS

(PREPARATIONS) - 1986

The medicine is dispensed with a doctor’s

prescription only

EXELON

®

1.5 mg, 3 mg, 4.5 mg, 6 mg

Capsules

Active ingredient:

Each capsule contains Rivastigmine (as hydrogen tartrate)

1.5 mg, 3 mg, 4.5 mg, 6 mg

Inactive ingredients:

See section 6 ‘Further Information’.

Read the 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 ailment is similar.

1. WHAT IS THE MEDICINE INTENDED FOR?

For the treatment of patients with mild to moderate-severe

Alzheimer’s-type dementia, also called Alzheimer’s

disease.

For the treatment of the symptoms of mild to moderate-

severe Alzheimer’s disease dementia.

For symptomatic treatment of mild to moderate-severe

dementia associated with Parkinson’s disease.

Rivastigmine belongs to a class of substances called

cholinesterase inhibitors. In patients with dementia as

a result of either Alzheimer’s or Parkinson’s disease,

certain nerve cells in the brain die, causing low levels

of the neurotransmitter acetylcholine (a substance that

allows nerve cells to communicate with each other).

Rivastigmine works by blocking the enzymes that

break down acetylcholine: acetylcholinesterase and

butyrylcholinesterase. By blocking these enzymes, Exelon

allows levels of acetylcholine in the brain to be increased,

helping to reduce the symptoms of Alzheimer’s disease

and dementia associated with Parkinson’s disease.

Exelon is intended for the treatment of adult patients with

mild to moderate-severe Alzheimer’s disease dementia, a

progressive brain disorder that gradually affects memory,

intellectual ability and behavior. The capsules can also be

used for the treatment of dementia in adult patients with

Parkinson’s disease.

Therapeutic group:

Cholinesterase inhibitors.

2. BEFORE USING THE MEDICINE

X

Do not use the medicine if:

you are sensitive (allergic) to rivastigmine (the active

ingredient of Exelon), or to any of the additional

ingredients contained in the medicine, listed in

section 6.

you have had a skin reaction while using the Exelon

patch, that spread beyond the Exelon patch size, if

you had an intense local reaction (such as blisters,

increased skin inflammation, swelling) and if this

condition did not improve within 48 hours after

removal of the patch.

you are pregnant or breast-feeding.

If these conditions apply to you, notify the doctor and

do not take Exelon.

Special warnings regarding use of the medicine

!

Before treatment with Exelon, tell the doctor if:

you have, or have ever had, an irregular or slow

heartbeat.

you have, or have ever had, an active stomach ulcer.

you have, or have ever had, difficulties in passing urine.

you have, or have ever had, seizures.

you have, or have ever had, asthma or a severe

respiratory disease.

you have, or have ever had, impaired kidney function.

you have, or have ever had, impaired liver function.

you suffer from trembling.

you have a low body weight.

you have gastrointestinal reactions such as a sick feeling

of nausea, vomiting and diarrhea. You may become

dehydrated (due to loss of too much fluid), if the vomiting

or diarrhea persist.

If any of these apply to you, your doctor may need to

monitor you more closely during the course of treatment

with the medicine.

If you have not taken Exelon for more than three days, do

not resume taking the medicine without consulting with

the attending doctor.

!

Children and adolescents

Use of Exelon is not relevant for the treatment of

Alzheimer’s disease in children.

!

Drug interactions

If you are taking, or have recently taken, other

medicines, including non-prescription medicines

and nutritional supplements, tell the doctor or

pharmacist.

Do not take Exelon at the same time as other medicines

with effects similar to Exelon.

Exelon may interfere with anticholinergic medicines

(medicines used to relieve stomach cramps or spasms,

to treat Parkinson’s disease or to prevent travel sickness).

Do not take Exelon together with metoclopramide (a

medicine used to relieve or prevent nausea and vomiting).

Taking the two medicines together may cause problems

such as stiff limbs and trembling hands.

If you are about to undergo surgery while taking Exelon,

inform the doctor before you are given any anesthetics as

Exelon can increase the effects of some muscle relaxants

during anesthesia.

Caution should be exercised when Exelon is taken

together with beta-blockers (medicines such as atenolol

used to treat hypertension, angina pectoris and other heart

conditions). Taking the two medicines together may cause

problems such as slow heartbeat (bradycardia) that may

result in fainting or loss of consciousness.

!

Use of Exelon and food

Take Exelon twice a day, once with breakfast and once

with dinner.

!

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you are

pregnant or are planning a pregnancy, ask your doctor or

pharmacist for advice before taking the medicine.

If you are pregnant, the benefits of using Exelon should

be assessed against the possible effects on your unborn

child.

Do not use Exelon during pregnancy, unless its use is

absolutely necessary.

Do not breast-feed during treatment with Exelon.

!

Driving and operating machinery

The doctor will tell you whether your illness allows you to

drive a car and safely operate machinery.

Exelon may cause dizziness and somnolence, mainly at

the start of treatment or when increasing the dosage. If

you feel dizzy or sleepy, do not drive, operate machinery

or engage in any activity that requires concentration.

3. HOW SHOULD YOU USE THE MEDICINE?

Always use the preparation according to the doctor’s

instructions. Check with the doctor or pharmacist if you

are uncertain regarding the dosage and treatment regimen

of the preparation.

How to start treatment?

The dosage and the treatment regimen will be determined

by the doctor only.

Treatment generally begins with a low dose.

The doctor will gradually increase your dose, depending

on your response to the treatment.

The highest dose that should be taken is 6 mg twice a

day.

During the course of treatment, the doctor will regularly

check if your medicine is working for you. The doctor will

also monitor your weight while you are taking the medicine.

If you have not taken Exelon for more than three days, do

not take the next dose until you consult with your doctor.

Do not exceed the recommended dosage.

Treatment duration -

Tell your caregiver that you are taking Exelon.

To benefit from the medicine, take the medicine every

day.

Take Exelon twice a day, in the morning and evening,

with food.

Method of administration

Do not chew! Swallow the capsules whole with a drink.

Do not open or crush the capsules.

If you took a higher dosage of Exelon than required, tell

your doctor. You may require medical supervision. 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.

There have been patients who accidentally took an

overdose of Exelon and showed signs of feeling malaise:

nausea, vomiting, diarrhea, high blood pressure and

hallucinations. Slow heartbeat and fainting may also occur.

If you forget to take Exelon

If you forgot to take your Exelon dose at the scheduled

time, do not take a double dose to compensate for the

forgotten dose. Take the next dose at the scheduled time.

If you have further questions regarding use of the

medicine, ask your doctor or the pharmacist.

Adhere to the treatment regimen as recommended by your

doctor. Even if there is an improvement in your health, do

not stop treatment with the medicine without consulting

the doctor.

Do not take medicines in the dark! Check the label and

the dose each time you take medicine. Wear glasses

if you need them.

If you have further questions regarding use of the

medicine, consult the doctor or the pharmacist.

4. SIDE EFFECTS

As with any medicine, use of Exelon may cause side

effects in some users. Do not be alarmed when reading

the list of side effects. You may not suffer from any of them.

The frequency of side effects may be higher at the

beginning of treatment or when increasing the dose of the

medicine. The side effects will most probably disappear

gradually as the body gets used to the medicine.

Very common side effects (may occur in more than 1

in 10 users):

Dizziness

Loss of appetite

Stomach problems such as feeling sick (nausea) or

being sick (vomiting), diarrhea

Common side effects (may occur in up to 1 in 10 users):

Anxiety

Sweating

Headache

Heartburn

Weight loss

Stomach pain

Feeling agitated

Feeling tired or weak

Generally feeling unwell

Trembling or feeling confused

Loss of appetite

Nightmares

Uncommon side effects (may occur in up to 1 in 100

users):

Depression

Difficulty sleeping

Fainting or accidental falls

Changes in liver function

Rare side effects (may occur in up to 1 in 1,000 users):

Chest pain

Rash, itching

Fits

Ulcers in the stomach or intestine

Very rare side effects (may occur in up to 1 in 10,000

users):

High blood pressure

Urinary tract infection

Hallucinations

Heartbeat problems, such as: fast or slow heartbeat

Bleeding in the intestines – shows as blood in stools or

when vomiting

Inflammation of the pancreas – symptoms include severe

upper stomach pain, often with nausea or vomiting

Worsening of Parkinson’s disease symptoms or

development of similar symptoms – such as stiff

muscles, difficulty in carrying out movements

Side effects of unknown frequency (frequency cannot

be estimated from the available data):

Being violently sick, with vomiting that can cause tearing

of the oesophagus, a tube that connects the mouth and

the stomach

Dehydration (loss of a lot of fluid)

Liver disorders (yellow skin, yellowing of the whites of

the eyes, abnormal darkening of the urine or unexplained

nausea, vomiting, tiredness and lack of appetite)

Aggression, feeling restless

Irregular heartbeat

Patients with Parkinson’s disease-associated

dementia:

In these patients, side effects are more common. They

also have some additional side effects:

Very common side effects (may occur in more than 1

in 10 users):

Trembling

Fainting

Accidental falls

Common side effects (may occur in up to 1 in 10 users):

Anxiety

Feeling restless

Slow heartbeat

Difficulty sleeping

Too much saliva and dehydration

Unusually slow movements or movements that cannot

be controlled

Worsening of Parkinson’s disease symptoms or

development of similar symptoms, such as stiff muscles,

difficulty in carrying out movements and muscle

weakness

Uncommon side effects (may occur in up to 1 in 100

users):

Irregular heartbeat and poor control of movements.

Other side effects that have been reported with

Exelon patches and which may also occur with the

capsules:

Common side effects (may occur in up to 1 in 10 users):

Fever

Severe confusion

Urinary incontinence (lack of control of passing urine)

Uncommon side effects (may occur in up to 1 in 100

users):

Hyperactivity (high level of activity, restlessness)

Side effects of unknown frequency (frequency cannot

be estimated from the available data):

Localized allergic reaction when a patch was used, such

as blisters or skin inflammation

If you experience any of these side effects, refer to your

doctor as you may need medical assistance.

If a side effect occurs, if one of the side effects worsens

or if you suffer from a side effect not mentioned in

the 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:

http://sideeffects.health.gov.il

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 and sight

of children and/or infants 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.

Do not store the medicine above 30°C.

Do not dispose of medicines in waste water or a

household waste bin. Ask the pharmacist how to

dispose of medicines that are no longer needed. These

measures will protect the environment.

6. FURTHER INFORMATION

In addition to the active ingredient, rivastigmine hydrogen

tartrate, the medicine also contains:

Microcrystalline cellulose, Hypromellose, Magnesium

stearate, Silica, colloidal anhydrous, Gelatin, Titanium

dioxide (E171), Yellow iron oxide (E172), Red iron

oxide (E172), Shellac.

What the medicine looks like and the contents of

the package

- Exelon 1.5 mg hard capsules containing an off-white to

slightly yellow powder. The color of the capsule cap and

body is yellow. “EXELON 1.5 mg” is imprinted in red on

the body of the capsule.

- Exelon 3 mg hard capsules containing an off-white to

slightly yellow powder. The color of the capsule cap and

body is orange. “EXELON 3 mg” is imprinted in red on

the body of the capsule.

- Exelon 4.5 mg hard capsules containing an off-white to

slightly yellow powder. The color of the capsule cap and

body is red. “EXELON 4.5 mg” is imprinted in white on

the body of the capsule.

- Exelon 6 mg hard capsules containing an off-white to

slightly yellow powder. The color of the capsule cap is

red and the body is orange. “EXELON 6 mg” is imprinted

in red on the body of the capsule.

All dosages are marketed in packages of 28 capsules.

Registration holder and Importer and its address:

Novartis Israel Ltd., P.O.B 7126, Tel Aviv.

Registration numbers of the medicine in the National

Drug Registry of the Ministry of Health:

Exelon 1.5 mg

110 66 29189

Exelon 3 mg

110 67 29190

Exelon 4.5 mg

110 68 29191

Exelon 6 mg

110 69 29192

The leaflet was revised in June 2020

SH EXE CAP APL JUN20 V1

SH EXE CAP APL JUN20 V1

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(oesophagus) ﺓﺪﻌﻤﻟﺍﻭ ﻢﻔﻟﺍ ﻦﻴﺑ ﻞﺻﺍﻮﻟﺍ ﺏﻮﺒﻧﻷﺍ (ﺮﻴﺜﻛ ﻞﺋﺍﻮﺳ ﻥﺍﺪﻘﻓ) ﻑﺎﻔﺠﺗ ﻦﻛﺍﺩ ﻝﻮﺑ ،ﻦﻴﻨﻴﻌﻟﺍ ﺽﺎﻴﺑ ﺭﺍﺮﻔﺻﺇ ،ﺪﻠﺠﻟﺍ ﺭﺍﺮﻔﺻﺇ) ﺪﺒﻜﻟﺍ ﻲﻓ ﺕﺎﺑﺍﺮﻄﺿﺇ (ﻡﺎﻌﻄﻠﻟ ﺔﻴﻬﺸﻟﺍ ﻥﺍﺪﻘﻓﻭ ﻕﺎﻫﺭﺇ ،ﺕﺍﺆﻴﻘﺗ ،ﺐﺒﺴﻟﺍ ﻝﻮﻬﺠﻣ ﻥﺎﻴﺜﻏ ﻭﺃ ﺫﺎﺷ ﻞﻜﺸﺑ ﺔﺣﺍﺭ ﻡﺪﻌﺑ ﺭﻮﻌﺸﻟﺍ ،ﺔﻴﻧﺍﻭﺪﻋ ﺐﻠﻘﻟﺍ ﺕﺎﺑﺮﺿ ﻖﺳﺎﻨﺗ ﻡﺪﻋ ﺽﺮﻤﺑ ﻖﻠﻌﺘﻤﻟﺍ (

dementia

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ﺎﻋﻮﻴﺷ ﺮﺜﻛﺃ ﻲﻫ ﻰﺿﺮﻤﻟﺍ ﺀﻻﺆﻫ ﻯﺪﻟ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ :ﺔﻴﻓﺎﺿﺇ ﺔﻨﻴﻌﻣ ﺔﻴﺒﻧﺎﺟ ﻞﻤﻌﺘﺴﻣ ﻦﻣ ﺮﺜﻛﺃ ﻯﺪﻟ ﺮﻬﻈﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ)

ً

ﺍﺪﺟ ﺔﻌﺋﺎﺷ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ :(10 ﻦﻴﺑ ﻦﻣ 1 ﻑﺎﺠﺗﺭﺇ ﺕﺍﺀﺎﻤﻏﺇ ﺔﻳﻮﻔﻋ ﺕﺎﻃﻮﻘﺳ :(10 ﻦﻴﺑ ﻦﻣ 1 ﻞﻤﻌﺘﺴﻣ ﻰﺘﺣ ﻯﺪﻟ ﺮﻬﻈﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ) ﺔﻌﺋﺎﺷ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻖﻠﻗ

ﺔﺣﺍﺭ ﺔﻠﻘﺑ ﺭﻮﻌﺸﻟﺍ

ﺐﻠﻘﻟﺍ ﺕﺎﺑﺮﺿ ﺆﻃﺎﺒﺗ

ﻡﻮﻨﻟﺍ ﻲﻓ ﺕﺎﺑﻮﻌﺻ ﻑﺎﻔﺠﺗﻭ ﻡﺯﻼﻟﺍ ﻦﻋ ﺏﺎﻌﻠﻟﺍ ﺓﺩﺎﻳﺯ

ﺎﻬﻴﻠﻋ ﺮﻄﻴﺴﻣ ﺮﻴﻏ ﺕﺎﻛﺮﺣ ﻭﺃ ﻱﺩﺎﻋ ﺮﻴﻏ ﻞﻜﺸﺑ ﺔﺌﻴﻄﺑ ﺕﺎﻛﺮﺣ

ﺐﻠﺼﺗ ﻞﺜﻣ ﺔﻬﺑﺎﺸﻣ ﺽﺍﺮﻋﺃ ﺭﻮﻄﺗ ﻭﺃ ﻥﻮﺴﻨﻴﻛﺭﺎﭘ ﺽﺮﻣ ﺽﺍﺮﻋﺃ ﻢﻗﺎﻔﺗ ﺕﻼﻀﻌﻟﺍ ﻒﻌﺿﻭ ﺔﻨﻴﻌﻣ ﺕﺎﻛﺮﺣ ﺬﻴﻔﻨﺗ ﻲﻓ ﺔﺑﻮﻌﺻ ،ﺕﻼﻀﻌﻟﺍ 1 ﻞﻤﻌﺘﺴﻣ ﻰﺘﺣ ﻯﺪﻟ ﺮﻬﻈﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ) ﺔﻌﺋﺎﺷ ﺮﻴﻏ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ :(100 ﻦﻴﺑ ﻦﻣ .ﺕﺎﻛﺮﺤﻟﺍ ﻰﻠﻋ ﺓﺮﻄﻴﺴﻟﺍ ﻒﻌﺿﻭ ﺐﻠﻘﻟﺍ ﺕﺎﺑﺮﺿ ﻖﺳﺎﻨﺗ ﻡﺪﻋ ﻥﻮﻠﻴﺴﻛﺇ ﺕﺎﻘﺼﻟ ﻝﺎﻤﻌﺘﺳﺇ ﺪﻨﻋ ﺎﻬﻨﻋ ﻎﻠﺑ ﻲﺘﻟﺍ ﺔﻴﻓﺎﺿﺇ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ :ﺕﻻﻮﺴﺒﻜﻟﺍ ﻊﻣ

ً

ﺎﻀﻳﺃ ﺮﻬﻈﺗ ﻥﺃ ﻦﻜﻤﻳ ﻲﺘﻟﺍﻭ :(10 ﻦﻴﺑ ﻦﻣ 1 ﻞﻤﻌﺘﺴﻣ ﻰﺘﺣ ﻯﺪﻟ ﺮﻬﻈﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ) ﺔﻌﺋﺎﺷ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﺔﻧﻮﺨﺳ ﺪﻳﺪﺷ ﻙﺎﺒﺗﺭﺇ (ﻝﻮﺒﺘﻟﺍ ﻰﻠﻋ ﺓﺮﻄﻴﺴﻟﺍ ﻡﺪﻋ) ﻲﻟﻮﺑ ﺲﻠﺳ

1 ﻞﻤﻌﺘﺴﻣ ﻰﺘﺣ ﻯﺪﻟ ﺮﻬﻈﺗ ﻥﺃ ﺎﻬﻧﺄﺷ ﻦﻣ) ﺔﻌﺋﺎﺷ ﺮﻴﻏ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ :(100 ﻦﻴﺑ ﻦﻣ (ﺔﺣﺍﺭ ﺔﻠﻗ ،ﻁﺎﺸﻨﻟﺍ ﻯﻮﺘﺴﻣ ﺓﺩﺎﻳﺯ) ﻁﺎﺸﻨﻟﺍ ﻁﺮﻓ ﻉﻮﻴﺸﻟﺍ ﺮﻳﺪﻘﺗ ﻥﺎﻜﻣﻹﺎﺑ ﺲﻴﻟ) ﻑﻭﺮﻌﻣ ﺮﻴﻏ ﻉﻮﻴﺷ ﺕﺍﺫ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ :(ﺓﺮﻓﻮﺘﻤﻟﺍ ﺕﺎﻣﻮﻠﻌﻤﻟﺍ ﺔﻠﻗ ﺀﺍﺮﺟ ﻭﺃ ﺕﻼﺼﻳﻮﺣ ﻞﺜﻣ ،ﺔﻘﺼﻠﻟﺍ ﻝﺎﻤﻌﺘﺳﺇ ﺪﻨﻋ ﻲﻌﺿﻮﻣ ﻲﺴﺴﺤﺗ ﻞﻌﻓ ﺩﻭﺩﺭ ﺪﻠﺠﻟﺍ ﻲﻓ ﺏﺎﻬﺘﻟﺇ ﺰﺋﺎﺠﻟﺍ ﻦﻣ ﻪﻧﻷ ،ﻚﺒﻴﺒﻃ ﻊﺟﺍﺭ ،ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ ﻚﻠﺗ ﻦﻣ ﺪﺣﺍﻮﺑ ﺮﻌﺸﺗ ﺖﻨﻛ ﺍﺫﺇ .ﺔﻴﺒﻃ ﺓﺪﻋﺎﺴﻤﻟ ﺝﺎﺘﺤﺗ ﻥﺃ ﺎﻣﺪﻨﻋ ﻭﺃ ﺔﻴﺒﻧﺎﺠﻟﺍ ﺽﺍﺮﻋﻷﺍ ﻯﺪﺣﺇ ﺖﻤﻗﺎﻔﺗ ﺍﺫﺇ ،ﻲﺒﻧﺎﺟ ﺽﺮﻋ ﺮﻬﻇ ﺍﺫﺇ .ﺐﻴﺒﻄﻟﺍ ﺓﺭﺎﺸﺘﺳﺇ ﻚﻴﻠﻋ ،ﺓﺮﺸﻨﻟﺍ هﺬﻫ ﻲﻓ ﺮﻛﺬﻳ ﻢﻟ ﻲﺒﻧﺎﺟ ﺽﺮﻋ ﻦﻣ ﻲﻧﺎﻌﺗ ﻰﻠﻋ ﻂﻐﻀﻟﺍ ﺔﻄﺳﺍﻮﺑ ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻮﻟ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻦﻋ ﻎﻴﻠﺒﺘﻟﺍ ﻥﺎﻜﻣﻹﺎﺑ ﺔﺤﻔﺼﻟﺍ ﻰﻠﻋ ﺩﻮﺟﻮﻤﻟﺍ «ﻲﺋﺍﻭﺩ ﺝﻼﻋ ﺐﻘﻋ ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻦﻋ ﻎﻴﻠﺒﺗ» ﻂﺑﺍﺮﻟﺍ ﻰﻟﺇ ﻚﻬﺟﻮﻳ ﻱﺬﻟﺍ (www.health.gov.il) ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻭ ﻊﻗﻮﻤﻟ ﺔﻴﺴﻴﺋﺮﻟﺍ :ﻂﺑﺍﺮﻟﺍ ﺢﻔﺼﺗ ﻖﻳﺮﻃ ﻦﻋ ﻭﺃ ،ﺔﻴﺒﻧﺎﺟ ﺽﺍﺮﻋﺃ ﻦﻋ ﻎﻴﻠﺒﺘﻠﻟ ﺮﺷﺎﺒﻤﻟﺍ ﺝﺫﻮﻤﻨﻟﺍ

https://sideeffects.health.gov.il

؟ﺀﺍﻭﺪﻟﺍ ﻦﻳﺰﺨﺗ ﺔﻴﻔﻴﻛ (5

ﺍﺪﻴﻌﺑ ﻖﻠﻐﻣ ﻥﺎﻜﻣ ﻲﻓ ﺮﺧﺁ ﺀﺍﻭﺩ ﻞﻛﻭ ﺀﺍﻭﺪﻟﺍ ﺍﺬﻫ ﻆﻔﺣ ﺐﺠﻳ !ﻢﻤﺴﺘﻟﺍ ﺐﻨﺠﺗ ﻢﻬﺘﺑﺎﺻﺇ ﻱﺩﺎﻔﺘﻟ ﻚﻟﺫﻭ ،ﻊﺿﺮﻟﺍ ﻭﺃ/ﻭ ﻝﺎﻔﻃﻷﺍ ﺔﻳﺅﺭ ﻝﺎﺠﻣﻭ ﻱﺪﻳﺃ ﻝﻭﺎﻨﺘﻣ ﻦﻋ .ﺐﻴﺒﻄﻟﺍ ﻦﻣ ﺔﺤﻳﺮﺻ ﺕﺎﻤﻴﻠﻌﺗ ﻥﻭﺪﺑ ﺆﻴﻘﺘﻟﺍ ﺐﺒﺴﺗ ﻻ .ﻢﻤﺴﺘﻟﺎﺑ ﻱﺬﻟﺍ (exp.date) ﺔﻴﺣﻼﺼﻟﺍ ﺦﻳﺭﺎﺗ ﺀﺎﻀﻘﻧﺇ ﺪﻌﺑ ﺀﺍﻭﺪﻟﺍ ﻝﺎﻤﻌﺘﺳﺇ ﺯﻮﺠﻳ ﻻ

ﺲﻔﻧ ﻦﻣ ﺮﻴﺧﻷﺍ ﻡﻮﻴﻟﺍ ﻰﻟﺇ ﺔﻴﺣﻼﺼﻟﺍ ﺦﻳﺭﺎﺗ ﺮﻴﺸﻳ .ﺔﺒﻠﻌﻟﺍ ﺮﻬﻇ ﻰﻠﻋ ﺮﻬﻈﻳ .ﺮﻬﺸﻟﺍ .ﺔﻳﻮﺌﻣ ﺔﺟﺭﺩ 30 ﻦﻋ ﺪﻳﺰﺗ ﺓﺭﺍﺮﺣ ﺔﺟﺭﺪﺑ ﻦﻳﺰﺨﺘﻟﺍ ﺯﻮﺠﻳ ﻻ

ﻦﻋ ﻲﻟﺪﻴﺼﻟﺍ ﻝﺄﺳﺇ ،ﺔﻴﻟﺰﻨﻤﻟﺍ ﺔﻣﺎﻤﻘﻠﻟ ﻭﺃ ﻱﺭﺎﺠﻤﻟﺍ ﻰﻟﺇ ﺔﻳﻭﺩﻷﺍ ﻲﻣﺭ ﺯﻮﺠﻳ ﻻ ﻲﻓ ﻞﺋﺎﺳﻮﻟﺍ هﺬﻫ ﺪﻋﺎﺴﺗ .ﻝﺎﻤﻌﺘﺳﻹﺍ ﺪﻴﻗ ﺪﻌﺗ ﻢﻟ ﺔﻳﻭﺩﺃ ﻦﻣ ﺺﻠﺨﺘﻟﺍ ﺔﻴﻔﻴﻛ .ﺔﺌﻴﺒﻟﺍ ﻰﻠﻋ ﻅﺎﻔﺤﻟﺍ ﺔﻴﻓﺎﺿﺇ ﺕﺎﻣﻮﻠﻌﻣ (6 ﺀﺍﻭﺪﻟﺍ ﻱﻮﺘﺤﻳ ﺕﺍﺮﺗﺭﺎﺗ ﻦﻴﺟﻭﺭﺪﻴﻫ ﻦﯿﻤﭽﯿﺘﺳﺎﭭﻳﺭ ﺔﻟﺎﻌﻔﻟﺍ ﺓﺩﺎﻤﻠﻟ ﺔﻓﺎﺿﻹﺎﺑ :ﻰﻠﻋ

ﺎﻀﻳﺃ

Microcrystalline cellulose, Hypromellose, Magnesium

stearate, Silica, colloidal anhydrous, Gelatin, Titanium

dioxide (E171), Yellow iron oxide (E172), Red iron

oxide (E172), Shellac.

ﺔﺒﻠﻌﻟﺍ ﻯﻮﺘﺤﻣ ﻮﻫ ﺎﻣﻭ ﺀﺍﻭﺪﻟﺍ ﻭﺪﺒﻳ ﻒﻴﻛ ﻱﺪﺑﺯ ﺾﻴﺑﺃ ﻥﻮﻠﺑ ﻕﻮﺤﺴﻣ ﻰﻠﻋ ﻱﻮﺘﺤﺗ ،ﺔﻴﺳﺎﻗ ﺕﻻﻮﺴﺒﻛ ﻎﻠﻣ 1.5 ﻥﻮﻠﻴﺴﻛﺇ

ﺮﻤﺣﺃ ﻥﻮﻠﺑ ﺔﻋﺎﺒﻄﻟﺍ ،ﺮﻔﺻﺃ ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟﻭ ﺀﺎﻄﻏ ﻥﻮﻟ ،ﺮﻔﺻﻸﻟ ﻞﺋﺎﻣ ﻰﺘﺣ "EXELON 1.5 mg" :ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟ ﻰﻠﻋ ﻱﺪﺑﺯ ﺾﻴﺑﺃ ﻥﻮﻠﺑ ﻕﻮﺤﺴﻣ ﻰﻠﻋ ﻱﻮﺘﺤﺗ ،ﺔﻴﺳﺎﻗ ﺕﻻﻮﺴﺒﻛ ﻎﻠﻣ 3 ﻥﻮﻠﻴﺴﻛﺇ

ﻥﻮﻠﺑ ﺔﻋﺎﺒﻄﻟﺍ ،ﻲﻟﺎﻘﺗﺮﺑ ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟﻭ ﺀﺎﻄﻏ ﻥﻮﻟ ،ﺮﻔﺻﻸﻟ ﻞﺋﺎﻣ ﻰﺘﺣ "EXELON 3 mg" :ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟ ﻰﻠﻋ ﺮﻤﺣﺃ ﻱﺪﺑﺯ ﺾﻴﺑﺃ ﻥﻮﻠﺑ ﻕﻮﺤﺴﻣ ﻰﻠﻋ ﻱﻮﺘﺤﺗ ،ﺔﻴﺳﺎﻗ ﺕﻻﻮﺴﺒﻛ ﻎﻠﻣ 4.5 ﻥﻮﻠﻴﺴﻛﺇ

ﺾﻴﺑﺃ ﻥﻮﻠﺑ ﺔﻋﺎﺒﻄﻟﺍ ،ﺮﻤﺣﺃ ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟﻭ ﺀﺎﻄﻏ ﻥﻮﻟ ،ﺮﻔﺻﻸﻟ ﻞﺋﺎﻣ ﻰﺘﺣ "EXELON 4.5 mg" :ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟ ﻰﻠﻋ ﻱﺪﺑﺯ ﺾﻴﺑﺃ ﻥﻮﻠﺑ ﻕﻮﺤﺴﻣ ﻰﻠﻋ ﻱﻮﺘﺤﺗ ،ﺔﻴﺳﺎﻗ ﺕﻻﻮﺴﺒﻛ ﻎﻠﻣ 6 ﻥﻮﻠﻴﺴﻛﺇ

،ﻲﻟﺎﻘﺗﺮﺑ ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟ ﻥﻮﻟﻭ ﺮﻤﺣﺃ ﺔﻟﻮﺴﺒﻜﻟﺍ ﺀﺎﻄﻏ ﻥﻮﻟ ،ﺮﻔﺻﻸﻟ ﻞﺋﺎﻣ ﻰﺘﺣ "EXELON 6 mg" :ﺔﻟﻮﺴﺒﻜﻟﺍ ﻢﺴﺟ ﻰﻠﻋ ﺮﻤﺣﺃ ﻥﻮﻠﺑ ﺔﻋﺎﺒﻄﻟﺍ .ﺔﻟﻮﺴﺒﻛ 28 ﺕﺍﺫ ﺐﻠﻋ ﻦﻤﺿ ﺕﺍﺭﺎﻴﻌﻟﺍ ﺔﻓﺎﻛ ﻕﻮﺴﺗ .ﺏ.ﺹ ،.ﺽ.ﻡ ﻞﻴﺋﺍﺮﺳﺇ ﺲﻴﺗﺭﺎﭬﻮﻧ :ﻪﻧﺍﻮﻨﻋﻭ ﺩﺭﻮﺘﺴﻤﻟﺍﻭ ﺯﺎﻴﺘﻣﻹﺍ ﺐﺣﺎﺻ .ﺐﻴﺑﺃ ﻞﺗ ،7126 :ﺔﺤﺼﻟﺍ ﺓﺭﺍﺯﻭ ﻲﻓ ﻲﻣﻮﻜﺤﻟﺍ ﺔﻳﻭﺩﻷﺍ ﻞﺠﺳ ﻲﻓ ﺀﺍﻭﺪﻟﺍ ﻞﺠﺳ ﻡﺎﻗﺭﺃ

110 66 29189

ـ ﻎﻠﻣ 1.5 ﻥﻮﻠﻴﺴﻛﺇ

110 67 29190

ـ ﻎﻠﻣ 3 ﻥﻮﻠﻴﺴﻛﺇ

110 68 29191

ـ ﻎﻠﻣ 4.5 ﻥﻮﻠﻴﺴﻛﺇ

110 69 29192

ـ ﻎﻠﻣ 6 ﻥﻮﻠﻴﺴﻛﺇ .ﺮﻛﺬﻤﻟﺍ ﺔﻐﻴﺼﺑ ﺓﺮﺸﻨﻟﺍ هﺬﻫ ﺔﻏﺎﻴﺻ ﺖﻤﺗ ،ﺓﺀﺍﺮﻘﻟﺍ ﻦﻳﻮﻬﺗﻭ ﺔﻟﻮﻬﺳ ﻞﺟﺃ ﻦﻣ .ﻦﻴﺴﻨﺠﻟﺍ ﻼﻜﻟ ﺺﺼﺨﻣ ﺀﺍﻭﺪﻟﺍ ﻥﺈﻓ ،ﻚﻟﺫ ﻦﻣ ﻢﻏﺮﻟﺍ ﻰﻠﻋ 2020 ﻥﺍﺮﻳﺰﺣ ﻲﻓ ﺓﺮﺸﻨﻟﺍ ﺩﺍﺪﻋﺇ ﻢﺗ

EXE CAP API JUN 20 V1

1. NAME OF THE MEDICINAL PRODUCT

Exelon

1.5 mg

Exelon

3 mg

Exelon

4.5 mg

Exelon

6 mg

Rivastigmine

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Exelon

1.5 mg hard capsules

Each capsule contains rivastigmine hydrogen tartrate corresponding to 1.5 mg rivastigmine.

Exelon

3 mg hard capsules

Each capsule contains rivastigmine hydrogen tartrate corresponding to 3.0 mg rivastigmine.

Exelon

4.5 mg hard capsules

Each capsule contains rivastigmine hydrogen tartrate corresponding to 4.5 mg rivastigmine.

Exelon

6 mg hard capsules

Each capsule contains rivastigmine hydrogen tartrate corresponding to 6.0 mg rivastigmine.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Hard capsules

Exelon

1.5 mg hard capsules

Off-white to slightly yellow powder in a capsule with yellow cap and yellow body, with red imprint

“EXELON 1.5 mg” on body.

Exelon

3 mg hard capsules

Off-white to slightly yellow powder in a capsule with orange cap and orange body, with red imprint

“EXELON 3 mg” on body.

Exelon

4.5 mg hard capsules

Off-white to slightly yellow powder in a capsule with red cap and red body, with white imprint

“EXELON 4.5 mg” on body.

Exelon

6 mg hard capsules

Off-white to slightly yellow powder in a capsule with red cap and orange body, with red imprint

“EXELON 6 mg” on body.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of patients with mild to moderately severe dementia of the Alzheimer type, also termed

probable Alzheimer’s Disease or Alzheimer’s Disease.

Symptomatic treatment of mild to moderately severe Alzheimer’s dementia.

Symptomatic treatment of mild to moderately severe dementia associated with Parkinson’s disease.

4.2 Posology and method of administration

Posology

Initial dose

1.5 mg twice a day. Patients known to be particularly sensitive to the effects of cholinergic drugs should

be started at a dose of 1 mg twice a day.

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Dose titration

The starting dose is 1.5 mg twice a day. If this dose is well tolerated after a minimum of two weeks of

treatment, the dose may be increased to 3 mg twice a day. Subsequent increases to 4.5 mg and then 6

mg twice a day should also be based on good tolerability of the current dose and may be considered

after a minimum of two weeks’ treatment at that dose level.

If adverse effects (e.g. nausea, vomiting, abdominal pain or loss of appetite) or weight decrease are

observed during treatment, these may respond to omitting one or more doses. If adverse effects persist,

the daily dose should be reduced to the previous well-tolerated dose.

Maintenance dose

1.5 mg to 6 mg twice a day; to achieve maximum therapeutic benefit patients should be maintained on

their highest well-tolerated dose.

The recommended maximum daily dose is 6 mg twice a day.

Re-initiation of therapy

The incidence and severity of adverse events are generally increased with higher doses.

If treatment is interrupted for longer than three days, treatment should be re-initiated with 1.5 mg twice

daily and titrated as described above.

Administration

Exelon hard capsules should be administered twice a day, with morning and evening meals.

Special population

Paediatric population

Children and adolescents (age below 18 years): The use of Exelon in children has not been studied and

is therefore not recommended

Renal and hepatic impairment

No dose adjustment is necessary for patients with renal or hepatic impairment.

However, due to increased exposure in moderate renal and mild to moderate hepatic impairment, dosing

recommendations to titrate according to individual tolerability should be closely followed as patients with

clinically significant renal or hepatic impairment might experience more dose dependent adverse

reactions. Patients with severe hepatic impairment have not been studied, however, Exelon capsules

may be used in this patient population provided close monitoring is exercised (see sections 4.4 and 5.2).

4.3 Contraindications

Hypersensitivity to the active substance rivastigmine, to other carbamate derivatives or to any of the

excipients listed in section 6.1.

Previous history of application site reactions suggestive of allergic contact dermatitis with rivastigmine

patch (see section 4.4).

4.4 Special warnings and precautions for use

The incidence and severity of adverse reactions generally increase with higher doses. If treatment is

interrupted for more than three days, it should be re-initiated at 1.5 mg twice daily to reduce the

possibility of adverse reactions (e.g. vomiting).

Skin application site reactions may occur with rivastigmine patch and are usually mild or moderate in

intensity. These reactions are not in themselves an indication of sensitisation. However, use of

rivastigmine patch may lead to allergic contact dermatitis.

Allergic contact dermatitis should be suspected if application site reactions spread beyond the

patchsize, if there is evidence of a more intense local reaction (e.g. increasing erythema, oedema,

papules, vesicles) and if symptoms do not significantly improve within 48 hours after patch removal. In

these cases, treatment should be discontinued (see section 4.3).

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Patients who develop application site reactions suggestive of allergic contact dermatitis to rivastigmine

patch and who still require rivastigmine treatment should only be switched to oral rivastigmine after

negative allergy testing and under close medical supervision. It is possible that some patients

sensitised to rivastigmine by exposure to rivastigmine patch may not be able to take rivastigmine in

any form.

There have been rare post-marketing reports of patients experiencing allergic dermatitis

(disseminated) when administered rivastigmine irrespective of the route of administration (oral,

transdermal). In these cases, treatment should be discontinued (see section 4.3).

Patients and caregivers should be instructed accordingly.

Dose titration: Adverse reactions (e.g. hypertension and hallucinations in patients with Alzheimer’s

dementia and worsening of extrapyramidal symptoms, in particular tremor, in patients with dementia

associated with Parkinson’s disease) have been observed shortly after dose increase. They may

respond to a dose reduction. In other cases, Exelon has been discontinued (see section 4.8).

Gastrointestinal disorders such as nausea, vomiting and diarrhoea are dose-related, and may occur

particularly when initiating treatment and/or increasing the dose (see section 4.8). These adverse

reactions occur more commonly in women. Patients who show signs or symptoms of dehydration

resulting from prolonged vomiting or diarrhoea can be managed with intravenous fluids and dose

reduction or discontinuation if recognised and treated promptly. Dehydration can be associated with

serious outcomes.

Patients with Alzheimer’s disease may lose weight. Cholinesterase inhibitors, including rivastigmine,

have been associated with weight loss in these patients. During therapy patient’s weight should be

monitored.

In case of severe vomiting associated with rivastigmine treatment, appropriate dose adjustments as

recommended in section 4.2 must be made. Some cases of severe vomiting were associated with

oesophageal rupture (see section 4.8). Such events appeared to occur particularly after dose

increments or high doses of rivastigmine.

Rivastigmine may cause bradycardia which constitutes a risk factor in the occurrence of torsade de

pointes, predominantly in patients with risk factors. Caution is advised in patients at higher risk of

developing torsade de pointes; for example, those with uncompensated heart failure, recent

myocardial infarction, bradyarrhythmias, a predisposition to hypokalaemia or hypomagnesaemia, or

concomitant use with medicinal products known to induce QT prolongation and/or torsade de pointes

(see sections 4.5 and 4.8).

Care must be taken when using rivastigmine in patients with sick sinus syndrome or conduction

defects (sino-atrial block, atrio-ventricular block) (see section 4.8).

Rivastigmine may cause increased gastric acid secretions. Care should be exercised in treating

patients with active gastric or duodenal ulcers or patients predisposed to these conditions.

Cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or

obstructive pulmonary disease.

Cholinomimetics may induce or exacerbate urinary obstruction and seizures. Caution is recommended

in treating patients predisposed to such diseases.

The use of rivastigmine in patients with severe dementia of Alzheimer’s disease or associated with

Parkinson’s disease, other types of dementia or other types of memory impairment (e.g. age-related

cognitive decline) has not been investigated and therefore use in these patient populations is not

recommended.

Like other cholinomimetics, rivastigmine may exacerbate or induce extrapyramidal symptoms.

Worsening (including bradykinesia, dyskinesia, gait abnormality) and an increased incidence or

severity of tremor have been observed in patients with dementia associated with Parkinson’s disease

(see section 4.8). These events led to the discontinuation of rivastigmine in some cases (e.g.

discontinuations due to tremor 1.7% on rivastigmine vs 0% on placebo). Clinical monitoring is

recommended for these adverse reactions.

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Special populations

Patients with clinically significant renal or hepatic impairment might experience more adverse

reactions (see sections 4.2 and 5.2). Dosing recommendations to titrate according to individual

tolerability must be closely followed. Patients with severe hepatic impairment have not been studied.

However, Exelon may be used in this patient population and close monitoring is necessary.

Patients with body weight below 50 kg may experience more adverse reactions and may be more

likely to discontinue due to adverse reactions.

4.5 Interaction with other medicinal products and other forms of interaction

As a cholinesterase inhibitor, rivastigmine may exaggerate the effects of succinylcholine-type muscle

relaxants during anaesthesia. Caution is recommended when selecting anaesthetic agents. Possible

dose adjustments or temporarily stopping treatment can be considered if needed.

In view of its pharmacodynamic effects and possible additive effects, rivastigmine should not be given

concomitantly with other cholinomimetic substances. Rivastigmine might interfere with the activity of

anticholinergic medicinal products (e.g oxybutynin, tolterodine).

Additive effects leading to bradycardia (which may result in syncope) have been reported with the

combined use of various beta-blockers (including atenolol) and rivastigmine. Cardiovascular beta

blockers are expected to be associated with the greatest risk, but reports have also been received in

patients using other beta-blockers. Therefore, caution should be exercised when rivastigmine is

combined with beta-blockers and also other bradycardia agents (e.g. class III antiarrhythmic agents,

calcium channel antagonists, digitalis glycoside, pilocarpin).

Since bradycardia constitutes a risk factor in the occurrence of torsades de pointes, the combination

of rivastigmine with torsades de pointes-inducing medicinal products such as antipsychotics i.e. some

phenothiazines (chlorpromazine, levomepromazine), benzamides (sulpiride, sultopride, amisulpride,

tiapride, veralipride), pimozide, haloperidol, droperidol, cisapride, citalopram, diphemanil, erythromycin

IV, halofantrin, mizolastin, methadone, pentamidine and moxifloxacine should be observed with

caution and clinical monitoring (ECG) may also be required.

No pharmacokinetic interaction was observed between rivastigmine and digoxin, warfarin, diazepam

or fluoxetine in studies in healthy volunteers. The increase in prothrombin time induced by warfarin is

not affected by administration of rivastigmine. No untoward effects on cardiac conduction were

observed following concomitant administration of digoxin and rivastigmine.

According to its metabolism, metabolic interactions with other medicinal products appear unlikely,

although rivastigmine may inhibit the butyrylcholinesterase mediated metabolism of other substances.

4.6 Fertility, pregnancy and lactation

Pregnancy

In pregnant animals, rivastigmine and/or metabolites crossed the placenta. It is not known if this

occurs in humans. No clinical data on exposed pregnancies are available. In peri/postnatal studies in

rats, an increased gestation time was observed. Rivastigmine should not be used during pregnancy

unless clearly necessary.

Breast-feeding

In animals, rivastigmine is excreted in milk. It is not known if rivastigmine is excreted into human milk.

Therefore, women on rivastigmine should not breast-feed.

Fertility

No adverse effects of rivastigmine were observed on fertility or reproductive performance in rats (see

section 5.3). Effects of rivastigmine on human fertility are not known.

4.7 Effects on ability to drive and use machines

Alzheimer’s disease may cause gradual impairment of driving performance or compromise the ability

to use machinery. Furthermore, rivastigmine can induce dizziness and somnolence, mainly when

initiating treatment or increasing the dose. As a consequence, rivastigmine has minor or moderate

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influence on the ability to drive and use machines. Therefore, the ability of patients with dementia on

rivastigmine to continue driving or operating complex machines should be routinely evaluated by the

treating physician.

4.8 Undesirable effects

Summary of the safety profile

The most commonly reported adverse drug reactions (ADRs) are gastrointestinal, including nausea

(38%) and vomiting (23%), especially during titration. Female patients in clinical studies were found to

be more susceptible to gastrointestinal adverse reactions and weight loss.

Tabulated list of adverse reactions

Adverse reactions in Table 1 and Table 2 are listed according to the MedDRA system organ class and

frequency category. Frequency categories are defined using the following convention: Very common

(≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000); very rare

(<1/10,000); not known (cannot be estimated from the available data).

The following adverse reactions, listed below in Table 1, have been accumulated in patients with

Alzheimer’s dementia treated with Exelon.

Table 1

Infections and

infestations

Very rare

Urinary infection

Metabolism and nutrition disorders

Very common

Anorexia

Common

Decreased appetite

Not known

Dehydration

Psychiatric disorders

Common

Nightmares

Common

Agitation

Common

Confusion

Common

Anxiety

Uncommon

Insomnia

Uncommon

Depression

Very rare

Hallucinations

Not known

Aggression, restlessness

Nervous system disorders

Very common

Dizziness

Common

Headache

Common

Somnolence

Common

Tremor

Uncommon

Syncope

Rare

Seizures

Very rare

Extrapyramidal symptoms (including worsening of

Parkinson’s disease)

Cardiac disorders

Rare

Angina pectoris

Very rare

Cardiac arrhythmia (e.g. bradycardia, atrio-ventricular block,

atrial fibrillation and tachycardia)

Not known

Sick sinus syndrome

Vascular disorders

Very rare

Hypertension

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Gastrointestinal disorders

Very common

Nausea

Very common

Vomiting

Very common

Diarrhoea

Common

Abdominal pain and dyspepsia

Rare

Gastric and duodenal ulcers

Very rare

Gastrointestinal haemorrhage

Very rare

Pancreatitis

Not known

Some cases of severe vomiting were associated with

oesophageal rupture (see section 4.4)

Hepatobiliary disorders

Uncommon

Elevated liver function tests

Not known

Hepatitis

Skin and subcutaneous tissue disorders

Common

Hyperhydrosis

Rare

Rash

Not known

Pruritus, allergic dermatitis (disseminated)

General disorders and administration site

conditions

Common

Fatigue and asthenia

Common

Malaise

Uncommon

Fall

Investigations

Common

Weight loss

The following additional adverse reactions have been observed with Exelon transdermal patches:

delirium, pyrexia, decreased appetite, urinary incontinence (common), psychomotor hyperactivity

(uncommon), erythema, urticaria, vesicles, allergic dermatitis (not known).

Table 2 shows the adverse reactions reported during clinical studies conducted in patients with

dementia associated with Parkinson’s disease treated with Exelon capsules.

Table 2

Metabolism and nutrition disorders

Common

Decreased appetite

Common

Dehydration

Psychiatric disorders

Common

Common

Common

Common

Common

Not known

Insomnia

Anxiety

Restlessness

Hallucination, visual

Depression Aggression

Nervous system disorders

Very common

Tremor

Common

Dizziness

Common

Somnolence

Common

Headache

Common

Parkinson’s disease (worsening)

Common

Bradykinesia

Common

Dyskinesia

Common

Hypokinesia

Common

Cogwheel rigidity

Uncommon

Dystonia

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Cardiac disorders

Common

Bradycardia

Uncommon

Atrial Fibrillation

Uncommon

Atrioventricular block

Not known

Sick sinus syndrome

Vascular disorders

Common

Hypertension

Uncommon

Hypotension

Gastrointestinal disorders

Very common

Nausea

Very common

Vomiting

Common

Diarrhoea

Common

Abdominal pain and dyspepsia

Common

Salivary hypersecretion

Hepatobiliary disorders

Not known

Hepatitis

Skin and subcutaneous tissue disorders

Common

Hyperhydrosis

Not known

Allergic dermatitis (disseminated)

General disorders and administration site conditions

Very common

Fall

Common

Fatigue and asthenia

Common

Gait disturbance

Common

Parkinson gait

The following additional adverse reaction has been observed in a study of patients with dementia

associated with Parkinson’s disease treated with Exelon transdermal patches: agitation (common).

Table 3 lists the number and percentage of patients from the specific 24-week clinical study conducted

with Exelon in patients with dementia associated with Parkinson’s disease with pre-defined adverse

events that may reflect worsening of parkinsonian symptoms.

Table 3

Pre-defined adverse events that may reflect

worsening of parkinsonian symptoms in patients with

dementia

associated with Parkinson’s disease

Exelon

n(%)

Placebo

n (%)

Total patients studied

Total patients with pre-defined AE(s)

362 (100)

99 (27.3)

179 (100)

28 (15.6)

Tremor

37 (10.2)

7 (3.9)

Fall

21 (5.8)

11 (6.1)

Parkinson’s disease (worsening)

12 (3.3)

2 (1.1)

Salivary hypersecretion

Dyskinesia

1 (0.6)

Parkinsonism

1 (0.6)

Hypokinesia

Movement disorder

Bradykinesia

3 (1.7)

Dystonia

1 (0.6)

Gait abnormality

Muscle rigidity

Balance disorder

2 (1.1)

Musculoskeletal stiffness

Rigors

Motor dysfunction

(0.3

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorization of the medicinal product is important. It

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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 form https://sideeffects.health.gov.il/

4.9 Overdose

Symptoms

Most cases of accidental overdose have not been associated with any clinical signs or symptoms and

almost all of the patients concerned continued rivastigmine treatment 24 hours after the overdose.

Cholinergic toxicity has been reported with muscarinic symptoms that are observed with moderate

poisonings such as miosis, flushing, digestive disorders including abdominal pain, nausea, vomiting

and diarrhoea, bradycardia, bronchospasm and increased bronchial secretions, hyperhidrosis,

involuntary urination and/or defecation, lacrimation, hypotension and salivary hypersecretion.

In more severe cases, nicotinic effects might develop such as muscular weakness, fasciculations,

seizures and respiratory arrest with possible fatal outcome.

Additionally there have been post-marketing cases of dizziness, tremor, headache, somnolence,

confusional state, hypertension, hallucinations and malaise.

Management

As rivastigmine has a plasma half-life of about 1 hour and a duration of acetylcholinesterase inhibition

of about 9 hours, it is recommended that in cases of asymptomatic overdose no further dose of

rivastigmine should be administered for the next 24 hours. In overdose accompanied by severe

nausea and vomiting, the use of antiemetics should be considered. Symptomatic treatment for other

adverse reactions should be given as necessary.

In massive overdose, atropine can be used. An initial dose of 0.03 mg/kg intravenous atropine

sulphate is recommended, with subsequent doses based on clinical response. Use of scopolamine as

an antidote is not recommended.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: psychoanaleptics, anticholinesterases; ATC-code: N06DA03.

Rivastigmine is an acetyl- and butyrylcholinesterase inhibitor of the carbamate type, thought to

facilitate cholinergic neurotransmission by slowing the degradation of acetylcholine released by

functionally intact cholinergic neurones. Thus, rivastigmine may have an ameliorative effect on

cholinergic-mediated cognitive deficits in dementia associated with Alzheimer’s disease and

Parkinson’s disease.

Rivastigmine interacts with its target enzymes by forming a covalently bound complex that temporarily

inactivates the enzymes. In healthy young men, an oral 3.0 mg dose decreases acetylcholinesterase

(AChE) activity in cerebro spinal fluid (CSF) by approximately 40% within the first 1.5 hours after

administration. Activity of the enzyme returns to baseline levels about 9 hours after the maximum

inhibitory

effect

been

achieved.

patients

with

Alzheimer’s

Disease

(AD),

inhibition

acetylcholinesterase in CSF by rivastigmine was dose-dependent up to 6 mg given twice daily, the

highest dose tested. Inhibition of BuChE activity in CSF of 14 Alzheimer patients treated by rivastigmine

was similar to that of AchE.

Clinical studies in Alzheimer’s dementia

The efficacy of rivastigmine has been established through the use of three independent, domain

specific, assessment tools which were assessed at periodic intervals during 6 month treatment

periods. These include the ADAS-Cog (Alzheimer’s Disease Assessment Scale – Cognitive subscale,

a performance based measure of cognition), the CIBIC-Plus (Clinician’s Interview Based Impression of

Change-Plus, a comprehensive global assessment of the patient by the physician incorporating

caregiver input), and the PDS (Progressive Deterioration Scale, a caregiver-rated assessment of the

activities of daily living including personal hygiene, feeding, dressing, household chores such as

shopping, retention of ability to orient oneself to surroundings as well as involvement in activities

relating to finances, etc.).

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The patients studied had an MMSE (Mini-Mental State Examination) score of 10–24.

The results for clinically relevant responders pooled from two flexible dose studies out of the three

pivotal 26-week multicentre studies in patients with mild-to-moderately severe Alzheimer’s Dementia,

are provided in Table 4 below. Clinically relevant improvement in these studies was defined a priori as

at least 4-point improvement on the ADAS-Cog, improvement on the CIBIC-Plus, or at least a 10%

improvement on the PDS.

In addition, a post-hoc definition of response is provided in the same table. The secondary definition of

response required a 4-point or greater improvement on the ADAS-Cog, no worsening on the CIBIC-

Plus, and no worsening on the PDS. The mean actual daily dose for responders in the 6–12 mg

group, corresponding to this definition, was 9.3 mg. It is important to note that the scales used in this

indication vary and direct comparisons of results for different therapeutic agents are not valid.

Table 4

Patients with Clinically Significant Response (%)

Intent to Treat

Last Observation Carried

Forward

Response Measure

Rivastigmin

e 612 mg

N=473

Placebo

N=472

Rivastigmin

e 612 mg

N=379

Placebo

N=444

ADAS-Cog: improvement

of at least 4 points

21***

25***

CIBIC-Plus: improvement

29***

32***

PDS: improvement of at

least 10%

26***

30***

At least 4 points

improvement on ADAS-

Cog with no worsening on

CIBIC-Plus and PDS

12**

*p<0.05, **p<0.01, ***p<0.001

Clinical studies in dementia associated with Parkinson’s disease

The efficacy of rivastigmine in dementia associated with Parkinson’s disease has been demonstrated

in a 24-week multicentre, double-blind, placebo-controlled core study and its 24-week open-label

extension phase. Patients involved in this study had an MMSE (Mini-Mental State Examination) score

of 10–24. Efficacy has been established by the use of two independent scales which were assessed

at regular intervals during a 6-month treatment period as shown in Table 5 below: the ADAS-Cog, a

measure of cognition, and the global measure ADCS-CGIC (Alzheimer’s Disease Cooperative Study-

Clinician’s Global Impression of Change).

Table 5

Dementia associated

with Parkinson’s Disease

ADAS-Cog

Exelon

ADAS-Cog

Placebo

ADCS-

CGIC

Exelon

ADCS-CGIC

Placebo

ITT + RDO population

(n=329)

(n=161)

(n=329)

(n=165)

Mean baseline ± SD

23.8 ± 10.2

24.3 ± 10.5

Mean change at 24 weeks

2.1 ± 8.2

-0.7 ± 7.5

3.8 ± 1.4

4.3 ± 1.5

± SD

Adjusted treatment

difference

p-value versus placebo

2.88

<0.001

0.007

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ITT - LOCF population

(n=287)

(n=154)

(n=289)

(n=158)

Mean baseline ± SD

24.0 ± 10.3

24.5 ± 10.6

Mean change at 24 weeks

2.5 ± 8.4

-0.8 ± 7.5

3.7 ± 1.4

4.3 ± 1.5

± SD

Adjusted treatment

difference

p-value versus placebo

3.54

<0.001

<0.001

Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A

positive change indicates improvement.

Mean data shown for convenience, categorical analysis performed using van Elteren test

ITT: Intent-To-Treat; RDO: Retrieved Drop Outs; LOCF: Last Observation Carried Forward

Although a treatment effect was demonstrated in the overall study population, the data suggested that

a larger treatment effect relative to placebo was seen in the subgroup of patients with moderate

dementia associated with Parkinson’s disease. Similarly a larger treatment effect was observed in

those patients with visual hallucinations (see Table 6).

Table 6

Dementia associated

with Parkinson’s Disease

ADAS-Cog

Exelon

ADAS-Cog

Placebo

ADAS-Cog

Exelon

ADAS-Cog

Placebo

Patients with

visual

hallucinations

Patients without

visual hallucinations

ITT + RDO population

(n=107)

(n=60)

(n=220)

(n=101)

Mean baseline ± SD

25.4 ± 9.9

27.4 ± 10.4

23.1 ± 10.4

22.5 ± 10.1

Mean change at 24 weeks

1.0 ± 9.2

-2.1 ± 8.3

2.6 ± 7.6

0.1 ± 6.9

± SD

Adjusted treatment

difference

p-value versus placebo

4.27

0.002

2.09

0.015

Patients with moderate

dementia (MMSE 10-17)

Patients with mild dementia

(MMSE 18-24)

ITT + RDO population

(n=87)

(n=44)

(n=237)

(n=115)

Mean baseline ± SD

32.6 ± 10.4

33.7 ± 10.3

20.6 ± 7.9

20.7 ± 7.9

Mean change at 24 weeks

2.6 ± 9.4

-1.8 ± 7.2

1.9 ± 7.7

-0.2 ± 7.5

± SD

Adjusted treatment

difference

p-value versus placebo

4.73

0.002

2.14

0.010

1 Based on ANCOVA with treatment and country as factors and baseline ADAS-Cog as a covariate. A

positive change indicates improvement.

ITT: Intent-To-Treat; RDO: Retrieved Drop Outs

5.2 Pharmacokinetic properties

Absorption

Rivastigmine

rapidly

completely

absorbed.

Peak

plasma

concentrations

reached

approximately 1 hour. As a consequence of the rivastigmine’s interaction with its target enzyme, the

increase in bioavailability is about 1.5-fold greater than that expected from the increase in dose.

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Absolute bioavailability after a 3 mg dose is about 36% 13%.. Administration of rivastigmine capsules

with food delays absorption (t

) by 90 min and lowers C

and increases AUC by approximately 30%.

Distribution

Protein binding of rivastigmine is approximately 40%. It readily crosses the blood brain barrier and has

an apparent volume of distribution in the range of 1.8–2.7 l/kg.

Biotranformation

Rivastigmine is rapidly and extensively metabolised (half-life in plasma approximately 1 hour), primarily

via cholinesterase-mediated hydrolysis to the decarbamylated metabolite. In vitro, this metabolite shows

minimal inhibition of acetylcholinesterase (<10%).

Based on in vitro studies, no pharmacokinetic drug interaction is expected with medical products

metabolised by the following cytochrome isoenzymes: CYP1A2, CYP2D6, CYP3A4/5, CYP2E1,

CYP2C9, CYP2C8, CYP2C19, or CYP2B6. Based on evidence from animal studies, the major

cytochrome P450 isoenzymes are minimally involved in rivastigmine metabolism.

Total plasma

clearance of rivastigmine was approximately 130 l/h after a 0.2 mg intravenous dose and decreased to

70 l/h after a 2.7 mg intravenous dose.

Elimination

Unchanged rivastigmine is not found in the urine; renal excretion of the metabolites is the major route

of elimination. Following administration of

C-rivastigmine, renal elimination was rapid and essentially

complete (>90 %) within 24 hours. Less than 1% of the administered dose is excreted in the faeces.

There is no accumulation of rivastigmine or the decarbamylated metabolite in patients with Alzheimer’s

Disease.

A population pharmacokinetic analysis showed that nicotine use increases the oral clearance of

rivastigmine by 23% in patients with Alzheimer’s disease (n=75 smokers and 549 non-

smokers) following rivastigmine oral capsule doses of up to 12 mg/day.

Special populations

Elderly

While bioavailability of rivastigmine is greater in elderly than in young healthy volunteers, studies in

Alzheimer patients aged between 50 and 92 years showed no change in bioavailability with age.

Hepatic impairment

The C

of rivastigmine was approximately 60% higher and the AUC of rivastigmine was more than

twice as high in subjects with mild to moderate hepatic impairment than in healthy subjects.

Renal impairment

and AUC of rivastigmine were more than twice as high in subjects with moderate renal

impairment compared with healthy subjects; however there were no changes in C

and AUC of

rivastigmine in subjects with severe renal impairment.

5.3 Preclinical safety data

Repeated-dose toxicity studies in rats, mice and dogs revealed only effects associated with an

exaggerated pharmacological action. No target organ toxicity was observed. No safety margins to

human exposure were achieved in the animal studies due to the sensitivity of the animal models used.

Rivastigmine was not mutagenic in a standard battery of in vitro and in vivo tests, except in a

chromosomal aberration test in human peripheral lymphocytes at a dose 10

times the maximum

clinical exposure. The in vivo micronucleus test was negative. The major metabolite NAP226-90 also

did not show a genotoxic potential.

No evidence of carcinogenicity was found in studies in mice and rats at the maximum tolerated dose,

although the exposure to rivastigmine and its metabolites was lower than the human exposure. When

normalised to body surface area, the exposure to rivastigmine and its metabolites was approximately

equivalent to the maximum recommended human dose of 12 mg/day; however, when compared to the

maximum human dose, a multiple of approximately 6-fold was achieved in animals.

In animals, rivastigmine crosses the placenta and is excreted into milk. Oral studies in pregnant rats

and rabbits gave no indication of teratogenic potential on the part of rivastigmine. In oral studies with

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EXE CAP API JUN20 V1

male and female rats, no adverse effects of rivastigmine were observed on fertility or reproductive

performance of either the parent generation or the offspring of the parents.

A mild eye/mucosal irritation potential of rivastigmine was identified in a rabbit study.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Microcrystalline cellulose

Hypromellose

Magnesium stearate

Silica, colloidal anhydrous

Gelatin

Titanium dioxide (E171)

Yellow iron oxide (E172)

Red iron oxide (E172)

Shellac

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

The expiry date of the product is indicated on the packaging materials.

6.4 Special precautions for storage

Do not store above 30°C.

6.5 Nature and contents of container

Blister of clear PVC tray with blue lidding foil with 14 capsules. Each box contains 28, capsules.

6.6 Special precautions for disposal

No special requirements

7. Importer and Registration Holder:

Novartis Israel Ltd., P.O.B. 7126, Tel-Aviv, Israel

The leaflet was revised in June 2020

העדוה

לע

הרמחה

(

עדימ

)תוחיטב ןולעב

אפורל ןכדועמ(

05.2013

)

:ךיראת םש

רישכת

:תילגנאב

Exelon 1.5 mg, Exelon 3 mg, Exelon 4.5 mg, Exelon 6 mg

רפסמ

:םושירה

[

29189-92

]

םש

לעב

:םושירה סיטרבונ

המראפ

ססיורס

ייא

י'ג ספוט

הז

דעוימ

טוריפל

תורמחהה

!דבלב

רוחש טסקט

רשואמ טסקט

יתחת וק םע טסקט

ןולעל טסקט תפסוה רשואמה

הצוח וק םע טסקט

ןולעהמ טסקט תקיחמ רשואמה

בוהצב ןמוסמה טסקט

הרמחה תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

Dosage and

administration

Re-initiation of therapy

If treatment is interrupted for longer than

several days, treatment should be re-

initiated with 1.5 mg twice daily and

titrated as described above.

Re-initiation of therapy

If treatment is interrupted for longer than

several three

days, treatment should be re-

initiated with 1.5 mg twice daily and

titrated as described above.

Warnings and

precautions

If treatment is interrupted for longer than

several days, treatment should be re-

initiated with the lowest daily dose to

reduce the possibility of adverse reactions

(e.g. severe vomiting)

Like other cholinomimetics, rivastigmine

may exacerbate extrapyramidal

symptoms.

If treatment is interrupted for longer than

several three

days, treatment should be re-

initiated with the lowest daily dose to

reduce the possibility of adverse reactions

(e.g. severe vomiting)

Like other cholinomimetics, rivastigmine

may induce

exacerbate extrapyramidal

symptoms.

Adverse drug

reactions

Additional adverse drug reactions from

post-marketing spontaneous reports

(frequency not known)

extrapyramidal symptoms in patients with

Alzheimer’s dementia

Interactions

Anticipated interactions resulting in a

concomitant use not recommended

Metoclopramide

Considering the possibility of an additive

extra-pyramidal effect the concomitant

use of metoclopramide and rivastigmine is

not recommended

Observed interactions to be considered

Beta-blockers

Additive effects leading to bradycardia

(which may result in syncope) have been

reported with the combined use of various

beta-blockers (including atenolol) and

rivastigmine. Cardioselective beta-

blockers are expected to be associated

with the greatest risk, but reports have

also been received in patients using other

beta-blockers

Interaction with nicotine

A population pharmacokinetic analysis

showed that nicotine use increases the oral

clearance of rivastigmine by 23% in

patients

with

Alzheimer’s dementia

(n=75

smokers and 549 non-smokers) following

rivastigmine oral capsule doses of up to 12

mg/day

Women of

child-bearing

potential,

pregnancy,

breast-feeding

and fertility

Pregnancy

In pregnant animals, rivastigmine and/or

metabolites crossed the placenta

. It is not

known if this occurs in humans.

Overdosage

Symptoms

Most cases of accidental overdosage have

not been associated with any clinical

signs or symptoms and almost all of the

patients concerned continued Exelon

treatment. Where symptoms have

occurred, they have included nausea,

vomiting, diarrhoea, hypertension and

hallucinations. Due to the known

vagotonic effect of cholinesterase

inhibitors on heart rate, bradycardia

and/or syncope may also occur.

Symptoms

Most cases of accidental overdosage have

not been associated with any clinical signs

or symptoms and almost all of the patients

concerned continued Exelon treatment.

Where symptoms have occurred, they

have included nausea, vomiting,

diarrhoea, abdominal pain, dizziness,

tremor, headache, somnolence,

bradycardia, confusional state,

hyperhidrosis

hypertension, and

hallucinations

and malaise

. Overdosage

with cholinesterase inhibitors can result in

cholinergic crisis characterized by severe

nausea, vomiting, salivation, sweating,

bradycardia, hypotension, respiratory

depression, and convulsions. Muscle

weakness is a possibility and may result in

death if respiratory muscles are involved

Due to the known vagotonic effect of

cholinesterase inhibitors on heart rate,

bradycardia and/or syncope may also

occur.

Non-clinical

safety data

Local tolerance

A mild eye/mucosal irritation potential of

rivastigmine was identified in a rabbit

study

העדוה

לע

הרמחה

(

עדימ

)תוחיטב ןולעב

ןכרצל ןכדועמ(

05.2013

)

:ךיראת םש

רישכת

:תילגנאב

Exelon 1.5 mg, Exelon 3 mg, Exelon 4.5 mg, Exelon 6 mg

רפסמ

:םושירה

[

29189-92

]

םש

לעב

:םושירה סיטרבונ

המראפ

ססיורס

ייא

י'ג ספוט

הז

דעוימ

טוריפל

תורמחהה

!דבלב

רוחש טסקט

רשואמ טסקט

יתחת וק םע טסקט

ןולעל טסקט תפסוה רשואמה

הצוח וק םע טסקט

ןולעהמ טסקט תקיחמ רשואמה

בוהצב ןמוסמה טסקט

הרמחה תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח תורהזא

תודחוימ תועגונה

שומישל הפורתב םא

אל

תלטנ

ןולסקא

ךשמב

רפסמ לא ,םימי

שדחת

תא

תליטנ

הפורתה ילבמ

ץעוויהל

אפורב

.לפטמה םא

אל

תלטנ

ןולסקא

ךשמל

רתוי

השולשמ

םימי

ךשמב

רפסמ

םימי לא , שדחת

תא

תליטנ

הפורתה

ילבמ ץעוויהל

אפורב

.לפטמה תליטנ

תופורת תורחא ןיא

לוטיל

ןולסקא

דחי

םע

דימרפולקוטמ

הפורת(

תשמשמה

לקהל

וא

עונמל

תוליחב

.)תואקהו

ונכתי

תועפשה

תופסונ

ןוגכ

םייפג

תושקונ

םיידיו

תודעור

תוריהז

תליטנב

ןולסקא

דחי

םע

אטב-ימסוח

תופורת(

ןוגכ

לולונטא

תושמשמה

לופיטל

רתיב

ץחל

,םד

תקועת

הזח

םיבצמו

םייבבל

.)םירחא

ונכתי

תועפשה

תופסונ

ןוגכ

הידרקידרב

קפוד(

םילולעש )יטיא

רמגהל

ןופליעב

דוביא(

.)הרכהה

דציכ

שמתשת הפורתב ךילע

עדיל

תא

לפטמה

ךלש

ךנהש ךשמ

לופיטה

ךילע

עדיל

תא

לפטמה

ךלש

ךנהש

לטונ

ןכ-ומכ .ןולסקא

עדי

תא

לפטמה ךלש

םא

אל

תלטנ

ןולסקא

רפסמ .םימי

םא

אל

תלטנ

ןולסקא

ךשמב

רפסמ ,םימי ןיא

לוטיל

תא

הנמה

האבה ילבמ

ץעוויהל

אפורב

לטונ

ןכ-ומכ .ןולסקא

עדי

תא

לפטמה ךלש

םא

אל

תלטנ

ןולסקא

ךשמל רתוי

השולשמ

םימי

רפסמ

םימי

תקספה

לופיטה םא

אל

תלטנ

ןולסקא

ךשמל

רתוי

השולשמ

םימי

ךשמב

רפסמ

םימי

ןיא לוטיל

תא

הנמה

האבה

ילבמ

ץעוויהל אפורב

תועפות

יאוול תועפות

יאוול

תופסונ

העזה תועפות

יאוול

תומיוסמ

תויושע תויהל

תויניצר

םייפג

םיידי ,תושקונ

תודעור

םינימסת(

)םילדימריפרטסקא

תועפות

יאוול

תופסונ

העזה

תעזה

רתי

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