EXFORGE 5 MG160 MG

Israel - English - Ministry of Health

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Active ingredient:
AMLODIPINE AS BESYLATE; VALSARTAN
Available from:
NOVARTIS ISRAEL LTD
ATC code:
C08CA01
Pharmaceutical form:
FILM COATED TABLETS
Composition:
AMLODIPINE AS BESYLATE 5 MG; VALSARTAN 160 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
NOVARTIS PHARMACEUTICA SA, SPAIN
Therapeutic group:
AMLODIPINE
Therapeutic area:
AMLODIPINE
Therapeutic indications:
Treatment of essential hypertension. Exforge is indicated for patients whose blood pressure is not adequately controlled on monotherapy.
Authorization number:
138 41 31567 01
Authorization date:
2013-04-30

Documents in other languages

Patient Information leaflet Patient Information leaflet - Arabic

17-01-2021

Patient Information leaflet Patient Information leaflet - Hebrew

04-02-2020

Very rare side effects (occur in up to 1 user in 10,000):

Decreased number of white blood cells, decrease in number of

blood platelets which may result in unusual bruising or bleeding

(red blood cell damage), excess sugar in blood (hyperglycemia),

swelling of the gums, abdominal bloating (gastritis), abnormal

liver function, inflammation of the liver (hepatitis), yellowing of

the skin (jaundice), increase in liver enzymes which may have an

effect on some medical tests, increased muscle tension (tone),

inflammation of blood vessels occasionally accompanied by

skin rash, sensitivity to light, disorders combining rigidity, tremor

and/or movement disorders.

Valsartan

Side effects whose frequency is unknown (frequency cannot be

estimated from the available data): Decrease in red blood cells,

fever, sore throat or mouth sores due to infections; spontaneous

bleeding or bruising; high levels of potassium in the blood;

abnormal liver test results; decreased renal function or a severe

reduction in renal function; swelling mainly of the face and the

throat; muscle pain; rash, purplish-red spots, fever; itching;

allergic reactions; skin blisters (symptoms of a condition called

dermatitis bullous).

If you experience these effects, refer to your doctor

immediately!

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.

Reporting side effects

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:

/https://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 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.

Do not store above 30°C. Store in the original package to

protect from moisture.

Do not use if the package is damaged.

6. FURtHeR InFoRMatIon

In addition to the active ingredients, the medicine also

contains:

exforge 5 mg/80 mg, 5 mg/160 mg, 10 mg/160 mg film-

coated tablets:

Microcrystalline cellulose

Crospovidone

Magnesium stearate

Silica, colloidal anhydrous

exforge 5 mg/80 mg film-coated tablets

Film-coating composition:

Hypromellose

Titanium dioxide (E171)

Iron oxide, yellow (E172)

Macrogol 4000

Talc

exforge 5 mg/160 mg film-coated tablets

Film-coating composition:

Hypromellose

Titanium dioxide (E171)

Iron oxide, yellow (E172)

Macrogol 4000

Talc

exforge 10 mg/160 mg film-coated tablets

Film-coating composition:

Hypromellose

Titanium dioxide

Iron oxide, yellow

Iron oxide, red

Macrogol 4000

Talc

what the medicine looks like and the contents of the

package:

exforge 5 mg/80 mg: dark yellow, round, film-coated tablet

with bevelled edges, imprinted with ”NVR“ on one side and ”NV“

on the other side. The package contains 28 tablets.

exforge 5 mg/160 mg: dark yellow, oval, film-coated tablet with

bevelled edges, imprinted with ”NVR“ on one side and ”ECE“ on

the other side. The package contains 28 tablets.

exforge 10 mg/160 mg: light yellow, oval, film-coated tablet

with bevelled edges, imprinted with ”NVR“ on one side and ”UIC“

on the other side. The package contains 28 tablets.

Registration holder and address: Novartis Israel Ltd., P.O.B

7126, Tel Aviv.

Manufacturer name and address: Novartis Pharmaceutica

S.A., Barcelona, Spain for Novartis Pharma AG, Basel,

Switzerland.

The format of this leaflet was determined by the Ministry of

Health and its content was checked and approved by the

Ministry of Health in June 2015 and was updated in accordance

with the Ministry of Health guidelines in November 2019

Registration number of the medicine in the national Drug

Registry of the Ministry of Health:

exforge 5 mg/80 mg:

138 40 31566

exforge 5 mg/160 mg:

138 41 31567

exforge 10 mg/160 mg:

138 42 31568

SH EXF APL 27NOV19

PatIent PacKaGe InSeRt In accoRDance

wItH tHe PHaRMacIStS’ ReGULatIonS

)PREPARATIONS( - 1986

The medicine is dispensed with a doctor’s prescription only.

exforge

®

5 mg/80 mg

Film-coated tablets

composition:

Each film-coated tablet contains:

Amlodipine (as besylate) 5 mg

Valsartan 80 mg

exforge

®

5 mg/160 mg

Film-coated tablets

composition:

Each film-coated tablet contains:

Amlodipine (as besylate) 5 mg

Valsartan 160 mg

exforge

®

10 mg/160 mg

Film-coated tablets

composition:

Each film-coated tablet contains:

Amlodipine (as besylate) 10 mg

Valsartan 160 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?

Exforge tablets contain two substances called amlodipine and

valsartan. These two substances are intended for the treatment

of high blood pressure, when treatment with each ingredient

separately does not provide satisfactory results.

Amlodipine belongs to a group of substances called ”calcium

channel blockers“. Amlodipine stops calcium from penetrating

into the walls of the blood vessels, which prevents blood

vessels from tightening.

Valsartan belongs to a group of substances called

”angiotensin-II receptor antagonists“. Angiotensin II is a

substance produced by the body and causes the blood

vessels to tighten, thus increasing the blood pressure.

Valsartan works by blocking the effect of angiotensin II.

Both substances help prevent the blood vessels from tightening.

As a result, the blood vessels relax and blood pressure is

lowered.

Exforge is used to treat high blood pressure in adults in

whom the high blood pressure is not sufficiently controlled by

amlodipine or valsartan alone.

therapeutic group:

Amlodipine - calcium channel blocker.

Valsartan - angiotensin-II receptor antagonist.

2. BeFoRe USInG tHe MeDIcIne

X Do not use the medicine if:

you are sensitive )allergic( to amlodipine or to any other

calcium channel blockers. This may be manifested by

itching, skin redness or breathing difficulties.

you are sensitive )allergic( to valsartan or any of the

additional ingredients contained in the medicine (detailed

in section 6). If you think you may be allergic, refer to the

doctor before taking Exforge.

you have severe liver problems or bile problems such as

biliary cirrhosis or obstruction of biliary flow in the liver.

you are more than three months pregnant )it is preferable

to also avoid Exforge in early pregnancy, see ”Pregnancy

and breastfeeding“ section(.

you have severely low blood pressure )hypotension(.

you have narrowing of the aortic valve )aortic stenosis( or

cardiogenic shock (a condition where your heart is unable

to supply enough blood to the body).

you suffer from heart failure after a heart attack.

you have diabetes or impaired kidney function and you

are being treated with a blood pressure-lowering medicine

containing aliskiren.

If any of the above applies to you, inform your doctor

without taking exforge.

Special warnings regarding use of the medicine:

! Before treatment with exforge, tell the doctor if:

you are sick )vomiting or diarrhea(.

you have liver or kidney problems.

you have had a kidney transplant or you have been diagnosed

as suffering from narrowing of the kidney arteries.

you have a problem affecting adrenal gland function, called

primary hyperaldosteronism.

you have heart failure or have had a heart attack in the past.

Carefully follow the doctor’s instructions for the starting dose.

The doctor may also check your kidney function.

your doctor has told you that you are suffering from narrowing

of the valves in your heart (aortic or mitral stenosis) or from

abnormal thickening of your heart muscle (obstructive

hypertrophic cardiomyopathy).

you have ever had swelling, particularly of the face and throat,

while taking other medicines (including ACE inhibitors). If

these symptoms apply to you, stop taking exforge and

refer to your doctor immediately. In this case, never take

exforge again.

you are taking any of the following medicines used to treat

high blood pressure:

ACE inhibitors (e.g., enalapril, lisinopril, ramipril), in particular

if you have diabetes-related kidney problems.

◦ aliskiren.

! children and adolescents:

Exforge is not recommended for children and adolescents

under 18 years of age.

! test and follow up

Your doctor may regularly check your kidney function, blood

pressure and blood electrolyte (e.g., potassium) levels.

See additional information in ”Do not use the medicine

section.

If any of these apply to you, inform the doctor before

taking exforge.

! Drug interactions:

If you are taking, or have recently taken, other medicines,

including non-prescription medicines and nutritional

supplements, tell the doctor or pharmacist. Your doctor

may need to change the dosage or take other precautionary

measures. In certain cases, you will need to stop taking one of

the medicines. In particular, inform the doctor or pharmacist if

you are taking medicines from the following groups:

ACE inhibitors or aliskiren )see information in sections ”Do

not use the medicine“ and ”Special warnings regarding

use of the medicine“(;

diuretics )a type of medicine that increases urine output(;

lithium, a medicine used to treat certain types of depression;

potassium-sparing diuretics, potassium supplements, salt

substitutes containing potassium or other substances that

may increase potassium levels;

certain types of painkillers called non-steroidal anti-

inflammatory drugs (NSAIDs) or selective cyclooxygenase-2

inhibitors (COX-2 inhibitors). The doctor may also check your

kidney function;

anticonvulsants )e.g., carbamazepine, phenobarbital,

phenytoin, fosphenytoin, primidone);

a herbal extract for sedation – Hypericum perforatum )St.

John’s wort);

nitroglycerin and other nitrates, or other medicines belonging

to the vasodilator group;

medicines to treat HIV/AIDS )e.g., ritonavir, indinavir,

nelfinavir);

medicines used to treat fungal infections )e.g., ketoconazole,

itraconazole);

medicines used to treat bacterial infections (e.g., rifampicin,

erythromycin, clarithromycin, telithromycin);

verapamil, diltiazem )heart medicines(;

simvastatin )a medicine used to lower cholesterol levels(;

dantrolene )infusion for body temperature abnormalities(

medicines used to protect against transplant rejection

(ciclosporin).

! Use of the medicine and food:

Do not consume grapefruits and grapefruit juice when taking

Exforge. This is because grapefruits and grapefruit juice may

increase the levels of the active ingredient amlodipine in the

blood, which can cause an unexpected increase in the blood

pressure-lowering effect. Exforge may be taken with or without

food.

! Pregnancy and breastfeeding:

Pregnancy

Tell your doctor if you think you are pregnant or if you may

become pregnant. Your doctor will generally recommend that

you stop taking Exforge before you become pregnant or as soon

as you find out that you are pregnant and will recommend that

you take another medicine instead of Exforge. Exforge is not

recommended in early pregnancy (in the first three months of

pregnancy), and must not be taken if you are more than three

months pregnant, as it may cause serious harm to the unborn

baby if used after the third month of pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding or are planning to start

breastfeeding. Small amounts of amlodipine pass into breast

milk. It is not recommended to take Exforge when breastfeeding,

and your doctor may recommend another treatment for you if

you wish to breastfeed, especially if the baby was just born or

born prematurely.

Consult the doctor or pharmacist before using any medicine.

! Driving and operating machinery:

This medicine may cause dizziness and affect your ability to

concentrate. Therefore, if you do not know how this medicine will

affect you, do not drive, operate machinery and do not perform

other activities that require 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 about the dosage and treatment regimen of the

preparation.

This will help to achieve the best results and reduce the risk

of side effects.

The dosage and treatment regimen will be determined by the

doctor only. The usual dosage is generally one tablet per day:

- It is preferable to take the medicine at the same time each

day.

- Swallow the tablets with a glass of water.

- You can take Exforge with or without food. Do not take Exforge

with grapefruits or grapefruit juice.

- There is no information regarding crushing/halving or chewing

the tablets.

Depending on your response to treatment, the doctor may

recommend a higher or lower dosage.

Do not exceed the recommended dosage.

Exforge in the elderly )aged 65 and above(

Your doctor will exercise caution when increasing the dosage. If

you have further questions regarding use of the medicine, ask

your doctor or pharmacist.

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.

If you forget to take the medicine

If you forgot to take the medicine at the designated time, take a

dose as soon as you remember. Then, take the next dose at the

regular time. However, if it is almost time to take the next dose,

do not take the forgotten dose. Do not take a double dose to

compensate for the forgotten dose. Take the next dose at the

regular time and consult the doctor.

Adhere to the treatment regimen as recommended by the doctor.

Even if there is an improvement in your health, do not stop

treatment with the medicine without consulting the doctor.

If you stop taking the medicine

Stopping Exforge treatment may cause worsening of your

illness. Do not stop taking the medicine unless the doctor has

instructed you to do so.

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

the dose each time you take a medicine. wear glasses if

you need them.

If you have further questions regarding use of the medicine,

consult the doctor or pharmacist.

4. SIDe eFFectS

As with any medicine, use of Exforge 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.

There are serious side effects that require immediate medical

treatment:

Few patients have experienced these serious side effects (occur

in up to 1 user in 1,000)

If any of the following effects occur, refer to a doctor

immediately:

Allergic reaction with symptoms such as rash, itching, swelling

of the face or lips or tongue, breathing difficulties, low blood

pressure (feeling faint, light-headedness).

other side effects that may occur with exforge:

Common side effects (occur in up to 1 user in 10): flu; stuffy

nose, sore throat and discomfort when swallowing; headache;

swelling of arms, palms of the hands, legs, ankles or feet;

tiredness; weakness; redness and feeling of warmth in the

face and/or neck.

Uncommon side effects (occur in up to 1 user in 100):

dizziness; nausea and abdominal pain; dry mouth; drowsiness;

tingling or numbness of the hands or feet; vertigo; fast heart

beat including palpitations; dizziness upon standing up; cough;

diarrhea; constipation; skin rash; redness of the skin; swelling

in the joints, back pain; pain in joints.

Rare side effects (occur in up to 1 user in 1,000): anxiety;

ringing in the ears; fainting; passing more urine than usual

or having an increased urge to urinate; inability to achieve

or maintain an erection; sensation of heaviness; low blood

pressure with symptoms such as dizziness, light-headedness;

increased sweating; skin rash all over the body; itching; muscle

spasm.

If any of the aforementioned effects affect you severely,

refer to your doctor.

Side effects that were reported upon use of amlodipine or

valsartan when taken alone, and do not occur when using

exforge or occur more frequently than when using exforge:

amlodipine

Refer to a doctor immediately if you experience any of these

very rare and severe side effects after taking the medicine:

- Sudden wheezing, chest pain, shortness of breath or difficulty

in breathing.

- Swelling of eyelids, face or lips.

- Swelling of the tongue and throat causing great difficulty in

breathing.

- Severe skin reactions, including intense skin rash, hives,

redness of the skin throughout the body, intense itching,

blistering, peeling and swelling of the skin, inflammation of

the mucous membranes (Stevens-Johnson Syndrome, toxic

epidermal necrolysis) or other allergic reactions.

- Myocardial infarction, irregular heart rate.

- Inflammation of the pancreas, which may cause severe

abdominal and back pains accompanied by a general unwell

feeling.

The following side effects have been reported. If the following

effects cause you problems or if they last for more than one

week, refer to your doctor.

Common side effects (occur in up to 1 user in 10): dizziness,

sleepiness, palpitations (awareness of heart beat), flushing,

swelling of the ankles (edema), abdominal pain, nausea.

Uncommon side effects (occur in up to 1 user in 100): Mood

swings, anxiety, depression, insomnia, trembling, changes

in sense of taste, fainting, loss of pain sensation, visual

disturbances, visual impairment, ringing in the ears, low

blood pressure, sneezing/runny nose caused by inflammation

of the nasal tissue (rhinitis), indigestion, vomiting (being ill),

hair loss, increased sweating, itchy skin, skin discoloration,

urination disorder, increased need to urinate at night, more

frequent urination, inability to achieve an erection, discomfort or

enlargement of the breasts in men, pain, feeling unwell, muscle

pain, muscle cramps, weight gain or loss.

Rare side effects (occur in up to 1 user in 1,000): Confusion.

SH EXF APL 27NOV19

:مويلا يف دحاو صرق وه ةداع يدايتعلإا .موي لك ﻦم ةعاسلا سفنب ءاودلا لوانت لضف

.ءاملا ﻦم سأك عم صارقلأا علب بجي

جروفسكيإ لوانت زوجي لا .ماعط نودب وأ عم جروفسكيإ لوانت ناكملإاب

.تورف پيرﭽلا ريصع عم وأ تورف پيرﭽلا عم .صارقلأا غضم وأ رطش / قحس لوح تامولعم دجوت لا

كتباجتسإ بسحب كلذو ،رغصأ وأ ربكأ

ايئاود

ارادقم حرتقي نأ بيبطلا نأش ﻦم .جلاعلل .هب ىصوملا يئاودلا رادقملا زواجت زوجي لا )قوف امو ةنس 65 رمع نم( نينسملا ىدل جروفسكيإ .يئاودلا رادقملا عفر ءانثأ رذحب فرصتلاب كبيبط موقي .يلديصلا وأ كبيبط لأسإ ،ءاودلا لامعتسإ لوح ةيفاضإ ةلئسأ كيدل ترفوت اذإ ربكأ

ً

ايئاود

ً

ارادقم أطخلاب تلوانت اذإ هجوت ،ءاودلا ﻦم أطخلاب لفط علب اذإ وأ

اطرفم

ايئاود

ارادقم تلوانت اذإ .ءاودلا ةبلع كعم رضحأو ىفشتسملا يف ئراوطلا ةفرغل وأ بيبطلا ىلإ

لااح ءاودلا لوانت تيسن اذإ لاح ةيئاود ةعرج لوانت بجيف ،ددحملا تقولا يف ءاودلا لوانت تيسن اذإ .يدايتعلإا تقولا يف ةمداقلا ةيئاودلا ةعرجلا لوانت بجي ،كلذ دعب .كركذت لوانت زوجي لا ،ةمداقلا ةيئاودلا ةعرجلا لوانت دعوم

ابيرقت ناح اذإ ،ﻦكل .ةيسنملا ةيئاودلا ةعرجلا .ةيسنملا ةيئاودلا ةعرجلا ﻦع ضيوعتلل ةفعاضم ةيئاود ةعرج لوانت زوجي لا .بيبطلا رشتسإو يدايتعلإا تقولا يف ةمداقلا ةيئاودلا ةعرجلا لوانت .بيبطلا تايصوت بسحب جلاعلا ىلع ةبظاوملا بجي أرط ولو ىتح ،بيبطلا ةراشتسإ نودب ءاودلاب جلاعلا ﻦع فقوتلا زوجي لا .ةيحصلا كتلاح ىلع ﻦسحت ءاودلا لوانت نع كفقوت لاح يف ﻦع فقوتت لا .كضرم مقافتل يدؤي دق جروفسكيإ ـب جلاعلا ﻦع فقوتلا نإ .بيبطلا تاميلعتب لاإ ءاودلا لوانت دكأتلاو ءاودلا عباط صيخشت بجي !ةمتعلا يف ةيودلأا لوانت زوجي لا ةيبطلا تاراظنلا عض .ءاود اهيف لوانتت ةرم لك يف يئاودلا رادقملا نم .كلذ رملأا مزل اذإ بيبطلا رشتسإ ،ءاودلا لامعتسإ لوح ةيفاضإ ةلئسأ كيدل ترفوت اذإ .يلديصلا وأ ةيبناجلا ضارعلأا )4 ضعب دنع ةيبناج

اضارعأ ببسي دق جروفسكيإ لامعتسإ نإ ،ءاود لكب امك .اهنم

ايأ يناعت لاأ زئاجلا ﻦم .ةيبناجلا ضارعلأا ةمئاق ﻦم شهدنت لا .ﻦيلمعتسملا

ايروف

ايبط

اجلاع بلطتت ةريطخ ةيبناج ضارعأ كانه ىدل رهظت( ةيلاتلا ةريطخلا ةيبناجلا ضارعلأا ﻦم ىضرملا ﻦم ليلق ىناع دقل )لمعتسم 1,000 نيب نم 1 ىتح :بيبطلا ىلإ

ً

لااح هجوتلا بجي ،ةيلاتلا ضارعلأا نم

ً

ايأ ثودح لاح يف ،ناسللا وأ ﻦيتفشلا وأ هجولا خافتنإ ،ةكح ،حفط لثم ضارعأ عم يسسحت لعف در .)ةخودب روعشلا ،ءامغإب روعشلا( ضفخنم مد طغض ،سفنتلا يف تابوعص :جروفسكيإ لامعتسإ دنع ثدحت نأ زئاجلا نم يتلا ىرخأ ةيبناج ضارعأ :)نيلمعتسم 10 نيب نم 1 ىتح ىدل رهظت( ةعئاش ةيبناج ضارعأ خافتنإ ؛عادص ؛علبلا ءانثأ جاعزنإو ةرجنحلا يف ملأ ،فنلأا دادسنإ ؛ازنإولفنإ فعض ؛قاهرإ ؛ﻦيمدقلا يتحار وأ ﻦيلحاكلا ،ﻦيلجرلا ،ﻦيديلا يتحار ،ﻦيعارذلا .قنعلا يف وأ/و هجولا يف ةنوخسب روعشلاو رارمحإ ؛ماع :)لمعتسم 100 نيب نم 1 ىتح ىدل رهظت( ةعئاش ريغ ةيبناج ضارعأ يتحار يف ردخ وأ زخو ؛ساعن ؛مفلا فافج ؛ﻦطبلا يف ملأو نايثغ ؛راود ؛بلقلا ناقفخ كلذ يف امب بلقلا مظن عرست ؛وﭽﯿتريﭬ ؛ﻦيمدقلا وأ ﻦيديلا خافتنإ ؛دلجلا رارمحإ ؛يدلج حفط ؛كاسمإ ؛لاهسإ ؛لاعس ؛فوقولا دنع راود .لصافملا يف ملأ ؛رهظلا يف ملأ ،لصافملا يف :)لمعتسم 1,000 نيب نم 1 ىتح ىدل رهظت( ةردان ةيبناج ضارعأ ةدايزب روعشلا وأ داتعملا ﻦم رثكأ لوبتلا ؛ءامغإ ؛ﻦينذلأا يف ﻦينط ؛قلق بيضقلا باصتنإ ىلع ةظفاحملا وأ قيقحت ىلع ةردقلا مدع ؛لوبتلا ىلع حاحللإا روعشلا ،راود لثم ضارعأ عم مدلا طغض ضافخنإ ؛لقثب روعشلا ؛يلسانتلا .ةيلضع تاصلقت ؛ةكح ؛مسجلا لماكب يدلج حفط ؛دئاز قرعت ؛ةفيفخ ةخودب .كبيبط عجار ،ةديدش ةروصب هلاعأ ةروكذملا ضارعلأا كيلع ترثأ اذإ ناتراسلاڤ وأ نيپيدولمأ لامعتسإ ءانثأ اهنع غلب يتلا ةيبناجلا ضارعلأا وأ جروفسكيإ لامعتسإ دنع رهظت مل يتلاو درفنم لكشب نلامعتسملا :جروفسكيإ عم هيلع وه امم ربكأ ةريتوب رهظت نيپيدولمأ ةيبناجلا ضارعلأا ىدحإب رعشت تنك اذإ يروف لكشب بيبطلا عجار :ءاودلا لوانت دعب ةيلاتلا ةريطخلاو

ً

ادج ةردانلا يف تابوعص وأ سفنت قيض ،ردصلا يف ملأ ،سفنتلا ءانثأ ئجافم ريفص

.سفنتلا .ﻦيتفشلا وأ هجولا ،ﻦينفجلا يف خافتنإ

.سفنتلا يف ةريبك ةبوعص ببست يتلا ةرجنحلاو ناسللا خافتنإ

لماكب دلجلا رارمحإ ،ىرش ،ديدش يدلج حفط لمشت ةريطخ ةيدلج ضارعأ

جيسنلا يف باهتلإ ،دلجلا خافتنإو رشقت ،تلاصيوح ،ةديدش ةكح ،مسجلا ،)يمسلا ةرشبلا رخن ،Steven-Johnson Syndrome( يطاخملا .ىرخأ ةيسسحت لعف دودر وأ .مظتنم ريغ بلق مظن ،بلقلا ةلضع ءاشتحإ

قفارتت يتلا رهظلاو ﻦطبلا يف ملاآ ببسي دق يذلا سايركنبلا باهتلإ

.ديج ريغ ماع روعشب لكاشم ةيلاتلا ضارعلأا كل تببس اذإ .ةيلاتلا ةيبناجلا ضارعلأا ثودح ﻦع غل

:كبيبط عجار ،عوبسأ ﻦم رثكلأ ترمتسإ اذإ وأ ،راود :)نيلمعتسم 10 نيب نم 1 ىتح ىدل رهظت( ةعئاش ةيبناج ضارعأ ﻦيلحاكلا خافتنإ ،دروت ،)بلقلا تابرضب ساسحلإا( بلقلا ناقفخ ،ساعن .نايثغ ،ﻦطبلا يف ملأ ،)ةمذو( :)لمعتسم 100 نيب نم 1 ىتح ىدل رهظت( ةعئاش ريغ ةيبناج ضارعأ ،قاذملا ةساح يف تاريغت ،ةفجر ،قرأ ،بائتكإ ،قلق ،ةيسفنلا ةلاحلا يف تاريغت ﻦينط ،ةيؤرلا يف للخ ،ةيؤرلا يف تابارطضإ ،مللأاب ساسحلإا نادقف ،ءامغإ ﻦع مجنت يتلا فنلأا يف حشر / ساطع ،مدلا طغض ضافخنإ ،ﻦينذلأا يف ،)ةكعو( تاؤيقت ،مضهلا يف لكاشم ،)فنلأا باهتلإ( فنلأا جيسن يف باهتلإ يف بارطضإ ،دلجلا نول ريغت ،دلجلا يف ةكح ،دئاز قرعت ،رعشلا نادقف ىلع ةردقلا مدع ،لوبتلا ةريتو ةدايز ،ليللا يف لوبتلل ةجاحلا ةدايز ،لوبتلا ،ملأ ،لاجرلا ىدل ﻦييدثلا مخضت وأ جاعزنإ ،يلسانتلا بيضقلل باصتنإ قيقحت .نزولا صقانت وأ ةدايز ،ةيلضع تاصلقت ،تلاضعلا يف ملاآ ،ةكعوب روعشلا كابترإ :)لمعتسم 1,000 نيب نم 1 ىتح ىدل رهظت( ةردان ةيبناج ضارعأ :)لمعتسم 10,000 نيب نم 1 ىتح ىدل رهظت(

ً

ادج ةردان ةيبناج ضارعأ يذلا رملأا ،ةيومدلا تاحيفصلا ددع صقانت ،ءاضيبلا مدلا ايلاخ ددع صقانت ةدايز ،)ءارمحلا مدلا تايرك ررضت( فزن وأ ةذاش تامدك ثودحل يدؤي دق ،)ةدعملا باهتلإ( ينطب خافتنإ ،ةثللا خافتنإ ،)مدلا ركس طرف( مدلا يف ركسلا تاميزنإ عافترإ ،)ناقري( دلجلا رارفصإ ،دبكلا باهتلإ ،ذاش يدبك يفيظو ءادأ ،تلاضعلا رتوت ةدايز ،ةيبطلا صوحفلا ضعب ىلع رثؤي دق يذلا رملأا ،دبكلا ،ءوضلل ةيساسح ،يدلج حفطب

انايحأ قفارتي يذلا ةيومدلا ةيعولأا يف باهتلإ .ةكرحلا يف تابوعص وأ/و نافجر ،بلصت ﻦمضتت تابارطضإ ناتراسلاڤ تايطعملا نم ةريتولا ريدقت نكمي لا( فورعم ريغ عويش تاذ ةيبناج ضارعأ تاحرقت وأ ةرجنحلا يف ملأ ،ةنوخس ،ءارمحلا مدلا تايرك صقانت :)ةرفوتملا مويساتوﭙلا بسن عافترإ ؛ةيوفع تامدك وأ فزن ؛تاثولتلا ﻦع ةجتان مفلا يف يولكلا يفيظولا ءادلأا يف صقانت ؛دبكلا صوحف جئاتن ةملاس مدع ؛مدلا يف ؛ةرجنحلاو هجولا يف ةصاخ خافتنإ ؛يولكلا يفيظولا ءادلأا يف ديدش صقانت وأ ؛ةيسسحت لعف دودر ؛ةكح ،ةنوخس ،ءارمح – ةيجسفنب عقب ،حفط ؛ةيلضع ملاآ .(Dermatitis bullous ىمس

ت ةلاحل ةمزلاتم( دلجلا يف تلاصيوح

!

ً

لااح كبيبط ىلإ هجوت ،ضارعلأا كلتب رعشت تنك اذإ امدنع وأ ةيبناجلا ضارعلأا ىدحإ تمقافت اذإ ،يبناج ضرع رهظ اذإ .بيبطلا ةراشتسإ كيلع ،ةرشنلا هذه يف ركذي مل يبناج ضرع نم يناعت :ةيبناج ضارعأ نع غيلبتلا 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 ريخلأا مويلا ىلإ ةيحلاصلا ءاضقنإ خيرات ريشي .ةبلعلا رهظ ىلع رهظي .رهشلا سفن ﻦم ﻦيزختلا بجي .ةيوئم ةجرد 30 ﻦع ديزت ةرارح ةجردب ﻦيزختلا زوجي لا ةبوطرلا ﻦم ةيامحلل ةيلصلأا ةبلعلا يف .ةررضتم ةبلعلا تناك اذإ لامعتسلإا زوجي لا ةيفاضإ تامولعم )6

:

ً

اضيأ ةلاعفلا داوملل ةفاضلإاب ءاودلا يوتحي ،غلم 160/غلم 5 ،غلم 80/غلم 5 :ةيلطم صارقأ جروفسكيإ غلم 160/غلم 10

Microcrystalline cellulose

Crospovidone

Magnesium stearate

Silica, colloidal anhydrous

:ءلاطلا بيكرت ةيلطم صارقأ غلم 80/غلم 5 جروفسكيإ

Hypromellose

Titanium dioxide (E171)

Iron oxide, yellow (E172)

Macrogol 4000

Talc

:ءلاطلا بيكرت ةيلطم صارقأ غلم 160/غلم 5 جروفسكيإ

Hypromellose

Titanium dioxide (E171)

Iron oxide, yellow (E172)

Macrogol 4000

Talc

:ءلاطلا بيكرت ةيلطم صارقأ غلم 160/غلم 10 جروفسكيإ

Hypromellose

Titanium dioxide

Iron oxide, yellow

Iron oxide, red

Macrogol 4000

Talc

:ةبلعلا ىوتحم وه امو ءاودلا ودبي فيك وذ قماغ رفصأ نولب ريدتسم يلطم صرق :غلم 80/غلم 5 جروفسكيإ بناجلا ﻦم ”NV“ -و دحاو بناج ﻦم ”NVR“ ةعابطلا هيلع ،ةلئام فارطأ

اصرق 28 ىلع ةبلعلا يوتحت .يناثلا وذ قماغ رفصأ نولب يوضيب يلطم صرق :غلم 160/غلم 5 جروفسكيإ بناجلا ﻦم ”ECE“ -و دحاو بناج ﻦم ”NVR“ ةعابطلا هيلع ،ةلئام فارطأ

اصرق 28 ىلع ةبلعلا يوتحت .يناثلا وذ حتاف رفصأ نولب يوضيب يلطم صرق :غلم 160/غلم 10 جروفسكيإ بناجلا ﻦم ”UIC“ -و دحاو بناج ﻦم ”NVR“ ةعابطلا هيلع ،ةلئام فارطأ

اصرق 28 ىلع ةبلعلا يوتحت .يناثلا .بيبأ لت ،7126 ب.ص ،ض.م ليئارسإ سيتراﭬون :هناونعو زايتملإا بحاص ،اينابسا ،ةنولشرب ،.يإ.سإ اكيتيوس امراف سيتراﭬون :هناونعو جتنملا مسإ ارسيوس ،لزاب ،يج ييا امراف سيتراﭬون لجأ ﻦم خيرات يف صخ

رو صح

ف اهاوتحمو ةرشنلا هذه ةغيص ةحصلا ةرازو ترقأ ﻦيرشت خيرات يف ةحصلا ةرازو تاميلعت بسحب اهليدعت متو 2015 ناريزح 2019 يناثلا :ةحصلا ةرازو يف يموكحلا ةيودلأا لجس يف ءاودلا لجس مقر 138 40 31566 :غلم 80/غلم 5 جروفسكيإ 138 41 31567 :غلم 160/غلم 5 جروفسكيإ 138 42 31568 :غلم160/غلم 10 جروفسكيإ ىلع .ركذملا ةغيصب ةرشنلا هذه ةغايص تمت ،ةءارقلا ﻦيوهتو ةلوهس لجأ ﻦم .ﻦيسنجلا لاكل صصخم ءاودلا نإف ،كلذ ﻦم مغرلا

EXF API

2019

1.

NAME OF THE MEDICINAL PRODUCT

Exforge

®

5 mg/80 mg

Exforge

®

5 mg/160 mg

Exforge

®

10 mg/160 mg

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Exforge

®

5 mg/80 mg film-coated tablets

Each film-coated tablet contains 5 mg of amlodipine (as amlodipine besylate) and 80 mg of

valsartan.

Exforge

®

5 mg/160 mg film-coated tablets

Each film-coated tablet contains 5 mg of amlodipine (as amlodipine besylate) and 160 mg of

valsartan.

Exforge

®

10 mg/160 mg film-coated tablets

Each film-coated tablet contains 10 mg of amlodipine (as amlodipine besylate) and 160 mg

of valsartan.

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Film-coated tablet

Exforge 5 mg/80 mg film-coated tablets

Dark yellow, round film-coated tablet with bevelled edges, imprinted with “NVR” on one side

and “NV” on the other side. Approximate size: diameter 8.20 mm.

Exforge 5 mg/160 mg film-coated tablets

Dark yellow, oval film-coated tablet with bevelled edges, imprinted with “NVR” on one side

and “ECE” on the other side. Approximate size: 14.2 mm (length) x 5.7 mm (width).

Exforge 10 mg/160 mg film-coated tablets

Light yellow, oval film-coated tablet with bevelled edges, imprinted with “NVR” on one side

and “UIC” on the other side. Approximate size: 14.2 mm (length) x 5.7 mm (width).

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

Treatment of essential hypertension.

EXF API

2019

Exforge is indicated for patients whose blood pressure is not adequately controlled on

monotherapy.

4.2

Posology and method of administration

Posology

General target population

A patient whose blood pressure is not adequately controlled on monotherapy may be

switched to combination therapy with Exforge. The recommended dose is one tablet per day

(see section 2).

Individual dose titration with the components (i.e. amlodipine and valsartan) is recommended

before changing to the fixed dose combination. When clinically appropriate direct change

from monotherapy to the fixed-dose combination may be considered.

For convenience, patients receiving valsartan and amlodipine from separate tablets may be

switched to Exforge containing the same component doses.

The maximum dose is 10/320 mg.

Exforge can be taken with or without food. It is recommended to take Exforge with some

water.

Special population

Geriatric patients (aged 65 years or above)

Since both components of the combination are equally well tolerated when used at similar

doses in elderly (aged 65 years or above) or younger patients, no dose adjustment of the

starting dose is required (see section 5.1). Starting with the lowest available dose of

amlodipine should be considered. The lowest strength of Exforge contains 5 mg of

amlodipine.

In elderly patients, caution is required when increasing the dosage.

Pediatric patients (below 18 years)

Exforge is not recommended for use in patients aged below 18 years due to a lack of data

on safety and efficacy.

Renal impairment

No dose adjustment is required for patients with mild to moderate renal impairment.

Monitoring of potassium levels and creatinine is advised in moderate renal impairment.

Hepatic impairment

Due to amlodipine and valsartan, caution should be exercised when administering Exforge to

patients with hepatic impairment or biliary obstructive disorders. Amlodipine dosage

recommendations have not been established in patients with mild to moderate hepatic

impairment.

Starting with the lowest available dose of amlodipine should be considered. The lowest

strength of Exforge contains 5 mg of amlodipine (see sections 4.4).

In patients with mild to moderate hepatic impairment without cholestasis, the maximum

recommended dose is 80 mg valsartan.

Method of administration

Oral use.

It is recommended to take Exforge with some water.

EXF API

2019

4.3

Contraindications

Hypersensitivity to the active substances, to dihydropyridine derivatives, or to any of

the excipients listed in section 6.1.

Severe hepatic impairment, biliary cirrhosis or cholestasis.

Concomitant use of Exforge with aliskiren-containing products in patients with diabetes

mellitus or renal impairment (GFR <60 ml/min/1.73 m

) (see sections 4.5 and 5.1).

Second and third trimesters of pregnancy (see sections 4.4 and 4.6).

Severe hypotension.

Shock (including cardiogenic shock).

Obstruction of the outflow tract of the left ventricle (e.g. hypertrophic obstructive

cardiomyopathy and high grade aortic stenosis).

Haemodynamically unstable heart failure after acute myocardial infarction.

4.4

Special warnings and precautions for use

The safety and efficacy of amlodipine in hypertensive crisis have not been established.

Pregnancy

Angiotensin II Receptor Antagonists (AIIRAs) should not be initiated during pregnancy.

Unless continued AIIRA therapy is considered essential, patients planning pregnancy should

be changed to alternative antihypertensive treatments which have an established safety

profile for use in pregnancy. When pregnancy is diagnosed, treatment with AIIRAs should be

stopped immediately, and, if appropriate, alternative therapy should be started (see

sections 4.3 and 4.6).

Sodium- and/or volume-depleted patients

Excessive hypotension was seen in 0.4% of patients with uncomplicated hypertension

treated with Exforge in placebo-controlled studies. In patients with an activated renin-

angiotensin system (such as volume- and/or salt-depleted patients receiving high doses of

diuretics) who are receiving angiotensin receptor blockers, symptomatic hypotension may

occur. Correction of this condition prior to administration of Exforge or close medical

supervision at the start of treatment is recommended.

If hypotension occurs with Exforge, the patient should be placed in the supine position and, if

necessary, given an intravenous infusion of normal saline. Treatment can be continued once

blood pressure has been stabilised.

Hyperkalaemia

Concomitant use with potassium supplements, potassium-sparing diuretics, salt substitutes

containing potassium, or other medicinal products that may increase potassium levels

(heparin, etc.) should be undertaken with caution and with frequent monitoring of potassium

levels.

Renal artery stenosis

Exforge should be used with caution to treat hypertension in patients with unilateral or

bilateral renal artery stenosis or stenosis to a solitary kidney since blood urea and serum

creatinine may increase in such patients.

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2019

Kidney transplantation

To date there is no experience of the safe use of Exforge in patients who have had a recent

kidney transplantation.

Hepatic impairment

Valsartan is mostly eliminated unchanged via the bile. The half life of amlodipine is

prolonged and AUC values are higher in patients with impaired liver function; dosage

recommendations have not been established. Particular caution should be exercised when

administering Exforge to patients with mild to moderate hepatic impairment or biliary

obstructive disorders.

In patients with mild to moderate hepatic impairment without cholestasis, the maximum

recommended dose is 80 mg valsartan.

Renal impairment

No dosage adjustment of Exforge is required for patients with mild to moderate renal

impairment (GFR >30 ml/min/1.73 m

). Monitoring of potassium levels and creatinine is

advised in moderate renal impairment.

Primary hyperaldosteronism

Patients with primary hyperaldosteronism should not be treated with the angiotensin II

antagonist valsartan as their renin-angiotensin system is affected by the primary disease.

Angioedema

Angioedema, including swelling of the larynx and glottis, causing airway obstruction and/or

swelling of the face, lips, pharynx and/or tongue, has been reported in patients treated with

valsartan. Some of these patients previously experienced angioedema with other medicinal

products, including ACE inhibitors. Exforge should be discontinued immediately in patients

who develop angioedema and should not be re-administered.

Heart failure/post-myocardial infarction

As a consequence of the inhibition of the renin-angiotensin-aldosterone system, changes in

renal function may be anticipated in susceptible individuals. In patients with severe heart

failure whose renal function may depend on the activity of the renin-angiotensin-aldosterone

system, treatment with ACE inhibitors and angiotensin receptor antagonists has been

associated with oliguria and/or progressive azotaemia and (rarely) with acute renal failure

and/or death. Similar outcomes have been reported with valsartan. Evaluation of patients

with heart failure or post-myocardial infarction should always include assessment of renal

function.

In a long-term, placebo-controlled study (PRAISE-2) of amlodipine in patients with NYHA

(New York Heart Association Classification) III and IV heart failure of non-ischaemic

aetiology, amlodipine was associated with increased reports of pulmonary oedema despite

no significant difference in the incidence of worsening heart failure as compared to placebo.

Calcium channel blockers, including amlodipine, should be used with caution in patients with

congestive heart failure, as they may increase the risk of future cardiovascular events and

mortality.

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2019

Aortic and mitral valve stenosis

As with all other vasodilators, special caution is indicated in patients suffering from mitral

stenosis or significant aortic stenosis that is not high grade.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ACE inhibitors, ARBs or aliskiren increases

the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal

failure). Dual blockade of RAAS through the combined use of ACE inhibitors, ARBs or

aliskiren is therefore not recommended (see sections 4.5 and 5.1).

If dual blockade therapy is considered absolutely necessary, this should only occur under

specialist supervision and subject to frequent close monitoring of renal function, electrolytes

and blood pressure. ACE inhibitors and ARBs should not be used concomitantly in patients

with diabetic nephropathy.

Exforge has not been studied in any patient population other than hypertension.

4.5

Interaction with other medicinal products and other forms of interaction

Interactions common to the combination

No drug-drug interaction studies have been performed with Exforge and other medicinal

products.

To be taken into account with concomitant use

Other antihypertensive agents

Commonly used antihypertensive agents (e.g. alpha blockers, diuretics) and other medicinal

products which may cause hypotensive adverse effects (e.g. tricyclic antidepressants, alpha

blockers for treatment of benign prostate hyperplasia) may increase the antihypertensive

effect of the combination.

Interactions linked to amlodipine

Concomitant use not recommended

Grapefruit or grapefruit juice

Administration of amlodipine with grapefruit or grapefruit juice is not recommended as

bioavailability may be increased in some patients, resulting in increased blood pressure

lowering effects.

Caution required with concomitant use

CYP3A4 inhibitors

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease

inhibitors, azole antifungals, macrolides like erythromycin or clarithromycin, verapamil or

diltiazem) may give rise to significant increase in amlodipine exposure. The clinical

translation of these pharmacokinetic variations may be more pronounced in the elderly.

Clinical monitoring and dose adjustment may thus be required.

CYP3A4 inducers (anticonvulsant agents [e.g. carbamazepine, phenobarbital, phenytoin,

fosphenytoin, primidone], rifampicin, Hypericum perforatum)

Upon co-administration of known inducers of the CYP3A4, the plasma concentration of

amlodipine may vary. Therefore, blood pressure should be monitored and dose regulation

considered both during and after concomitant medication particularly with strong CYP3A4

inducers (e.g. rifampicin, hypericum perforatum).

EXF API

2019

Simvastatin

Co-administration of multiple doses of 10 mg amlodipine with 80 mg simvastatin resulted in a

77% increase in exposure to simvastatin compared to simvastatin alone. It is recommended

to limit the dose of simvastatin to 20 mg daily in patients on amlodipine.

Dantrolene (infusion)

In animals, lethal ventricular fibrillation and cardiovascular collapse are observed in

association with hyperkalaemia after administration of verapamil and intravenous dantrolene.

Due to risk of hyperkalaemia, it is recommended that the co-administration of calcium

channel blockers such as amlodipine be avoided in patients susceptible to malignant

hyperthermia and in the management of malignant hyperthermia.

To be taken into account with concomitant use

Others

In clinical interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin,

digoxin, warfarin or ciclosporin.

Interactions linked to valsartan

Concomitant use not recommended

Lithium

Reversible increases in serum lithium concentrations and toxicity have been reported during

concomitant administration of lithium with angiotensin converting enzyme inhibitors or

angiotensin II receptor antagonists, including valsartan. Therefore, careful monitoring of

serum lithium levels is recommended during concomitant use. If a diurectic is also used, the

risk of lithium toxicity may presumably be increased further with Exforge.

Potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium

and other substances that may increase potassium levels

If a medicinal product that affects potassium levels is to be prescribed in combination with

valsartan, monitoring of potassium plasma levels is advised.

Caution required with concomitant use

Non-steroidal anti-inflammatory medicines (NSAIDs), including selective COX-2 inhibitors,

acetylsalicylic acid (>3 g/day), and non-selective NSAIDs

When angiotensin II antagonists are administered simultaneously with NSAIDs attenuation

of the antihypertensive effect may occur. Furthermore, concomitant use of angiotensin II

antagonists and NSAIDs may lead to an increased risk of worsening of renal function and an

increase in serum potassium. Therefore, monitoring of renal function at the beginning of the

treatment is recommended, as well as adequate hydration of the patient.

Inhibitors of the uptake transporter (rifampicin, ciclosporin) or efflux transporter (ritonavir)

The results of an in vitro study with human liver tissue indicate that valsartan is a substrate

of the hepatic uptake transporter OATP1B1 and of the hepatic efflux transporter MRP2. Co-

administration of inhibitors of the uptake transporter (rifampicin, ciclosporin) or efflux

transporter (ritonavir) may increase the systemic exposure to valsartan.

Dual blockade of the RAAS with ARBs, ACE inhibitors or aliskiren

Clinical trial data have shown that dual blockade of the RAAS through the combined use of

ACE inhibitors, ARBs or aliskiren is associated with a higher frequency of adverse events

such as hypotension, hyperkalaemia and decreased renal function (including acute renal

failure) compared to the use of a single RAAS-acting agent (see sections 4.3, 4.4 and 5.1).

Others

In monotherapy with valsartan, no interactions of clinical significance have been found with

the following substances: cimetidine, warfarin, furosemide, digoxin, atenolol, indometacin,

EXF API

2019

hydrochlorothiazide, amlodipine, glibenclamide.

4.6

Fertility, pregnancy and lactation

Pregnancy

Amlodipine

The safety of amlodipine in human pregnancy has not been established. In animal studies,

reproductive toxicity was observed at high doses (see section 5.3). Use in pregnancy is only

recommended when there is no safer alternative and when the disease itself carries greater

risk for the mother and foetus.

Valsartan

The use of Angiotensin II Receptor Antagonists (AIIRAs) is not recommended during the first

trimester of pregnancy (see section 4.4). The use of AIIRAs is contraindicated during the

second and third trimesters of pregnancy (see sections 4.3 and 4.4).

Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE

inhibitors during the first trimester of pregnancy has not been conclusive; however a small

increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the

risk with Angiotensin II Receptor Antagonists (AIIRAs), similar risks may exist for this class

of drugs. Unless continued AIIRA therapy is considered essential, patients planning

pregnancy should be changed to alternative antihypertensive treatments which have an

established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment

with AIIRAs should be stopped immediately, and, if appropriate, alternative therapy should

be started.

Exposure to AIIRA therapy during the second and third trimesters is known to induce human

foetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and

neonatal toxicity (renal failure, hypotension, hyperkalaemia) (see section 5.3).

Should exposure to AIIRAs have occurred from the second trimester of pregnancy,

ultrasound check of renal function and skull is recommended.

Infants whose mothers have taken AIIRAs should be closely observed for hypotension (see

sections 4.3 and 4.4).

Breast-feeding

Amlodipine is excreted in human milk . The proportion of the maternal dose received by the

infant has been estimated with an interquartile range of 3–7%, with a maximum of 15%. The

effect of amlodipine on infants is unknown. No information is available regarding the use of

Exforge during breast-feeding, therefore Exforge is not recommended and alternative

treatments with better established safety profiles during breast-feeding are preferable,

especially while nursing a newborn or preterm infant.

Fertility

There are no clinical studies on fertility with Exforge.

Valsartan

Valsartan had no adverse effects on the reproductive performance of male or female rats at

oral doses up to 200 mg/kg/day. This dose is 6 times the maximum recommended human

dose on a mg/m

basis (calculations assume an oral dose of 320 mg/day and a 60-kg

patient).

EXF API

2019

Amlodipine

Reversible biochemical changes in the head of spermatozoa have been reported in some

patients treated by calcium channel blockers. Clinical data are insufficient regarding the

potential effect of amlodipine on fertility. In one rat study, adverse effects were found on

male fertility (see section 5.3).

4.7

Effects on ability to drive and use machines

Patients taking Exforge and driving vehicles or using machines should take into account that

dizziness or weariness may occasionally occur.

Amlodipine can have mild or moderate influence on the ability to drive and use machines. If

patients taking amlodipine suffer from dizziness, headache, fatigue or nausea the ability to

react may be impaired.

4.8

Undesirable effects

Summary of the safety profile

The safety of Exforge has been evaluated in five controlled clinical studies with

5,175 patients, 2,613 of whom received valsartan in combination with amlodipine. The

following adverse reactions were found to be the most frequently occurring or the most

significant or severe: nasopharyngitis, influenza, hypersensitivity, headache, syncope,

orthostatic hypotension, oedema, pitting oedema, facial oedema, oedema peripheral,

fatigue, flushing, asthenia and hot flush.

Tabulated list of adverse reactions

Adverse reactions have been ranked under headings of frequency using the following

convention: 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).

MedDRA

System organ

class

Adverse reactions

Frequency

Exforge

Amlodipin

e

Valsartan

Infections and

infestations

Nasopharyngitis

Common

Influenza

Common

Blood and

lymphatic

system

disorders

Haemoglobin and

haematocrit decreased

Not known

Leukopenia

Very rare

Neutropenia

Not known

Thrombocytopenia,

sometimes with purpura

Very rare

Not known

Immune system

disorders

Hypersensitivity

Rare

Very rare

Not known

Metabolism and

nutrition

disorders

Anorexia

Uncommon

Hypercalcaemia

Uncommon

Hyperglycaemia

Very rare

Hyperlipidaemia

Uncommon

Hyperuricaemia

Uncommon

Hypokalaemia

Common

Hyponatraemia

Uncommon

EXF API

2019

Psychiatric

disorders

Depression

Uncommon

Anxiety

Rare

Insomnia/sleep disorders

Uncommon

Mood swings

Uncommon

Confusion

Rare

Nervous

system

disorders

Coordination abnormal

Uncommon

Dizziness

Uncommon

Common

Dizziness postural

Uncommon

Dysgeusia

Uncommon

Extrapyramidal syndrome

Not known

Headache

Common

Common

Hypertonia

Very rare

Paraesthesia

Uncommon

Uncommon

Peripheral neuropathy,

neuropathy

Very rare

Somnolence

Uncommon

Common

Syncope

Uncommon

Tremor

Uncommon

Hypoesthesia

Uncommon

Eye disorders

Visual disturbance

Rare

Uncommon

Visual impairment

Uncommon

Uncommon

Ear and

labyrinth

disorders

Tinnitus

Rare

Uncommon

Vertigo

Uncommon

Uncommon

Cardiac

disorders

Palpitations

Uncommon

Common

Syncope

Rare

Tachycardia

Uncommon

Arrhythmias (including

bradycardia, ventricular

tachycardia, and atrial

fibrillation)

Very rare

Myocardial infarction

Very rare

Vascular

disorders

Flushing

Common

Hypotension

Rare

Uncommon

Orthostatic hypotension

Uncommon

Vasculitis

Very rare

Not known

Respiratory,

thoracic and

mediastinal

disorders

Cough

Uncommon

Very rare

Uncommon

Dyspnoea

Uncommon

Pharyngolaryngeal pain

Uncommon

Rhinitis

Uncommon

Gastrointestinal

disorders

Abdominal discomfort,

abdominal pain upper

Uncommon

Common

Uncommon

Change of bowel habit

Uncommon

Constipation

Uncommon

Diarrhoea

Uncommon

Uncommon

Dry mouth

Uncommon

Uncommon

Dyspepsia

Uncommon

Gastritis

Very rare

Gingival hyperplasia

Very rare

Nausea

Uncommon

Common

Pancreatitis

Very rare

Vomiting

Uncommon

EXF API

2019

Hepatobiliary

disorders

Liver function test

abnormal, including blood

bilirubin increase

Very rare*

Not known

Hepatitis

Very rare

Intrahepatic cholestasis,

jaundice

Very rare

Skin and

subcutaneous

tissue disorders

Alopecia

Uncommon

Angioedema

Very rare

Not known

Dermatitis bullous

Not known

Erythema

Uncommon

Erythema multiforme

Very rare

Exanthema

Rare

Uncommon

Hyperhidrosis

Rare

Uncommon

Photosensitivity reaction

Uncommon

Pruritus

Rare

Uncommon

Not known

Purpura

Uncommon

Rash

Uncommon

Uncommon

Not known

Skin discolouration

Uncommon

Urticaria and other forms

of rash

Very rare

Exfoliative dermatitis

Very rare

Stevens-Johnson

syndrome

Very rare

Quincke oedema

Very rare

Toxic Epidermal

Necrolysis

Not known

Musculoskeleta

l and

connective

tissue disorders

Arthralgia

Uncommon

Uncommon

Back pain

Uncommon

Uncommon

Joint swelling

Uncommon

Muscle spasm

Rare

Uncommon

Myalgia

Uncommon

Not known

Ankle swelling

Common

Sensation of heaviness

Rare

Renal and

urinary

disorders

Blood creatinine

increased

Not known

Micturition disorder

Uncommon

Nocturia

Uncommon

Pollakiuria

Rare

Uncommon

Polyuria

Rare

Renal failure and

impairment

Not known

Reproductive

system and

breast

disorders

Impotence

Uncommon

Erectile dysfunction

Rare

Gynaecomastia

Uncommon

General

disorders and

administration

site conditions

Asthenia

Common

Uncommon

Discomfort, malaise

Uncommon

Fatigue

Common

Common

Uncommon

Facial oedema

Common

Flushing, hot flush

Common

Non cardiac chest pain

Uncommon

Oedema

Common

Common

Oedema peripheral

Common

Pain

Uncommon

Pitting oedema

Common

העדוה

לע

הרמחה

(

עדימ

)תוחיטב ןולעב

אפורל ןכדועמ(

05.2013

)

:ךיראת

27.1.2015

םש

רישכת

:תילגנאב

Exforge 5mg/80mg; Exforge 5mg/160mg; Exforge 10mg/160mg

רפסמ

:םושירה

[

31566

;

31567

;

31568

]

םש

לעב

:םושירה סיטרבונ

המראפ

ססיורס

ייא

י'ג ספוט

הז

דעוימ

טוריפל

תורמחהה

!דבלב

רוחש טסקט

רשואמ טסקט

יתחת וק םע לוחכב טסקט

טסקט תפסוה

רשואמה ןולעל

יתחת וק םע םודאב טסקט

טסקט תפסוה

יאפוריא ןולע לע ךמתסהב רשואמה ןולעל רשואמ

בוהצב ןמוסמה טסקט

הרמחה תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

Dosage and

administration

Special population

Geriatric patients (aged 65 years or

above)

Since both components of the

combination are equally well tolerated

when used at similar doses in elderly

(aged 65 years or above) or younger

patients, no dose adjustment of the

starting dose is required (see section 11

Clinical pharmacology).

In elderly patients, caution is required

when increasing the dosage

Special population

Geriatric patients (aged 65 years or

above)

Since both components of the combination

are equally well tolerated when used at

similar doses in elderly (aged 65 years or

above) or younger patients, no dose

adjustment of the starting dose is required

(see section 11 Clinical pharmacology).

Starting with the lowest available dose of

amlodipine should be considered. The

lowest strength of Exforge contains 5 mg

of amlodipine

In elderly patients, caution is required

when increasing the dosage.

Dosage and

administration

Special population

Hepatic impairment

Due to amlodipine and valsartan,

caution should be exercised when

administering Exforge to patients with

hepatic impairment or biliary

obstructive disorders (see sections 6

Warnings and precautions and 11

Special population

Hepatic impairment

Due to amlodipine and valsartan, caution

should be exercised when administering

Exforge to patients with hepatic

impairment or biliary obstructive

disorders. Amlodipine dosage

recommendations have not been

Clinical pharmacology).

In patients with mild to moderate

hepatic impairment without

cholestasis, the maximum

recommended dose is 80 mg valsartan.

established in patients with mild to

moderate hepatic impairment

Starting with the lowest available dose of

amlodipine should be considered. The

lowest strength of Exforge contains 5 mg

of amlodipine

see sections 6 Warnings

and precautions and 11 Clinical

pharmacology).

In patients with mild to moderate hepatic

impairment without cholestasis, the

maximum recommended dose is 80 mg

valsartan.

Warnings and

precautions

The safety and efficacy of amlodipine in

hypertensive crisis have not been

established.

Warnings and

precautions

Patients with hepatic impairment

Valsartan is mostly eliminated

unchanged via the bile whereas

amlodipine is extensively metabolized

by the liver.

Particular caution should be exercised

when administering Exforge to patients

with hepatic impairment or biliary

obstructive disorders (see section 11

Clinical pharmacology).

In patients with mild to moderate

hepatic impairment without

cholestasis, the maximum

recommended dose is 80 mg valsartan

Patients with hepatic impairment

Valsartan is mostly eliminated unchanged

via the bile whereas amlodipine is

extensively metabolized by the liver.

The half life of amlodipine is prolonged and

AUC values are higher in patients with

hepatic impairment; dosage

recommendations have not been

established .Particular caution should be

exercised when administering Exforge to

patients with hepatic impairment or biliary

obstructive disorders (see section 11

Clinical pharmacology).

In patients with mild to moderate hepatic

impairment without cholestasis, the

maximum recommended dose is 80 mg

valsartan.

Interactions

CYP3A4 inhibitors:

Co-administration of a 180 mg daily

dose of diltiazem with 5 mg amlodipine

in elderly hypertensive patients

resulted in a 1.6 fold increase in

amlodipine systemic exposure.

However, strong inhibitors of CYP3A4

(e.g., ketoconazole, itraconazole,

ritonavi) may increase the plasma

concentrations of amlodipine to a

greater extent than diltiazem. Caution

should therefore be exercised when co-

CYP3A4 inhibitors:

Co-administration of a 180 mg daily dose

of diltiazem with 5 mg amlodipine in

elderly hypertensive patients resulted in a

1.6 fold increase in amlodipine systemic

exposure. However, strong inhibitors of

CYP3A4 (e.g., ketoconazole, itraconazole,

ritonavir, indinavir) may increase the

plasma concentrations of amlodipine to a

greater extent than diltiazem. Caution

should therefore be exercised when co-

administering amlodipine with CYP3A4

administering amlodipine with CYP3A4

inhibitors.

inhibitors.

Interactions

Grapefruit Juice

:

The exposure of amlodipine may be

increased when co-administered with

grapefruit juice due to CYP3A4 inhibition.

However, co-administration of 240 mL of

grapefruit juice with a single oral dose of

amlodipine 10 mg in 20 healthy volunteers

had no significant effect on the

pharmacokinetics of amlodipine

Effects on

ability to drive

and use

machines

Effects on ability to drive and use

machines

Patients taking Exforge and driving vehicles

or using machines should take into account

that dizziness or weariness may

occasionally occur.

Amlodipine can have mild or moderate

influence on the ability to drive and use

machines. If patients taking amlodipine

suffer from dizziness, headache, fatigue or

nausea the ability to react may be

impaired

ב"צמ

ןולעה

ובש

תונמוסמ

תורמחהה

תושקובמה

לע

עקר

.בוהצ םייוניש

םניאש

רדגב

תורמחה

ונמוס

ןולעב עבצב )

שי .הנוש

ןמסל

קר

ןכות

יתוהמ

אלו

םייוניש

םוקימב .טסקטה רבעוה

ראודב

ינורטקלא

ךיראתב

26.1.2015

העדוה

לע

הרמחה

(

עדימ

)תוחיטב ןולעב

ןכרצל ןכדועמ(

05.2013

)

:ךיראת

27.1.2015

םש

רישכת

:תילגנאב

Exforge 5mg/80mg; Exforge 5mg/160mg; Exforge 10mg/160mg

רפסמ

:םושירה

[

31566

;

31567

;

31568

]

םש

לעב

:םושירה סיטרבונ

המראפ

ססיורס

ייא

י'ג

ספוט

הז

דעוימ

טוריפל

תורמחהה

!דבלב

רוחש טסקט

רשואמ טסקט

יתחת וק םע טסקט

רשואמה ןולעל טסקט תפסוה

הצוח וק םע טסקט

רשואמה ןולעהמ טסקט תקיחמ

בוהצב ןמוסמה טסקט

הרמחה תורמחהה

תושקובמה קרפ

ןולעב טסקט

יחכונ טסקט

שדח

2

.

ינפל

שומיש הפורתב םא

התא

חקול

,

וא

םא

תחקל ,הנורחאל תופורת

תורחא ללוכ

תופורת אלל

םשרמ יפסותו

הנוזת

,

רפס

לע

ךכ אפורל

וא

חקורל םא

התא

חקול וא ,

םא

תחקל ,הנורחאל תופורת

תורחא

ללוכ תופורת

אלל

םשרמ

יפסותו

,הנוזת רפס

לע

ךכ

אפורל

וא

.חקורל ןכתי יכ

היהי

ךרוצ

תונשל

תא

וא ,ןונימה םירקמב

םימיוסמ

קיספהל

לוטיל

תא תחא

דחוימב .תופורתה

שי

עדייל

תא אפורה

וא

חקורה

םא

התא

חקול תופורת

תוצובקהמ

:תואבה תופורת

תושמשמה

תדרוהל

ץחל

םד

רקיעב

םינתשמ

עמ יבכ

ACE (ACE

inhibitors)

וא

;ןריקסילא תופורת תורצוא

,ןגלשא

יפסות

ןגלשא

וא יפילחת

חלמ

םיליכמה

.ןגלשא אפורה יושע

קודבל

תא

תומכ

ןגלשאה

ךמדב תעמ

תעל

םיגוס

םימיוסמ

לש

יככשמ םיבאכ

םיארקנה

ידגונ

תקלד

םניאש םידיאורטס

NSAIDs

וא )

םיבכעמ םייביטקלס

לש

זאנגיסקואולקיצ

Cox-2 inhibitors

אפורה

םג

יושע קודבל

תא

דוקפת

הילכה

;ךלש הפורת ,םויתיל

תשמשמה

לופיטל םיגוסב

םימיוסמ

לש

תולחמ תופורת ;תוירטאיכיספ

לופיטל םיסוכריפב

ןוגכ(

ירישכת

,ןיפזמברק ;)ןודימירפ ,ןיאוטינפ ,לאטיברבונפ ןירצילגורטינ

םיטרטינו

וא ,םירחא תופורת

תורחא

תוכיישה

תצובקל יביחרמ

ילכ

םד

vasodilators

שי

חוודל

אפורל

לפטמה

וא

חקורל םא

ךנה

לטונ

וא

תלטנ

הנורחאל תופורת

תופסונ

תולוכיש

תונשל

תא םא

התא

חקול וא ,

םא

תחקל ,הנורחאל תופורת

תורחא

ללוכ תופורת

אלל

םשרמ

יפסותו

,הנוזת רפס

לע

ךכ

אפורל

וא

.חקורל ןכתי יכ

היהי

ךרוצ

תונשל

תא

וא ,ןונימה םירקמב

םימיוסמ

קיספהל

לוטיל

תא תחא

דחוימב .תופורתה

שי

עדייל

תא אפורה

וא

חקורה

םא

התא

חקול תופורת

תוצובקהמ

:תואבה תופורת

תושמשמה

תדרוהל

ץחל

םד

רקיעב

םינתשמ

עמ יבכ

ACE (ACE

inhibitors)

וא

;ןריקסילא תופורת תורצוא

,ןגלשא

יפסות

,ןגלשא וא יפילחת

חלמ

םיליכמה

ןגלשא

וא

תא תולעהל תולולעש תורחא תופורת

ןגלשאה תומר

אפורה

יושע

קודבל תא

תומכ

ןגלשאה

ךמדב

תעמ

תעל

םיגוס

םימיוסמ

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יככשמ

םיבאכ םיארקנה

ידגונ

תקלד

םניאש םידיאורטס

NSAIDs

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םיבכעמ םייביטקלס

לש

זאנגיסקואולקיצ

Cox-2 inhibitors

אפורה

םג

יושע קודבל

תא

דוקפת

הילכה

;ךלש הפורת ,םויתיל

תשמשמה

לופיטל םיגוסב

םימיוסמ

לש

תולחמ תופורת ;תוירטאיכיספ

לופיטל םיסוכריפב

ןוגכ(

ירישכת

,ןיפזמברק ,ןודימירפ ,ןיאוטינפ ,לאטיברבונפ ןיאוטינפסופ ןירצילגורטינ ;)

םיטרטינו וא ,םירחא

תופורת

תורחא

תוכיישה תצובקל

יביחרמ

ילכ

םד

vasodilators

תומכ

ןיפידולמאה

ךפוגב

דחוימב תופורת

תוצובקהמ

תופורת :תואבה תושמשמה

העינמל

לופיטו

ימוהיז רוע

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לוזאנוקארטיא

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תומיוסמ

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יאוול ומכ

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שומישה ,הפורת לולע 'גרופסקאב

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קלחב

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ארקמל

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דימ

אפורל

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שי

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םימוטפמיס

ןוגכ תוחיפנ ,דרג ,החירפ

לש

םינפה

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,המישנ ץחל

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ךומנ

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וא

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רבגומ

תתל

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תלוכי גישהל

וא

קיזחהל

תשגרה ;הפקז ץחל ;תודבכ

םד

ךומנ

םע

םימוטפמיס ןוגכ

תרוחרחס ,תרוחרחס

;הלק העזה

החירפ ;תרבגומ

תיללכ

;רועב תוצווכתה ;דרג

,םירירש תוערפה הייארב

םא

תועפותה

וניוצש

ליעל

תועיפשמ ךילע

הרוצב

הנפ ,הרומח

אפורל .ךלש

......

ב"צמ

ןולעה

ובש

תונמוסמ

תורמחהה

תושקובמה

לע

עקר

.בוהצ םייוניש

םניאש

רדגב

תורמחה

ונמוס

ןולעב עבצב )

שי .הנוש

ןמסל

קר

ןכות

יתוהמ

אלו

םייוניש

םוקימב .טסקטה רבעוה

ראודב

ינורטקלא

:ךיראתב

26.1.2015

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