INTELENCE 200 MG

Israel - English - Ministry of Health

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Active ingredient:
ETRAVIRINE
Available from:
J-C HEALTH CARE LTD
ATC code:
J05AG04
Pharmaceutical form:
TABLETS
Composition:
ETRAVIRINE 200 MG
Administration route:
PER OS
Prescription type:
Required
Manufactured by:
JANSSEN CILAG S.P.A., ITALY
Therapeutic group:
ETRAVIRINE
Therapeutic area:
ETRAVIRINE
Therapeutic indications:
Intelence is indicated in combination with other antiretroviral medicinal products for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients including those with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance. Treatment history and when available resistance testing should guide the use of Intelence. In patients who have experienced virological failure on an NNRTI- and nucleoside or nucleotide reverse transcriptase inhibitor (N[t]RTI)- containing regimen Intelence is not recommended for use in combination with N(t)RTIs only.
Authorization number:
149 61 33666 00
Authorization date:
2018-03-31

Documents in other languages

Patient Information leaflet Patient Information leaflet - Hebrew

01-08-2019

.مويلا يف نيترم غلم 200 :وه ةداع يدايتعلإا يئاودلا رادقملا :غلم 100 تاذ صارقأ لوانتت تنك اذإ ماعطلا ةبجو دعب حابصلا يف غلم 100 سنليتنيإ نم نيصرق لوانت بجي .ماعطلا ةبجو دعب ءاسملا يف غلم 100 سنليتنيإ نم نيصرق لوانت بجيو :غلم 200 تاذ صارقأ لوانتت تنك اذإ ماعطلا ةبجو دعب حابصلا يف غلم 200 سنليتنيإ نم دحاو صرق لوانت بجي .ماعطلا ةبجو دعب ءاسملا يف غلم 200 سنليتنيإ نم دحاو صرق لوانت بجيو ةيواخ ةدعم ىلع ءاودلا لوانت نإ .ماعطلا ةبجو دعب ءاودلا لوانت

ادج مهملا نم بيبطلا ةراشتسإ بجي .فصنلل ةصتمملا ةيمكلا صلقيو هصاصتمإ نم لقرعي .بسانملا ماعطلا عونل ةبسنلاب .صرقلا غضم زوجي لا .ءاملا نم ةئيلم سأك عم هلمكأب صرقلا علب بجي .صرقلا رطش ناكملإاب :ةيلاتلا تاميلعتلا بجومب فرصت ءاجرلا ،هلمكأب صرقلا علب ىلع رداق ريغ تنك اذإ ةيطغتل يفكت لئاس ةيمكب وأ ،ءاملا نم )ةريغص ةقعلم( للم 5 ـب صرقلا عض

.لقلأا ىلع صرقلا .بيلحلاك ءاملا ودبي ىتح ديجلا طلخلاب مق - بيلحلا وأ لاقتربلا ريصع كلذ نع

لادب وأ ءاملا نم ديزملا ةفاضإ ناكملإاب

.)بيلحلا وأ لاقتربلا ريصع يف ةرشابم صرقلا عضو زوجي لا(

لااح اهبرشب مق - لماكلاب اهبرشب مقو بيلحلا وأ لاقتربلا ريصع ،ءاملاب تارم ةدع سأكلا لسغإ

.ةيئاودلا ةعرجلا لماك لوانت نم دكأتلل ةرم لك يف تابورشملا وأ )قوف امو ةيوئم ةجرد 40( نخاسلا ءاملا لامعتسإ زوجي لا - .سنليتنيإ لوانت دنع ةيزاغلا نم ةفدصلاب هحتف عنمي نامأ ءاطغ ةنينقلل دجوي :ةنينقلا حتفل تاميلعت )

.لافطلأا لبق لفسلأا هاجتإب ءاطغلا ىلع طغضلاب ةنينقلا حتف بجي .ءاطغلا عزنو ةعاسلا براقع سكعب هريودت للاخ نم .هب ىصوملا يئاودلا رادقملا زواجت زوجي لا .يلديصلا وأ بيبطلا ىلإ

لااح هجوت ،ربكأ

ً

ايئاود

ً

ارادقم أطخلاب تلوانت اذإ )

X

(

عادصو نايثغ ،لاهسإ ،حفط يه سنليتنيإ ـل

اعويش رثكلأا ةيبناجلا ضارعلأا .)”ةيبناجلا ضارعلأا“ 4 ةرقفلا رظنأ( 6 ىتح كلذب تركذتو ددحملا تقولا يف ءاودلا اذه لوانت تيسن اذإ )

X

(

لاح ةعرج لوانت بجيف ،هيف ءاودلا لوانت كيلع بجوت يذلا دعوملا نم تاعاس .داتعملاك ةمداقلا ةعرجلا لوانت ةلصاومو ،ماعطلا ةبجو دعب

امئادو كركذت بجيف ،هيف ءاودلا لوانت كيلع بجوت يذلا دعوملا نم تاعاس 6 نم رثكأ ترم اذإ .داتعملاك ةمداقلا ةعرجلا لوانت ةلصاومو ةيسنملا ةعرجلا تيوفت نع ضيوعتلل ةيوس نييئاود نيرادقم لوانت لاوحلأا نم لاح يأب زوجي لا !يسنملا يئاودلا رادقملا دعب يفاضإ صرق لوانت ،سنليتنيإ لوانت نم تاعاس 4 نم لقأ دعب تأيقت اذإ ةجاح لاف ،سنليتنيإ لوانت نم تاعاس 4 نم رثكأ دعب تأيقت اذإ .ماعطلا ةبجو .ءاودلا لوانت هيف كيلع بجوتي يذلا يلاتلا دعوملا ىتح يفاضإ صرق لوانتب ؟جلاعلا حاجن يف ةمهاسملا كنكمي فيك نع فقوتلا زوجي لا .بيبطلا ةيصوت بسحب جلاعلا ىلع ةبظاوملا بجي )

.بيبطلا ةقفاوم لبق سنليتنيإ لامعتسإ نع فقوتلا زوجي لا .لضفأ لكشب روعشلا جلاعلا كل ببسي نأ زئاجلا نم )

،بيبطلا ةراشتسإ نودب

ـل ةداضملا ىرخلأا ةيودلأاب وأ ءاودلاب جلاعلا ةقفاوم نودب جلاعلا نع فقوتلا نإ .ةيحصلا كتلاح ىلع نسحت أرط ولو ىتح .ةمواقم سورﯿﭭلا روطي نأ ةروطخ نم ديزي دق بيبطلا 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 اذه لامعتسإ لوح ةيفاضإ ةلئسأ كيدل ترفوت اذإ .يلديصلا وأ ةيبناجلا ضارعلأا )4 .نيلمعتسملا ضعب دنع ةيبناج

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

ايأ يناعت لاأ زئاجلا نم .ةيبناجلا ضارعلأا ةمئاق نم شهدنت لا نم رثكأ ىدل رهظت ضارعأ( )

very common

ادج ةعئاش ةيبناج ضارعأ :)ةرشع نيب نم دحاو لمعتسم ثودح نع ةردان تلااح يف غلب .ةدشلا طسوتم وأ فيفط ةداع يدلج حفط )

نم حفط روطت اذإ كلذلو ةايحلا ىلع

ارطخ لكشي نأ نكمي يذلا ديدش حفط فقوتلا بجوت اذإ اميفو هتجلاعم ةيفيكب كيصوي يكل

لااح بيبطلا غلابإ مهملا .ءاودلاب جلاعلا نع عادص )

نايثغ ،لاهسإ )

نيلمعتسم 10 - 1 ىدل رهظت ضارعأ( )

common

( ةعئاش ةيبناج ضارعأ :)100 نيب نم )ةيساسح طرف( يسسحت لعف در )

ماعطلل ةيهشلا صقانت ،يركسلا )

.مونلا يف لكاشم ،مونلا ةلق ،ساعن ،قلق )

نادقف ،دلجلا يف سحلا نادقف ،ردخ ،نيلجرلا وأ نيديلا يف ملأ وأ زخو )

.قاهرإ ،ةركاذلا ةيؤرلا ةيبابض )

.دهجلا ءانثأ سفنت قيض ،ةيبلق ةبون ،مدلا طغض عافترإ ،يولك لشف )

،ةدعملا باهتلإ ،نطبلا ةقطنم يف ةخفن ،نطبلا يف ملأ ،ناقرح ،تاؤيقت )

.مفلا فافج ،مفلا باهتلإ ،كاسمإ ،تازاغ .دلجلا فافج ،ةكح ،يليل قرعت )

ضافخنإ :

لاثم .كلذ بيبطلا كل حرشي .لوبلا وأ مدلا صوحف ميق يف ريغت )

.ءارمحلا مدلا تايرك 10 - 1 ىدل رهظت ضارعأ( )

uncommon

( ةعئاش ريغ ةيبناج ضارعأ :)1000 نيب نم نيلمعتسم ءاضيبلا مدلا ايلاخ دادعت ضافخنإ )

)ةنوخسو ةيوافمللا ددغلا مخضت لثم( ثولت ضارعأ )

.سيباوك ،ةيبصع ،ناهوت ،كابترإ ،ةيداع ريغ ملاحأ )

.ءاغصلإا يف تابارطضإ ،تابون ،ءامغإ ،ةفجر ،ساعن )

لقث ،راود )

بلقلا مظن ماظتنإ مدع ،ردصلا يف طغض/ردصلا يف ملأ )

سفنتلا يف تابوعص )

.مد ؤيقت ،سايركنبلا باهتلإ ،ؤيقتلل ةلشاف تلاواحم )

.دبكلا مخضت ،دبكلا باهتلإ لثم دبكلا يف لكاشم )

.ةرجنحلا وأ/و هجولا خافتنإ ،دئاز قرعت )

لاجرلا ىدل نييدثلا مخضت )

نم نيلمعتسم 10 - 1 ىدل رهظت ضارعأ( )

rare

( ةردان ةيبناج ضارعأ :)10000 نيب ةتكس )

:)دعب اهعويش ددح

ي مل ضارعأ( فورعم ريغ عويش تاذ ةيبناج ضارعأ باهتلإبو ةنوخسب قفارتي حفطب زيمتت يتلا ةديدش ةيساسح طرفل لعف دودر )

.دبكلا باهتلإ لثم وضع يأ امدنع وأ ةيبناجلا ضارعلأا ىدحإ تمقافت اذإ ،يبناج ضرع رهظ اذإ .بيبطلا ةراشتسإ كيلع ،ةرشنلا هذه يف ركذي مل يبناج ضرع نم يناعت طبارلا ىلع طغضلا ةطساوب ةحصلا ةرازول ةيبناج ضارعأ نع غيلبتلا ناكملإاب ةيسيئرلا ةحفصلا ىلع دوجوملا »يئاود جلاع بقع ةيبناج ضارعأ نع غيلبت« رشابملا جذومنلا ىلإ كهجوي يذلا )

www.health.gov.il

( ةحصلا ةرازو عقومل .ةيبناج ضارعأ نع غيلبتلل ؟ءاودلا نيزخت ةيفيك )5 نع

اديعب قلغم ناكم يف رخآ ءاود لكو ءاودلا اذه ظفح بجي !ممستلا بنجت .ممستلاب مهتباصإ يدافتل كلذو ،عضرلا وأ/و لافطلأا ةيؤر لاجمو يديأ لوانتم .بيبطلا نم ةحيرص تاميلعت نودب ؤيقتلا ببست لا رهظي يذلا )

exp.date

( ةيحلاصلا خيرات ءاضقنإ دعب ءاودلا لامعتسإ زوجي لا مويلا ىلإ ةيحلاصلا خيرات ريشي .ةنينقلا ةقصلم/ةيجراخلا ةبلعلا رهظ ىلع .رهشلا سفن نم ريخلأا نيزخت بجي .ةيوئم ةجرد 30 نع ديزت ةرارح ةجردب نيزختلا زوجي لا )

نم ةيامحلل قلاغلإا ةمكحم ةنينقلا ظفح بجي .ةيلصلأا ةنينقلا يف صارقلأا .ةبوطرلا ةبوطرلل ةصام ةدام ىلع يوتحت يتلا ةريغص سايكأ 3 ىلع ةنينقلا يوتحت ةنينقلا نمض سايكلأا ءاقبإ بجي .صارقلأا فافج ىلع ةظفاحملاب حمست كلذبو .لكلأل ةصصخم ريغ سايكلأا .تقو لك يف زواجتي امب ءاودلا اذه لامعتسإ زوجي لا ،ةرم لولأ ةنينقلا حتف دعب .نينثإ نيرهش ةيفاضإ تامولعم )6

اضيأ ةلاعفلا ةداملل ةفاضلإاب ءاودلا يوتحي

Intelence 100 mg: hypromellose; microcrystalline cellulose;

croscarmellose sodium; magnesium stearate; colloidal anhydrous

silica

:كلذل ةفاضلإابو

lactose monohydrate 160.0 mg

Intelence 200 mg: hypromellose; silicified microcrystalline

cellulose; microcrystalline cellulose; croscarmellose sodium;

magnesium stearate; colloidal anhydrous silica

:ةبلعلا ىوتحم وه امو ءاودلا ودبي فيك ةباتكلا هيلع جيب - ضيبأ نول وذ يوضيب صرق نع ةرابع وه غلم 100 سنليتنيإ .يناثلا بناجلا نم

ةباتكلاو دحاو بناج نم

T125

سنليتنيإ نم

اصرق 120 ىلع يوتحت كيتسلاﭙلا نم ةدحاو ةنينق كانه ةبلع لكب ةدام ىلع يوتحت ةريغص سايكأ 3 ةنينق لكب دجوي كلذل ةفاضلإاب .غلم 100 ءاقبإ بجي .صارقلأا فافج ىلع ةظفاحملاب حمست كلذبو ةبوطرلل ةصام .تقو لك يف ةنينقلا نمض سايكلأا نول وذ ،نيبناجلا بدحم ،لواطم صرق نع ةرابع وه غلم 200 سنليتنيإ .دحاو بناج نم

T200

ةباتكلا هيلع ،جيب – ضيبأ كلذل ةفاضلإاب .غلم 200 سنليتنيإ نم

اصرق 60 ىلع كيتسلاﭙلا ةبلع يوتحت حمست كلذبو ةبوطرلل ةصام ةدام ىلع يوتحت ةريغص سايكأ 3 ةنينق لكب دجوي .تقو لك يف ةنينقلا نمض سايكلأا ءاقبإ بجي .صارقلأا فافج ىلع ةظفاحملاب ، 60٩٩000 مييافش ستوبيك ، . ض.م ريك ثليه يس ـ ييج :زايتملإا بحاص

ليئارسإ

ايلاطيإ

،انيتلا ،ليشيم ناس وچروب ،04100 نسناي .يس ايڤ ،چلايس نسناي :جتنملا خيرات يف صخ

رو صح

ف اهاوتحمو ةرشنلا هذه ةغيص ةحصلا ةرازو ترقأ خيرات يف ةحصلا ةرازو تاميلعت بسحب اهثيدحت متو 2016/03/03 201٩/01/07 :ةحصلا ةرازو يف يموكحلا ةيودلأا لجس يف ءاودلا لجس مقر

141293178900

:غلم 100 سنليتنيإ

149613366600

:غلم 200 سنليتنيإ .ركذملا ةغيصب ةرشنلا هذه ةغايص تمت ،ةءارقلا نيوهتو ةلوهس لجأ نم .نيسنجلا لاكل صصخم ءاودلا نإف ،كلذ نم مغرلا ىلع

PATIENT PACKAGE INSERT IN ACCORDANCE WITH THE

PHARMACISTS’ REGULATIONS (PREPARATIONS) - 1986

The medicine is dispensed with a doctor’s prescription

only

Name of the medicine and its form:

Intelence

®

100 mg,

Intelence

®

200 mg,

Tablets

Active ingredient and its quantity in each tablet:

Etravirine 100 mg, 200 mg

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.

Intelence is intended for the treatment of adults. Intelence is

not intended for treatment of patients under 18 years of age.

This preparation is not usually intended for patients over 65

years of age, unless so instructed by the doctor.

1. WHAT IS THE MEDICINE INTENDED FOR?

Intelence contains the active ingredient etravirine.

Intelence is a medicine used for the treatment of HIV

(Human Immunodeficiency Virus) infection. Intelence acts by

reducing the level of the virus in the body, which will improve

the functioning of the immune system and reduce the risk of

developing illnesses associated with HIV infection.

Intelence, in combination with other anti-HIV medicines, is used

to treat adult HIV carriers, who have been treated in the past

with other anti-HIV medicines. Consult the doctor regarding the

most suitable combination of medicines for you.

Therapeutic group: The medicine belongs to a group of anti-HIV

medicines called non-nucleoside reverse transcriptase

inhibitors (NNRTIs).

2. BEFORE USING THE MEDICINE

Do not use the medicine if:

You are allergic to the active ingredient etravirine or to any of

the additional ingredients contained in the medicine, listed

in section 6 ”Further Information“.

You are taking elbasvir/grazoprevir (a medicine to treat

hepatitis C infection).

Special warnings regarding use of the medicine:

Before treatment with Intelence, tell the doctor if:

(X) Intelence does not cure the HIV infection, but rather,

constitutes a component of treatment intended to reduce the

level of the virus in the blood. You can still pass on HIV when

taking this medicine, although the risk is lowered by effective

antiretroviral therapy.

Consult the doctor regarding precautions necessary to prevent

infecting others with the virus.

(X) This preparation is not approved in Israel for patients under

18 years of age.

(X) Elderly: Intelence has been used in a limited number

of patients aged 65 and over. If you belong to this age

group, you should consult the doctor regarding use of

the medicine.

(X) Weight and increased blood lipids and glucose: During

HIV therapy, there may be an increase in weight and in

levels of blood lipids and glucose. This is partly linked

to restored health and life style, and in certain cases of

blood lipids, to the anti-HIV medicines themselves. The

doctor will test for these changes.

(X) Bone problems: Some patients, who are taking a

combination of antiretroviral medicines, may develop a

bone disease called osteonecrosis (death of bone tissue

caused by loss of blood supply to the bone). The length of

combination antiretroviral therapy, use of corticosteroids,

alcohol consumption, severe immunosuppression, higher body

mass index, among others, may be some of the risk factors

for developing this disease. Symptoms of osteonecrosis are

joint stiffness, pain (mainly in the hip, knee and shoulder) and

difficulty in movement. If you notice any of these symptoms,

inform the doctor.

Inform the doctor of the following conditions:

Check the following points and inform the doctor if they apply

to you:

(X) Tell the doctor if a rash develops. If a rash develops, it

usually appears soon after initiation of anti-HIV treatment with

Intelence and usually disappears within a week or two, even

with continued use of the medicine. Occasionally, during the

course of treatment with Intelence, a hypersensitivity reaction

may occur (an allergic reaction including rash and fever, and

even swelling of the face, tongue or throat, and difficulty in

breathing or swallowing), which could be life-threatening. Inform

the doctor immediately if you experience a hypersensitivity

reaction. The doctor will advise you on how to deal with the

symptoms or whether you should stop taking the medicine. If

you have stopped treatment due to a hypersensitivity reaction,

do not restart therapy with Intelence.

(X) Inform the doctor if you suffer or have suffered from

liver problems, including hepatitis B and/or C. Your doctor

will assess the severity of your liver disease before deciding if

you can take the medicine.

(X) Inform the doctor immediately if you notice any symptoms

of infection. In some patients with advanced HIV infection

and a history of opportunistic infections, signs and symptoms

of previous infections can be manifested immediately after

initiation of the treatment with the medicine. The symptoms may

occur due to the improvement in the body’s immune response

and its ability to fight infections that may have been present in

the body without any obvious symptoms.

(X) In addition to the opportunistic infections, autoimmune

disorders (a condition that occurs when the immune system

attacks healthy body tissues) may also occur after beginning

to take medicines for the treatment of an HIV infection.

Autoimmune disorders can also occur many months after

starting treatment. If you notice any symptoms of infection or

symptoms such as muscle weakness, weakness beginning

in the hands and feet and moving up towards the trunk of the

body, palpitations, tremor or hyperactivity, inform the doctor

immediately in order to receive the necessary treatment.

Children and adolescents

Intelence is not intended for treatment of patients under 18

years of age.

Drug interactions:

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

including non-prescription medicines and nutritional

supplements, tell the doctor or pharmacist. Especially

if you are taking:

In most cases, Intelence can be combined with other anti-HIV

medicines belonging to another class. However, some

combinations are not recommended, and in certain cases,

increased monitoring and/or a change in the dose of the

medicine are necessary. Therefore, always tell the doctor which

other anti-HIV medicines you are taking and carefully follow his

instructions regarding the medicines that can be combined. It

is important to carefully read the patient leaflet provided with

these medicines.

(X) It is not recommended to take Intelence together with

the following medicines:

(X) Tipranavir/ritonavir, efavirenz, nevirapine, rilpivirine,

indinavir, nelfinavir, atazanavir/cobicistat, darunavir/cobicistat

(medicines to treat HIV infection)

(X) Carbamazepine, phenobarbital and phenytoin (for

treatment of seizures)

(X) Rifampicin because it is contraindicated with protease

inhibitors (boosted protease inhibitors), and rifapentine (for

treatment of infections such as tuberculosis)

(X) Preparations that contain St. John’s Wort (Hypericum

perforatum) (a herbal product for treatment of depression).

(X) Daclatasvir, simeprevir (medicines to treat hepatitis C

infection)

Consult the doctor if you are taking any of these medicines.

(X) If you are taking any of the following medicines together

with Intelence, their action or that of Intelence may be

affected. The dosage of some medicines might need to

be changed since their therapeutic effect or side effects

may be influenced when combined with Intelence. Tell the

doctor if you are taking any of the following medicines:

(X) Dolutegravir, maraviroc, amprenavir/ritonavir and

fosamprenavir/ritonavir (anti-HIV medicines).

(X) Amiodarone, bepridil, digoxin, disopyramide, flecainide,

lidocaine, mexiletine, propafenone and quinidine (for treatment

of heart problems, such as abnormal heart beat).

(X) Warfarin (to reduce blood clotting); your doctor will instruct

you to have blood tests performed.

(X) Fluconazole, itraconazole, ketoconazole, posaconazole or

voriconazole (to treat fungal infections)

(X) Clarithromycin, rifabutin (antibiotics)

(X) Artemether/lumefantrine (a medicine for treatment of

malaria)

(X) Diazepam (to treat sleep disturbances and/or anxiety)

(X) Dexamethasone (a corticosteroid to treat a variety of

conditions, such as inflammation and allergic reactions)

(X) Boceprevir (a medicine to treat hepatitis C infection)

(X) Atorvastatin, fluvastatin, lovastatin, rosuvastatin or

simvastatin (to lower blood cholesterol levels).

(X) Cyclosporine, sirolimus or tacrolimus (immunosuppressants)

(X) Sildenafil, vardenafil or tadalafil (to treat erectile dysfunction

and/or pulmonary arterial hypertension)

(X) Clopidogrel (a medicine to prevent formation of blood clots)

Use of the medicine and food:

It is very important to take the medicine after a meal. Taking

the medicine on an empty stomach impairs its absorption

and reduces the amount that is absorbed by half. For further

information, see section 3 ”How should you use the medicine?“.

Pregnancy, breastfeeding and fertility:

Inform your doctor immediately if you are pregnant.

Do not take this medicine if you are pregnant, unless explicitly

instructed to do so by the doctor.

HIV infected mothers must not breastfeed, as there is a chance

of infecting the baby with the virus.

Driving and operating machinery:

Do not drive or operate machinery if you feel drowsy or dizzy

after taking the medicine.

Important information about some of the ingredients

in this medicine:

Intelence 100 mg tablet contains lactose. Each tablet contains

160 mg lactose monohydrate.

If you have been told by your doctor that you suffer from an

intolerance to some sugars such as lactose, consult the doctor

before starting to use the medicine.

3. HOW SHOULD yOU USE THE MEDICINE?

Always use the medicine according to the doctor’s instructions.

Check with the doctor or pharmacist if you are uncertain about

the dosage and treatment regimen for the medicine.

The dosage and the treatment regimen will be determined

by the doctor only.

The usual dosage is generally: 200 mg, twice a day.

If you are taking 100 mg tablets:

In the morning, take 2 Intelence 100 mg tablets after a meal and

in the evening, take 2 Intelence 100 mg tablets after a meal.

If you are taking 200 mg tablets:

In the morning, take one Intelence 200 mg tablet after a meal

and in the evening, take one Intelence 200 mg tablet after

a meal.

It is very important to take the medicine after a meal. Taking

the medicine on an empty stomach impairs its absorption and

reduces the amount that is absorbed by half. Consult the doctor

regarding the type of food that is suitable.

Swallow the tablet whole with a full glass of water. Do not chew

the tablet. The tablet can be halved.

If you are unable to swallow the tablet whole, please follow the

following instructions:

- Place the tablet in 5 ml (a teaspoon) of water, or at least in

an amount of fluid sufficient to cover the tablet.

- Mix well until the water looks milky.

- More water may be added, or, alternatively, orange juice or

milk (do not place the tablet directly in orange juice or milk).

- Drink immediately.

- Rinse the glass several times with water, orange juice or milk

and drink all of it each time to ensure that the entire dose is

taken.

- Do not use hot water (40 degrees and above) or carbonated

drinks when taking Intelence.

(X) Instructions for opening the bottle: The bottle has a safety

cap which prevents inadvertent opening by children.

Open the bottle by pressing down on the

cap while turning counterclockwise, and

remove the cap.

Do not exceed the recommended dose.

(X) If you accidentally took a higher dosage, refer to the

doctor or pharmacist immediately. The most common side

effects of Intelence are rash, diarrhea, nausea, and headache

(see section 4 ”Side effects“).

(X) If you forgot to take this medicine at the scheduled time

and remember within 6 hours of the scheduled time, take a

dose as soon as you remember, and always following a meal,

and continue taking the next dose as usual. If more than 6

hours have elapsed since the time you should have taken the

medicine, skip the forgotten dose and continue to take the

next dose as usual.

Never take two doses together to make up for a forgotten dose!

If you vomit less than 4 hours after taking Intelence, take

another tablet following a meal. If you vomit more than 4 hours

after taking Intelence, there is no need to take another dose

until the next time you have to take the medicine.

How can you contribute to the success of the treatment?

(X) Adhere to the treatment regimen as recommended by the

doctor. Do not stop using Intelence before the doctor gives

his approval.

(X) It is possible that the treatment may cause you to feel better.

Even if there is an improvement in the condition of your health,

do not stop treatment with the medicine or with other anti-HIV

medicines without consulting the doctor. Stopping treatment

without the doctor’s approval may increase the risk of the virus

developing resistance.

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 pharmacist.

4. SIDE EFFECTS

As with any medicine, use of Intelence may cause side effects

in some users. Do not be alarmed by reading the list of side

effects. You may not suffer from any of them.

Very common side effects (effects which occur in more than

one in ten users):

(X) Skin rash, usually of a mild or moderate degree. In rare

cases, serious rash has been reported, which could be

life-threatening. It is therefore important to tell the doctor

immediately if a rash develops, so that he can advise you how

to treat it and whether treatment with the medicine should be

discontinued.

(X) Headache

(X) Diarrhea, nausea

Common side effects (effects which occur in 1-10 in 100 users):

(X) Allergic reaction (hypersensitivity)

(X) Diabetes, decreased appetite

(X) Anxiety, sleepiness, sleeplessness, sleep disorders.

(X) Tingling or pain in hands or feet, numbness, loss of skin

sensibility, loss of memory, tiredness.

(X) Blurred vision

(X) Kidney failure, high blood pressure, heart attack, shortness

of breath when exercising.

(X) Vomiting, heartburn, abdominal pain, distension of

the abdomen, inflammation of the stomach, flatulence,

constipation, mouth inflammation, dry mouth.

(X) Night sweats, itching, dry skin.

(X) Changes in blood and urine test values. The doctor will

explain these to you. For example: low red blood cells.

Uncommon side effects (effects which occur in 1-10 in 1,000

users):

(X) Decreased number of white blood cells

(X) Symptoms of infection (for example, enlarged lymph nodes

and fever)

(X) Abnormal dreams, confusion, disorientation, nervousness,

nightmares.

(X) Drowsiness, trembling, fainting, seizures, attention

disturbances.

(X) Dizziness, sluggishness

(X) Angina, irregular heart rhythm

(X) Difficulty breathing

(X) Retching, inflammation of the pancreas, vomiting blood.

(X) Liver problems, such as hepatitis, enlarged liver.

(X) Excessive sweating, swelling of the face and/or throat.

(X) Swelling of breasts in men

Rare side effects (effects which occur in 1-10 in 10,000 users):

(X) Stroke

Side effects of unknown frequency (effects whose frequency

has not yet been determined):

(X) Severe hypersensitivity reactions characterized by rash

accompanied by fever and inflammation of any organ, such

as hepatitis.

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.

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 outer package/bottle label. The expiry date

refers to the last day of that month.

(X) Do not store above 30°C. Store the tablets in the original

bottle. Keep the bottle tightly closed in order to protect from

moisture. The bottle contains 3 small pouches which contain a

desiccant, thereby keeping the tablets dry. Leave the pouches

in the bottle at all times. The pouches are not to be eaten.

After first opening the bottle, do not use this medicine

for more than 2 months.

6. FURTHER INFORMATION

In addition to the active ingredient, the medicine also contains:

Intelence 100 mg: hypromellose; microcrystalline cellulose;

croscarmellose sodium; magnesium stearate; colloidal

anhydrous silica

and in addition: lactose monohydrate 160.0 mg

Intelence 200 mg: hypromellose; silicified microcrystalline

cellulose; microcrystalline cellulose; croscarmellose sodium;

magnesium stearate; colloidal anhydrous silica

What the medicine looks like and the contents of the package:

Intelence 100 mg is an oval-shaped, white-beige tablet with

T125 imprinted on one side and 100 imprinted on the other

side.

Each box contains one plastic bottle containing 120 Intelence

100 mg tablets. In addition, inside the bottle, there are 3

pouches that contain a desiccant, which keep the tablets dry.

Leave the pouches in the bottle at all times.

Intelence 200 mg is an elongated, biconvex, white-beige tablet,

with T200 imprinted on one side.

The plastic bottle contains 60 Intelence 200 mg tablets. In

addition, inside the bottle, there are 3 pouches that contain a

desiccant, which keep the tablets dry. Leave the pouches in

the bottle at all times.

Registration Holder: J-C Health Care Ltd, Kibbutz Shefayim

6099000, Israel.

Manufacturer: Janssen-Cilag, Via C Janssen 04100, Borgo

San Michele, Latina, Italy.

The format of this leaflet was determined by the Ministry

of Health and its content was checked and approved by

the Ministry of Health on 03/03/2016, and was updated,

in accordance with the Ministry of Health guidelines, on

07/01/2019.

Registration number of the medicine in the National Drug

Registry of the Ministry of Health:

Intelence 100 mg:

141293178900

Intelence 200 mg:

149613366600

J-C 2019

Intelence SH 03/19

Intelence SH 03/19

לע העדוה לע העדוה לע העדוה ( הרמחה ( הרמחה ( הרמחה

עדימ עדימ עדימ ןכרצל ןולעב )תוחיטב ןכרצל ןולעב )תוחיטב ןכרצל ןולעב )תוחיטב

ןכדועמ( ןכדועמ( ןכדועמ(

.102.50

.102.50

.102.50

רשוא

61.3

__ ךיראת

1.2.16

_____

תילגנאב רישכת םש

םושירה רפסמו

Intelence

Intelence 100mg (1412931789);

200mg (1496133666)

םושירה לעב םש

____

.

C Health Care Ltd

-

J

___

ה טורפל דעוימ הז ספוט מחה דבלב תור

תורמחהה שקובמה תו

ןולעב קרפ

יחכונ טסקט

שדח טסקט

?רישכתב שמתשהל ןיא יתמ

ךנה רשאכ רישכתב ישמתשת לא אלא ןוירהב .אפורהמ שרופמ רושיאב

ןמזב קינהל ןיא .הז רישכתב שומישה

ל תושיגר העודי םא שמתשהל ןיא רמוח דחאל וא ןיריורטא ליעפה הפורתה יביכרממ

רחאה ףיעסב םימושרה םי

"ףסונ עדימ"

ךנה רשאכ רישכתב ישמתשת לא שרופמ רושיאב אלא ןוירהב .אפורהמ

.הז רישכתב שומישה ןמזב קינהל ןיא

םא שמתשהל ןיא יגרלא ךנה תושיגר העודי

ליעפה רמוח

דחאל וא ןיריורטא הפורתה יביכרממ

ףיעסב םימושרה םירחאה

"ףסונ עדימ"

תורהזא תודחוימ תועגונה שומישל :הפורתב

ה ףיגנב םוהיזה תא תאפרמ אל סנלטניא

,HIV

תיחפהל דעונש לופיטמ קלח הווהמ אלא תמר תא

התיחפמ אל סנלטניא .םדב ףיגנה ה ףיגנב םירחא תקבדהל ןוכיסה תא

ךישמהל שי ,ןכל םד וא ינימ עגמ תועצמאב םודנוק( םימיאתמ העינמ יעצמאב שמתשהלו וטיש וא תונגמה תורחא ת

)ףיגנה רבעמ ינפמ ףוג ילזונ םע עגמל יוכיסה תא תיחפהל ידכ תושרפה ,ערז ומכ

,םד וא קיתרנהמ

תעב .ינימ עגמ

תוחתפתה ןכתת ,סנלטניא תליטנ ןמזב ב םוהיזב תורושקה תורחא תולחמ וא םימוהיז

שי .

םע ףטוש רשק םייקל דיפקהל .לפטמה אפורה

יא הז רישכת תחתמ םילפוטמב רשואמ ונ ליגל

ללכ ךרדב דעוימ וניא הז רישכת ) ליג לעמ םילפוטמל

אפור תארוהב אלא

.

.סנלטניא תליטנ םרט חקורה וא לפטמה אפורה םע חחוש )

ה ףיגנב םוהיזה תא תאפרמ אל סנלטניא

,HIV

הווהמ אלא תמר תא תיחפהל דעונש לופיטמ קלח

.םדב ףיגנה ךלהמב םג ב םירחא קיבדהל רשפא ןיידע ,הפורתב לופיטה

יכ םא לופיטל תודוה דרוי ןוכיסה ףיגנה דגנכ ליעי

התיחפמ אל סנלטניא ה ףיגנב םירחא תקבדהל ןוכיסה תא

וא ינימ עגמ תועצמאב םימיאתמ העינמ יעצמאב שמתשהלו ךישמהל שי ,ןכל םד תונגמה תורחא תוטיש וא םודנוק(

ידכ )ףיגנה רבעמ ינפמ תושרפה ,ערז ומכ ףוג ילזונ םע עגמל יוכיסה תא תיחפהל

,םד וא קיתרנהמ

.ינימ עגמ תע

ידכב םישרדנה תוריהזה יעצמא יבגל אפורה םע ץעווהל שי .ףיגנב םירחא תקבדה עונמל

םג

וא םימוהיז תוחתפתה ןכתת ,סנלטניא תליטנ ןמזב ב םוהיזב תורושקה תורחא תולחמ

שי .

רשק םייקל דיפקהל .לפטמה אפורה םע ףטוש

רשואמ וניא הז רישכת לארשיב

ילפוטמב ליגל תחתמ ם

תלחמ םע םימייוסמ םילוחב )

תופורת לש היצניבמוק םילטונה תמדקתמ ,ךורא םהלש לופיטה ךשמש ,תוילריוורטריטנא תארקנה םצע תלחמ חתפל םילולע וומ( סיזורקנואטסוא םצע תמקיר לש ת .)םצעל םד תקפסא ןדבואמ האצותכ תמרגנה תופורת תייצניבמוקב לופיטה ךשמ שומיש ,תוילריוורטריטנא יוכיד ,לוהוכלא תכירצ ,םידיאורטסוקיטרוקב ןיב ,רתוי הובג ףוג תסמ דדמ ,רומח ינוסיח ןוכיסה ימרוגמ קלח תויהל םילולע ,רתיה לש םינימסת .וז הלחמ תוחתפתהל אטסוא באכ ,םיקרפמ תוחישק םניה סיזורקנו .העונתב ישוקו )ףתכבו ךרבב ,ךריב רקיעב( ךילע , הלא םינימסתמ דחאב ןיחבמ ךניה םא .אפורה תא עדייל

תחתפתמ םא אפורל חוודל שי .החירפ

ללכ ךרדב איה החירפ תחתפתמו הדימב דימ העיפומ

רחאל

ה ףיגנ דגנ לופיטה תלחתה

ללכ ךרדבו לענ עובש ךות תמ

רשאכ םג ,םייעובש םיכישממ

םיתיעל .הפורתב שמתשהל החירפה הלולע

תויהל

תנכסמ ףאו הרומח ךל שי םאב תידיימ אפורל חוודל שי .םייח םע דדומתהל דציכ ךל ץעיי אפורה .החירפ תליטנ תא קיספהל שי םאה וא םינימסתה .הפורתה

,סנלטניא םע לופיטה ךלהמב םיתיעל ) י התא רתי תושיגר לש הבוגת תווחל לוכ םג ךא ,םוחו החירפ תללוכה תיגרלא הבוגת( יישק ,ןורגה וא ןושלה ,םינפה לש תוחפנתה תויהל הלוכי רשא )העילב יישק וא המישנ התאו הדימב תידיימ אפורל הנפ .םייח תנכסמ ךל ץעיי אפורה .רתי תושיגר לש הבוגת הווח י םאהו םינימסתב לופיטה ןפוא והמ קיספהל ש .סנלטניאב לופטה תא

התאו הדימב אפורל חוודל שי לבוס דבכב תויעבמ סיטיטפה ללוכ ,

וא/ו

תלחמ הרומח המכ דע ךירעי ךלש אפורה תא חקית םאה טילחי אוהש ינפל ךלש דבכה .אל וא הפורתה

ליג לעמ םילפוטמל ללכ ךרדב דעוימ וניא הז רישכת )

אלא אפור תארוהב

.

םימייוסמ םילוח תלחמ םע

תמדקתמ םילטונה תוילריוורטריטנא תופורת לש היצניבמוק םהלש לופיטה ךשמש , ךורא תוומ( סיזורקנואטסוא תארקנה םצע תלחמ חתפל םילולע , םצע תמקיר לש .)םצעל םד תקפסא ןדבואמ האצותכ תמרגנה שומיש ,תוילריוורטריטנא תופורת תייצניבמוקב לופיטה ךשמ דדמ ,רומח ינוסיח יוכיד ,לוהוכלא תכירצ ,םידיאורטסוקיטרוקב ןוכיסה ימרוגמ קלח תויהל םילולע ,רתיה ןיב ,רתוי הובג ףוג תסמ ק םניה סיזורקנואטסוא לש םינימסת .וז הלחמ תוחתפתהל תוחיש םא .העונתב ישוקו )ףתכבו ךרבב ,ךריב רקיעב( באכ ,םיקרפמ .אפורה תא עדייל ךילע , הלא םינימסתמ דחאב ןיחבמ ךניה

תחתפתמ םא אפורל חוודל שי .החירפ

תחתפתמו הדימב דימ העיפומ ללכ ךרדב איה החירפ

רחאל

ה ףיגנ דגנ לופיטה תלחתה

עובש ךות תמלענ ללכ ךרדבו

םיכישממ רשאכ םג ,םייעובש

םיתיעל .הפורתב שמתשהל רתי תושיגר תבוגת שחרתתו ןכתיי סנלטניאב לופיטה ךלהמב ,םינפה לש תוחפנתה ףאו םוחו החירפ תללוכה תיגרלא הבוגת( תנכסמ תויהל הלולעש )העילב וא המישנ יישקו ןורגה וא ןושלה םייח

החירפה תויהל הלולע

םייח תנכסמ ףאו הרומח

חוודל שי םאב תידיימ אפורל ךל שי

החירפ

תושיגר תבוגת הווח התא רתי שי םאה וא םינימסתה םע דדומתהל דציכ ךל ץעיי אפורה . .הפורתה תליטנ תא קיספהל

תבוגת ללגב לופיט תקספה םא .סנלטניאב לופיט שדחמ ליחתהל ןיא ,רתי תושיגר

ל לוכי התא ,סנלטניא םע לופיטה ךלהמב םיתיעל תווח ךא ,םוחו החירפ תללוכה תיגרלא הבוגת( רתי תושיגר לש הבוגת יישק וא המישנ יישק ,ןורגה וא ןושלה ,םינפה לש תוחפנתה םג תידיימ אפורל הנפ .םייח תנכסמ תויהל הלוכי רשא )העילב והמ ךל ץעיי אפורה .רתי תושיגר לש הבוגת הווח התאו הדימב פהל שי םאהו םינימסתב לופיטה ןפוא .סנלטניאב לופטה תא קיס

הדימב אפורל חוודל שי התאו

ךניהו

לבוס תלבס וא

תויעבמ דבכב סיטיטפה ללוכ ,

וא/ו

המכ דע ךירעי ךלש אפורה . תא חקית םאה טילחי אוהש ינפל ךלש דבכה תלחמ הרומח .אל וא הפורתה

ןיחבמ ךניה םא אפורל חוודל שי וא ףוגה תרוצב יונישב

ןיחבמ ךניה םא אפורל חוודל שי יונישב וא ףוגה תרוצב

וגב ןמושה תומכב

הילע רוזיפ וא לקשמ ןדבוא ,לקשמב

ליגרהמ הנוש לטונ ךנה םא תורקל לולע ףוגה ןמוש לש ה ףיגנ תודגונ תופורת לש בוליש

ל שי תנחבה םא תידיימ אפורל חווד תקלד וא םוהיז ינימסתב .םהשלכ

קלחב ה ףיגנ יאשנמ

םדקתמ בלשב

ילעב

םיוולנ םימוהיז לש רבע

(opportunistic

infections)

םינמיס ,

םימוהיז לש םינימסתו ירחא דימ יוטיב ידיל אובל םילוכי םימדוק .הפורתב לופיטה תלחתה

םינימסתהו ןכתי

םיעיפומ

תינוסיחה הבוגתב רופישה תובקעב ףוגה לש

ןכתייש םימוהיזב םחלהל ותלוכי ףוגב םיחכונ ויהו

אלל

.םיטלוב םינימסת

לינה םימוהיזל ףסונב ) ( םיוו

(opportunistic

infections

בצמ( תוינומיאוטוא תויעב , תפקות ןוסיחה תכרעמ רשאכ שחרתמה שחרתהל םג תולולע )תואירב ףוג תומקר ב לופיטל תופורת תליטנ תלחתה רחאל

םג עיפוהל תולוכי תוינומיאוטוא תויעב . םא .לופיטה תלחתה תרחאל םיבר םישדוח שלכ םינימסתב ןיחבמ ךניה וא םוהיז לש םה השלוח ,םירירש תשלוח ןוגכ םינימסת הלוע רשא םיילגרה תופכבו םיידיב הליחתמה תוריהמ בל תוקיפד ,ףוגה זכרמ ןוויכל הלעמ תא עדיי ,תויביטקארפיה וא דער ,)היצטיפלפ( .ידיימ ןפואב אפורה

הפורתל וא והשלכ ןוזמל ה/שיגר ךניה םא אפורל ךכ לע עידוהל ךילע ,יהשלכ

תליטנ ינפל .הפורתה

ומכב .ףוגב ןמושה ת

רוזיפ וא לקשמ ןדבוא ,לקשמב הילע

הנוש לש בוליש לטונ ךנה םא תורקל לולע ףוגה ןמוש לש ליגרהמ ה ףיגנ תודגונ תופורת

ל שי תנחבה םא תידיימ אפורל חווד םוהיז ינימסתב וא תקלד

.םהשלכ

ה ףיגנ יאשנמ קלחב

םדקתמ בלשב

ילעב

םיוולנ םימוהיז לש רבע

(opportunistic infections)

םינמיס ,

ירחא דימ יוטיב ידיל אובל םילוכי םימדוק םימוהיז לש םינימסתו .הפורתב לופיטה תלחתה

םינימסתהו ןכתי

םיעיפומ

תובקעב םימוהיזב םחלהל ותלוכיו ףוגה לש תינוסיחה הבוגתב רופישה ףוגב םיחכונ ויהו ןכתייש

אלל

.םיטלוב םינימסת

ףסונב ) ( םיוולינה םימוהיזל

(opportunistic infections

תויעב , תפקות ןוסיחה תכרעמ רשאכ שחרתמה בצמ( תוינומיאוטוא תליטנ תלחתה רחאל שחרתהל םג תולולע )תואירב ףוג תומקר לופיטל תופורת םוהיזב

תולוכי תוינומיאוטוא תויעב . יה םא .לופיטה תלחתה תרחאל םיבר םישדוח םג עיפוהל ךנ תשלוח ןוגכ םינימסת וא םוהיז לש םהשלכ םינימסתב ןיחבמ הלוע רשא םיילגרה תופכבו םיידיב הליחתמה השלוח ,םירירש וא דער ,)היצטיפלפ( תוריהמ בל תוקיפד ,ףוגה זכרמ ןוויכל הלעמ .ידיימ ןפואב אפורה תא עדיי ,תויביטקארפיה

לע ,יהשלכ הפורתל וא והשלכ ןוזמל ה/שיגר ךניה םא עידוהל ךי .הפורתה תליטנ ינפל אפורל ךכ לע

:תויתופורת ןיב תובוגת

,הנורחאל תחקל םא וא ,חקול התא םא םשרמ אלל תופורת ללוכ תורחא תופורת חקורל וא אפורל ךכ לע רפס ,הנוזת יפסותו

םא חקורה וא אפורה תא עדייל שי דחוימב :חקול התא

ריבנוטירו ריבנאזטא לש בוליש

ל ןתינ( בלש )ןונימה תמאתהב ךרוצ אלל

(

X

)

םע דחיב סנלטניא לוטיל ץלמומ אל :תואבה תופורתה

ללוכ תורחא תופורת ,הנורחאל תחקל םא וא ,חקול התא םא וא אפורל ךכ לע רפס ,הנוזת יפסותו םשרמ אלל תופורת חקורל עדייל שי דחוימב .

:חקול התא םא חקורה וא אפורה תא

תודגונ תורחא תופורתו סנלטניא תליטנ בלשל ןתינ םירקמה בורב ה ףיגנ

תוכייתשמה

קלח תאז םע .תרחא הצובקל תרבגהב ךרוצ שי םימייוסמ םירקמבו םיצלמומ םניא םיבולישהמ

אפורל חוודל שי דימת ךכל יא .הפורתה תנמב יוניש וא/ו רוטינה פורת וליא ה ףיגנ תודגונ תו

רחא אלמלו ,לטונ התא תורחא .ןבלשל ןתינש תופורתה יבגל תוריהזב ויתוארוה תא אורקל בושח

לש בוליש ,ריבנוטירו ריבנרפיט לש בוליש ) ריבנוטירו ריבנרפמאסופ

ןיאותינפו לטיברבונפ ,ןיפזמברק םע

)היספליפאב לופיטל

ןיפמאפיר( ןיציפמאפיר םע

ןיטובאפיר לופיטל( ןיטנפאפירו )תפחש ןוגכ םימוהיזב

ה תחפשממ םירחא םירישכת םע )

NNRTI

)ןידריבלד ,ןיפריבנ ,זנריבאפא(

םע תא םיליכמה םירישכת חמצה

John's Wort

)םוטרופרפ םוקירפיה(

לופיטל

ןואכידב

תחא לטונ ךניה םא אפורב ץעווהל שי .ולא תופורתמ

X

)

תואבה תופורתהמ תחא לטונ ךניה םא

לע העפשה ןכתית ,סנלטניא םע דחיב תוליעפ וא ןתוליעפ

חוודל שי .סלטניא תופורתהמ תחא לטונ ךנה םא אפורל :תואבה

,דימריפוזיד ,ןיסקוגיד ,לידירפב ,ןורדוימא וא ןונפאפורפ ,ןיטליסקמ ,ןיאקודיל ,דיניאקלפ לופיטל( ןידיניוק

אל בל בצק ןוגכ בלב תויעבב .)ןיקת

ןירפרו

ךאפור ,)םדה תוישירק תתחפהל( .םד תוקידב עצבל ךל הרוי

,לוזאנוקוטק ,לוזאנוקרטיא ,לוזאנוקולפ םימוהיזב לופיטל( לוזאנוקירו וא לוזאנוקאסופ )םיתיירטפ

)הקיטויביטנא( ןיצימורטיראלק

תופורת( ןירטנאפמול וא רטמטרא )הירלמב לופיטל

לופיטל הפורת( ןיטובאפיר )תפחשב

וא/ו הניש תוערפהב לופיטל( םאפזאיד )הדרחב

לופיטל דיאורטסוקיטרוק( ןוזאתמאסקד )תיגרלא הבוגתו תקלד ומכ םיבצמ ןווגמב

,ןיטאטסאבולפ ,ןיטאטסברוטא ,ןיטאטסאוואטיפ ,ןיטאטסאוול ןיטטסאבמיס וא ןיטאטסאברוזור

תדרוהל(

.)םדב לורטסלוכה תמר

סומילורקט וא סומילוריס ,ןירופסולקיצ ןוסיחה תכרעמ תא תואכדמה תופורת( .ולא תופורתל ףרוצמה ןכרצל ןולעה

ריבנוטירו ריבנאזטא לש בוליש

תמאתהב ךרוצ אלל בלשל ןתינ( )ןונימה

(

X

)

:תואבה תופורתה םע דחיב סנלטניא לוטיל ץלמומ אל

לש בולי

ריבנרפיט

ריבנוטיר ןוהיזב לופיטל הפורת(

ריבנוטירו ריבנרפמאסופ לש בוליש

םע

ןיאותינפו לטיברבונפ ,ןיפזמברק

לופיטל םיסוכריפב היספליפאב

םע ןיציפמאפיר ןיפמאפיר(

יבכעמ םע דגנ תיוותה ללגב ( זאטורפ

boosted protease inhibitors

ןיטובאפיר

רו ןיטנפאפי )תפחש ןוגכ םימוהיזב לופיטל(

ה תחפשממ םירחא םירישכת םע )

NNRTI

,זנריבאפא( )ןידריבלד ,ןיפריבנ

םע תא םיליכמה םירישכת חמצה

St. John's Wort

)םוטרופרפ םוקירפיה(

לופיטל

ןואכידב

.ולא תופורתמ תחא לטונ ךניה םא אפורב ץעווהל שי

X

)

חא לטונ ךניה םא ,סנלטניא םע דחיב תואבה תופורתהמ ת תוליעפ וא ןתוליעפ לע העפשה ןכתית

חוודל שי .סלטניא :תואבה תופורתהמ תחא לטונ ךנה םא אפורל

,דיניאקלפ ,דימריפוזיד ,ןיסקוגיד ,לידירפב ,ןורדוימא לופיטל( ןידיניוק וא ןונפאפורפ ,ןיטליסקמ ,ןיאקודיל

בלב תויעבב ת אל בל בצק ןוגכ .)ןיק

עצבל ךל הרוי ךאפור ,)םדה תוישירק תתחפהל( ןירפרו .םד תוקידב

וא לוזאנוקאסופ ,לוזאנוקוטק ,לוזאנוקרטיא ,לוזאנוקולפ )םיתיירטפ םימוהיזב לופיטל( לוזאנוקירו

,ןיצימורטיראלק ןיטובאפיר

)הקיטויביטנא(

רטמטרא

וא

פורת( ןירטנאפמול

תו

)הירלמב לופיטל

)תפחשב לופיטל הפורת( ןיטובאפיר

)הדרחב וא/ו הניש תוערפהב לופיטל( םאפזאיד

ומכ םיבצמ ןווגמב לופיטל דיאורטסוקיטרוק( ןוזאתמאסקד )תיגרלא הבוגתו תקלד

הפורת( ריוארפסוב תילאריו יטנא

לופיטל םוהיזב

סיטיטפהב

ןיטאטסאוול ,ןיטאטסאבולפ ,ןיטאטסברוטא

,ןיטאטסאוואטיפ

ןיטטסאבמיס וא ןיטאטסאברוזור

תדרוהל(

תמר .)םדב לורטסלוכה

תואכדמה תופורת( סומילורקט וא סומילוריס ,ןירופסולקיצ )לתש תייחד תעינמל ללכ ךרדב תונתינה

ליפאלאדט וא ליפאנדראוו ,ליפאדנליס םד ץחל רתי וא/ו הפקיז תויעבב לופיטל( )יתאר

תורצוויה תעינמל הפורת( לרגודיפולק ) )םד ישירק

הפורת( ריוארפסוב לופיטל תילאריו יטנא סיטיטפהב

ה ףיגנ תדגונ הפורת( ריוארגטולוד )

סנלטניא תליטנ בלשל ןתינ םירקמה בורב ה ףיגנ תודגונ תורחא תופורתו

תוכייתשמה

קלח תאז םע .תרחא הצובקל םימייוסמ םירקמבו םיצלמומ םניא םיבולישהמ תרבגהב ךרוצ שי

תנמב יוניש וא/ו רוטינה

וליא אפורל חוודל שי דימת ךכל יא .הפורתה ה ףיגנ תודגונ תופורת

לטונ התא תורחא רחא אלמלו

תופורתה יבגל תוריהזב ויתוארוה ןבלשל ןתינש

ןוסיחה תכרעמ תא לתש תייחד תעינמל ללכ ךרדב תונתינה

תויעבב לופיטל( ליפאלאדט וא ליפאנדראוו ,ליפאדנליס א/ו הפקיז )יתאר םד ץחל רתי ו

)םד ישירק תורצוויה תעינמל הפורת( לרגודיפולק )

סיטיטפהב לופיטל תילאריו יטנא הפורת( ריוארפסוב

ה ףיגנ תדגונ הפורת( ריוארגטולוד )

תורחא תופורתו סנלטניא תליטנ בלשל ןתינ םירקמה בורב ה ףיגנ תודגונ

תוכייתשמה

.תרחא הצובקל

קלח תאז םע תרבגהב ךרוצ שי םימייוסמ םירקמבו םיצלמומ םניא םיבולישהמ

אפורל חוודל שי דימת ךכל יא .הפורתה תנמב יוניש וא/ו רוטינה ה ףיגנ תודגונ תופורת וליא

רחא אלמלו לטונ התא תורחא .ןבלשל ןתינש תופורתה יבגל תוריהזב ויתוארוה

:הפורתב שמתשת דציכ

תחכש םא ןמזב וז הפורת לוטיל

בוצק

דע תרכזנו

ךירצ תייה וב דעומהמ תועש ,הפורתה תא לוטיל

דימ הנמ לוטיל שי תרכזנשכ

.החוראה רחאל דימתו

ורבע םא מ רתוי

לוטיל ךירצ תייה וב דעומהמ תועש החכשנש הנמה לע גלדל שי ,הפורתה תא .ליגרכ האבה הנמה תליטנב ךישמהלו

םושב וטיל ןיא ןפוא

דחיב תונמ יתש תוצפל ידכב החכשנש הנמ לע

לופיטה תחלצהל עייסל לכות דציכ

לע ץלמוהש לופיטה תא םילשהל ךילע )

אפורה ידי

ןיא ךתואירב בצמב רופיש לח םא םג ) הפורתב לופיטה קיספהל

תורחא תופורתב וא ה ףיגנ תודגונ

.אפור םע תוצעייתה אלל

לופיט

ה ףיגנב

תשוחת תא רפשל יושע תקספה ךא ,םייחה תוכיא תאו תוינויחה תא לידגהל הלולע אפורה רושיא אלל לופיטה תוחתפתהל ןוכיסה

.ףיגנה תודימע

ןמזב וז הפורת לוטיל תחכש םא

בוצק

דע תרכזנו

תועש ,הפורתה תא לוטיל ךירצ תייה וב דעומהמ

דימ הנמ לוטיל שי תרכזנשכ

אה רחאל דימתו החור האבה הנמה תא לוטיל ךישמהלו ליגרכ

מ רתוי ורבע םא

תא לוטיל ךירצ תייה וב דעומהמ תועש הנמה תליטנב ךישמהלו החכשנש הנמה לע גלדל שי ,הפורתה .ליגרכ האבה

לוטיל ןיא ןפוא םושב

דחיב תונמ יתש תוצפל ידכב החכשנש הנמ לע

לופיטה תחלצהל עייסל לכות דציכ

ל ךילע ) לע ץלמוהש לופיטה תא םילשה

אפורה ידי

לופיטה קיספהל ןיא ךתואירב בצמב רופיש לח םא םג ) הפורתב

ה ףיגנ תודגונ תורחא תופורתב וא

תוצעייתה אלל .אפור םע

לופיט

ה ףיגנב

תוינויחה תשוחת תא רפשל יושע ךא ,םייחה תוכיא תאו

הלולע אפורה רושיא אלל לופיטה תקספה גהל תוחתפתהל ןוכיסה תא ליד

.ףיגנה תודימע

:יאוול תועפות

לולע סנלטניאב שומישה ,הפורת לכב ומכ .םישמתשמהמ קלחב יאוול תועפותל םורגל .יאוולה תועפות תמישר ארקמל להבית לא .ןהמ תחא ףאמ לובסת אלו ןכתיי

תדחוימ תוסחייתה תובייחמה תועפות

אוול תועפותל םורגל לולע סנלטניאב שומישה ,הפורת לכב ומכ

.יאוולה תועפות תמישר ארקמל להבית לא .םישמתשמהמ קלחב .ןהמ תחא ףאמ לובסת אלו ןכתיי

תדחוימ תוסחייתה תובייחמה תועפות

ב לופיט ךלהמב

תומרבו לקשמב היילע שחרתהל לולע

דואמ ץופנ וחווד(

דחא שמתשממ רתויב ךותמ

)םישמתשמ

וא הלק הגרדב ללכ ךרדב תירוע החירפ תויהל הלוכי החירפה םירידנ םירקמב .תינוניב םייח תנכסמ

ןכלו

םא

תחתפתמ

בושח החירפ דציכ ךל ץעייש תנמ לע תידיימ אפורל חוודל .הפורתב לופיט קיספהל שי םאהו הב לפטל

תוינייפואה יאוול תועפות

תופורת בולישל ה ףיגנ תודגונ

תרוצב יונישב ןיחבמ ךניה םא אפורל חוודל שי וא ףוגה

,לקשמב הילע .ףוגב ןמושה תומכב רוזיפ וא לקשמ ןדבוא

ןמוש לש ליגרהמ הנוש לש בוליש לטונ ךנה םא תורקל לולע ףוגה ה ףיגנ תודגונ תופורת

תנחבה םא תידיימ אפורל חוודל שי ימסתב .םהשלכ םוהיז ינ

םימיוסמ םילוחב ה ףיגנב םוהיז לש םדקתמ בצמב

ילעבו

םיוולנ םימוהיז לש רבע

(opportunistic

infection)

םינמיס ,

םדוק םוהיז לש םינימסתו תלחתה ירחא דימ יוטיב ידיל אובל םילוכי .ףיגנה דגונ לופיטה

םינימסתהו ןכתי

םיעיפומ

נוסיחה הבוגתב רופישה תובקעב ףוגה לש תי םימוהיזב םחלהל ותלוכיו

םיחכונ ויהו ןכתייש

ףוגב

אלל

.םיטלוב םינימסת

יאוול תועפות השיגרמ ךנה ובש הרקמ לכב יוניש לח םא וא ,הז ןולעב ונייוצ אלש אפורה םע ץעיתהל ךילע תיללכה ךתשגרהב .דיימ

םיוולינה םימוהיזל ףסונב )

(opportunistic infections

ויעב

תכרעמ רשאכ שחרתמה בצמ( תוינומיאוטוא םג תולולע )תואירב ףוג תומקר תפקות ןוסיחה תופורת תליטנ תלחתה רחאל שחרתהל ב לופיטל

תולוכי תוינומיאוטוא תויעב . תלחתה רחאל םיבר םישדוח םג עיפוהל םהשלכ םינימסתב ןיחבמ ךנה םא .לופיטה ירירש תשלוח ןוגכ םינימסת וא םוהיז לש

םיילגרה תופכבו םיידיב הליחתמה השלוח תוקיפד ,ףוגה זכרמ ןוויכל הלעמ הלוע רשא וא דער ,)היצטיפלפ( תוריהמ בל ,תויביטקארפיה

.ידיימ ןפואב אפורה תא עדיי

תואירבה םוקישל תיקלח רושק רבדה .זוקולגהו םדב םידיפילה ילה לש הרקמבו ,םייח חרואו ה תופורתל םיתיעל םדב םידיפ

.הלא םייונישל ךתוא קודבי אפורה .ןמצע

דואמ ץופנ ךותמ דחא שמתשממ רתויב וחווד(

)םישמתשמ

םירידנ םירקמב .תינוניב וא הלק הגרדב ללכ ךרדב תירוע החירפ החווד

החירפ הרומח

םייח תנכסמ תויהל הלוכי

ןכלו

םא

תחתפתמ

ודל בושח החירפ ךל ץעייש תנמ לע תידיימ אפורל חו .הפורתב לופיט קיספהל שי םאהו הב לפטל דציכ

ה ףיגנ תודגונ תופורת בולישל תוינייפואה יאוול תועפות

וא ףוגה תרוצב יונישב ןיחבמ ךניה םא אפורל חוודל שי

תומכב רוזיפ וא לקשמ ןדבוא ,לקשמב הילע .ףוגב ןמושה

ליגרהמ הנוש ןמוש לש

תופורת לש בוליש לטונ ךנה םא תורקל לולע ףוגה ה ףיגנ תודגונ

.םהשלכ םוהיז ינימסתב תנחבה םא תידיימ אפורל חוודל שי

ה ףיגנב םוהיז לש םדקתמ בצמב םימיוסמ םילוחב

ילעבו

םיוולנ םימוהיז לש רבע

(opportunistic infection)

םינמיס ,

ילוכי םדוק םוהיז לש םינימסתו ירחא דימ יוטיב ידיל אובל ם .ףיגנה דגונ לופיטה תלחתה

םינימסתהו ןכתי

םיעיפומ

תובקעב םימוהיזב םחלהל ותלוכיו ףוגה לש תינוסיחה הבוגתב רופישה םיחכונ ויהו ןכתייש

אלל ףוגב

.םיטלוב םינימסת

,הז ןולעב ונייוצ אלש יאוול תועפות השיגרמ ךנה ובש הרקמ לכב יוניש לח םא וא אפורה םע ץעיתהל ךילע תיללכה ךתשגרהב .דיימ

( םיוולינה םימוהיזל ףסונב )

(opportunistic infections

ןוסיחה תכרעמ רשאכ שחרתמה בצמ( תוינומיאוטוא תויעב תלחתה רחאל שחרתהל םג תולולע )תואירב ףוג תומקר תפקות ב לופיטל תופורת תליטנ

תולוכי תוינומיאוטוא תויעב . הל ןיחבמ ךנה םא .לופיטה תלחתה רחאל םיבר םישדוח םג עיפו ,םירירש תשלוח ןוגכ םינימסת וא םוהיז לש םהשלכ םינימסתב הלעמ הלוע רשא םיילגרה תופכבו םיידיב הליחתמה השלוח וא דער ,)היצטיפלפ( תוריהמ בל תוקיפד ,ףוגה זכרמ ןוויכל ,תויביטקארפיה

.ידיימ ןפואב אפורה תא עדיי

וגת לע תויחופלש םע החירפב תאטבתמה הפירח תיגרלא הב ,העילבו המישנ יישק ,הפהו םייתפשה ,םינפה תוחפנתה ,רועה .ידיימ ןפואב אפורה תא עדי ,םוח

,ןיעה ןבולו רועה תבהצה ןוגכ דבכב תויעב לש םינימסתו םינמיס ןטבב באכ ,ןובאת ןדבוא ,האקהו הליחב ,הריהב האוצ ,ההכ ןתש ילעה תינמיה .הנו

םירירשה לש השלוח וא תושיגר ,באכ

תויהל םילולע הלא החירפב תאטבתמה הפירח תיגרלא הבוגת ,םינפה תוחפנתה ,רועה לע תויחופלש םע םוח ,העילבו המישנ יישק ,הפהו םייתפשה

.ידיימ ןפואב אפורה תא עדי

ןוגכ דבכב תויעב לש םינימסתו םינמיס האוצ ,ההכ ןתש ,ןיעה ןבולו רועה תבהצה באכ ,ןובאת ןדבוא ,האקהו הליחב ,הריהב .הנוילעה תינמיה ןטבב

םירירשה לש השלוח וא תושיגר ,באכ

הלא םירירשה קוריפ לש םינמיס תויהל םילולע

rhabdomyolysis)

פייע תוחפנתהו תקלד ,הפב םיעצפ ,הפירח תו .םייניעב

דע דחאב וחווד( תוצופנ יאוול תועפות

ךותמ םישמתשמ

:)םישמתשמ

:אמגודל ,םדה תוקידב יכרעב יוניש תויסט תריפס ,הכומנ תומודא תוירודכ תריפס תומר ,הכומנ םד

וא תוהובג םדב םינמוש םיהובג לורטסלוכ יכרע ,תוניקת יתלב תמר , .ההובג רכוס

וא םיידיב באכ וא תוריקד ,שאר באכ ,הדרח ,הניש ידודנ ,השוחת רסוח ,םיילגרב תופייע

,ןטב באכ ,תברצ ,תואקה ,הליחב ,לושלש .םיזג ,הביקב תקלד

,בל ףקתה ,הובג םד ץחל ,יתייליכ לשכ .תרכוס

ףוגב ןמושה תומכב וא ףוגה תרוצב יוניש

תעזה

הליל

ץבש

דע דחאב וחווד( תוצופנ אל יאוול תועפות

ךותמ םישמתשמ

8111

:)םישמתשמ

רידס אל בל בצק ,הזחב ץחל/ הזחב באכ

ןדבוא ,םיסוכרפ ,םונמינ ,רועב השוחת ןדבוא ,תוינונשי ,תונריעב הערפה ,תופלעתה ,ןורכיז דער

תרוחרחס ,הייאר שוטשיט

המישנ יישק

ד ,ןטבה לש תוחיפנ , תוריצע ,בלבלה תקל אלל איקהל ןויסינ ,םד לש האקה ,הפב שבוי הפב תקלד ,החלצה

םירירשה קוריפ לש םינמיס

rhabdomyolysis)

.םייניעב תוחפנתהו תקלד ,הפב םיעצפ ,הפירח תופייע

דע דחאב וחווד( תוצופנ יאוול תועפות

םישמתשמ ךותמ

םישמתשמ

כ תריפס :אמגודל ,םדה תוקידב יכרעב יוניש תומודא תוירוד תומר ,הכומנ םד תויסט תריפס ,הכומנ

וא תוהובג םדב םינמוש .ההובג רכוס תמר ,םיהובג לורטסלוכ יכרע ,תוניקת יתלב

,השוחת רסוח ,םיילגרב וא םיידיב באכ וא תוריקד ,שאר באכ תופייע ,הדרח ,הניש ידודנ

הביקב תקלד ,ןטב באכ ,תברצ ,תואקה ,הליחב ,לושלש

.םיזג

.תרכוס ,בל ףקתה ,הובג םד ץחל ,יתייליכ לשכ

ףוגב ןמושה תומכב וא ףוגה תרוצב יוניש הליל תעזה ,

ץבש

ב וחווד( תוצופנ אל יאוול תועפות דע

דחא ךותמ

םישמתשמ

דע

ךותמ םישמתשמ

8111

םישמתשמ

רידס אל בל בצק ,הזחב ץחל/ הזחב באכ

רועב השוחת ןדבוא ,תופלעתה ,ןורכיז ןדבוא ,םיסוכרפ ,םונמינ , ,דער ,תוינונשי ,תונריעב הערפה ץבש

תרוחרחס ,הייאר שוטשיט

המישנ יישק

לש האקה ,הפב שבוי , תוריצע ,בלבלה תקלד ,ןטבה לש תוחיפנ הפב תקלד ,החלצה אלל איקהל ןויסינ ,םד

גה וא/ו םינפה לש תוחפנתה ,רועב שבוי ,תרבגומ העזה ,דרג .ןור

ןובאתב הדירי

העונתב תויטיא

אמגודל( םוהיז לש םימוטפמיס ,)רתי תושיגר( תיגרלא הבוגת )תולדגומ הפמיל תוטולבו םוח

סיטיטפה ןוגכ דבכ תויעב

םירבגב םיידש תוחפנתה

,תואצמתה רסוח ,לובלב ,םיייתרגש אל תומולח ,הניש תויעב .תונבצע

רוזיפב יונישל רושקה ףוגה תרוצב יוניש .ןמושה

עדימהמ הכירעהל ןתינ אל( העודי אל ןתוחיכשש יאוול תועפות )םייקה

םוחב הוולמה החירפב תונייפואמה תורומח רתי תושיגר תובוגת .סיטיטפה ןוגכ והשלכ רביא לש תקלדבו

תולוכי םירירשב תוערפהה .השלוח וא תוחיתמ ,םירירשב באכ .תורומח תויהל

נייפוא יאוולה תועפותמ קלח ףיגנב לופיטל תויפיצפס תופורתל תוי

תללכנ וללה תועפותה ןיב

immune reconstitution

תוחפנתה ,רועב שבוי ,תרבגומ העזה ,דרג .ןורגה וא/ו םינפה לש

ןובאתב הדירי

העונתב תויטיא

לש םימוטפמיס ,)רתי תושיגר( תיגרלא הבוגת )תולדגומ הפמיל תוטולבו םוח אמגודל( םוהיז

וגכ דבכ תויעב סיטיטפה ן

םירבגב םיידש תוחפנתה

,לובלב ,םיייתרגש אל תומולח ,הניש תויעב .תונבצע ,תואצמתה רסוח

רוזיפב יונישל רושקה ףוגה תרוצב יוניש .ןמושה

ןתינ אל( העודי אל ןתוחיכשש יאוול תועפות )םייקה עדימהמ הכירעהל

תונייפואמה תורומח רתי תושיגר תובוגת ו םוחב הוולמה החירפב רביא לש תקלדב .סיטיטפה ןוגכ והשלכ

.השלוח וא תוחיתמ ,םירירשב באכ .תורומח תויהל תולוכי םירירשב תוערפהה

תופורתל תוינייפוא יאוולה תועפותמ קלח ה ףיגנב לופיטל תויפיצפס

תועפותה ןיב תללכנ וללה

immune reconstitution

syndrome

לש תוששואתה תנומסת( נוסיחה תכרעמה םע םילפוטמהמ קלחב .)תי ב םדקתמ םוהיז

םימוהיז לש הירוטסיהו , ( םיטסינוטרופוא לע םרגנש םוהיז

ידי הלחמ םרוג תורידנ םיתיעל קרש םזינגרוא תובורק םיתיעל םרוג ךא ,םיאירב םישנאב ,תשלחומ ןוסיח תכרעמ םע םישנאב הלחמ ילוחב ,המגודל

ב םוהיזב

םילוחב וא , כ ורבעש

ומ היפרת לש םימוטפמיסו םינמיסו ) שחרתהל םילוכי םימדוק םימוהיזמ תקלד ה ףיגנב לופיטה תלחתהל תוכימסב

.סנלטניאב ללוכ

תוערפה ,םיטסינוטרופואה םימוהיזל ףסונב תכרעמה רשאכ שחרתמה בצמ( תוינומיאוטוא תולוכי )תואירב ףוג תומקר תפקות תינוסיחה טיל ליחתמ התאש ירחא שחרתהל תופורת לו ה ףיגנב לופיטל

תוינומיאוטוא תוערפה . ירחא םישדוח הברה שחרתהל םג תולוכי .לופיטה תקספה

syndrome

.)תינוסיחה תכרעמה לש תוששואתה תנומסת( ב םדקתמ םוהיז םע םילפוטמהמ קלחב

לש הירוטסיהו , ( םיטסינוטרופוא םימוהיז לע םרגנש םוהיז

קרש םזינגרוא ידי םרוג תורידנ םיתיעל

םיתיעל םרוג ךא ,םיאירב םישנאב הלחמ ,המגודל ,תשלחומ ןוסיח תכרעמ םע םישנאב הלחמ תובורק ילוחב

ב םוהיזב

כ ורבעש םילוחב וא ,

היפרתומ םינמיסו ) שחרתהל םילוכי םימדוק םימוהיזמ תקלד לש םימוטפמיסו ה ףיגנב לופיטה תלחתהל תוכימסב

.סנלטניאב ללוכ ,

םימוהיזל ףסונב

בצמ( תוינומיאוטוא תוערפה ,םיטסינוטרופואה )תואירב ףוג תומקר תפקות תינוסיחה תכרעמה רשאכ שחרתמה לופיטל תופורת לוטיל ליחתמ התאש ירחא שחרתהל תולוכי ה ףיגנב

הברה שחרתהל םג תולוכי תוינומיאוטוא תוערפה . .לופיטה תקספה ירחא םישדוח

א ,הרימחמ יאוולה תועפותמ תחא םא לבוס התא רשאכ ו .אפורה םע ץעייתהל ךילע ,ןולעב ורכזוה אלש יאוול תועפותמ

הציחל תועצמאב תואירבה דרשמל יאוול תועפות לע חוודל ןתינ אצמנש "יתפורת לופיט בקע יאוול תועפות לע חוויד" רושיקה לע ( תואירבה דרשמ רתא לש תיבה ףדב

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הסינכ י"ע וא ,יאוול תועפות לע חווידל ןווקמה ספוטל הנפמה :רושיקל

https://forms.gov.il/globaldata/getsequence/getsequen

x?formType=AdversEffectMedic@moh.gov.il

ce.asp

רשאכ וא ,הרימחמ יאוולה תועפותמ תחא םא ,ןולעב ורכזוה אלש יאוול תועפותמ לבוס התא .אפורה םע ץעייתהל ךילע

ב"צמ נמוסמ ובש ,ןולעה תושקובמה תורמחהה תו בוהצ עקר לע

( ונמוס תורמחה רדגב םניאש םייוניש ןולעב עבצב ) הנוש םוקימב םייוניש אלו יתוהמ ןכות קר ןמסל שי . .טסקטה

ךיראתב ינורטקלא ראודב רבעוה

....

1.2.16

לע העדוה לע העדוה לע העדוה הרמחה הרמחה הרמחה

(

(

(

עדימ עדימ עדימ ל ןולעב )תוחיטב ל ןולעב )תוחיטב ל ןולעב )תוחיטב אפור אפור אפור

ןכדועמ( ןכדועמ( ןכדועמ(

.102.50

.102.50

.102.50

__ ךיראת

1.2.16

_____

םושירה רפסמו תילגנאב רישכת םש

Intelence

Intelence 100mg (1412931789

200mg (1496133666)

ה טורפל דעוימ הז ספוט דבלב תורמחה

תושקובמה תורמחהה

ןולעב קרפ

יחכונ טסקט

שדח טסקט

Posology, dosage &

administration

INTELENCE must always

be given in combination with

other antiretroviral medicinal

products.

Adults

The recommended dose of

INTELENCE is 200 mg (one

200 mg tablet or two 100 mg

tablets) taken orally twice

daily (b.i.d.), following a

meal (see section 5.2).

Children (less than 12 years

of age) and adolescents

(12 to 17 years of age)

Treatment with INTELENCE

is not approved in children

and adolescents.

Elderly

Limited information is

available in this population

(see sections 4.4 and 5.2).

Hepatic impairment

No dose adjustment is

required in patients with mild

or moderate hepatic

INTELENCE must always be given in

combination with other antiretroviral

medicinal products.

Adults

The recommended dose of INTELENCE

is 200 mg (one 200 mg tablet or two

100 mg tablets) taken orally twice daily

(b.i.d.), following a meal (see section

5.2).

Children (less than 12 years of age) and

adolescents (12 to 17 years of age)

Treatment with INTELENCE is not

approved in Israel in children and

adolescents.

Elderly

Limited information is available in this

population (see sections 4.4 and 5.2).

There is limited information regarding

the use of INTELENCE in patients > 65

years of age (see

section 5.2), therefore caution should be

used in this population.

Hepatic impairment

No dose adjustment is required in

patients with mild or moderate hepatic

impairment (Child-Pugh

score A or B). The

pharmacokinetics of

INTELENCE have not been

studied in patients with

severe hepatic impairment

(Child-Pugh score C) (see

sections 4.4 and 5.2).

Renal impairment

No dose adjustment is

required in patients with

renal impairment (see

sections 4.4 and 5.2).

impairment (Child-Pugh score A or B).

INTELENCE should be used with

caution in patients with moderate

hepatic

impairment. The pharmacokinetics of

INTELENCE have not been studied in

patients with severe hepatic impairment

(Child-Pugh score C) (see sections 4.4

and 5.2).

Renal impairment

No dose adjustment is required in

patients with renal impairment (see

sections 4.4 and 5.2).

Pregnancy and postpartum

Based on limited data available, no dose

adjustment is required during pregnancy

and postpartum (see

section 5.2).

Special Warnings and

Special Precautions

for Use

Patients should be advised

that current antiretroviral

therapy does not cure HIV

and has not been proven to

prevent the transmission of

HIV to others through blood

or sexual contact.

Appropriate precautions

should continue to be

employed.

Clinical studies are ongoing

in HIV-1 infected children

and adolescents (between the

ages of 6 and 17 years,

inclusive).

Severe Skin and

Hypersensitivity

Reactions

Severe, potentially

life-threatening, and fatal

skin reactions have been

reported with INTELENCE;

Stevens-Johnson Syndrome

and toxic epidermal

necrolysis have been rarely

(< 0.1%) reported.

Hypersensitivity reactions

including DRESS (Drug

Rash with Eosinophilia and

Systemic Symptoms)

have also been reported and

were characterized by rash,

constitutional findings, and

infrequently organ

Patients should be advised that current

antiretroviral therapy does not cure HIV

and has not been proven to prevent the

transmission of HIV to others through

blood or sexual contact. Appropriate

precautions should continue to be

employed.

INTELENCE should optimally be

combined with other antiretrovirals that

exhibit activity against the

patient’s virus (see section 5.1).

A decreased virologic response to

etravirine was observed in patients with

viral strains harbouring 3 or

more among the following mutations

V90I, A98G, L100I, K101E/P, V106I,

V179D/F, Y181C/I/V,

and G190A/S (see section 5.1).

Conclusions regarding the relevance of

particular mutations or mutational

patterns are subject to

change with additional data, and it is

recommended to always consult current

interpretation systems

for analysing resistance test results.

No data other than drug-drug interaction

data (see section 4.5) are available when

etravirine is

combined with raltegravir or maraviroc.

Clinical studies are ongoing in HIV-1

infected children and adolescents

(between the ages of 6 and 17 years,

dysfunction, including

hepatic failure (see section

4.8).

Discontinue INTELENCE

immediately if signs or

symptoms of severe skin

reactions or hypersensitivity

reactions develop (including,

but not limited to, severe rash

or rash accompanied by

fever, general malaise,

fatigue, muscle or joint

aches, blisters, oral lesions,

conjunctivitis, hepatitis,

eosinophilia). Clinical status

including liver transaminases

should be monitored and

appropriate therapy initiated.

Delay in stopping

INTELENCE treatment after

the onset of severe rash may

result in a life-threatening

reaction.

Rash

Rash has been reported with

INTELENCE. Most

frequently, rash was mild to

moderate, occurred in the

second week of therapy and

was infrequent after week 4.

Rash was mostly

self-limiting and generally

resolved within 1 to 2 weeks

on continued therapy. The

incidence of rash was higher

in females (see section 4.8).

Elderly

Experience in geriatric

patients is limited: In the

Phase III trials, 6 patients

aged 65 years or older and

53 patients aged 56-64 years

received INTELENCE. The

type and incidence of adverse

events in patients > 55 years

of age were similar to the

ones in younger patients (see

sections 4.2 and 5.2).

Patients with coexisting

conditions

Liver disease

No dose adjustment is

required in patients with mild

or moderate hepatic

impairment (Child-Pugh

score A or B). The

inclusive).

Severe Skin and

Hypersensitivity Reactions

Severe, potentially life-threatening, and

fatal skin reactions have been reported

with INTELENCE; Stevens-Johnson

Syndrome and toxic epidermal

necrolysis have been rarely (< 0.1%)

reported. Hypersensitivity reactions

including DRESS (Drug Rash with

Eosinophilia and Systemic Symptoms)

have also been reported and were

characterized by rash, constitutional

findings, and infrequently organ

dysfunction, including hepatic failure

(see section 4.8).

Discontinue INTELENCE immediately

if signs or symptoms of severe skin

reactions or hypersensitivity reactions

develop (including, but not limited to,

severe rash or rash accompanied by

fever, general malaise, fatigue, muscle

or joint aches, blisters, oral lesions,

conjunctivitis, hepatitis, eosinophilia).

Clinical status including liver

transaminases should be monitored and

appropriate therapy initiated. Delay in

stopping INTELENCE treatment after

the onset of severe rash may result in a

life-threatening reaction.

Severe cutaneous and

hypersensitivity reactions

Severe cutaneous adverse drug

reactions have been reported with

INTELENCE; Stevens-Johnson

Syndrome and erythema multiforme

have been rarely (< 0.1%) reported.

Treatment with INTELENCE should

be discontinued if a severe cutaneous

reaction develops.

The clinical data are limited and an

increased risk of cutaneous reactions

in patients with a history of

NNRTI-associated cutaneous

reactions cannot be excluded.

Caution should be observed in such

patients, especially in case of history

of a severe cutaneous drug reaction.

Cases of severe hypersensitivity

syndromes, including DRESS (Drug

Rash with Eosinophilia and Systemic

pharmacokinetics of

INTELENCE have not been

studied in patients with

severe hepatic impairment

(Child-Pugh score C) (see

sections 4.2 and 5.2).

Renal disease

Since the renal clearance of

etravirine is negligible

(< 1.2%), a decrease in total

body clearance is not

expected in patients with

renal impairment. No special

precautions or dose

adjustments are required in

patients with renal

impairment. As etravirine is

highly bound to plasma

proteins, it is unlikely that it

will be significantly removed

by haemodialysis or

peritoneal dialysis (see

sections 4.2 and 5.2).

Fat redistribution

Combination antiretroviral

therapy (CART) has been

associated with redistribution

of body fat (lipodystrophy) in

HIV infected patients. The

long-term consequences of

these events are currently

unknown. Knowledge about

the mechanism is incomplete.

A connection between

visceral lipomatosis and PIs

and lipoatrophy and

nucleoside reverse

transcriptase inhibitors

(NRTIs) has been

hypothesised. A higher risk

of lipodystrophy has been

associated with individual

factors such as older age and

with drug related factors such

as longer duration of

antiretroviral treatment and

associated metabolic

disturbances. Clinical

examination should include

evaluation for physical signs

of fat redistribution (see

section 4.8).

Immune reconstitution

syndrome

In HIV infected patients with

severe immune deficiency at

the time of institution of

Symptoms) and TEN (toxic

epidermal necrolysis), sometimes

fatal, have been reported with the use

of INTELENCE (see section 4.8).

The DRESS syndrome is

characterised by rash, fever,

eosinophilia and systemic

involvement (including, but not

limited to, severe rash or rash

accompanied by fever, general

malaise, fatigue, muscle or joint

aches, blisters, oral lesions,

conjunctivitis, hepatitis and

eosinophilia). Time to onset is

usually around 3-6 weeks and the

outcome in most cases is favourable

upon discontinuation and after

initiation of corticosteroid therapy.

Patients should be informed to seek

medical advice if severe rash or

hypersensitivity reactions occur.

Patients who are diagnosed with a

hypersensitivity reaction whilst on

therapy must discontinue

INTELENCE immediately.

Delay in stopping INTELENCE

treatment after the onset of severe

rash may result in a life-threatening

reaction.

Patients who have stopped treatment

due to hypersensitivity reactions

should not restart therapy with

INTELENCE.

Rash

Rash has been reported with

INTELENCE. Most frequently, rash was

mild to moderate, occurred in the second

week of therapy and was infrequent after

week 4. Rash was mostly self-limiting

and generally resolved within

1 to 2 weeks on continued therapy.

When prescribing INTELENCE to

females, prescribers should be aware

The incidence of rash was higher in

females (see section 4.8).

Elderly

Experience in geriatric patients is

limited: In the Phase III trials, 6 patients

aged 65 years or older and 53 patients

aged 56-64 years received

INTELENCE. The type and incidence of

adverse events in patients > 55 years of

CART, an inflammatory

reaction to asymptomatic or

residual opportunistic

pathogens may arise and

cause serious clinical

conditions, or aggravation of

symptoms. Typically, such

reactions have been observed

within the first weeks or

months of initiation of

CART. Relevant examples

are cytomegalovirus retinitis,

generalised and/or focal

mycobacterial infections and

Pneumocystis jirovecii

pneumonia. Any

inflammatory symptoms

should be evaluated and

treatment instituted when

necessary.

Autoimmune disorders such

as Graves’ disease have also

been reported to occur in the

setting of immune

reactivation; however, the

time to onset is more

variable, and can occur many

months after initiation of

treatment (see section 4.8).

Interactions with medicinal

products

For information on

interactions with medicinal

products see section 4.5.

Osteonecrosis

Although the etiology is

considered to be

multifactorial (including

corticosteroid use, alcohol

consumption, severe

immunosuppression, higher

body mass index), cases of

osteonecrosis have been

reported particularly in

patients with advanced HIV

disease and/or long-term

exposure to CART. Patients

should be advised to seek

medical advice if they

experience joint aches and

pain, joint stiffness or

difficulty in movement.

Lactose intolerance and

lactase deficiency

Each tablet of intelence 100

mg contains 160 mg of

lactose. Patients with rare

age were similar to the ones in younger

patients (see sections 4.2 and 5.2).

Pregnancy

Given the increased etravirine

exposure during pregnancy, caution

should be applied for those pregnant

patients that require concomitant

medications or have comorbidities

that may further increase etravirine

exposure.

Patients with coexisting conditions

Liver disease

No dose adjustment is required in

patients with mild or moderate hepatic

impairment (Child-Pugh score A or B).

The pharmacokinetics of INTELENCE

have not been studied in patients with

severe hepatic impairment (Child-Pugh

score C) (see sections 4.2 and 5.2).

Renal disease

Since the renal clearance of etravirine is

negligible (< 1.2%), a decrease in total

body clearance is not expected in

patients with renal impairment. No

special precautions or dose adjustments

are required in patients with renal

impairment. As etravirine is highly

bound to plasma proteins, it is unlikely

that it will be significantly removed by

haemodialysis or peritoneal dialysis (see

sections 4.2 and 5.2).

Patients with coexisting conditions

Hepatic impairment

Etravirine is primarily metabolised

and eliminated by the liver and

highly bound to plasma proteins.

Effects on unbound exposure could

be expected (has not been studied)

and therefore caution is advised in

patients with moderate hepatic

impairment. INTELENCE has not

been studied in patients with severe

hepatic impairment (Child-Pugh

Class C) and its use is therefore not

recommended in this group of

patients (see sections 4.2 and 5.2).

Co-infection with HBV (hepatitis B

virus) or HCV (hepatitis C virus)

Caution should be exercised in

patients co-infected with hepatitis B

or C virus due to the current limited

data available. A potential increased

risk of liver enzymes increase cannot

hereditary problems of

galactose intolerance, the

Lapp lactase deficiency or

glucose-galactose

malabsorption should not

take this medicine.

be excluded.

Weight and metabolic parameters

An increase in weight and in levels

of blood lipids and glucose may

occur during antiretroviral therapy.

Such changes may in part be linked

to disease control and life style. For

lipids, there is in some cases

evidence for a treatment effect, while

for weight gain there is no strong

evidence relating this to any

particular treatment. For monitoring

of blood lipids and glucose reference

is made to established HIV treatment

guidelines. Lipid disorders should be

managed as clinically appropriate.

Fat redistribution

Combination antiretroviral therapy

(CART) has been associated with

redistribution of body fat

(lipodystrophy) in HIV infected patients.

The long-term consequences of these

events are currently unknown.

Knowledge about the mechanism is

incomplete. A connection between

visceral lipomatosis and PIs and

lipoatrophy and nucleoside reverse

transcriptase inhibitors (NRTIs) has

been hypothesised. A higher risk of

lipodystrophy has been associated with

individual factors such as older age and

with drug related factors such as longer

duration of antiretroviral treatment and

associated metabolic disturbances.

Clinical examination should include

evaluation for physical signs of fat

redistribution (see section 4.8).

Immune reconstitution syndrome

In HIV infected patients with severe

immune deficiency at the time of

institution of CART, an inflammatory

reaction to asymptomatic or residual

opportunistic pathogens may arise and

cause serious clinical conditions, or

aggravation of symptoms. Typically,

such reactions have been observed

within the first weeks or months of

initiation of CART. Relevant examples

are cytomegalovirus retinitis,

generalised and/or focal mycobacterial

infections and Pneumocystis jirovecii

pneumonia. Any inflammatory

symptoms should be evaluated and

treatment instituted when necessary.

Autoimmune disorders (such as Graves’

disease) have also been reported to

occur in the setting of immune

reactivation; however, the time to onset

is more variable, and can occur many

months after initiation of treatment (see

section 4.8).

Interactions with medicinal products

For information on interactions with

medicinal products see section 4.5.

Osteonecrosis

Although the etiology is considered to

be multifactorial (including

corticosteroid use, alcohol consumption,

severe immunosuppression, higher body

mass index), cases of osteonecrosis have

been reported particularly in patients

with advanced HIV disease and/or long-

term exposure to CART. Patients should

be advised to seek medical advice if they

experience joint aches and pain, joint

stiffness or difficulty in movement.

Interactions with medicinal products

It is not recommended to combine

etravirine with tipranavir/ritonavir,

due to a marked pharmacokinetic

interaction (76% decrease of

etravirine AUC) that could

significantly impair the virologic

response to etravirine.

For further information on

interactions with medicinal products

see section 4.5.

Lactose intolerance and lactase

deficiency

Each tablet of intelence 100 mg contains

160 mg of lactose. Patients with rare

hereditary problems of galactose

intolerance, the Lapp lactase deficiency

or glucose-galactose malabsorption

should not take this medicine.

Interaction with

Other Medicaments

and Other Forms of

Interaction

Medicinal products that affect etravirine exposure

Etravirine is metabolised by cytochrome P450 (CYP) 3A, CYP2C9 and CYP2C19 followed

by glucuronidation of the metabolites by uridine diphosphate glucuronosyl transferase

(UDPGT). Medicinal products that induce CYP3A, CYP2C9, or CYP2C19 may increase the

clearance of etravirine resulting in lowered plasma concentrations of etravirine.

Co-administration of INTELENCE and medicinal products that inhibit CYP3A, CYP2C9, or

CYP2C19 may decrease the clearance of etravirine and may result in increased plasma

concentrations of etravirine.

Medicinal products that are affected by the use of etravirine

Etravirine is a weak inducer of CYP3A. Co-administration of INTELENCE with medicinal

products primarily metabolised by CYP3A may result in decreased plasma concentrations of

such medicinal products, which could decrease or shorten their therapeutic effects.

Etravirine is a weak inhibitor of CYP2C9 and CYP2C19. Etravirine is also a weak inhibitor

of P-glycoprotein but not a substrate. Co-administration with medicinal products primarily

metabolised by CYP2C9 or CYP2C19 or transported by P-glycoprotein may result in

increased plasma concentrations of such medicinal products, which could increase or prolong

their therapeutic effect or

alter their

adverse events profile.

Known and theoretical interactions with selected antiretrovirals and non-antiretroviral

medicinal products are listed in the tables below.1

Interaction table

Interactions between etravirine and co-administered medicinal products are listed in the tables

below.1 (increase is indicated as “↑”, decrease as “↓”, no change as “↔”, not done as “ND”,

once daily as “q.d.”, once daily in the morning as “q.a.m.” and twice daily as “b.i.d.”).

Drug Interactions – Etravirine co-administered with antiretroviral medicinal products

Co-administered

Medicinal Product

Dose of

Co-administered

Medicinal Product

(mg)

Medicinal

Product Assessed

AUC

C

min

Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

NNRTIs

(e.g., efavirenz,

nevirapine,

delavirdine, rilpivirine)

It is not recommended to co-administer INTELENCE with other

NNRTIs.

Nucleoside or Nucleotide Reverse Transcriptase Inhibitors (NRTIs/N[t]RTIs)

Didanosine

400 q.d.

didanosine

etravirine

The combination of INTELENCE and didanosine can be used

without dose adjustments. As didanosine is administered on an

empty stomach, didanosine should be administered one hour before

or two hours after INTELENCE (which should be administered

following a meal).

Tenofovir disoproxil

fumarate

300 q.d.

tenofovir

↑ 19%

etravirine

↓ 19%

↓ 18%

The combination of INTELENCE and tenofovir disoproxil

fumarate can be used without dose adjustments.

Other NRTIs

Based on the primarily renal elimination route for other NRTIs

(e.g., abacavir, emtricitabine, lamivudine, stavudine and

zidovudine), no drug interactions are expected between these

medicinal products and INTELENCE.

HIV Protease Inhibitors (PIs) - Unboosted (i.e., without co-administration of low dose

ritonavir)

Atazanavir, unboosted

400 q.d.

atazanavir

↓ 17%

↓ 47%

etravirine

↑ 50%

↑ 58%

It is not recommended to co-administer unboosted atazanavir and

INTELENCE.

Ritonavir

Concomitant use of INTELENCE with full-dose ritonavir (600 mg

b.i.d.) may cause a significant decrease in the plasma concentration

of etravirine. This may result in loss of therapeutic effect of

INTELENCE. It is not recommended to co-administer full-dose

ritonavir (600 mg b.i.d.) with INTELENCE.

Nelfinavir

Concomitant use of INTELENCE with nelfinavir may cause an

increase in the plasma concentrations of nelfinavir.

Fosamprenavir,

unboosted

Concomitant use of INTELENCE with unboosted fosamprenavir

may cause an increase in the plasma concentrations of amprenavir.

Other unboosted PIs

It is not recommended to co-administer INTELENCE with other

unboosted PIs (including indinavir and saquinavir).

HIV Protease Inhibitors (PIs) - Boosted (with low dose ritonavir)

Tipranavir/ritonavir

500/200 b.i.d.

tipranavir

↑ 18%

↑ 24%

etravirine

↓ 76%

↓ 82%

It is not recommended to co-administer tipranavir/ritonavir and

INTELENCE.

Fosamprenavir/

ritonavir

700/100 b.i.d.

amprenavir

↑ 69%

↑ 77%

etravirine

Amprenavir and fosamprenavir/ritonavir may require dose

adjustment when co-administered with INTELENCE.

Atazanavir/ritonavir

300/100 q.d.

atazanavir

↓ 14%

↓ 38%

etravirine

↑ 30%

↑ 26%

The combination of INTELENCE and atazanavir/ritonavir can be

used without dose adjustments.

Darunavir/ritonavir

600/100 b.i.d.

darunavir

etravirine

↓ 37%

↓ 49%

The combination of INTELENCE and darunavir/ritonavir can be

used without dose adjustments.

Lopinavir/ritonavir

(soft-gel capsule)

400/100 b.i.d.

lopinavir

↓ 20%

↓ 8%

etravirine

↑ 17%

↑ 23%

The combination of INTELENCE and lopinavir/ritonavir (soft-gel

capsule) can be used without dose adjustments.

Lopinavir/ritonavir

(melt extrusion tablet)

400/100 b.i.d.

lopinavir

↓ 20%

etravirine

↓ 35%

↓ 45%

The combination of INTELENCE and lopinavir/ritonavir (melt

extrusion tablet) can be used without dose adjustments.

Saquinavir/ritonavir

(soft-gel capsule)

1000/100 b.i.d.

saquinavir

↓ 20%

etravirine

↓ 33%

↓ 29%

The combination of INTELENCE and saquinavir/ritonavir can be

used without dose adjustments.

Dual boosted HIV Protease Inhibitors

Lopinavir/saquinavir/

ritonavir

400/800-1000/100

b.i.d.

lopinavir

↓ 18%

↓ 24%

saquinavir

↓ 13%

↓ 13%

etravirine

The combination of INTELENCE and

lopinavir/saquinavir/ritonavir can be used without dose

adjustments.

CCR5 Antagonists

Maraviroc

300 b.i.d.

maraviroc

↓ 53%

↓ 39%

etravirine

Concomitant use of INTELENCE with maraviroc may cause a

significant decrease in the plasma concentration of maraviroc.

When INTELENCE is co-administered with maraviroc in the

absence of a potent CYP3A inhibitor (e.g., a boosted PI), the

recommended dose of maraviroc is 600 mg b.i.d. No dose

adjustment for INTELENCE is needed.

Maraviroc/darunavir/

ritonavir

150/600/100 b.i.d.

maraviroc

↑ 3.1-fold*

↑ 5.3-fold*

etravirine

When INTELENCE is co-administered with maraviroc in the

presence of a potent CYP3A inhibitor (e.g., a boosted PI), refer to

the applicable prescribing information of maraviroc for the

recommended dose, treating INTELENCE as a CYP3A inducer

(such as efavirenz). No dose adjustment for INTELENCE is

needed.

compared to maraviroc 150 mg b.i.d

Fusion Inhibitors

Enfuvirtide

90 b.i.d.

enfuvirtide

etravirine*

No interaction is expected for either INTELENCE or enfuvirtide

when co-administered.

based on population pharmacokinetic analysis

Integrase Strand Transfer Inhibitors

Dolutegravir

50 mg q.d.

dolutegravir

↓ 0.29

↓ 0.12

etravirine

Dolutegravir/darunavir

50 mg q.d. + 600/100

dolutegravir

↓ 0.75

↓ 0.63

/ritonavir

mg b.i.d.

etravirine

Dolutegravir/lopinavir

50 mg q.d. + 400/100

dolutegravir

↑ 1.28

/ritonavir

mg b.i.d

etravirine

Etravirine significantly reduced plasma concentrations of

dolutegravir. The effect of etravirine on dolutegravir plasma

concentrations was mitigated by

co-administration of darunavir/ritonavir or lopinavir/ritonavir, and

expected to be mitigated by atazanavir/ritonavir.

INTELENCE should only be used with dolutegravir when co-

administered with atazanavir/ritonavir, darunavir/ritonavir, or

lopinavir/ritonavir. This combination can be used without dose

adjustment.

Elvitegravir/ritonavir

150/100 q.d.

etravirine

ritonavir

etravirine

The combination of INTELENCE and elvitegravir/ritonavir can be

used without dose adjustments.

Raltegravir

400 b.i.d.

raltegravir

↓ 10%

↓ 34%

etravirine

The combination of INTELENCE and raltegravir can be used

without dose adjustments.

Drug Interactions – Etravirine co-administered with non-antiretroviral medicinal

products

Co-administered

Medicinal Product

Dose of

Co-administered

Medicinal Product

(mg)

Medicinal

Product Assessed

AUC

C

min

Antiarrhythmics

Digoxin

0.5 mg single dose

digoxin

↑ 18%

etravirine

The combination of INTELENCE and digoxin can be used

without dose adjustments. It is recommended that digoxin levels

be monitored when digoxin is combined with INTELENCE.

Amiodarone

Bepridil

Disopyramide

Flecainide

Lidocaine (systemic)

Mexiletine

Propafenone

Quinidine

Concentrations of these antiarrhythmics may be decreased when

co-administered with INTELENCE. Caution is warranted and

therapeutic concentration monitoring, if available, is

recommended for antiarrhythmics when co-administered with

INTELENCE.

Anticoagulants

Warfarin

Warfarin concentrations may be affected when co-administered

with INTELENCE. It is recommended that the international

normalised ratio (INR) be monitored when warfarin is combined

with INTELENCE.

Anticonvulsants

Carbamazepine

Phenobarbital

Phenytoin

Carbamazepine, phenobarbital and phenytoin are inducers of

CYP450 enzymes. INTELENCE should not be used in

combination with carbamazepine, phenobarbital, or phenytoin as

co-administration may cause significant decreases in etravirine

plasma concentrations. This may result in loss of therapeutic

effect of INTELENCE.

Antifungals

Fluconazole

200 q.a.m.

fluconazole

etravirine

↑ 86%

↑ 109%

The incidence of adverse events was similar in patients

coadministering fluconazole and INTELENCE or placebo in the

Phase III trials. The combination of INTELENCE and

fluconazole can be used without dose adjustments.

Voriconazole

200 b.i.d.

voriconazole

↑ 14%

↑ 23%

etravirine

↑ 36%

↑ 52%

The combination of INTELENCE and voriconazole can be used

without dose adjustments.

Itraconazole

Ketoconazole

Posaconazole

Posaconazole, a potent inhibitor of CYP3A, may increase plasma

concentrations of etravirine. Itraconazole and ketoconazole are

potent inhibitors as well as substrates of CYP3A. Concomitant

systemic use of itraconazole or ketoconazole and INTELENCE

may increase plasma concentrations of etravirine.

Simultaneously, plasma concentrations of itraconazole or

ketoconazole may be decreased by INTELENCE. The

combination of INTELENCE and these antifungals can be used

without dose adjustments.

Antiinfectives

Azithromycin

Based on the renal elimination pathway of azithromycin, no drug

interactions are expected between azithromycin and

INTELENCE.

Clarithromycin

500 b.i.d.

clarithromycin

↓ 39%

↓ 53%

14-hydroxy-

clarithromycin

↑ 21%

etravirine

↑ 42%

↑ 46%

Clarithromycin exposure was decreased by etravirine; however,

concentrations of the active metabolite,

14-hydroxy-clarithromycin, were increased. Because

14-hydroxy-clarithromycin has reduced activity against

Mycobacterium avium complex (MAC), overall activity against

this pathogen may be altered; therefore, alternatives to

clarithromycin, such as azithromycin, should be considered for

the treatment of MAC.

Antimalarials

Artemether/Lumefantrine

80/480 mg, 6 doses

at 0, 8, 24, 36, 48,

and 60 hours

artemether

↓ 38%

↓ 18%

dihydroartemisinin

↓ 15%

↓ 17%

lumefantrine

↓ 13%

etravirine

No dose adjustment is needed for INTELENCE. Caution is

warranted when co-administering INTELENCE and

artemether/lumefantrine as it is unknown whether the decrease in

exposure of artemether or its active metabolite,

dihydroartemisinin, could result in decreased antimalarial

efficacy.

Antimycobacterials

Rifampicin/Rifampin

Rifapentine

Rifampicin and rifapentine are potent inducers of CYP450

enzymes. INTELENCE should not be used in combination with

rifampicin or rifapentine as co-administration may cause

significant decreases in etravirine plasma concentrations. This

may result in loss of therapeutic effect of INTELENCE.

Rifabutin

300 q.d.

rifabutin

↓ 17%

↓ 24%

25-O-

desacetylrifabutin

↓ 17%

↓ 22%

etravirine

↓ 37%

↓ 35%

If INTELENCE is not co-administered with a boosted protease

inhibitor, then INTELENCE and rifabutin can be used without

dose adjustments.

If INTELENCE is co-administered with boosted darunavir,

lopinavir or saquinavir, then the combination with rifabutin

should be used with caution due to the potential for significant

reductions in etravirine exposure.

When INTELENCE is co-administered with rifabutin and a

boosted protease inhibitor, the recommended dose of rifabutin is

determined by the prescribing information for the boosted

protease inhibitor component of the regimen.

Benzodiazepines

Diazepam

Concomitant use of INTELENCE with diazepam may increase

plasma concentrations of diazepam.

Corticosteroids

Dexamethasone

(systemic)

Systemic dexamethasone induces CYP3A and can decrease

etravirine plasma concentrations. This may result in loss of

therapeutic effect of INTELENCE. Systemic dexamethasone

should be used with caution or alternatives should be considered,

particularly for long-term use.

Estrogen-based Contraceptives

Ethinylestradiol

0.035 q.d.

ethinylestradiol

↑ 22%

Norethindrone

1 q.d.

norethindrone

↓ 22%

etravirine

The combination of estrogen- and/or progesterone-based

contraceptives and INTELENCE can be used without dose

adjustment.

Hepatitis C Virus (HCV) Direct-Acting Antivirals

Boceprevir/Etravirine

800 mg t.i.d/200mg

b.i.d.

boceprevir

↑ 1.10

↓ 0.88

etravirine

↓ 0.77

↓ 0.71

The combination of INTELENCE and boceprevir can be used

without dose adjustments.

Caution should be applied if INTELENCE is co-administered

with boceprevir and another drug that potentially decreases

etravirine plasma concentrations. Close monitoring for HIV and

HCV virologic response is recommended. Please refer to the

product information of the associated medications.

Ribavirin

Based on the renal elimination pathway of ribavirin, no drug

interactions are expected between ribavirin and INTELENCE.

Telaprevir

750 mg q8h

telaprevir

↓ 16%

↓ 25%

etravirine

The combination of INTELENCE and telaprevir can be used

without dose adjustments.

Herbal Products

St John's wort

(Hypericum perforatum)

INTELENCE should not be used concomitantly with products

containing St John’s wort because co-administration may cause

significant decreases in etravirine plasma concentrations. This

may result in loss of therapeutic effect of INTELENCE.

HMG Co-A Reductase Inhibitors

Atorvastatin

40 q.d.

atorvastatin

↓ 37%

2-hydroxy-

atorvastatin

↑ 27%

etravirine

Dose adjustment of atorvastatin may be necessary to tailor the

clinical response when combined with INTELENCE.

Fluvastatin

Lovastatin

Pitavastatin

Pravastatin

Rosuvastatin

Simvastatin

No interaction between pravastatin and INTELENCE is

expected.

Lovastatin, rosuvastatin and simvastatin are CYP3A substrates

and co-administration with INTELENCE may result in lower

plasma concentrations of the HMG Co-A reductase inhibitor.

Fluvastatin, rosuvastatin and, to a lesser extent, pitavastatin are

metabolised by CYP2C9 and co-administration with

INTELENCE may result in higher plasma concentrations of the

HMG Co-A reductase inhibitor. Dose adjustments for these

HMG Co-A reductase inhibitors may be necessary.

H

2

-Receptor Antagonists

Ranitidine

150 b.i.d.

etravirine

↓ 14%

INTELENCE can be co-administered with H

-receptor

antagonists without dose adjustments.

Immunosuppressants

Cyclosporine

Sirolimus

Tacrolimus

Co-administration with systemic immunosuppressants should be

done with caution because plasma concentrations of

cyclosporine, sirolimus, or tacrolimus may be affected when

co-administered with INTELENCE.

Narcotic Analgesics

Methadone

individual dose

ranging from 60 to

130 mg/day

R(-) methadone

S(+) methadone

etravirine

No changes in methadone dosage were required based on

clinical status during or after the period of INTELENCE

co-administration.

Phosphodiesterase, type 5 (PDE-5) inhibitors

Sildenafil

Vardenafil

Tadalafil

50 mg single dose

sildenafil

↓ 57%

N-desmethyl-

sildenafil

↓ 41%

Concomitant use of PDE-5 inhibitors with INTELENCE may

require dose adjustment of the PDE-5 inhibitor to attain the

desired clinical effect.

Platelet Aggregation Inhibitors

Clopidogrel

Activation of clopidogrel to its active metabolite may be

decreased when clopidogrel is co-administered with

INTELENCE. Alternatives to clopidogrel should be considered.

Proton Pump Inhibitors

Omeprazole

40 q.d.

etravirine

↑ 41%

INTELENCE can be co-administered with proton pump

inhibitors without dose adjustments.

Selective Serotonin Reuptake Inhibitors (SSRIs)

Paroxetine

20 q.d.

paroxetine

↓ 13%

etravirine

INTELENCE can be co-administered with paroxetine without

dose adjustments.

In drug-drug interaction studies, different formulations and/or doses of INTELENCE were used which led to

similar exposures and, therefore, interactions relevant for one formulation are relevant for the other.

Table 1: INTERACTIONS AND DOSE RECOMMENDATIONS WITH OTHER MEDICINAL

PRODUCTS

Medicinal products by

therapeutic areas

Effects on drug levels

Least Squares

Mean Ratio

(90% CI; 1.00 = No effect)

Recommendations

concerning

co-administration

ANTI-INFECTIVES

Antiretrovirals

NRTIs

Didanosine

400 mg once daily

didanosine

AUC ↔ 0.99 (0.79-1.25)

↔ 0.91 (0.58-1.42)

etravirine

AUC ↔ 1.11 (0.99-1.25)

↔ 1.05 (0.93-1.18)

↔ 1.16 (1.02-1.32)

No significant effect on

didanosine and etravirine PK

parameters is seen.

INTELENCE and didanosine

can be used without dose

adjustments.

Tenofovir disoproxil

fumarate

300 mg once daily

tenofovir

AUC ↔ 1.15 (1.09-1.21)

↑ 1.19 (1.13-1.26)

↑ 1.15 (1.04-1.27)

etravirine

AUC ↓ 0.81 (0.75-0.88)

↓ 0.82 (0.73-0.91)

↓ 0.81 (0.75-0.88)

No significant effect on

tenofovir and etravirine PK

parameters is seen.

INTELENCE and tenofovir

can be used without dose

adjustments.

Other NRTIs

Not studied, but no interaction expected based

on the primary renal elimination route for other

NRTIs (e.g., abacavir, emtricitabine,

lamivudine, stavudine and zidovudine).

Etravirine can be used with

these NRTIs without dose

adjustment.

NNRTIs

Efavirenz

Nevirapine

Rilpivirine

Combining two NNRTIs has not been shown to

be beneficial. Concomitant use of INTELENCE

with efavirenz or nevirapine may cause a

significant decrease in the plasma concentration

of etravirine and loss of therapeutic effect of

INTELENCE.

Concomitant use of INTELENCE with

rilpivirine may cause a decrease in the plasma

concentration of rilpivirine and loss of

therapeutic effect of rilpivirine.

It is not recommended to

co-administer INTELENCE

with other NNRTIs.

HIV PIs - Unboosted (i.e. without co-administration of low-dose ritonavir)

Indinavir

Concomitant use of INTELENCE with

indinavir may cause a significant decrease in

the plasma concentration of indinavir and loss

of therapeutic effect of indinavir.

It is not recommended to

co-administer INTELENCE

with indinavir.

Nelfinavir

Not studied. INTELENCE is expected to

increase nelfinavir plasma concentrations.

It is not recommended to

co-administer INTELENCE

with nelfinavir.

HIV PIs - Boosted (with low-dose ritonavir)

Atazanavir/ritonavir

300/100 mg once daily

atazanavir

AUC ↓ 0.86 (0.79-0.93)

↓ 0.62 (0.55-0.71)

↔ 0.97 (0.89-1.05)

etravirine

AUC ↑ 1.30 (1.18-1.44)

↑ 1.26 (1.12-1.42)

↑ 1.30 (1.17-1.44)

INTELENCE and

atazanavir/ritonavir can be

used without dose

adjustment.

Darunavir/ritonavir

600/100 mg twice daily

darunavir

AUC ↔ 1.15 (1.05-1.26)

↔ 1.02 (0.90-1.17)

↔ 1.11 (1.01-1.22)

etravirine

AUC ↓ 0.63 (0.54-0.73)

↓ 0.51 (0.44-0.61)

↓ 0.68 (0.57-0.82)

INTELENCE and

darunavir/ritonavir can be

used without dose

adjustments (see also

section 5.1).

Fosamprenavir/ritonavir

700/100 mg twice daily

amprenavir

AUC ↑ 1.69 (1.53-1.86)

↑ 1.77 (1.39-2.25)

↑ 1.62 (1.47-1.79)

etravirine

AUC ↔

Amprenavir/ritonavir and

fosamprenavir/ritonavir may

require dose reduction when

co-administered with

INTELENCE. Using the oral

solution may be considered

for dose reduction.

Lopinavir/ritonavir

(tablet)

400/100 mg twice daily

lopinavir

AUC ↔ 0.87 (0.83-0.92)

↓ 0.80 (0.73-0.88)

↔ 0.89 (0.82-0.96)

etravirine

AUC ↓ 0.65 (0.59-0.71)

↓ 0.55 (0.49-0.62)

↓ 0.70 (0.64-0.78)

INTELENCE and

lopinavir/ritonavir can be

used without dose

adjustments.

Saquinavir/ritonavir

1,000/100 mg twice daily

saquinavir

AUC ↔ 0.95 (0.64-1.42)

↓ 0.80 (0.46-1.38)

↔ 1.00 (0.70-1.42)

etravirine

AUC ↓ 0.67 (0.56-0.80)

↓ 0.71 (0.58-0.87)

↓ 0.63 (0.53-0.75)

INTELENCE and

saquinavir/ritonavir can be

used without dose

adjustments.

Tipranavir/ritonavir

500/200 mg twice daily

tipranavir

AUC ↑ 1.18 (1.03-1.36)

↑ 1.24 (0.96-1.59)

↑ 1.14 (1.02-1.27)

etravirine

AUC ↓ 0.24 (0.18-0.33)

↓ 0.18 (0.13-0.25)

↓ 0.29 (0.22-0.40)

It is not recommended to

co-administer

tipranavir/ritonavir and

INTELENCE (see

section 4.4).

CCR5 Antagonists

Maraviroc

300 mg twice daily

Maraviroc/darunavir/

ritonavir

150/600/100 mg twice

daily

maraviroc

AUC ↓ 0.47 (0.38-0.58)

↓ 0.61 (0.53-0.71)

↓ 0.40 (0.28-0.57)

etravirine

AUC ↔ 1.06 (0.99-1.14)

↔ 1.08 (0.98-1.19)

↔ 1.05 (0.95-1.17)

maraviroc*

AUC ↑ 3.10 (2.57-3.74)

↑ 5.27 (4.51-6.15)

↑ 1.77 (1.20-2.60)

compared to maraviroc 150 mg b.i.d.

The recommended dose for

maraviroc when combined

with INTELENCE in the

presence of potent CYP3A

inhibitors (e.g. boosted PIs)

is 150 mg b.i.d. except for

fosamprenavir/ritonavir

(maraviroc dose 300 mg

b.i.d.). No dose adjustment

for INTELENCE is

necessary.

See also section 4.4.

Fusion Inhibitors

Enfuvirtide

90 mg twice daily

etravirine*

AUC ↔

Enfuvirtide concentrations not studied and no

effect is expected.

based on population pharmacokinetic analyses

No interaction is expected for

either INTELENCE or

enfuvirtide when

co-administered.

Integrase Strand Transfer Inhibitors

Dolutegravir

50 mg once daily

Dolutegravir +

darunavir/ritonavir

50 mg once daily +

600/100 mg twice daily

Dolutegravir +

Lopinavir/ritonavir

50 mg once daily +

400/100 mg twice daily

dolutegravir

AUC ↓ 0.29 (0.26-0.34)

↓ 0.12 (0.09-0.16)

↓ 0.48 (0.43-0.54)

etravirine

AUC ↔

dolutegravir

AUC↓ 0.75 (0.69-0.81)

↓ 0.63 (0.52-0.77)

↓ 0.88 (0.78-1.00)

etravirine

AUC ↔

dolutegravir

AUC↔ 1.11(1.02-1.20)

↑ 1.28 (1.13-1.45)

↔ 1.07 (1.02-1.13)

etravirine

AUC ↔

Etravirine significantly

reduced plasma

concentrations of

dolutegravir. The effect of

etravirine on dolutegravir

plasma concentrations was

mitigated by

co-administration of

darunavir/ritonavir or

lopinavir/ritonavir, and is

expected to be mitigated by

atazanavir/ritonavir.

INTELENCE should only be

used with dolutegravir when

co-administered with

atazanavir/ritonavir,

darunavir/ritonavir, or

lopinavir/ritonavir. This

combination can be used

without dose adjustment.

Raltegravir

400 mg twice daily

raltegravir

AUC ↓ 0.90 (0.68-1.18)

↓ 0.66 (0.34-1.26)

↓ 0.89 (0.68-1.15)

etravirine

AUC ↔ 1.10 (1.03-1.16)

↔ 1.17 (1.10-1.26)

↔ 1.04 (0.97-1.12)

INTELENCE and raltegravir

can be used without dose

adjustments.

ANTIARRHYTHMICS

Digoxin

0.5 mg single dose

digoxin

AUC ↑ 1.18 (0.90-1.56)

↑ 1.19 (0.96-1.49)

INTELENCE and digoxin

can be used without dose

adjustments. It is

recommended that digoxin

levels be monitored when

digoxin is combined with

INTELENCE.

Amiodarone

Bepridil

Disopyramide

Flecainide

Lidocaine (systemic)

Mexiletine

Propafenone

Quinidine

Not studied. INTELENCE is expected to

decrease plasma concentrations of these

antiarrhythmics.

Caution is warranted and

therapeutic concentration

monitoring, if available, is

recommended for

antiarrhythmics when

co-administered with

INTELENCE.

ANTIBIOTICS

Azithromycin

Not studied. Based on the biliary elimination

pathway of azithromycin, no drug interactions

are expected between azithromycin and

INTELENCE.

INTELENCE and

azithromycin can be used

without dose adjustments.

Clarithromycin

500 mg twice daily

clarithromycin

AUC ↓ 0.61 (0.53-0.69)

↓ 0.47 (0.38-0.57)

↓ 0.66 (0.57-0.77)

14-OH-clarithromycin

AUC ↑ 1.21 (1.05-1.39)

↔ 1.05 (0.90-1.22)

↑ 1.33 (1.13-1.56)

etravirine

AUC ↑ 1.42 (1.34-1.50)

↑ 1.46 (1.36-1.58)

↑ 1.46 (1.38-1.56)

Clarithromycin exposure was

decreased by etravirine;

however, concentrations of

the active metabolite,

14-OH-clarithromycin, were

increased. Because

14-OH-clarithromycin has

reduced activity against

Mycobacterium avium

complex (MAC), overall

activity against this pathogen

may be altered; therefore

alternatives to clarithromycin

should be considered for the

treatment of MAC.

ANTICOAGULANTS

Warfarin

Not studied. INTELENCE is expected to

increase plasma concentrations of warfarin.

It is recommended that the

international normalised ratio

(INR) be monitored when

warfarin is combined with

INTELENCE.

ANTICONVULSANTS

Carbamazepine

Phenobarbital

Phenytoin

Not studied. Carbazamepine, phenobarbital and

phenytoin are expected to decrease plasma

concentrations of etravirine.

Combination not

recommended.

ANTIFUNGALS

Fluconazole

200 mg once in the

morning

fluconazole

AUC ↔ 0.94 (0.88-1.01)

↔ 0.91 (0.84-0.98)

↔ 0.92 (0.85-1.00)

etravirine

AUC ↑ 1.86 (1.73-2.00)

↑ 2.09 (1.90-2.31)

↑ 1.75 (1.60-1.91)

INTELENCE and

fluconazole can be used

without dose adjustments.

Itraconazole

Ketoconazole

Posaconazole

Not studied. Posaconazole, a potent inhibitor of

CYP3A4, may increase plasma concentrations

of etravirine. Itraconazole and ketoconazole are

potent inhibitors as well as substrates of

CYP3A4. Concomitant systemic use of

itraconazole or ketoconazole and INTELENCE

may increase plasma concentrations of

etravirine. Simultaneously, plasma

concentrations of itraconazole or ketoconazole

may be decreased by INTELENCE.

INTELENCE and these

antifungals can be used

without dose adjustments.

Voriconazole

200 mg twice daily

voriconazole

AUC ↑ 1.14 (0.88-1.47)

↑ 1.23 (0.87-1.75)

↓ 0.95 (0.75-1.21)

etravirine

AUC ↑ 1.36 (1.25-1.47)

↑ 1.52 (1.41-1.64)

↑ 1.26 (1.16-1.38)

INTELENCE and

voriconazole can be used

without dose adjustments.

ANTIMALARIALS

Artemether/

Lumefantrine

80/480 mg, 6 doses at 0,

8, 24, 36, 48, and

60 hours

artemether

AUC ↓ 0.62 (0.48-0.80)

↓ 0.82 (0.67-1.01)

↓ 0.72 (0.55-0.94)

dihydroartemisinin

AUC ↓ 0.85 (0.75-0.97)

↓ 0.83 (0.71-0.97)

↓ 0.84 (0.71-0.99)

lumefantrine

AUC ↓ 0.87 (0.77-0.98)

↔ 0.97 (0.83-1.15)

↔ 1.07 (0.94-1.23)

etravirine

AUC ↔ 1.10 (1.06-1.15)

↔ 1.08 (1.04-1.14)

↔ 1.11 (1.06-1.17)

Close monitoring of

antimalarial response is

warranted when

co-administering

INTELENCE and

artemether/lumefantrine as a

significant decrease in

exposure of artemether and

its active metabolite,

dihydroartemisinin, may

result in decreased

antimalarial efficacy. No

dose adjustment is needed for

INTELENCE.

ANTIMYCOBACTERIALS

Rifampicin

Rifapentine

Not studied. Rifampicin and rifapentine are

expected to decrease plasma concentrations of

etravirine.

INTELENCE should be used in combination

with a boosted protease inhibitor (PI).

Rifampicin is contraindicated in combination

with boosted PIs.

Combination not

recommended.

Rifabutin

300 mg once daily

With an associated boosted PI:

No interaction study has been performed. Based

on historical data, a decrease in etravirine

exposure may be expected whereas an increase

in rifabutin exposure and especially in

25-O-desacetyl-rifabutin may be expected.

With no associated boosted PI (out of the

recommended indication for etravirine):

rifabutin

AUC ↓ 0.83 (0.75-0.94)

↓ 0.76 (0.66-0.87)

↓ 0.90 (0.78-1.03)

25-O-desacetyl-rifabutin

AUC ↓ 0.83 (0.74-0.92)

↓ 0.78 (0.70-0.87)

↓ 0.85 (0.72-1.00)

etravirine

AUC ↓ 0.63 (0.54-0.74)

↓ 0.65 (0.56-0.74)

↓ 0.63 (0.53-0.74)

The combination of

INTELENCE with a boosted

PI and rifabutin should be

used with caution due to the

risk of decrease in etravirine

exposure and the risk of

increase in rifabutin and

25-O-desacetyl-rifabutin

exposures.

Close monitoring for

virologic response and for

rifabutin related adverse

reactions is recommended.

Please refer to the product

information of the associated

boosted PI for the dose

adjustment of rifabutin to be

used.

BENZODIAZEPINES

Diazepam

Not studied. Etravirine is expected to increase

plasma concentrations of diazepam.

Alternatives to diazepam

should be considered.

CORTICOSTEROIDS

Dexamethasone

(systemic)

Not studied. Dexamethasone is expected to

decrease plasma concentrations of etravirine

Systemic dexamethasone

should be used with caution

or alternatives should be

considered, particularly for

chronic use.

OESTROGEN-BASED CONTRACEPTIVES

Ethinylestradiol

0.035 mg once daily

Norethindrone

1 mg once daily

ethinylestradiol

AUC ↑ 1.22 (1.13-1.31)

↔ 1.09 (1.01-1.18)

↑ 1.33 (1.21-1.46)

norethindrone

AUC ↔ 0.95 (0.90-0.99)

↓ 0.78 (0.68-0.90)

↔ 1.05 (0.98-1.12)

etravirine

AUC ↔

The combination of

oestrogen- and/or

progesterone-based

contraceptives and

INTELENCE can be used

without dose adjustment.

HEPATITIS C VIRUS (HCV) DIRECT-ACTING ANTIVIRALS

Ribavirin

Not studied, but no interaction expected based

on the renal elimination pathway of ribavirin.

The combination of

INTELENCE and ribavirin

can be used without dose

adjustments.

Boceprevir

Boceprevir 800 mg

3 times daily + etravirine

200 mg every 12 hours

boceprevir

AUC ↑ 1.10 (0.94-1.28)

↑ 1.10 (0.94-1.29)

↓ 0.88 (0.66-1.17)

etravirine

AUC ↓ 0.77 (0.66-0.91)

↓ 0.76 (0.68-0.85)

↓ 0.71 (0.54-0.95)

The clinical significance of

the reductions in etravirine

pharmacokinetic parameters

and boceprevir C

in the

setting of the combination

therapy with HIV

antiretroviral medicines

which also affect the

pharmacokinetics of

etravirine and/or boceprevir

has not been directly

assessed. Increased clinical

and laboratory monitoring for

HIV and HCV suppression is

recommended.

Telaprevir

750 mg every 8 hours

telaprevir

AUC ↓ 0.84 (0.71-0.98)

↓ 0.90 (0.79-1.02)

↓ 0.75 (0.61-0.92)

etravirine

AUC ↔ 0.94 (0.85-1.04)

↔ 0.93 (0.84-1.03)

↔ 0.97 (0.86-1.10)

The combination of

INTELENCE and telaprevir

can be used without dose

adjustments.

HERBAL PRODUCTS

St John's wort

(Hypericum perforatum)

Not studied. St John’s wort is expected to

decrease the plasma concentrations of

etravirine.

Combination not

recommended.

HMG CO-A REDUCTASE INHIBITORS

Atorvastatin

40 mg once daily

atorvastatin

AUC ↓ 0.63 (0.58-0.68)

↑ 1.04 (0.84-1.30)

2-OH-atorvastatin

AUC ↑ 1.27 (1.19-1.36)

↑ 1.76 (1.60-1.94)

etravirine

AUC ↔ 1.02 (0.97-1.07)

↔ 1.10 (1.02-1.19)

↔ 0.97 (0.93-1.02)

The combination of

INTELENCE and

atorvastatin can be given

without any dose

adjustments, however, the

dose of atorvastatin may

need to be altered based on

clinical response.

Fluvastatin

Lovastatin

Pravastatin

Rosuvastatin

Simvastatin

Not studied. No interaction between pravastatin

and INTELENCE is expected.

Lovastatin, rosuvastatin and simvastatin are

CYP3A4 substrates and co-administration with

INTELENCE may result in lower plasma

concentrations of the HMG Co-A reductase

inhibitor. Fluvastatin, and rosuvastatin are

metabolised by CYP2C9 and co-administration

with INTELENCE may result in higher plasma

concentrations of the HMG Co-A reductase

inhibitor.

Dose adjustments for these

HMG Co-A reductase

inhibitors may be necessary.

H

-RECEPTOR ANTAGONISTS

Ranitidine

150 mg twice daily

etravirine

AUC ↓ 0.86 (0.76-0.97)

↓ 0.94 (0.75-1.17)

INTELENCE can be

co-administered with

-receptor antagonists

without dose adjustments.

IMMUNOSUPPRESSANTS

Cyclosporin

Sirolimus

Tacrolimus

Not studied. Etravirine is expected to decrease

plasma concentrations of cyclosporine,

sirolimus and tacrolimus.

Co-administration with

systemic

immunosuppressants should

be done with caution because

plasma concentrations of

cyclosporin, sirolimus and

tacrolimus may be affected

when co-administered with

INTELENCE.

NARCOTIC ANALGESICS

Methadone

individual dose ranging

from 60 mg to 130 mg

once daily

R(-) methadone

AUC ↔ 1.06 (0.99-1.13)

↔ 1.10 (1.02-1.19)

↔ 1.02 (0.96-1.09)

S(+) methadone

AUC ↔ 0.89 (0.82-0.96)

↔ 0.89 (0.81-0.98)

↔ 0.89 (0.83-0.97)

etravirine

AUC ↔

No changes in methadone

dosage were required based

on clinical status during or

after the period of

INTELENCE

co-administration.

PHOSPHODIESTERASE, TYPE 5 (PDE-5) INHIBITORS

Sildenafil 50 mg single

dose

Tadalafil

Vardenafil

sildenafil

AUC ↓ 0.43 (0.36-0.51)

↓ 0.55 (0.40-0.75)

N-desmethyl-sildenafil

AUC ↓ 0.59 (0.52-0.68)

↓ 0.75 (0.59-0.96)

Concomitant use of PDE-5

inhibitors with INTELENCE

may require dose adjustment

of the PDE-5 inhibitor to

attain the desired clinical

effect.

PLATELET AGGREGGATION INHIBITORS

Clopidogrel

In vitro data show that etravirine has inhibitory

properties on CYP2C19. It is therefore possible

that etravirine may inhibit the metabolism of

clopidogrel to its active metabolite by such

inhibition of CYP2C19 in vivo. The clinical

relevance of this interaction has not been

demonstrated.

As a precaution it is

recommended that

concomitant use of etravirine

and clopidogrel should be

discouraged.

PROTON PUMP INHIBITORS

Omeprazole

40 mg once daily

etravirine

AUC ↑ 1.41 (1.22-1.62)

↑ 1.17 (0.96-1.43)

INTELENCE can be

co-administered with proton

pump inhibitors without dose

adjustments.

SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIS)

Paroxetine

20 mg once daily

paroxetine

AUC ↔ 1.03 (0.90-1.18)

↓ 0.87 (0.75-1.02)

↔ 1.06 (0.95-1.20)

etravirine

AUC ↔ 1.01 (0.93-1.10)

↔ 1.07 (0.98-1.17)

↔ 1.05 (0.96-1.15)

INTELENCE can be

co-administered with

paroxetine without dose

adjustments.

Comparison based on historic control.

Note: In drug-drug interaction studies, different formulations and/or doses of etravirine were used which led to similar

exposures and, therefore, interactions relevant for one formulation are relevant for the other.

Paediatric population

Interaction studies have only been performed in adults.

תושקובמה תורמחהה

ןולעב קרפ

יחכונ טסקט

שדח טסקט

4.6

Pregnancy and

lactation

Pregnancy

There are no adequate and

well-controlled studies with

etravirine in pregnant

women. Studies in animals

have not shown evidence of

developmental toxicity or

effect on reproductive

function and fertility (see

section 5.3).

INTELENCE should be used

during pregnancy only if the

potential benefit justifies the

potential risk.

Lactation

It is not known whether

etravirine is excreted in

human milk. Because of both

the potential for HIV

transmission and the

potential for adverse events

in nursing infants, mothers

should be instructed not to

breastfeed if they are

receiving INTELENCE.

Pregnancy

There are no adequate and

well-controlled studies with etravirine in

pregnant women. Studies in animals

have not shown evidence of

developmental toxicity or effect on

reproductive function and fertility (see

section 5.3).

INTELENCE should be used during

pregnancy only if the potential benefit

justifies the potential risk.

As a general rule, when deciding to

use antiretroviral agents for the

treatment of HIV infection in

pregnant women, and consequently

for reducing the risk of HIV vertical

transmission to the newborn, the

animal data as well as the clinical

experience in pregnant women

should be taken into account in order

to characterise the safety for the

foetus.

Placental transfer has been seen in

pregnant rats, but it is not known

whether placental transfer of

INTELENCE also occurs in pregnant

women. Studies in animals do not

indicate direct or indirect harmful

effects with respect to pregnancy,

embryonal/foetal development,

parturition or postnatal development

(see section 5.3). Based on animal

data the malformative risk is unlikely

in humans. The clinical data do not

raise safety concern but are very

limited.

Lactation

It is not known whether etravirine is

excreted in human milk. Because of both

the potential for HIV transmission and

the potential for adverse events in

nursing infants, mothers should be

instructed not to breastfeed if they are

receiving INTELENCE.

As a general rule, it is recommended

that mothers infected by HIV do not

breast-feed their babies under any

circumstances in order to avoid

transmission of HIV.

Effects on ability to

drive and use

machines

No studies on the effects of

INTELENCE on the ability

to drive or operate machines

have been performed. There

is no evidence that

INTELENCE may alter the

patient’s ability to drive and

operate machines, however,

the adverse drug reaction

profile of INTELENCE

should be taken into account

(see section 4.8).

No studies on the effects of

INTELENCE on the ability to drive or

operate machines have been performed.

There is no evidence that INTELENCE

may alter the patient’s ability to drive

and operate machines, however, the

adverse drug reaction profile of

INTELENCE should be taken into

account (see section 4.8).

INTELENCE has no or negligible

influence on the ability to drive and

use machines. Adverse drug

reactions such as somnolence and

vertigo have been reported in

INTELENCE treated subjects at

incidences similar to placebo (see

section 4.8). There is no evidence

that INTELENCE may alter the

patient’s ability to drive and operate

machines, however, the adverse drug

reaction profile should be taken into

account.

4.9

Overdose

There are no data with regard to

symptomatic overdose with

INTELENCE, but it is possible that

the most frequent ADRs of

INTELENCE, i.e. rash, diarrhoea,

nausea, and headache would be the

most common symptoms noted.

There is no specific antidote for

overdose with INTELENCE. Human

experience of overdose with

INTELENCE is limited. Treatment of

overdose with INTELENCE consists of

general supportive measures including

monitoring of vital signs and

observation of the clinical status of the

patient. If indicated, elimination of

unabsorbed active substance is to be

achieved by emesis or gastric lavage.

Administration of activated charcoal

may also be used to aid in removal of

unabsorbed active substance. Since

etravirine is highly protein bound,

dialysis is unlikely to result in

significant removal of the active

substance.

4.8

Undesirable

effects

Adverse Drug Reactions from Clinical Trials

The safety assessment is based on all data from 1203 patients in the Phase III

placebo-controlled trials DUET-1 and DUET-2 in antiretroviral treatment-experienced HIV-1

infected adult patients, 599 of whom received INTELENCE (200 mg b.i.d.) (see section 5.1).

In these pooled trials, the median exposure for patients in the INTELENCE arm and placebo

arm was 52.3 and 51.0 weeks, respectively.

The most frequently reported adverse drug reactions (ADRs) (≥ 5%) that were at least grade 2

in severity were rash (10.0% in the INTELENCE arm and 3.5% in the placebo arm),

diarrhoea (7.0% in the INTELENCE arm and 11.3% in the placebo arm),

hypertriglyceridaemia (6.3% in the INTELENCE arm and 4.3% in the placebo arm) and

nausea (5.2% in the INTELENCE arm and 4.8% in the placebo arm) (see table below).

The majority of the ADRs reported during treatment with INTELENCE were grade 1 to 2 in

severity. Grade 3 or 4 ADRs were reported in 22.2% and 17.2% of the INTELENCE and

placebo treated patients, respectively. The most commonly reported grade 3 or 4 ADRs were

hypertriglyceridaemia (4.2% in the INTELENCE arm and 2.3% in the placebo arm),

hypercholesterolaemia (2.2% in the INTELENCE arm and 2.3% in the placebo arm), renal

failure (2.0% in the INTELENCE arm and 1.2% in the placebo arm) and anaemia (1.7% in

the INTELENCE arm and 1.3% in the placebo arm). For treatment emergent clinical

laboratory abnormalities (grade 3 or 4) reported in greater than or equal to 2% of

INTELENCE treated patients, see table “Treatment Emergent Laboratory Abnormalities”. All

other grade 3 and/or 4 ADRs were reported in less than 1.5% of the INTELENCE treated

patients. 5.2% of patients in the INTELENCE arm discontinued treatment due to ADRs

compared to 2.6% of patients in the placebo arm. The most common ADR leading to

discontinuation was rash (2.2% in the INTELENCE arm versus 0% in the placebo arm).

The most frequently reported adverse drug reactions (ADRs) (incidence ≥ 10% in the

INTELENCE arm) of all intensities occurring in the Phase III studies were rash

(19.2% in the INTELENCE arm versus 10.9% in the placebo arm), diarrhoea (18.0%

in the INTELENCE arm versus 23.5% in the placebo arm), nausea (14.9% in the

INTELENCE arm versus 12.7% in the placebo arm) and headache (10.9% in the

INTELENCE arm versus 12.7% in the placebo arm). The rates of discontinuation due

to any adverse reaction were 7.2% in patients receiving INTELENCE and 5.6% in

patients receiving placebo. The most common ADR leading to discontinuation was

rash (2.2% in the INTELENCE arm versus 0% in the placebo arm).

Rash was most frequently mild to moderate, generally macular to maculopapular or

erythematous, mostly occurred in the second week of therapy and was infrequent after

week 4. Rash was mostly self-limiting and generally resolved within 1-2 weeks on continued

therapy (see section 4.4). The incidence of rash was higher in women compared to men in the

INTELENCE arm in the DUET trials (rash ≥ Grade 2 was reported in 9/60 [15.0%] women

versus 51/539 [9.5%] men; discontinuations due to rash were reported in 3/60 [5.0%] women

versus 10/539 [1.9%] men) (see section 4.4). In patients with a history of NNRTI-related rash,

there was no apparent increased risk for the development of INTELENCE-related rash

compared to patients without a history of NNRTI-related rash.

There was no gender difference in severity or treatment discontinuation due to rash.

The clinical data are limited and an increased risk of cutaneous reactions in patients

with a history of NNRTI-associated cutaneous reaction cannot be excluded (see

section 4.4).

Tabulated list of adverse reactions

ADRs of moderate intensity or greater (≥ grade 2) reported in patients treated with

INTELENCE are summarised in table 2 (background regimen is indicated as “BR”).

Laboratory abnormalities considered ADRs are included in a paragraph below table 2.

The ADRs are listed by system organ class (SOC) and frequency. Within each

frequency grouping, ADRs are presented in order of decreasing seriousness.

Frequencies are defined as very common (≥ 1/10), common (≥ 1/100 to < 1/10) and

uncommon (≥ 1/1,000 to < 1/100). Rare and very rare ADRs cannot be detected based

on the number of patients included in the DUET trials.

Table 2: DUET-1 and DUET-2 trials

System Organ Class

(SOC)

Frequency

Category

ADRs (INTELENCE + BR versus Placebo +

BR)

Blood and lymphatic

system disorders

common

thrombocytopaenia (1.3% vs 1.5%), anaemia (4.0%

vs 3.8%)

Immune system

disorders

uncommon

immune reconstitution syndrome (0.2% vs 0.3%),

drug hypersensitivity (0.8% vs 1.2%)

Metabolism and

nutrition disorders

common

diabetes mellitus (1.3% vs 0.2%), hyperglycaemia

(1.5% vs 0.7%), hypercholesterolaemia (4.3% vs

3.6%), hypertriglyceridaemia (6.3% vs 4.3%),

hyperlipidaemia (2.5% vs 1.3%)

uncommon

anorexia (0.8% vs 1.5%), dyslipidaemia (0.8% vs

0.3%)

Psychiatric disorders

common

anxiety (1.7% vs 2.6%), insomnia (2.7% vs 2.8%)

uncommon

confusional state (0.2% vs 0.2%), disorientation

(0.2% vs 0.3%), nightmares (0.2% vs 0.2%), sleep

disorders (0.5% vs 0.5%), nervousness (0.2% vs

0.3%), abnormal dreams (0.2% vs 0.2%)

Nervous system

disorders

common

peripheral neuropathy (3.8% vs 2.0%), headache

(3.0% vs 4.5%)

uncommon

convulsion (0.5% vs 0.7%), syncope (0.3% vs

0.3%), amnesia (0.3% vs 0.5%), tremor (0.2% vs

0.3%), somnolence (0.7% vs 0.5%), paraesthesia

(0.7% vs 0.7%), hypoaesthesia (0.5% vs 0.2%),

hypersomnia (0.2% vs 0%), disturbance in

attention (0.2% vs 0.2%)

Eye disorders

uncommon

blurred vision (0.7% vs 0%)

Ear and labyrinth

disorders

uncommon

vertigo (0.2% vs 0.5%)

Cardiac disorders

common

myocardial infarction (1.3% vs 0.3%)

uncommon

atrial fibrillation (0.2% vs 0.2%), angina pectoris

(0.5% vs 0.3%)

Vascular disorders

common

hypertension (3.2% vs 2.5%)

Respiratory, thoracic

and mediastinal

disorders

uncommon

bronchospasm (0.2% vs 0%), exertional dyspnoea

(0.5% vs 0.5%)

Gastrointestinal

disorders

common

gastrooesophageal reflux disease (1.8% vs 1.0%),

diarrhoea (7.0% vs 11.3%), vomiting (2.8% vs

2.8%), nausea (5.2% vs 4.8%), abdominal pain

(3.5% vs 3.1%), flatulence (1.5% vs 1.0%),

gastritis (1.5% vs 1.0%)

uncommon

pancreatitis (0.7% vs 0.3%), haematemesis (0.2%

vs 0%), stomatitis (0.2% vs 0.2%), constipation

(0.3% vs 0.5%), abdominal distension (0.7% vs

1.0%), dry mouth (0.3% vs 0%), retching (0.2% vs

0%)

Hepatobiliary

disorders

uncommon

hepatitis (0.2% vs 0.3%), hepatic steatosis (0.3% vs

0%), cytolytic hepatitis (0.3% vs 0%),

hepatomegaly (0.5% vs 0.2%)

Skin and

subcutaneous tissue

disorders

very

common

rash (10.0% vs 3.5%)

common

night sweats (1.0% vs 1.0%)

uncommon

swelling face (0.3% vs 0%), hyperhidrosis (0.5%

vs 0.2%), prurigo (0.7% vs 0.5%), dry skin (0.3%

vs 0.2%)

Renal and urinary

disorders

common

renal failure (2.7% vs 2.0%)

Reproductive system

and breast disorders

uncommon

gynaecomastia (0.2% vs 0%)

General disorders and

administration site

conditions

common

fatigue (3.5% vs 4.6%)

uncommon

sluggishness (0.2% vs 0%)

Additional ADRs of at least moderate intensity observed in other trials were

angioneurotic oedema, erythema multiforme and haemorrhagic stroke, each reported

in no more than 0.5% of patients. Stevens-Johnson Syndrome (rare; < 0.1%) and toxic

epidermal necrolysis (very rare; < 0.01%) have been reported during clinical

development with INTELENCE.

Laboratory abnormalities

Treatment emergent clinical laboratory abnormalities (grade 3 or 4), considered

ADRs, reported in ≥ 2% of patients in the INTELENCE arm versus the placebo arm,

respectively, were increases in amylase (8.9% vs 9.4%), creatinine (2.0% vs 1.7%),

lipase (3.4% vs 2.6%), total cholesterol (8.1% vs 5.3%), low density lipoprotein

(LDL) (7.2% vs 6.6%), triglycerides (9.2% vs 5.8%), glucose (3.5% vs 2.4%), alanine

aminotransferase (ALT) (3.7% vs 2.0%), aspartate amino transferase (AST) (3.2% vs

2.0%) and decreases in neutrophils (5.0% vs 7.4%) and white blood cell count (2.0%

vs 4.3%).

Description of selected adverse reactions

Metabolic parameters

Weight and levels of blood lipids and glucose may increase during antiretroviral

therapy (see section 4.4)

Immune reconstitution syndrome

In HIV infected patients with severe immune deficiency at the time of initiation of

combination antiretroviral therapy (CART), an inflammatory reaction to

asymptomatic or residual opportunistic infections may arise. Autoimmune disorders

(such as Graves' disease) have also been reported; however, the reported time to onset

is more variable and these events can occur many months after initiation of treatment

(see section 4.4).

Osteonecrosis

Cases of osteonecrosis have been reported, particularly in patients with generally

acknowledged risk factors, advanced HIV disease or long-term exposure to

combination antiretroviral therapy. The frequency of this is unknown (see

section 4.4).

Other special populations

Patients co-infected with hepatitis B and/or hepatitis C virus

In the pooled analysis for DUET-1 and DUET-2, the incidence of hepatic events

tended to be higher in co-infected subjects treated with INTELENCE compared to

co-infected subjects in the placebo group. INTELENCE should be used with caution

in these patients (see also sections 4.4 and 5.2).

Adverse drug reactions identified through post marketing experience with

INTELENCE

Hypersensitivity reactions, including DRESS, have been reported with INTELENCE.

These hypersensitivity reactions were characterised by rash, fever and sometimes

organ involvement (including, but not limited to, severe rash or rash accompanied by

fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions,

conjunctivitis, hepatitis and eosinophilia) (see section 4.4).

Reporting suspected adverse reactions after authorisation of the medicinal product is

important. It allows continued monitoring of the benefit/risk balance of the medicinal

product.

Any suspected adverse events should be reported to the Ministry of Health according

to the National Regulation by using an online form

http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=Adve

rsEffectMedic@moh.gov.il

ADRs of moderate intensity or greater (

grade 2) and reported in

1% of patients treated

with INTELENCE are summarised in the table below. The ADRs are listed by system organ

class (SOC) and frequency. Laboratory abnormalities considered ADRs are included in a

table below (see Treatment Emergent Grade 3 to 4 Laboratory Abnormalities Reported in

≥ 2% of Patients).

ADRs of moderate intensity or greater (≥ grade 2) and reported in ≥ 1% of adult

patients treated with INTELENCE

DUET-1 and DUET-2 Trials

System Organ Class (SOC)

Adverse Drug Reaction

INTELENCE + BR

N=599

Placebo + BR

N=604

Cardiac disorders

Myocardial infarction

1.3%

0.3%

Blood and lymphatic system

disorders

Anaemia

4.0%

3.8%

Thrombocytopaenia

1.3%

1.5%

Nervous system disorders

Peripheral neuropathy

3.8%

2.0%

Headache

3.0%

4.5%

Gastrointestinal disorders

Diarrhoea

7.0%

11.3%

Nausea

5.2%

4.8%

Abdominal pain

3.5%

3.1%

Vomiting

2.8%

2.8%

Gastroesophageal reflux disease

1.8%

1.0%

Flatulence

1.5%

1.0%

Gastritis

1.5%

1.0%

Renal and urinary disorders

Renal failure

2.7%

2.0%

Skin and subcutaneous tissue

disorders

Rash

10.0%

3.5%

Lipohypertrophy

1.0%

0.3%

Night sweats

1.0%

1.0%

Metabolism and nutrition disorders

Hypertriglyceridaemia

6.3%

4.3%

Hypercholesterolaemia

4.3%

3.6%

Hyperlipidaemia

2.5%

1.3%

Hyperglycaemia

1.5%

0.7%

Diabetes mellitus

1.3%

0.2%

Vascular disorders

Hypertension

3.2%

2.5%

General disorders and

administration site conditions

Fatigue

3.5%

4.6%

Psychiatric disorders

Insomnia

2.7%

2.8%

Anxiety

1.7%

2.6%

Treatment emergent ADRs of moderate intensity or greater (

grade 2) and occurring in less

than 1% of patients receiving INTELENCE were:

cardiac disorders: angina pectoris, atrial fibrillation

nervous system disorders: paraesthesia, somnolence, convulsion, hypoaesthesia,

amnesia, syncope, disturbance in attention, hypersomnia, tremor

eye disorders: blurred vision

ear and labyrinth disorders: vertigo

respiratory, thoracic and mediastinal disorders: exertional dyspnoea, bronchospasm

gastrointestinal disorders: abdominal distension, pancreatitis, constipation, dry mouth,

haematemesis, retching, stomatitis

skin and subcutaneous tissue disorders: prurigo, hyperhidrosis, dry skin, swelling face

metabolism and nutrition disorders: anorexia, dyslipidaemia

general disorders and administration site conditions: sluggishness

immune system disorders: drug hypersensitivity, immune reconstitution syndrome

hepatobiliary disorders: hepatomegaly, cytolytic hepatitis, hepatic steatosis, hepatitis

reproductive system and breast disorders: gynaecomastia

psychiatric disorders: sleep disorders, abnormal dreams, confusional state,

disorientation, nervousness, nightmares

Additional ADRs of at least moderate intensity observed in other trials were acquired

lipodystrophy, angioneurotic edema, erythema multiforme and haemorrhagic stroke, each

reported in no more than 0.5% of patients. Stevens-Johnson Syndrome (rare; < 0.1%) and

toxic epidermal necrolysis (very rare; < 0.01%) have been reported during clinical

development with INTELENCE.

Laboratory abnormalities

Treatment emergent clinical laboratory abnormalities (grade 3 or 4), considered ADRs,

reported in ≥ 2% of INTELENCE treated patients are shown in the table below.

Treatment emergent grade 3 to 4 laboratory abnormalities reported in ≥ 2% of patients

Pooled DUET-1 and DUET-2

Trials

Laboratory Parameter

Preferred Term, n (%)

DAIDS Toxicity

Range

INTELENCE +

BR N=599

Placebo + BR

N=604

GENERAL BIOCHEMISTRY

Pancreatic Amylase

53 (8.9)

57 (9.4)

grade 3

> 2-5 x ULN

44 (7.4)

51 (8.4)

grade 4

> 5 x ULN

9 (1.5)

6 (1.0)

Creatinine

12 (2.0)

10 (1.7)

grade 3

> 1.9-3.4 x ULN

12 (2.0)

9 (1.5)

grade 4

> 3.4 x ULN

0 (0)

1 (0.2)

Lipase

20 (3.4)

16 (2.6)

grade 3

> 3-5 x ULN

12 (2.0)

13 (2.2)

grade 4

> 5 x ULN

8 (1.3)

3 (0.5)

GENERAL HEMATOLOGY

White blood cell count

12 (2.0)

26 (4.3)

grade 3

1.0-1.499 giga/l

1,000-1,499/mm

6 (1.0)

22 (3.6)

grade 4

< 1.0 giga/l

< 1,000/mm

6 (1.0)

4 (0.7)

HEMATOLOGY DIFFERENTIAL COUNTS

Neutrophils

30 (5.1)

45 (7.5)

grade 3

0.5-0.749 giga/l

500-749/mm

21 (3.5)

26 (4.3)

grade 4

< 0.5 giga/l

< 500/mm

9 (1.5)

19 (3.1)

LIPIDS AND GLUCOSE

Total cholesterol

48 (8.1)

32 (5.3)

grade 3

> 7.77 mmol/l

> 300 mg/dl

48 (8.1)

32 (5.3)

Low density lipoprotein

42 (7.2)

39 (6.6)

grade 3

> 4.9 mmol/l

> 190 mg/dl

42 (7.2)

39 (6.6)

Triglycerides

55 (9.2)

35 (5.8)

grade 3

8.49-13.56 mmol/l

751 - 1200 mg/dl

34 (5.7)

24 (4.0)

grade 4

> 13.56 mmol/l

> 1200 mg/dl

21 (3.5)

11 (1.8)

Elevated Glucose Levels

21 (3.5)

14 (2.3)

grade 3

13.89-27.75 mmol/l

251–500 mg/dl

21 (3.5)

13 (2.2)

grade 4

> 27.75 mmol/l

> 500 mg/dl

0 (0)

1 (0.2)

HEPATIC PARAMETERS

Alanine amino transferase

22 (3.7)

12 (2.0)

grade 3

5.1-10 x ULN

16 (2.7)

10 (1.7)

grade 4

> 10 x ULN

6 (1.0)

2 (0.3)

Aspartate amino transferase

19 (3.2)

12 (2.0)

grade 3

5.1-10 x ULN

16 (2.7)

10 (1.7)

grade 4

> 10 x ULN

3 (0.5)

2 (0.3)

ULN=Upper Limit of Normal

Lipodystrophy

Combination antiretroviral therapy has been associated with redistribution of body fat

(lipodystrophy) in HIV infected patients, including loss of peripheral and facial subcutaneous

fat, increased intra-abdominal and visceral fat, breast hypertrophy and dorsocervical fat

accumulation (buffalo hump) (see section 4.4).

Immune Reconstitution Syndrome

In HIV infected patients with severe immune deficiency at the time of initiation of

combination antiretroviral therapy (CART), an inflammatory reaction to asymptomatic or

residual opportunistic infections may arise (immune reconstitution syndrome). Autoimmune

disorders such as Graves’ disease have also been reported in the context of Immune

Reconstitution syndrome , the reported time to onset is more variable and these events can

occur many months after initiation of treatment. (see section 4.4).

Osteonecrosis

Cases of osteonecrosis have been reported, particularly in patients with generally

acknowledged risk factors, advanced HIV disease or long-term exposure to combination

antiretroviral therapy. The frequency of this is unknown (see section 4.4).

Additional information on special populations

Patients co-infected with hepatitis B and/or hepatitis C virus

Among co-infected patients (n=139) in the pooled analysis for DUET-1 and DUET-2, grade 3

or 4 elevations in AST developed in 9.7% of the 72 patients in the INTELENCE arm and in

6.0% of the 67 patients in the placebo arm and grade 3 or 4 elevations in ALT developed in

11.1% of patients in the INTELENCE arm and in 7.5% of patients in the placebo arm. Among

co-infected patients, 1.4% of those treated with INTELENCE and 3.0% in the placebo arm

discontinued because of liver or biliary system disorders. Standard clinical monitoring of

patients with chronic hepatitis is considered adequate.

Adverse Drug Reactions Identified During Postmarketing Experience with INTELENCE

Immune system disorders

Hypersensitivity reactions including DRESS (Drug Rash with Eosinophilia and Systemic

Symptoms) have been reported and were characterized by rash, constitutional findings, and

infrequently organ dysfunction, including hepatic failure (see section 4.4).

Musculoskeletal and connective tissue disorders

Rhabdomyolysis

ב"צמ נמוסמ ובש ,ןולעה תושקובמה תורמחהה תו בוהצ עקר לע

( ונמוס תורמחה רדגב םניאש םייוניש ןולעב ל שי .הנוש עבצב ) םוקימב םייוניש אלו יתוהמ ןכות קר ןמס .טסקטה

.........ךיראתב ינורטקלא ראודב רבעוה

1.2.16

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