KIVEXA 300 mg/600 mg Film-Coated Tablets

Зміст інструкції

1. Kivexa 600 mg/300 mg film-coated tablets
   1. What is Kivexa and what is it used for
   2. What you need to know before taking Kivexa
   3. How to take Kivexa
   4. Possible side effects
   5. How to store Kivexa
   6. Package Contents and Other Information

Kivexa 600 mg/300 mg film-coated tablets

abacavir/lamivudine

Read this leaflet carefully before taking this medicine as it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others, even if their symptoms are the same as yours, as it could be harmful.
• If any side effects occur, including those not listed in this leaflet, tell your doctor or pharmacist immediately. See section 4.

IMPORTANT — Hypersensitivity Reactions
Kivexa contains abacavir(which is also the active substance contained in medicines such as Trizivir,
Triumeqand Ziagen). Some people taking abacavir may develop a hypersensitivity
reaction(a serious allergic reaction) which can be life-threatening if they continue to
take medicines containing abacavir.

Read carefully all the information provided in ‘Hypersensitivity Reactions’ in the boxed
section of paragraph 4.
The Kivexa pack includes a Warning Cardto remind you and healthcare professionals
of your abacavir hypersensitivity. Remove this card and carry it with you at all times.
Contents of this leaflet:

• 1. What Kivexa is and what it is used for
• 2. What you need to know before you take Kivexa
• 3. How to take Kivexa
• 4. Possible side effects
• 5. How to store Kivexa
• 6. Contents of the pack and other information

1. What is Kivexa and what is it used for

Kivexa is used to treat HIV (Human Immunodeficiency Virus) infection in adults,
adolescents and children weighing at least 25 kg.
Kivexa contains two active ingredients used in the treatment of HIV infection:
abacavir and lamivudine. These medicines belong to a group of antiretroviral drugs
called nucleoside reverse transcriptase inhibitors (NRTIs).
Kivexa does not completely cure HIV infection; it reduces the viral load in the body and keeps it
at low levels. It also increases the number of CD4 cells in the blood. CD4 cells are
a type of white blood cells that are important in helping the body fight infection.
Not all people respond to treatment with Kivexa in the same way. The doctor will monitor
the effectiveness of the treatment.

2. What you need to know before taking Kivexa

Do not take Kivexa:

• if you are allergic( hypersensitive) to abacavir (or to any other medicine containing abacavir -

for example Trizivir, Triumeqor Ziagen), to lamivudine or to any of the other ingredients of this medicine (listed in section 6).

Read carefully all the information on hypersensitivity reactions in section 4.
Consult your doctorif you think this applies to you. Do not take Kivexa.
Take special care with Kivexa
Some people taking Kivexa or other combination therapies for the treatment of HIV are at a higher risk of serious side effects. You need to be aware of these additional risks:

• if you have moderate or severe liver disease
• if you have had liver diseaseincluding hepatitis B or C (if you have hepatitis B infection do not stop taking Kivexa without consulting your doctor as hepatitis may return)
• if you are severely overweight(especially if you are a woman)
• if you have a kidney problem

Tell your doctor if any of these situations apply to you before using Kivexa.
You may need further checks, including blood tests, while you are taking the medicine. See section 4 for further information.
Hypersensitivity reactions to abacavir
Even patients who do not have the HLA-B*5701 gene can still develop a hypersensitivity reaction(a severe allergic reaction).

Read carefully all the information on hypersensitivity reactions in Section 4 of
this leaflet.
Risk of cardiovascular events
It cannot be excluded that abacavir may be associated with an increased risk of cardiovascular events.

Tell your doctorif you have cardiovascular problems, are a smoker or suffer from conditions that increase the risk of cardiovascular disease such as high blood pressure or diabetes.
Do not stop taking Kivexa unless this is recommended by your doctor.

Pay attention to important symptoms
Some people taking medicines for HIV infection develop other diseases that can be serious. You need to be informed about important signs and symptoms so that you can pay attention while taking Kivexa.

Read the information in ‘Other possible side effects of combination therapy for
HIV’ in Section 4 of this leaflet.
Other medicines and Kivexa
Tell your doctor or pharmacist if you are taking any other medicines, or if you have taken any recently, including herbal medicines or other medicines you bought without a prescription.
Remember to tell your doctor or pharmacist if you start taking a new medicine during treatment with Kivexa.

These medicines must not be taken with Kivexa:

• emtricitabine for treating HIV infection
• other medicines containing lamivudine used to treat HIV infectionor hepatitis B virus infection
• high doses of trimethoprim/sulfamethoxazole,an antibiotic
• cladribine, used to treat hairy cell leukemia.

Tell your doctorif you are being treated with any of these medicines.

Some medicines interact with Kivexa
These include:

• phenytoinfor treating epilepsy. Tell your doctorif you are taking phenytoin. Your doctor may need to monitor you while you are taking Kivexa.
• methadone,used as a heroin substitute.Abacavir increases the speed at which methadone is eliminated from the body. If you are taking methadone you will be monitored for any symptoms of withdrawal. It may be necessary to change the dose of methadone. Tell your doctorif you are taking methadone.
• medicines (usually liquid) containing sorbitol and other sweeteners(such as xylitol, mannitol, lactitol or maltitol), if taken regularly. Tell your doctor or pharmacistif you are taking any of these.
• riociguat, for the treatment of high blood pressure in the blood vessels(pulmonary arteries) that carry blood from the heart to the lungs. Your doctor may need to reduce the dose of riociguat, as abacavir can increase the levels of riociguat in the blood.

Pregnancy
The use of Kivexa during pregnancy is not recommended.Kivexa and similar medicines can cause unwanted effects in unborn babies.
If you have already taken Kivexa during pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of the baby. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV outweighed the risk of side effects.

Breastfeeding
Breastfeeding is not recommendedfor HIV-positive women as HIV infection can be transmitted to the baby through breast milk. A small amount of the ingredients of Kivexa can also pass into breast milk.
If you are breastfeeding or are thinking about breastfeeding you should talk to your doctor as soon as possible.
Driving and using machines
Kivexa can cause side effects that may affect your ability to drive and use machines.

Talk to your doctorabout your ability to drive and use machines while taking Kivexa.

Important information about some of the excipients in Kivexa tablets
Kivexa contains a colouring agent called sunset yellow (E110) which may cause allergic reactions in some individuals.
This medicine contains less than 1 mmol (23 mg) of sodium per dose, i.e. it is essentially ‘sodium-free’.

3. How to take Kivexa

Always take this medicine exactly as your doctor has told you. Check with your
doctor or pharmacist if you are not sure.

The recommended dose of Kivexa in adults, adolescents and children weighing 25 kg or
more is one tablet once a day.
Swallow the tablets whole with water. Kivexa can be taken with or without food.

Stay in constant contact with your doctor
Kivexa helps to control the disease. You need to take it every day to prevent the disease
from getting worse. You may still develop other infections and diseases related to HIV infection.

Stay in contact with your doctor,anddo not stop taking Kivexawithout your doctor’s advice.

If you take more Kivexa than you should
If you accidentally take more Kivexa, tell your doctor or pharmacist or contact the Emergency Room
of the nearest hospital for further advice.

If you forget to take Kivexa
If you forget to take a dose, take it as soon as you remember. Then continue your
treatment as before. Do not take a double dose to make up for a missed dose.
It is important to take Kivexa regularly as taking it at irregular intervals may increase
the risk of having a hypersensitivity reaction.

If you stop taking Kivexa
If you have stopped taking Kivexa for any reason - in particular because you thought you had
undesirable effects or because you had other diseases:

talk to your doctor before starting to take it again.Your doctor will check if the symptoms
were related to a hypersensitivity reaction. If your doctor thinks that these symptoms
may have been related to a hypersensitivity reaction, you will be told to never take
Kivexa or any other medicine containing abacavir again (for example Trizivir,
Triumeq or Ziagen). It is important that you follow this advice.
If your doctor advises you to start taking Kivexa again, you will be asked to take the first doses
in a place where you will be able to receive, if necessary, medical assistance.

4. Possible side effects

During HIV therapy, an increase in weight and levels of lipids and glucose in the blood may occur.
This is partly related to the restoration of health and lifestyle, and in the case of blood lipids, sometimes to the HIV medications themselves. The doctor will check for these changes.
Like all medicines, this medicine can cause side effects, although not everyone will experience them.
During HIV treatment, it may be difficult to tell whether a symptom is a side effect of Kivexa or other medicines you are taking, or an effect of the HIV disease itself. For this reason, it is very important to inform your doctor about any changes in your health.
Even patients who do not have the HLA-B*5701 gene can still develop a hypersensitivity reaction(a severe allergic reaction), described in this leaflet in a section entitled ‘Hypersensitivity reactions’.

It is very important to read and understand the information about this serious reaction.
During combination therapy for HIV, both the side effects listed below for Kivexaand other illnesses may occur.
It is important to read the information in another part of this leaflet under ‘Other possible side effects of combination therapy for HIV’.

Hypersensitivity reactions
Kivexacontains abacavir(which is also the active ingredient contained in medicines such as Trizivir, Triumeqand Ziagen). Abacavir can cause a severe allergic reaction known as a hypersensitivity reaction. These hypersensitivity reactions have been observed more frequently in people who are taking medicines that contain abacavir.

Who is at risk of these reactions?
Anyone taking Kivexa could develop a hypersensitivity reaction to abacavir, which could be life-threatening if Kivexa continues to be taken.
You are more likely to develop this reaction if you have a gene called HLA-B*5701(but you can still have this reaction even if you do not have this type of gene). You will be tested to detect the presence of this gene before Kivexa is prescribed to you. If you know you have this type of gene, tell your doctor before taking Kivexa.
In a clinical study, out of 100 patients treated with abacavir who did not have the gene called HLA-B*5701, about 3 to 4 patients developed a hypersensitivity reaction.

What are the symptoms?
The most common symptoms are:

• feverand rash.

Other common symptoms are:

• nausea, vomiting, diarrhea, abdominal pain (stomach pain), severe fatigue.

Other symptoms include:
muscle or joint pain, swelling of the neck, shortness of breath, sore throat, cough, occasional headache, eye inflammation (conjunctivitis), mouth ulcers, low blood pressure, tingling or numbness in the hands or feet.

When do these reactions occur?
Hypersensitivity reactions can start at any time during treatment with Kivexa, but are more likely during the first 6 weeks of treatment.

Contact your doctor immediately:
1if you develop a rash, OR
2if you develop symptoms from at least 2 of the following groups:

• fever
• shortness of breath, sore throat or cough
• nausea or vomiting, diarrhea or abdominal pain
• severe fatigue or feeling unwell, or a general feeling of being sick.

Your doctor may recommend that you stop taking Kivexa.
If you have stopped taking Kivexa
If you have stopped taking Kivexa due to a hypersensitivity reaction, you MUST NEVER take Kivexa again, or any other medicine containing abacavir (e.g. Trizivir, Triumeq or Ziagen).If this happens, your blood pressure could drop dangerously within hours, which could be fatal.
If you have stopped taking Kivexa for any reason - in particular because you thought you had side effects or other illnesses:

talk to your doctor before starting to take it again.The doctor will check if the symptoms were related to a hypersensitivity reaction. If the doctor thinks that these symptoms may have been related to a hypersensitivity reaction, you will be told not to ever take Kivexa or any other medicine containing abacavir (e.g. Trizivir, Triumeq or Ziagen) again. It is important that you follow this advice.
Hypersensitivity reactions have sometimes occurred in patients who started taking medicines containing abacavir again, but who had also reported only one of the symptoms described in the Alert Card before stopping the medicine.
Very rarely, patients who had previously taken medicines containing abacavir without any symptoms of hypersensitivity, have then developed a hypersensitivity reaction when they started taking these medicines again.
If your doctor recommends starting to take Kivexa again, you will be asked to take the first doses in a place where you will be able to receive medical help if necessary.

If you are hypersensitive to Kivexa, you must return all unused Kivexa tablets for safe disposal.Ask your doctor or pharmacist for advice.
The Kivexa pack includes an Alert Cardto remind you and healthcare professionals about hypersensitivity reactions. Detach this card and keep it with you at all times.
Common side effects
These may affect up to 1 in 10patients:

• hypersensitivity reaction
• headache
• vomiting
• nausea
• diarrhea
• stomach pains
• loss of appetite
• fatigue, lack of energy
• fever (high temperature)
• general feeling of being unwell
• sleep disorders (insomnia)
• muscle discomfort and pain
• joint pain
• cough
• irritation of the nasal mucous membranes or runny nose
• rash
• hair loss

Uncommon side effects
These may affect up to 1 in 100patients and may be detected by blood tests:

• low number of red blood cells (anemia) or low number of white blood cells (neutropenia)
• increased liver enzymes
• reduction in the number of cells involved in blood clotting (thrombocytopenia)

Rare side effects
These may affect up to 1 in 1000patients:

• liver disorders such as jaundice, enlarged liver or fatty liver, inflammation (hepatitis)
• inflammation of the pancreas (pancreatitis)
• breakdown of muscle tissue

Rare side effects that may be detected by blood tests are:

• increased levels of an enzyme called amylase

Very rare side effects
These may affect up to 1 in 10,000patients:

• feeling of numbness or tingling in the skin (pins and needles)
• feeling of weakness in the arms and legs
• rash with blister-like formations resembling small targets (a dark spot in the center surrounded by a pale area with a black ring around the edge) (erythema multiforme)
• widespread rash with blisters and peeling of the skin, especially around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome) and a more severe form that causes the skin to peel off in more than 30% of the body surface (toxic epidermal necrolysis).
• lactic acidosis (excess lactic acid in the blood)

If you notice any of these symptoms, contact your doctor urgently.
A very rare side effect that may be detected by blood tests is:

• bone marrow failure to produce new red blood cells (pure red cell aplasia).

If you get side effects
Tell your doctor or pharmacistif any of the side effects gets serious or troublesome, or if you notice any side effects not listed in this leaflet.

Other possible side effects of combination therapy for HIV
Combination therapy such as Kivexa can cause the development of other illnesses during treatment for HIV.

Symptoms of infection and inflammation
Old infections can reactivate
People with advanced HIV infection (AIDS) have a weakened immune system and are more likely to develop serious infections (opportunistic infections). These infections may be “silent” and not detected by the weakened immune system before treatment begins. After treatment begins, the immune system becomes stronger and may react against infections causing symptoms of infection or inflammation. The symptoms generally include fever,plus some of the following symptoms:

• headache
• stomach pain
• difficulty breathing

In rare cases, as the immune system strengthens, it may also attack healthy tissues of the body (autoimmune disorders). The symptoms of autoimmune disorders can develop many months after starting to take medicine to treat HIV infection. The symptoms may include:

• palpitations (rapid or irregular heartbeat) or tremor
• hyperactivity (agitation and excessive movement)
• weakness starting in the hands and feet and spreading to the body. If you develop any symptoms of infectionand inflammation or if you notice any of the symptoms listed above: tell your doctor immediately. Do not take any other medicines for the infection without your doctor’s advice.

You may have problems with your bones
Some people taking combination antiretroviral therapy for HIV infection develop a condition called osteonecrosis. As a result of this disease, part of the bone tissue dies due to reduced blood flow to the bone. People may be more likely to develop this disease:

• if they have been taking combination therapy for a long period
• if they are also taking anti-inflammatory drugs called corticosteroids
• if they drink alcohol
• if their immune system is very weak
• if they are overweight.

Signs of osteonecrosis include:

• stiffness of the joints
• pain (especially in the hip, knee or shoulder)
• difficulty moving If you notice any of these symptoms: tell your doctor.

Reporting of side effects
If you get any side effects, even if not listed in this leaflet, tell your doctor or pharmacist. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Kivexa

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack. The expiry date refers to the last day of that month.
Do not store at a temperature above 30°C.
Do not dispose of any medicine in waste water or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package Contents and Other Information

What Kivexa contains
The active ingredients contained in each film-coated tablet of Kivexa are 600 mg of abacavir
(as sulfate) and 300 mg of lamivudine.
The excipients are microcrystalline cellulose, sodium starch glycolate and magnesium stearate in the core of the
tablet. The tablet coating contains Opadry Orange YS-1-13065-A which in turn contains
hypromellose, titanium dioxide, macrogol 400, polysorbate 80 and the colourant sunset yellow FCF (E110).

Description of Kivexa’s appearance and package contents
Kivexa film-coated tablets have ‘GS FC2’ imprinted on one side. They are orange in
colour, capsule-shaped and are supplied in blister packs containing 30 tablets and in
multiple blister packs containing 90 (3x30) tablets.

Marketing Authorisation Holder
ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, The Netherlands.

Manufacturer
Glaxo Wellcome S.A., Avenida de Extremadura 3, 09400 Aranda de Duero Burgos, Spain.
For further information on this medicinal product, contact the local representative of the marketing
authorisation holder.

Lietuva
ViiV Healthcare BV
Tel: + 370 80000334

България
ViiV Healthcare BV
Тел.: + 359 80018205

België/Belgique/Belgien
ViiV Healthcare srl/bv
Tél/Tel: + 32 (0) 10 85 65 00

Luxembourg/Luxemburg
ViiV Healthcare srl/bv
Belgique/Belgien
Tél/Tel: + 32 (0) 10 85 65 00

Česká republika
GlaxoSmithKline s.r.o.
Tel: + 420 222 001 111
[email protected]

Magyarország
ViiV Healthcare BV
Tel.: + 36 80088309

Danmark
GlaxoSmithKline Pharma A/S
Tlf: + 45 36 35 91 00
[email protected]

Malta
ViiV Healthcare BV
Tel: + 356 80065004

Deutschland
ViiV Healthcare GmbH
Tel.: + 49 (0)89 203 0038-10
[email protected]

Nederland
ViiV Healthcare BV
Tel: + 31 (0) 33 2081199

Eesti
ViiV Healthcare BV
Tel: + 372 8002640

Norge
GlaxoSmithKline AS
Tlf: + 47 22 70 20 00

Ελλάδα
GlaxoSmithKline Μονοπρόσωπη A.E.B.E.
Τηλ: + 30 210 68 82 100

Österreich
GlaxoSmithKline Pharma GmbH
Tel: + 43 (0)1 97075 0
[email protected]

España
Laboratorios ViiV Healthcare, S.L.
Tel: +34 900 923 501
[email protected]

Polska
GSK Services Sp. z o.o.
Tel.: + 48 (0)22 576 9000

France
ViiV Healthcare SAS
Tél.: + 33 (0)1 39 17 6969
[email protected]

Portugal
VIIVHIV HEALTHCARE,
UNIPESSOAL, LDA
Tel: + 351 21 094 08 01
[email protected]

Hrvatska
ViiV Healthcare BV
Tel: + 385 800787089

România
ViiV Healthcare BV
Tel: + 40800672524

Ireland
GlaxoSmithKline (Ireland) Limited
Tel: + 353 (0)1 4955000

Slovenija
ViiV Healthcare BV
Tel: + 40800672524

Ísland
Vistor hf.
Sími: +354 535 7000

Slovenská republika
ViiV Healthcare BV
Tel: + 421 800500589

Italia
ViiV Healthcare S.r.l
Tel: + 39 (0)45 7741600

Suomi/Finland
GlaxoSmithKline Oy
Puh/Tel: + 358 (0)10 30 30 30

Κύπρος
ViiV Healthcare BV
Τηλ: + 357 80070017

Sverige
GlaxoSmithKline AB
Tel: + 46 (0)8 638 93 00
[email protected]

Latvija
ViiV Healthcare BV
Tel: + 371 80205045

United Kingdom (Northern Ireland)
ViiV Healthcare BV
Tel: + 44 (0)800 221441
[email protected]
More detailed information on this medicinal product is available on the website of the European Medicines
Agency: http://www.ema.europa.eu

ANNEX IV
SCIENTIFIC CONCLUSIONS AND JUSTIFICATION FOR THE VARIATION OF THE TERMS
OF THE MARKETING AUTHORISATION
Scientific conclusions
Taking into account the assessment of the Pharmacovigilance and Risk Assessment Committee
(PRAC) of the Periodic Safety Update Report (PSUR) for abacavir / lamivudine, the scientific
conclusions of the PRAC are as follows:
In light of the available literature data on cardiovascular events relating to abacavir, including a
plausible mechanism of action, the PRAC considers that the warnings and precautions for use of
medicines containing abacavir should be reviewed to adequately reflect the current level of
information on cardiovascular events and, in line with current therapeutic guidelines, that a
recommendation should also be included in the product information discouraging the use of
medicines containing abacavir in patients at high cardiovascular risk. The PRAC concluded that the
product information for medicines containing abacavir / lamivudine should be amended accordingly.
After reviewing the PRAC recommendation, the Committee for Human Medicinal Products
(CHMP) agrees with the general conclusions and the reasons for the PRAC recommendation.

Justification for the variation of the terms of the marketing authorisation
Based on the scientific conclusions on abacavir / lamivudine, the CHMP considers that the benefit/risk
ratio of medicines containing abacavir / lamivudine remains unchanged, subject to the proposed changes
to the medicine information.
The CHMP recommends the variation of the terms of the marketing authorisation.