Kivexa - patient leaflet, side effects, dosage

1. What Kivexa is and what it is used for

Kivexa is used to treat HIV (human immunodeficiency virus) infection in adults, adolescents and in children weighing at least 25 kg.

Kivexa contains two active ingredients that are used to treat HIV infection: abacavir and lamivudine. These belong to a group of anti-retroviral medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Kivexa does not completely cure HIV infection; it reduces the amount of virus in your body, and keeps it at a low level. It also increases the CD4 cell count in your blood. CD4 cells are a type of white blood cells that are important in helping your body to fight infection.

Not everyone responds to treatment with Kivexa in the same way. Your doctor will monitor the effectiveness of your treatment.

2. What you need to know before you take Kivexa

Do not take Kivexa:

• if you are allergic (hypersensitive) to abacavir (or any other medicine containing abacavir — (e.g. Trizivir, Triumeq or Ziagen), lamivudine or any of the other ingredients of this medicine (listed in Section 6)

Carefully read all the information about hypersensitivity reactions in Section 4.

Check with your doctor if you think this applies to you. Do not take Kivexa

Take special care with Kivexa

Some people taking Kivexa or other combination treatments for HIV are more at risk of serious side effects. You need to be aware of the extra risks:

• if you have moderate or severe liver disease
• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B infection, do not stop Kivexa without your doctor’s advice, as your hepatitis may come back)
• if you are seriously overweight (especially if you are a woman)
• if you have a kidney problem

Talk to your doctor if any of these apply to you before using Kivexa. You may need extra check-ups, including blood tests, while you are taking your medicine. See Section 4 for more information.

Abacavir hypersensitivity reactions

Even patients who don’t have the HLA-B*5701 gene may still develop a hypersensitivity reaction (a serious allergic reaction)

Carefully read all the information about hypersensitivity reactions in Section 4 of this leaflet.

Risk of heart attack

It cannot be excluded that abacavir may increase the risk of having a heart attack.

Tell your doctor if you have heart problems, if you smoke, or have other illnesses that may increase your risk of heart disease such as high blood pressure, or diabetes. Do not stop taking Kivexa unless your doctor advises you to do so.

Look out for important symptoms

Some people taking medicines for HIV infection develop other conditions, which can be serious. You need to know about important signs and symptoms to look out for while you are taking Kivexa.

Read the information ‘Other possible side effects of combination therapy for HIV’ in Section 4 of this leaflet

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Protect other people

HIV infection is spread by sexual contact with someone who has the infection, or by transfer of infected blood (for example, by sharing injection needles). You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor the precautions needed to avoid infecting other people.

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 begin taking a new medicine while you are taking Kivexa.

These medicines should not be used with Kivexa:

• Emtricitabine, to treat HIV infection
• other medicinal products containing lamivudine, used to treat HIV infection or hepatitis B infection
• high doses of trimethoprim/sul­famethoxazole, an antibiotic
• cladribine, used to treat hairy cell leukaemia

Tell your doctor if you are being treated with any of these.

Some medicines interact with Kivexa

These include:

• phenytoin, for treating epilepsy.

Tell your doctor if 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 rate at which methadone is

removed from the body. If you are taking methadone, you will be checked for any withdrawal symptoms. Your methadone dose may need to be changed.

Tell your doctor if you are taking methadone.

• medicines (usually liquids) containing sorbitol and other sugar alcohols (such as xylitol, mannitol, lactitol or maltitol), if taken regularly.

Tell your doctor or pharmacist if you are taking any of these.

• Riociguat, for treating high blood pressure in the blood vessels (the pulmonary arteries)

that carry blood from the heart to the lungs. Your doctor may need to reduce your riociguat dose, as abacavir may increase riociguat blood levels.

Pregnancy

Kivexa is not recommended for use during pregnancy. Kivexa and similar medicines may cause side effects in unborn babies.

If you have taken Kivexa during your pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects.

Breast-feeding

Women who are HIV-positive must not breast-feed , because HIV infection can be passed on to the baby in breast milk. A small amount of the ingredients in Kivexa can also pass into your breast milk.

If you are breast-feeding, or thinking about breast-feeding:

Talk to your doctor immediately.

Driving and using machines

Kivexa may cause side effects which could affect your ability to drive or use machines.

Talk to your doctor about your ability to drive or operate machines while taking Kivexa.

Important information about some of the other ingredients of Kivexa tablets

Kivexa contains a colouring called sunset yellow (E110), this may cause allergic reactions in some people.

This medicine contains less than 1 mmol sodium (23 mg) per dosage unit, that is to say 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 for adults, adolescents and children weighing 25 kg or more is one tablet once a day.

Swallow the tablets whole, with some water. Kivexa can be taken with or without food.

Stay in regular contact with your doctor

Kivexa helps to control your condition. You need to keep taking it every day to stop your illness getting worse. You may still develop other infections and illnesses linked to HIV infection.

Keep in touch with your doctor, and do not stop taking Kivexa without your doctor’s advice.

If you take more Kivexa than you should

If you accidentally take too much Kivexa, tell your doctor or your pharmacist, or contact your nearest hospital emergency department 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 forgotten dose.

It is important to take Kivexa regularly, because if you take it at irregular intervals, you may be more likely to have a hypersensitivity reaction.

If you have stopped taking Kivexa

If you have stopped taking Kivexa for any reason — especially because you think you are having side effects, or because you have other illness:

Talk to your doctor before you start taking it again. Your doctor will check whether your symptoms were related to a hypersensitivity reaction. If the doctor thinks they may have been related, you will be told never again to take Kivexa, or any other medicine containing abacavir (e. g.Trizivir, Triumeq or Ziagen). It is important that you follow this advice.

If your doctor advises that you can start taking Kivexa again, you may be asked to take your first doses in a place where you will have ready access to medical care if you need it.

4. Possible side effects

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 the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.

Like all medicines, this medicine can cause side effects, although not everyone gets them.

When you are being treated for HIV, it can be hard 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. So it is very important to talk to your doctor about any changes in your health.

Even patients who don’t have the HLA-B*5701 gene may still develop a hypersensitivity reaction (a serious allergic reaction), described in this leaflet in the panel headed ‘Hypersensitivity reactions’.

It is very important that you read and understand the information about this serious reaction.

As well as the side effects listed below for Kivexa , other conditions can develop during combination therapy for HIV.

It is important to read the information later in this section under ‘Other possible side effects of combination therapy for HIV’.

Hypersensitivity reactions

Kivexa contains abacavir (which is also an active substance in medicines such as Trizivir, Triumeq and Ziagen ). Abacavir can cause a serious allergic reaction known as a hypersensitivity reaction. These hypersensitivity reactions have been seen more frequently in people taking medicines that contain abacavir.

Who gets these reactions?

Anyone taking Kivexa could develop a hypersensitivity reaction to abacavir, which could be life threatening if they continue to take Kivexa.

You are more likely to develop this reaction if you have a gene called HLA-B*5701 (but you can get a reaction even if you do not have this gene). You should have been tested for this gene before Kivexa was prescribed for you. If you know you have this gene, tell your doctor before you take Kivexa.

About 3 to 4 in every 100 patients treated with abacavir in a clinical trial who did not have the HLA-B*5701 gene developed a hypersensitivity reaction.

What are the symptoms?

The most common symptoms are:

• fever (high temperature) and skin rash.

Other common symptoms are:

• nausea (feeling sick), vomiting (being sick), diarrhoea, abdominal (stomach) pain, severe tiredness.

Other symptoms include:

Pains in the joints or muscles, swelling of the neck, shortness of breath, sore throat, cough, occasional headaches, inflammation of the eye (conjunctivitis), mouth ulcers, low blood pressure, tingling or numbness of the hands or feet.

When do these reactions happen?

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:

• 1 if you get a skin rash, OR

• 2 if you get symptoms from at least 2 of the following groups:

• – fever

• – shortness of breath, sore throat or cough

• – nausea or vomiting, diarrhoea or abdominal pain

• – severe tiredness or achiness, or generally feeling ill.

Your doctor may advise you to stop taking Kivexa.

If you have stopped taking Kivexa

If you have stopped taking Kivexa because of a hypersensitivity reaction, you must NEVER AGAIN take Kivexa, or any other medicine containing abacavir (e.g. Trizivir, Triumeq or Ziagen). If you do, within hours, your blood pressure could fall dangerously low, which could result in death.

If you have stopped taking Kivexa for any reason — especially because you think you are having side effects, or because you have other illness:

Talk to your doctor before you start again. Your doctor will check whether your symptoms were related to a hypersensitivity reaction. If the doctor thinks they may have been, you will then be told never again to take Kivexa, or any other medicine containing abacavir (e.g. Trizivir, Triumeq or Ziagen). It is important that you follow this advice.

Occasionally hypersensitivity reactions have developed in people who start taking abacavir containing products again, but who had only one symptom on the Alert Card before they stopped taking it.

Very rarely patients who have taken medicines containing abacavir in the past without any symptoms of hypersensitivity have developed a hypersensitivity reaction when they start taking these medicines again.

If your doctor advises that you can start taking Kivexa again, you may be asked to take your first doses in a place where you will have ready access to medical care if you need it.

If you are hypersensitive to Kivexa, return all your unused Kivexa tablets for safe disposal. Ask your doctor or pharmacist for advice.

The Kivexa pack includes an Alert Card , to remind you and medical staff about hypersensitivity reactions. Detach this card and keep it with you at all times.

Common side effects

These may affect up to 1 in 10 people:

• hypersensitivity reaction
• headache
• being sick (vomiting)
• feeling sick (nausea)
• diarrhoea
• stomach pains
• loss of appetite
• tiredness, lack of energy
• fever (high temperature)
• general feeling of being unwell
• difficulty in sleeping (insomnia)
• muscle pain and discomfort
• joint pain
• cough
• irritated or runny nose
• skin rash
• hair loss

Uncommon side effects

These may affect up to 1 in 100 people and may show up in blood tests:

• a low red blood cell count (anaemia) or low white blood cell count (neutropenia)
• an increase in the level of liver enzymes
• a decrease in the number of cells involved in blood clotting (thrombocytopenia).

Rare side effects

These may affect up to 1 in 1000 people:

• 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 show up in blood tests are:

• increase in an enzyme called amylase.

Very rare side effects

These may affect up to 1 in 10,000 people:

• numbness, tingly feelings in the skin (pins and needles)
• sensation of weakness in the limbs
• skin rash, which may form blisters and looks like small targets (central dark spots surrounded by a paler area, with a dark ring around the edge) (erythema multiforme)
• a widespread rash with blisters and peeling skin, particularly around the mouth, nose, eyes and genitals (Stevens-Johnson syndrome), and a more severe form causing skin peeling 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 a doctor urgently.

Very rare side effects that may show up in blood tests are:

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

If you get side effects

Tell your doctor or pharmacist if any of the side effects gets severe 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 may cause other conditions to develop during HIV treatment.

Symptoms of infection and inflammation

Old infections may flare up

People with advanced HIV infection (AIDS) have weak immune systems, and are more likely to develop serious infections (opportunistic infections ). Such infections may have been “silent” and not detected by the weak immune system before treatment was started. After starting treatment, the immune system becomes stronger, and may attack the infections, which can cause symptoms of infection or inflammation. Symptoms usually include fever , plus some of the following:

• headache
• stomach ache
• difficulty breathing

In rare cases, as the immune system becomes stronger, it can also attack healthy body tissue (autoimmune disorders ). The symptoms of autoimmune disorders may develop many months after you start taking medicine to treat your HIV infection. Symptoms may include:

• palpitations (rapid or irregular heartbeat) or tremor
• hyperactivity (excessive restlessness and movement)
• weakness beginning in the hands and feet and moving up towards the trunk of the body

If you get any symptoms of infection and inflammation or if you notice any of the symptoms above:

Tell your doctor immediately. Do not take other medicines for the infection without your doctor’s advice.

You may have problems with your bones

Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this condition, parts of the bone tissue die because of reduced blood supply to the bone. People may be more likely to get this condition:

• if they have been taking combination therapy for a long time
• if they are also taking anti-inflammatory medicines called corticosteroids
• if they drink alcohol
• if their immune systems are very weak
• if they are overweight.

Signs of osteonecrosis include:

• stiffness in the joints
• aches and pains (especially in the hip, knee or shoulder)
• difficulty moving.

5. How to store Kivexa

Keep this medicine out of the sight and reach of children.

Do not take this medicine after the expiry date shown on the carton. The expiry date refers to the last day of that month.

Do not store above 30°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Kivexa contains

The active substances in each Kivexa film-coated tablet are 600 mg of abacavir (as sulfate) and 300 mg of lamivudine.

The other ingredients are microcrystalline cellulose, sodium starch glycollate and magnesium stearate in the core of the tablet. The tablet coating contains Opadry Orange YS-1–13065-A containing hypromellose, titanium dioxide, macrogol 400, polysorbate 80 and sunset yellow FCF (E110).

What Kivexa looks like and contents of the pack

Kivexa film-coated tablets are engraved with ‘GS FC2’ on one side. They are orange and capsuleshaped and are provided in blister packs containing 30 tablets and multipack blister packs containing 90(3 × 30) tablets.

Marketing Authorisation Holder

ViiV Healthcare BV, Van Asch van Wijckstraat 55H, 3811 LP Amersfoort, Netherlands

Manufacturer

Glaxo Wellcome S.A., Avenida de Extremadura 3, 09400 Aranda de Duero Burgos, Spain.

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien

ViiV Healthcare srl/bv

Tél/Tel: + 32 (0) 10 85 65 00

Etnrapw«

ViiV Healthcare BV

Ten.: + 359 80018205

Česká republika

GlaxoSmithKline s.r.o.

Tel: + 420 222 001 111

Danmark

GlaxoSmithKline Pharma A/S

Tlf: + 45 36 35 91 00

Deutschland

ViiV Healthcare GmbH

Tel.: + 49 (0)89 203 0038–10

Eesti

ViiV Healthcare BV

Tel: + 372 8002640

E/./.áňa

GlaxoSmithKline Movonpôaœnn A.E.B.E.

T@ + 30 210 68 82 100

This leaflet was last revised in {MM/YYYY}

Detailed information on this medicine is available on the European Medicines Agency web site:

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