ZIAGEN 300 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Ziagen 300mg film-coated tablets

abacavir

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

IMPORTANT — Hypersensitivity Reactions

Ziagen contains abacavir(which is also an active substance in medicines such as Kivexa, Triumeqand Trizivir). Some people who take abacavir may develop a hypersensitivity reaction(a severe allergic reaction), which can be life-threatening if they continue to take medicines containing abacavir.

You must read the information under “Hypersensitivity reactions” in section 4 of this leaflet carefully.

The packaging of Ziagen includes an Information Cardto remind you and your healthcare professionals of abacavir hypersensitivity. You must take out this card and always carry it with you.

Contents of the package leaflet

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

1. What is Ziagen and what is it used for

Ziagen is used in the treatment of infection caused by the HIV (Human Immunodeficiency Virus).

Ziagen contains the active substance abacavir. Abacavir belongs to a group of antiretroviral medicines called nucleoside analogue reverse transcriptase inhibitors(NRTIs).

Ziagen 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 number of CD4 cells in your blood. CD4 cells are a type of white blood cell that plays an important role in helping your body fight infection.

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

2. What you need to know before you take Ziagen

Do not take Ziagen

• if you are allergic(hypersensitive)to abacavir (or to any other medicine that contains abacavir — such as Triumeq,Triziviror Kivexa) or to any of the other ingredients of this medicine (listed in section 6).

Read the information under “Hypersensitivity reactions” in section 4 of this leaflet carefully.

Consult your doctorif you think any of these apply to you.

Be especially careful with Ziagen

Some people who take Ziagen for HIV have a higher risk of getting serious side effects. You need to know that there is a higher risk:

• if you have moderate or severe liver disease
• if you have ever had liver disease, including hepatitis B or C
• if you are overweight(especially if you are a woman)
• if you have severe kidney disease.

Consult your doctorif you have any of these conditions. You may need extra check-ups, including blood tests, while taking this medicine. See section 4 for more information.

Hypersensitivity reactions to abacavir

Even patients who do not have the HLA-B*5701 gene may still get a hypersensitivity reaction(a severe allergic reaction).

Read the information under “Hypersensitivity reactions” in section 4 of this leaflet carefully.

Risk of cardiovascular events

It is not known whether abacavir increases the risk of having a heart attack or stroke.

Tell your doctorif you have heart problems, if you smoke, or if you have diseases that may increase the risk of heart disease, such as high blood pressure or diabetes. Do not stop taking Ziagen unless your doctor advises you to.

Be aware of the important signs

Some people who take medicines for HIV infection develop other conditions that can be serious. You need to know the signs and symptoms to look out for while you are taking Ziagen.

Read the information under “Other possible side effects of combination therapy for HIV” in section 4 of this leaflet.

Other medicines and Ziagen

Tell your doctor or pharmacistif you are takingor have recently takenany other medicines, including those obtained without a prescription, and herbal medicines. Remember to tell your doctor or pharmacist if you start taking any new medicines while you are taking Ziagen.

Some medicines interact with Ziagen

These include:

• phenytoin, used to treat epilepsy.

Tell your doctorif you are taking phenytoin. Your doctor may need to monitor you while you are taking Ziagen.

• 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 need to be checked for signs of withdrawal. You may need your methadone dose to be changed.

Tell your doctorif you are taking methadone.

• riociguat, used to treat high blood pressure in the blood vessels(pulmonary arteries) that carry blood from the heart to the lungs. Your doctor may need to reduce your dose of riociguat, as abacavir can increase the levels of riociguat in your blood.

Pregnancy

Ziagen should not be used during pregnancy. Ziagen and similar medicines may harm your unborn baby. If you have taken Ziagen during your pregnancy, your doctor may request that you have regular blood tests and other diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV was greater than the risk of side effects.

Breast-feeding

It is recommended that women with HIV do not breast-feedbecause HIV can be passed to the baby through breast milk. A small amount of the ingredients of Ziagen can also pass into breast milk.

If you are breast-feeding or thinking of breast-feeding, consult your doctor as soon as possible.

Driving and using machines

Do not drive or operate machineryunless you feel well.

Important information about some of the ingredients of Ziagen tablets

This medicine contains less than 1 mmol sodium (23 mg) per dose, i.e., it is essentially “sodium-free”.

3. How to take Ziagen

Always take this medicine exactly as your doctor or pharmacist has told you. If you are not sure, check with your doctor or pharmacist.

Swallow the tablets with a little water. Ziagen can be taken with or without food.

If you cannot swallow the tablets whole, you can break them and mix with a small amount of food or drink; take the whole dose immediately.

Stay in regular contact with your doctor

Ziagen helps to control your condition. You must take it every day to stop your disease getting worse. You may still develop other infections and illnesses associated with HIV.

Stay in contact with your doctor and do not stop taking Ziagenwithout discussing it with your doctor first.

How much to take

Adults, adolescents and children weighing at least 25 kg:

The usual dose of Ziagen is 600 mg a day. This can be taken either as one 300 mg tablet twice a day or two 300 mg tablets once a day.

Children from 1 year of age weighing less than 25 kg

The dose depends on your child’s weight. The recommended dose is:

• Children weighing between 20 kg and less than 25 kg:The usual dose of Ziagen is 450 mg a day. This can be taken either as 150 mg (half a tablet) in the morning and 300 mg (one tablet) in the evening, or 450 mg (one and a half tablets) once a day, as advised by your doctor.

• Children weighing between 14 kg and less than 20 kg:The usual dose of Ziagen is 300 mg a day. This can be taken either as 150 mg (half a tablet) twice a day or 300 mg (one tablet) once a day, as advised by your doctor.

The tablet can be divided into equal doses.

A liquid oral solution (20 mg of abacavir/ml) is available for the treatment of children over 3 months and weighing less than 14 kg, as well as for patients who require a dose reduction or who are unable to take tablets.

If you take more Ziagen than you should

If you accidentally take more Ziagen than you should, tell your doctor or pharmacist, or contact the nearest hospital emergency department for more information.

If you forget to take Ziagen

If you miss a dose, take it as soon as you remember and then continue with your normal routine.

Do not take a double dose to make up for a forgotten dose.

It is important to take Ziagen regularly to prevent the development of a hypersensitivity reaction.

If you have stopped taking Ziagen

If for any reason you have stopped taking Ziagen — especially because you think you may be having side effects or because of another illness:

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

If your doctor advises you to restart Ziagen, they may ask you to take the first doses in a place where you can be closely monitored for signs of a reaction.

4. Possible Adverse Effects

During treatment for HIV, there may be an increase in weight and levels of glucose and lipids in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication can produce adverse effects, although not all people will experience them.

When you are being treated for HIV, it may be difficult to distinguish whether a symptom is an adverse effect of Ziagen or other medications you are taking, or if it is due to an effect of the HIV disease itself. Therefore, it is very important that you inform your doctor about any change in your health.

Even patients who do not have the HLA-B*5701 gene can develop a hypersensitivity reaction(a severe allergic reaction), described in this prospectus in the section called “Hypersensitivity Reactions”.

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

In addition to the adverse effects listed below for Ziagen, other disorders can develop during combined treatment for HIV.

It is essential that you read the information under the heading “Other Possible Adverse Effects of Combined HIV Treatment”.

Hypersensitivity Reactions

Ziagencontains abacavir(the active ingredient also present in Trizivir, Triumeq, and Kivexa).

Abacavir can produce a severe allergic reaction known as a hypersensitivity reaction. These hypersensitivity reactions have been observed more frequently in people taking medications containing abacavir.

Who suffers from these reactions?

Anyone taking Ziagen could develop a hypersensitivity reaction to abacavir, which can be life-threatening if they continue taking Ziagen.

You are more likely to develop this reaction if you have a gene called HLA-B*5701(but you can suffer from this reaction even if you do not have this gene). Before starting treatment with Ziagen, you should have been tested for this gene. If you know you have this gene, tell your doctor before taking Ziagen.

Around 3 to 4 out of 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 frequent symptoms are:

• fever (high temperature) and skin rash.

Other frequently observed signs are:

• nausea (discomfort), vomiting, diarrhea, abdominal pain (stomach), and excessive fatigue.

Other symptoms may include:

Pain in the joints or muscles, swelling of the neck, difficulty breathing, sore throat, cough, occasional headache, eye inflammation (conjunctivitis), mouth ulcers, low blood pressure, and tingling or numbness of the hands or feet.

When do these reactions occur?

Allergic reactions can appear at any time during treatment with Ziagen, but it is more likely to happen in the first 6 weeks of treatment.

If you are caring for a child being treated with Ziagen, it is essential that you understand the information about this hypersensitivity reaction. If the child presents the symptoms described belowit is crucialthat you follow the instructions indicated.

Contact your doctor immediately:

1if you have a skin rash OR

2if you have symptoms included in at least 2 of the following groups:

• fever
• difficulty breathing, sore throat, or cough
• nausea or vomiting, diarrhea, or abdominal pain
• excessive fatigue or pain or general discomfort.

Your doctor may advise you to stop taking Ziagen.

While taking Ziagen, always carry the Patient Information Card with you.

If you have stopped taking Ziagen

If you have stopped taking Ziagen due to a hypersensitivity reaction, NEVER TAKE Ziagen or any other medication containing abacavir (e.g., Trizivir, Triumeq, or Kivexa) AGAIN. If you do, you may experience a drop in blood pressure that can be life-threatening or cause death within hours.

If, for any reason, you have interrupted treatment with Ziagen — especially because you think you have adverse effects or another illness:

Consult your doctor before restarting treatment.

Your doctor will check if your symptoms were related to a hypersensitivity reaction. If your doctor considers that there may have been a relationship, they will indicatethat you should never take Ziagen or any other medication containing abacavir (e.g., Trizivir, Triumeq, or Kivexa) again. It is essential that you follow this warning.

Occasionally, hypersensitivity reactions have developed in people who restart abacavir after having had a single symptom of those included in the Patient Information Card before they stopped taking it.

Very rarely, patients who have taken medications containing abacavir in the past without symptoms of hypersensitivity have developed a hypersensitivity reaction when restarting it.

If your doctor advises you to restart treatment with Ziagen, they may ask you to take the first doses in a place where you have easy access to medical assistance if needed.

If you are hypersensitive to Ziagen, you must return all unused Ziagen tablets to be safely disposed of. Consult your doctor or pharmacist.

The packaging of Ziagen includes a Patient Information Cardto remind you and healthcare personnel about hypersensitivity reactions. Separate the card from the packaging and always carry it with you.

Common Adverse Effects

May affect up to 1 in 10people:

• hypersensitivity reaction
• discomfort (nausea)
• headache
• vomiting
• diarrhea
• loss of appetite
• fatigue, lack of energy
• fever (high temperature)
• skin rash.

Rare Adverse Effects

May affect up to 1 in 1,000people:

• pancreatitis (inflammation of the pancreas).

Very Rare Adverse Effects

May affect up to 1 in 10,000people:

• skin rash that can form blisters resembling small targets (a dark central spot surrounded by a paler area, with a dark ring around the edge) (erythema multiforme)
• widespread rash with blisters and skin peeling, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome), and a more severe form that causes skin peeling over more than 30% of the body surface (toxic epidermal necrolysis)
• lactic acidosis (excess of lactic acid in the blood).

If you notice any of these symptoms, contact a doctor urgently.

If you experience adverse effects

Consult your doctor or pharmacistif you experience adverse effects, even if they are not listed in this prospectus.

Other Possible Adverse Effects of Combined HIV Treatment

Combined treatments, including Ziagen, can cause other diseases to develop during HIV treatment.

Symptoms of Infection and Inflammation

Exacerbation of Old Infections

People with advanced HIV infection (AIDS) have a weakened immune system and are more likely to develop severe infections (opportunistic infections). When these people start treatment, they may find that old, hidden infections flare up, causing signs and symptoms of inflammation. These symptoms are probably due to an improvement in the body's immune response, which allows it to fight these infections. The symptoms usually include fever, plus any of the following:

• headache
• stomach pain
• difficulty breathing.

In rare cases, since the immune system becomes stronger, it can also attack healthy body tissue (autoimmune disorders). The symptoms of autoimmune disorders can appear many months after starting HIV treatment medications. The symptoms may include:

• palpitations (rapid or irregular heartbeats) or tremors
• hyperactivity (excessive movement or agitation)
• weakness starting in the hands and feet and moving towards the body trunk.

If you notice any symptoms of infection while taking Ziagen:

Tell your doctor immediately. Do not take any other medication for the infection without your doctor's advice.

You may have bone problems

Some patients receiving combined HIV treatment develop a bone disease called osteonecrosis. In this disease, part of the bone tissue dies due to a reduction in blood supply to the bone. People are more likely to suffer from this disease:

• if they have been taking combined treatment for a long time
• if they also take anti-inflammatory medications called corticosteroids
• if they drink alcohol
• if their immune system is severely weakened
• if they are overweight.

The signs of osteonecrosis include:

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

If you notice any of these symptoms:

Tell your doctor.

Reporting Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Ziagen

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the box. The expiration date is the last day of the month indicated.

Do not store above 30°C.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Ziagen Composition

The active ingredient in each film-coated Ziagen tablet is 300 mg of abacavir (as sulfate).

The other ingredients are microcrystalline cellulose, sodium carboxymethyl starch, magnesium stearate, and anhydrous colloidal silica in the tablet core. The coating contains triacetin, hypromellose (E464), titanium dioxide (E171), polysorbate 80 (E433), and yellow iron oxide.

Appearance of Ziagen and Package Contents

Ziagen film-coated tablets are engraved on both sides with “GX 623”. They are scored, yellow, capsule-shaped tablets and are available in blister packs containing 60 tablets.

Marketing Authorization Holder

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

Manufacturer(s)

Delpharm Poznan Spólka Akcyjna, ul., Grunwaldzka 189, 60-322 Poznan, Poland.

You can request more information about this medication from the local representative of the marketing authorization holder.

Detailed information about this medication is available on the European Medicines Agency website: http://www.ema.europa.eu/.