ZIAGEN 20 MG/ML ORAL SOLUTION

Introduction

Package Leaflet: Information for the User

Ziagen 20mg/ml Oral Solution

abacavir

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

• Keep this leaflet, 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 experience 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(severe allergic reaction), which can be life-threatening if they continue to take medicines containing abacavir.

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

The packaging of Ziagen includes a Warning Cardto remind you and your medical staff of hypersensitivity to abacavir. 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. Storing Ziagen
6. Package contents 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 effectiveness 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 on hypersensitivity reactions in section 4 of this leaflet carefully.

Tell your doctorif you think any of these conditions apply to you.

Be especially careful with Ziagen

Some people who take Ziagen for HIV have a higher risk of developing severe 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 have significant overweight(especially if you are a woman)
• if you have severe kidney disease.

Tell your doctorif you have any of these conditions. You may need to have additional tests, including blood tests, while taking this medicine . For more information, see section 4.

Hypersensitivity reactions to abacavir

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

Read the information on hypersensitivity reactions in section 4 of this leaflet carefully.

Risk of cardiovascular events

It cannot be excluded that abacavir increases the risk of cardiovascular events.

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

Be aware of important symptoms

Some people who take medicines for HIV infection develop other diseases, which can be severe. You need to know what important signs and symptoms to look out for while taking Ziagen.

Read the information on “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.

Remember to tell your doctor or pharmacist if you start taking a new medicine while 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 may need to be monitored for signs of withdrawal. You may need your methadone dose to be changed.

Tellyour 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 may increase the levels of riociguat in your blood.

Pregnancy

Ziagen is not recommended during pregnancy. Ziagen and similar medicines may cause side effects in babies during pregnancy. If you have been takingZiagenduring your pregnancy, your doctor may ask you to 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 not recommendedthat HIV-positive women breast-feed their babies because HIV infection can be passed to the baby through breast milk. A small amount of the components of Ziagen may also pass into breast milk.

If you are breast-feeding or thinking of breast-feeding, you should 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 Oral Solution

This medicine contains the sweetener sorbitol (approximately 5 g per 15 ml dose) which can have a mild laxative effect. Do not take medicines containing sorbitol if you have hereditary fructose intolerance. The caloric value of sorbitol is 2.6 kcal/g.

Ziagen Oral Solution also contains preservatives (parahydroxybenzoates) that may cause allergic reactions (possibly delayed).

This medicine contains less than 1 mmol of sodium (23 mg) per dose; this is, essentially “sodium-free”.

The oral solution of Ziagen contains 50 mg/ml of propylene glycol. When taken as recommended, each 15 ml dose contains approximately 750 mg of propylene glycol.

• If your child is under 5 years old, consult your doctor or pharmacist before giving them this medicine, especially if they have been given other medicines that contain propylene glycol or alcohol.

• If you are pregnant or breast-feeding, do not take this medicine unless your doctor recommends it. Your doctor may perform additional checks while you are taking this medicine.

• If you have liver or kidney disease, do not take this medicine unless your doctor recommends it. Your doctor may perform additional checks while you are taking this medicine.

3. How to take Ziagen

Follow the instructions for taking this medicine exactly as your doctor or pharmacist has told you. If you are not sure, ask your doctor or pharmacist again. Ziagen can be taken with or without food.

Stay in regular contact with your doctor

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

Stay in touch with your doctor and do not stop taking Ziagenwithout talking to your doctor first.

How much to take

Adults, adolescents and children weighing at least 25 kg:

The usual dose of Ziagen is 600 mg (30 ml) per day.It can be taken as 300 mg (15 ml) twice a day, or as 600 mg (30 ml) once a day.

Children from 3 months of age with a weight of less than 25 kg:

The dose depends on the child's body weight. The recommended dose is 8 mg/kg twice a day or 16 mg/kg once a day, up to a maximum daily dose of 600 mg.

How to measure and take your dose of medicine

Use the oral dosing syringe provided with the pack to measure your dose accurately. When full, the syringe contains 10 ml of solution.

1. Remove the plastic wrapper from the syringe/adapter.
2. Remove the cap from the bottle. Put it in a safe place.
3. Remove the adapter from the syringe.
4. While holding the bottle firmly, insert the plastic adapter into the neck of the bottle.
5. Insert the syringefirmly into the adapter.
6. Turn the bottle upside down.
7. Pull the syringe plungeruntil you have the first part of the full dose.
8. Turn the bottle the right way up again and remove the syringefrom the adapter.
9. Put the syringe in your mouth, placing the end of the syringe inside your cheek. Push the plunger slowly, giving yourself time to swallow the medicine. Do notpush the solution too quickly into the back of your throat, as you may choke.
10. Clean the syringe well each time you empty it.
11. Repeat steps 5 to 10in the same way until you have taken the full dose. For example, if your dose is 30 ml, you will need to take 3 syringes of medicine.
12. After you have taken your full dose, washthe syringe well with clean water. Let it dry completely before using it again.
13. Close the bottle tightlywith the cap, leaving the adapter inside.

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 emergency department of your nearest hospital for more information.

If you forget to take Ziagen

If you forget to take a dose, take it as soon as you remember and then continue with your normal treatment schedule.

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

It is important to take Ziagen regularly, as irregular intake of Ziagen may increase the risk of developing a hypersensitivity reaction.

If you have stopped taking Ziagen

If for any reason you have stopped taking Ziagen — especially because you think you have had 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 they may be, they will tell you that you should never take Ziagen or any other medicine containing abacavir (e.g. Triumeq, Trizivir or Kivexa) again. It is important that you follow this advice.

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 care, in case you need it.

4. Possible Adverse Effects

During HIV treatment, there may be an increase in weight and glucose and lipid levels 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 may produce adverse effects, although not all people experience them.

When you are undergoing HIV treatment, 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 may 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 may develop during combined HIV treatment.

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 may 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 could put their life in danger 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 undergone a test to detect 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:

Joint or muscle pain, 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 that they will occur 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 fundamentalthat you follow the indicated instructions.

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 general pain or 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 AGAIN take Ziagen or any other medication containing abacavir (e.g., Trizivir, Triumeq, or Kivexa). If you do, within hours, you may experience a drop in blood pressure that can be life-threatening or cause death.

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 again take Ziagen or any other medication containing abacavir (e.g., Trizivir, Triumeq, or Kivexa). 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 necessary.

If you are hypersensitive to Ziagen, you must return all unused Ziagen oral solution for safe disposal. Consult your doctor or pharmacist.

The Ziagen packaging 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.

Frequent 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 (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 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, may 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 one or more 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 may 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 trunk of the body.

If you notice any symptoms of infection while taking Ziagen:

Inform 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:

Inform 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 25°C.

Discard the oral solution two months after it was first opened.

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 of Ziagen oral solution is 20 mg of abacavir (as sulfate) per ml of solution.

The other components are sorbitol 70% (E420), sodium saccharin, sodium citrate, anhydrous citric acid, methyl parahydroxybenzoate (E218), propyl parahydroxybenzoate (E216), propylene glycol (E1520), maltodextrin, lactic acid, glycerol triacetate, artificial strawberry and banana flavor, purified water, sodium hydroxide, and/or hydrochloric acid for pH adjustment.

Ziagen Appearance and Package Contents

Ziagen oral solution is a clear or yellowish solution that may turn brown over time, with a strawberry/banana flavor. It is presented in cartons containing a white polyethylene bottle with a child-resistant closure. The bottle contains 240 ml (20 mg of abacavir/ml) of solution. The packaging includes a 10 ml oral dosing syringe and a plastic adapter for the bottle.

Marketing Authorization Holder

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

Manufacturer

ViiV Healthcare Trading Services UK Limited, 12 Riverwalk, Citywest Business Campus, Dublin 24, Ireland

You can request more information about this medication by contacting 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/.