Ziagen 20 mg/ml oral solution

Package leaflet: Information for the user

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 questions, ask your doctor or pharmacist.

• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may harm them.

• If you experience any adverse effects, talk to your doctor or pharmacist, even if they are effects not listed in this leaflet. See section 4.

IMPORTANT — Hypersensitivity reactions

Ziagen contains abacavir (which is also the active substance in medicines such as Kivexa, Triumeq, and Trizivir). Some people taking abacavir may develop a hypersensitivity reaction (a serious allergic reaction), which may be life-threatening if they continue taking abacavir-containing medicines.

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

The Ziagen package includes an Information Card to remind you and medical personnel about abacavir hypersensitivity. You must remove this card and carry it with you at all times.

Contents of the leaflet

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

1. What Ziagen is and what it is used for

Ziagen is used to treat infection caused by HIV (human immunodeficiency virus).

Ziagen contains abacavir as its active substance. Abacavir belongs to a group of antiretroviral medicines known as nucleoside reverse transcriptase inhibitors (NRTIs).

Ziagen does not completely cure HIV infection; it reduces the amount of virus in the body and keeps it at a low level. It also increases the number of CD4 cells in the blood. CD4 cells are a type of white blood cell that play an important role in helping the body fight infection.

Not everyone responds to treatment with Ziagen in the same way. Your doctor will monitor how well the treatment is working for you.

2. What you need to know before taking Ziagen

Do not take Ziagen

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

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

Consult your doctor if you think any of the following apply to you.

Take special care with Ziagen

Some people taking Ziagen for HIV have a higher risk of developing serious side effects. You need to be aware that the risk is greater:

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

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

Hypersensitivity reactions to abacavir

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

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

Risk of cardiovascular events

It cannot be ruled out that abacavir may increase the risk of cardiovascular events.

Inform your doctor if you have cardiovascular problems, if you smoke, or if you have conditions 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 do so.

Be alert to important symptoms

Some people taking medicines for HIV infection develop other diseases, which may be serious. You need to know which signs and symptoms to watch for while taking Ziagen.

Read the information on “Other possible side effects of combination HIV treatment” in section 4 of this leaflet.

Other medicines and Ziagen

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including herbal and over-the-counter medicines.

Remember to inform your doctor or pharmacist if you start taking a new medicine while on Ziagen.

Some medicines interact with Ziagen

These include:

• phenytoin, used to treat epilepsy.

Inform your doctor if 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 eliminated from the body. If you are taking methadone, you should be monitored for symptoms of withdrawal. Your methadone dose may need to be adjusted.

Inform your doctor if you are taking methadone.

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

Pregnancy

Use of Ziagen during pregnancy is not recommended. Ziagen and similar medicines may cause adverse effects in babies during pregnancy. If you have taken Ziagen during pregnancy, your doctor may recommend periodic blood tests and other diagnostic tests to monitor your baby's development. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV outweighed the risk of adverse effects.

Breast-feeding

Breast-feeding is not recommended for women living with HIV, because HIV infection can be transmitted 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 planning to breast-feed, you must consult your doctor as soon as possible.

Driving and use of machines

Do not drive or operate machinery unless 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 may 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) which may cause allergic reactions (possibly delayed).

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

Ziagen oral solution contains 50 mg/ml of propylene glycol. When taken according to the recommended dosage, each 15 ml dose contains approximately 750 mg of propylene glycol.

• If your child is under 5 years of age, consult your doctor or pharmacist before administering this medicine, especially if they have been given other medicines containing propylene glycol or alcohol.

• If you are pregnant or breast-feeding, do not take this medicine unless recommended by your doctor. Your doctor may carry out additional checks while you are taking this medicine.

• If you have liver or kidney disease, do not take this medicine unless recommended by your doctor. Your doctor may carry out additional checks while you are taking this medicine.

3. How to take Ziagen

Follow exactly the instructions given by your doctor or pharmacist for taking this medicine. If you are unsure, consult your doctor or pharmacist again. Ziagen may be taken with or without food.

Maintain regular contact with your doctor

Ziagen helps control your condition. You will need to take it every day to prevent your illness from worsening. You may still develop other infections and diseases associated with HIV infection.

Stay in contact with your doctor and do not stop taking Ziagen without first talking to your doctor.

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. This can be taken as 300 mg (15 ml) twice daily, or as 600 mg (30 ml) once daily.

Children from 3 months of age weighing less than 25 kg:

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

How to measure and take the medicine dose

Use the oral dosing syringe supplied with the package to measure your dose accurately. When filled, the syringe holds 10 ml of solution.

1. Remove the plastic wrapping from the syringe/dosing adapter.
2. Remove the cap from the bottle. Keep 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 syringe firmly into the adapter.
6. Turn the bottle upside down.
7. Pull back the syringe plunger to draw up the first part of the full dose.
8. Turn the bottle back to its upright position and remove the syringe from the adapter.
9. Place the syringe in your mouth, positioning the tip inside your cheek. Slowly push the plunger to administer the medicine, allowing time to swallow. Do not inject the solution too forcefully into the back of the throat, as this could cause choking.
10. Clean the syringe thoroughly each time after emptying.
11. Repeat steps 5 to 10 in the same way until the full dose has been taken. For example, if your dose is 30 ml, you will need to take 3 syringes of medicine.
12. After taking your full dose, wash the syringe well with clean water. Allow it to dry completely before using it again.
13. Close the bottle securely with the cap, leaving the adapter inside.

If you take more Ziagen than you should

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

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 regular dosing schedule.

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

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

If you have stopped taking Ziagen

If for any reason you have stopped taking Ziagen — especially because you think you had side effects or another illness:

Consult your doctor before restarting treatment. Your doctor will assess whether your symptoms were related to a hypersensitivity reaction. If your doctor considers that there may have been a link, you will be advised never to take Ziagen again, or any other medicine containing abacavir (e.g., Triumeq, Trizivir, or Kivexa). It is important that you follow this warning.

If your doctor advises restarting 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.

4. Possible adverse effects

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

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

When receiving HIV treatment, it may be difficult to determine whether a symptom is an adverse effect of Ziagen or of other medicines you are taking, or is due to 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 carry the HLA-B*5701 gene may develop a hypersensitivity reaction (a serious allergic reaction), described in this leaflet in the section called “Hypersensitivity reactions”.

It is very important that you read and understand the information about this serious reaction. In addition to the adverse effects listed below for Ziagen, other disorders may develop during combination HIV treatment.

It is important that you read the information under the heading “Other possible adverse effects of combination HIV treatment”.

Hypersensitivity reactions

Ziagen contains abacavir (the active substance also present in Trizivir, Triumeq, and Kivexa).

Abacavir may cause a serious allergic reaction known as a hypersensitivity reaction. These hypersensitivity reactions have been observed more frequently in people taking medicines containing abacavir.

Who experiences these reactions?

Any person taking Ziagen could develop a hypersensitivity reaction to abacavir, which could be life-threatening if you continue taking Ziagen.

Your risk of developing this reaction is higher if you have a gene called HLA-B*5701 (but you may still have 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.

Approximately 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 common symptoms are:

•fever (elevated temperature) and skin rash.

Other commonly observed signs are:

• nausea (feeling unwell), vomiting, diarrhoea, abdominal pain (stomach), and excessive tiredness.

Other possible symptoms 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 in the hands or feet.

When do these reactions occur?

Allergic reactions can occur at any time during treatment with Ziagen, but are most likely to occur within the first 6 weeks of treatment.

If you are caring for a child being treated with Ziagen, it is important that you understand the information about this hypersensitivity reaction. If the child develops the symptoms described below, it is essential that you follow the instructions given.

Contact your doctor immediately:

1if you develop a skin rash OR

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

• fever
• difficulty breathing, sore throat, or cough
• nausea or vomiting, diarrhoea, or abdominal pain
• excessive tiredness or general aches and discomfort.

Your doctor may advise you to stop taking Ziagen.

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

If you have stopped taking Ziagen

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

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

Consult your doctor before restarting treatment.

Your doctor will assess whether your symptoms were related to a hypersensitivity reaction. If your doctor considers there may have been a link, you will be advised never to restart Ziagen or any other medicine containing abacavir (e.g. Trizivir, Triumeq, or Kivexa). It is important that you follow this warning.

Occasionally, hypersensitivity reactions have occurred in people who restart abacavir after having experienced only one symptom listed on the Information Card before stopping.

Very rarely, patients who previously took abacavir-containing medicines without experiencing hypersensitivity symptoms have developed a hypersensitivity reaction upon re-exposure.

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

If you are hypersensitive to Ziagen, you must return all unused Ziagen oral solution so it can be safely disposed of. Please consult your doctor or pharmacist.

The Ziagen packaging includes an Information Card to remind you and healthcare professionals about hypersensitivity reactions. Separate the card from the packaging and always carry it with you.

Frequent adverse effects

May affect up to 1 in 10 people:

• hypersensitivity reaction
• feeling unwell (nausea)
• headache
• vomiting
• diarrhoea
• loss of appetite
• tiredness, lack of energy
• fever (elevated temperature)
• skin rash.

Rare adverse effects

May affect up to 1 in 1,000 people:

• inflammation of the pancreas (pancreatitis).

Very rare adverse effects

May affect up to 1 in 10,000 people:

• skin rash that may 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 peeling of the skin, especially around the mouth, nose, eyes, and genitals (Stevens–Johnson syndrome), and a more severe form causing 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 pharmacist if you experience adverse effects, even if they are not listed in this leaflet.

Other possible adverse effects of combination HIV treatment

Combination treatments, including Ziagen, may cause other conditions to develop during HIV treatment.

Symptoms of infection and inflammation

Exacerbation of previous infections

People with advanced HIV infection (AIDS) have a weakened immune system and are more likely to develop serious infections (opportunistic infections). When these individuals start treatment, previously hidden infections may flare up, causing signs and symptoms of inflammation. These symptoms are likely due to an improved immune response, enabling the body to fight these infections. Symptoms usually include fever, plus one or more of the following:

• headache
• stomach pain
• difficulty breathing.

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

• palpitations (rapid or irregular heartbeat) or tremors
• hyperactivity (excessive movement or agitation)
• weakness starting in the hands and feet and moving toward the body's trunk.

If you notice any symptoms of infection while taking Ziagen:

Inform your doctor immediately. Do not take any other medicine for infection without your doctor's advice.

You may have problems with your bones

Some patients receiving combination HIV treatment develop a bone disease called osteonecrosis. In this condition, part of the bone tissue dies due to reduced blood supply to the bone. The risk of developing this disease is higher in people who:

• have been on combination treatment for a long time
• also take anti-inflammatory medicines called corticosteroids
• drink alcohol
• have a severely weakened immune system
• are overweight.

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 of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly via the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Ziagen

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

Do not use this medicine after the expiry date stated on the carton. The expiry date is the last day of the month indicated.

Do not store above 25°C.

Discard the oral solution two months after first opening.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This helps protect the environment.

6. Contents of the pack and other information

Composition of Ziagen

The active substance in 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, methylparaben (E218), propylparaben (E216), propylene glycol (E1520), maltodextrin, lactic acid, glyceryl triacetate, artificial strawberry and banana flavoring, purified water, sodium hydroxide and/or hydrochloric acid (for pH adjustment).

Appearance of Ziagen and contents of the pack

Ziagen oral solution is a clear or yellowish solution which may turn brown over time, with a strawberry/banana flavor. It is supplied in cartons containing one white polyethylene bottle with a child-resistant closure. The bottle contains 240 ml (20 mg abacavir/ml) of solution. The pack 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, The Netherlands

Manufacturer

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

Further information on this medicinal product is available upon request to the local representative of the Marketing Authorization Holder.

Detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu/.