TRIZIVIR 300 MG/150 MG/300 MG FILM-COATED TABLETS

2. What you need to know before you take Trizivir

Do not take Trizivir

• If you are allergic(hypersensitive)to abacavir (or to any other medicine that contains abacavir — Kivexa, Triumeqor Ziagen), lamivudine or zidovudine, 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.

• if you have severe kidney problems
• if you have a very low red blood cell count(anaemia) or a very low white blood cell count(neutropenia).

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

Be especially careful with Trizivir

Some people who take Trizivir have a higher risk of suffering from 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 have hepatitis B, do not stop taking Trizivir without your doctor's advice, as it may get worse)

if you are significantly overweight(especially if you are a woman).

Talk to your doctor before you start taking Trizivir ifyou 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(a severe allergic reaction). Read carefully all the information about hypersensitivity reactions in section 4 of this leaflet.

Risk of cardiovascular events

Abacavir may increase the risk of cardiovascular events.

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

Be aware of important symptoms

Some people who take Trizivir develop other disorders, which can be serious. You need to know what important signs and symptoms to look out for while taking Trizivir.

Read the information about “Other possible side effects of Trizivir” in section 4 of this leaflet.

Using Trizivir with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines,including herbal medicines and those bought without a prescription.

Remember to tell your doctor or pharmacist if you start taking a new medicine while taking Trizivir.

The following medicines must not be used with Trizivir:

stavudine or emtricitabine to treat HIV infection

other medicines that contain lamivudine, used to treat HIV infectionor hepatitis B

ribavirin or ganciclovir injections to treat viral infections

high doses of co-trimoxazole(a combination of trimethoprim and sulfamethoxazole), an antibiotic

cladribine, used to treat hairy cell leukaemia.

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

Some medicines may increase the risk of side effects or make them worse

These include:

• valproic acid, to treat epilepsy
• interferon, to treat viral infections
• pyrimethamine, to treat malariaand other parasitic infections
• dapsone, to prevent neumoniaand treat skin infections
• fluconazole or flucytosine, to treat fungal infectionssuch as Candida
• pentamidine or atovaquone, to treat parasitic infections such as Pneumocystis jiroveciipneumonia (often referred to as PCP)
• amphotericin or co-trimoxazole, to treat fungal and bacterial infections
• probenecid, to treat goutand similar conditions, and given with some antibiotics to make them more effective
• methadone, used as a heroin substitute
• vincristine, vinblastine or doxorubicin, to treat cancer.

Tell your doctorif you are taking any of these medicines.

Some medicines interact with Trizivir

These include:

• clarithromycin, an antibiotic

If you are taking clarithromycin, take your dose at least 2 hours before or after taking Trizivir.

• phenytoin, to treat epilepsy.

Tell your doctorif you are taking phenytoin. Your doctor may decide to monitor you while you are taking Trizivir.

• medicines (usually liquids) that contain sorbitol and other polyols(such as xylitol, mannitol, lactitol or maltitol), if taken regularly.

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

• Riociguat, to treat high blood pressure in the blood vessels(arteries) that carry blood from the heart to the lungs.

It may be necessary for your doctor to reduce your dose of riociguat, as abacavir may increase the levels of riociguat in the blood

Methadone and Trizivir

Abacavir increases the rate at which methadone is removed from the body. If you are taking methadone, you will need to be monitored for signs of withdrawal. You may need to have your methadone dose changed.

Pregnancy

If you are pregnant, if you become pregnant, or if you are planning to become pregnant, talk to your doctor about the risks and benefits to you and your baby of taking Trizivir during your pregnancy.

Trizivir and similar medicines may cause side effects in babies during pregnancy. If you have been taking Trizivir during your pregnancy, your doctor may ask for 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 women with HIV breast-feed their babies because HIV infection can be passed to the baby through breast milk. A small amount of the components of Trizivir may also pass into breast milk.

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

Driving and using machines

Trizivir may cause dizzinessand have other effects that reduce your alertness.

Do not drive or operate machineryunless you feel well.

Important information about some of the ingredients of Trizivir tablets

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

3. How to take Trizivir

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

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

How much to take

The usual dose for adults is one tablet twice a day.

Take the tablets at regular intervals, allowing approximately 12 hours between each tablet.

Swallow the tablets whole, with a little water. Trizivir can be taken with or without food.

If you take more Trizivir than you should

If you accidentally take too much Trizivir, tell your doctor or pharmacist or contact the nearest hospital emergency department for advice.

If you forget to take Trizivir

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

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

It is important to take Trizivir regularly, as irregular intake can make it less effective against HIV infection and increase the risk of hypersensitivity reactions.

If you have stopped taking Trizivir

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

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

If your doctor advises you to restart treatment with Trizivir, they may ask you to take the first doses in a place where you have easy access to medical care, in case it is needed.

4. Possible side 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 due to the recovery of your health and, in the case of blood lipids, to the HIV medicines themselves. Your doctor will monitor these changes.

Treatment with Trizivir often causes loss of fat from the legs, arms, and face (lipoatrophy). This loss of body fat has been shown to be not completely reversible after stopping zidovudine. Your doctor should monitor you for signs of lipoatrophy. If you notice any loss of fat from your legs, arms, and face, tell your doctor. When these symptoms occur, you should stop taking Trizivir and change your HIV treatment.

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

When you are being treated for HIV, it can be difficult to tell whether a symptom is a side effect of Trizivir or of other medicines you are taking, or a result of the HIV infection itself. Therefore, it is very important that you report any changes in your health to your doctor.

Even patients who do not have the HLA-B*5701 gene may develop a hypersensitivity reaction(a severe 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 side effects listed below for Trizivir, other disorders can occur during treatment.

It is important that you read on the other side of the leaflet the information under the heading “Other possible side effects of Trizivir”.

Hypersensitivity Reactions

Trizivircontains abacavir(the active ingredient that is also present in Kivexa, Triumeqand Ziagen).

Abacavir can cause a severe 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 who is taking Trizivir could develop a hypersensitivity reaction to abacavir, which could be life-threatening if they continue to take Trizivir.

You are more likely to develop this reaction if you have a gene called HLA-B*5701(but you can still have the reaction even if you do not have this gene). Before you start taking Trizivir, you should have been tested for this gene. If you know you have this gene, tell your doctor before you take Trizivir.

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 signs include:

• nausea (feeling sick), vomiting, diarrhoea, abdominal pain and extreme tiredness.

Other symptoms may include:

joint or muscle pain, swelling of the neck, difficulty breathing, sore throat, cough, headache, inflammation of the eye (conjunctivitis), mouth ulcers, low blood pressure and numbness or tingling of the hands or feet.

When do these reactions occur?

Hypersensitivity reactions can occur at any time during treatment with Trizivir, but are more likely to occur in the first 6 weeks of treatment.

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, diarrhoea or abdominal pain
• extreme tiredness or aches or general feeling of being unwell.

Your doctor may advise you to stop taking Trizivir.

If you have stopped taking Trizivir

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

If for any reason you have interrupted treatment with Trizivir - especially because you think you have side 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 Trizivir or any other medication that contains abacavir (Kivexa, Triumeq, or Ziagen) AGAIN. It is essential that you follow this warning.

Occasionally, hypersensitivity reactions have developed in people who restart taking abacavir after having had a single symptom of those included in the Information Card before stopping 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 Trizivir, 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 (allergic) to Trizivir, you must return all your unused Trizivir tablets to be safely disposed of. Consult your doctor or pharmacist.

The Trizivir packaging includes an Information Cardto remind you and healthcare staff about hypersensitivity reactions. Separate the card from the packaging and always carry it with you.

Very common side effects

May affect more than 1 in 10people:

• headache
• discomfort (nausea).

Common side effects

May affect up to 1 in 10people:

• hypersensitivity reaction (severe allergic reaction)
• vomiting
• diarrhea
• stomach pain
• loss of appetite
• feeling of dizziness
• fatigue, lack of energy
• fever (high temperature)
• feeling of general discomfort
• difficulty sleeping (insomnia)
• muscle pain and discomfort
• joint pain
• cough
• irritated or runny nose (rhinorrhea)
• skin rash
• hair loss.

Common side effects that may appear in blood tests are:

• low red blood cell count (anemia)or low white blood cell count (neutropenia or leucopenia)
• increased level of liver enzymes
• increased bilirubin in the blood (a substance produced by the liver) that can cause a yellowish color of the skin.

Uncommon side effects

May affect up to 1 in 100people:

• difficulty breathing
• flatulence (gas)
• itching
• muscle weakness.

Uncommon side effects that may appear in blood tests are:

• a decrease in the number of cells involved in blood clotting (thrombocytopenia)or in all classes of blood cells (pancytopenia).

Rare side effects

May affect up to 1 in 1,000people:

• liver disorders, such as jaundice, increased liver size, fatty liver, inflammation (hepatitis)
• lactic acidosis (excess of lactic acid in the blood, see the following section "Other possible side effects of Trizivir")
• pancreatitis (inflammation of the pancreas)
• chest pain, heart muscle disease (cardiomyopathy)
• seizures (convulsions)
• feeling of depression or anxiety, difficulty concentrating, drowsiness
• indigestion, taste disturbances
• changes in the color of the nails, skin, or mucous membranes inside the mouth
• feeling of flu - chills and sweating
• tingling sensation on the skin (pins and needles)
• feeling of weakness in the limbs
• muscle tissue rupture
• numbness
• frequent urination
• increase in breast size in men.

Rare side effects that may appear in blood tests are:

• increase in an enzyme called amylase
• failure of the bone marrow to produce new red blood cells (pure red cell aplasia).

Very rare side effects

May affect up to 1 in 10,000people:

• skin rash that can form blisters that look like small targets (dark center 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 on more than 30% of the body surface (toxic epidermal necrolysis).

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

Very rare side effects that may appear in blood tests are:

• failure of the bone marrow to produce new red or white blood cells (aplastic anemia).

If you have side effects

If you consider that any of the side effects you are suffering from is serious or if you notice any side effect not mentioned in this leaflet, tell your doctor or pharmacist.

Other possible side effects of Trizivir

Trizivir may cause other disorders to develop during treatment for HIV.

Symptoms of infection and inflammation

Exacerbation of old infections

People with advanced HIV infection (AIDS) have weakened immune systems and are more likely to suffer from serious infections (opportunistic infections). When these people start treatment, they may find that old infections, which were hidden, flare up, causing signs and symptoms of inflammation. These symptoms are likely 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 may appear many months after you have started taking medications for HIV treatment. The symptoms may include:

• palpitations (rapid or irregular heartbeats) or tremors
• hyperactivity (excessive movement or agitation)
• weakness that starts in the hands and feet and moves towards the trunk of the body.

If you notice any symptoms of infection while taking Trizivir:

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

Lactic acidosis is a rare but serious side effect

Some people taking Trizivir develop a condition called lactic acidosis, along with an increase in liver size.

Lactic acidosis is due to an increase in lactic acid levels in the body. It is rare, and if it occurs, it usually develops after a few months of treatment. It can be life-threatening, causing failure of internal organs.

Lactic acidosis is more likely to develop in patients who have some liver condition or in obese people (with significant overweight), especially women.

Signs of lactic acidosis include:

• discomfort (nausea), vomiting
• stomach pain
• feeling of general discomfort
• loss of appetite, weight loss

• difficult, rapid, and deep breathing
• numbness or weakness of the limbs.

During treatment, your doctor will closely monitor any signs that may indicate you are developing lactic acidosis. If you notice any of the symptoms listed above or are concerned about any other symptom:

See your doctor as soon as possible.

You may have bone problems

Some people receiving combination therapy for HIV may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). People are more likely to have this disease:

• if they have been taking combination therapy for a long time
• if they also take anti-inflammatory medications called corticosteroids
• if they consume alcohol
• if their immune system is severely weakened
• if they 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:

Tell your doctor.

Other effects that may appear in blood tests

Trizivir may also cause:

• an increase in lactic acid levels in the blood, which can rarely lead to lactic acidosis.

Reporting of side effects

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

5. Storage of Trizivir

Keep this medication out of sight and reach of children.

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

Do not store above 30°C.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and further information

Composition of Trizivir

The active ingredients of each film-coated tablet are 300 mg of abacavir (as sulfate), 150 mg of lamivudine, and 300 mg of zidovudine.

The other ingredients are microcrystalline cellulose, sodium carboxymethylcellulose, and magnesium stearate in the tablet core. The film coating of the tablet contains hypromellose, titanium dioxide, polyethylene glycol, aluminum lake of indigo carmine, and yellow iron oxide.

Appearance and packaging of the product

Trizivir film-coated tablets are marked with “GX LL1” on one side. They are green-blue in color and have a capsule shape. They are available in blister packs containing 60 tablets or in bottles of 60 tablets with a child-resistant closure.

Marketing authorization holder

ViiV Healthcare BV

Van Asch van Wijckstraat 55H

3811 LP Amersfoort

Netherlands

Manufacturer

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

You can obtain more information about this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet:

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