Combivir

Package Leaflet: Information for the User

Combivir 150 mg/300 mg film-coated tablets

lamivudine/zidovudine
Please read this leaflet carefully before 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 their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

1. What Combivir is and what it is used for

Combivir is used to treat HIV (Human Immunodeficiency Virus) infection in adults and children.
Combivir contains two active substances used in the treatment of HIV infection: lamivudine and zidovudine. Both of these medicines belong to a class of antiretroviral drugs known as nucleoside reverse transcriptase inhibitors (NRTIs).
Combivir does not completely cure HIV infection; it reduces the amount of virus in the body and keeps it at low levels. It also increases the number of CD4 cells in the blood. CD4 cells are a type of white blood cell important in helping the body fight infection.
Not all people respond to treatment with Combivir in the same way. Your doctor will monitor the effectiveness of the treatment.

2. What you should know before taking Combivir

Do not take Combivir:

• if you are allergic to lamivudine or zidovudine, or to any of the other ingredients of this medicine (listed in section 6).
• if you have a very low red blood cell count ( anaemia ) or a very low white blood cell count ( neutropenia ). Consult your doctor if you think either of these conditions applies to you.

Take special care with Combivir
Some people taking Combivir or other combination therapies for the treatment of HIV are at increased risk of serious side effects. You should be aware of these additional risks:

• if you have had liver disease, including hepatitis B or C (if you have hepatitis B infection, do not stop taking Combivir without consulting your doctor, as hepatitis may worsen)
• if you have kidney disease
• if you are severely overweight (especially if you are female). Inform your doctor if any of these conditions apply to you. Your doctor will decide whether the active substances are suitable for you. You may need additional monitoring, including blood tests, while taking this medicine. See section 4 for further information.

Be aware of important symptoms
Some people taking medicines for HIV infection develop other conditions that may be serious. You should be informed about important signs and symptoms so that you can remain vigilant while taking Combivir.
Read the information under ‘Other possible side effects of combination therapy for HIV’ in section 4 of this leaflet.

Other medicines and Combivir
Tell your doctor or pharmacist if you are taking any other medicines, or have recently taken any, including herbal remedies or other medicines purchased without a prescription.
Remember to inform your doctor or pharmacist if you start taking a new medicine while being treated with Combivir.

The following medicines must not be taken with Combivir:

• other medicines containing lamivudine used to treat HIV infection or hepatitis B
• emtricitabine for treating HIV infection
• stavudine for treating HIV infection
• intravenous ribavirin or ganciclovir for treating viral infections
• high doses of co-trimoxazole, an antibiotic
• cladribine, used to treat hairy cell leukaemia. Inform your doctor if you are being treated with any of these medicines.

Some medicines may increase the likelihood of side effects or make them worse.
These include:

• sodium valproate for treating epilepsy
• interferon, for treating viral infections
• pyrimethamine, for treating malaria and other parasitic infections
• dapsone, for preventing pneumonia and treating skin infections
• fluconazole or flucytosine for treating fungal infections such as candida
• pentamidine or atovaquone, for treating parasitic infections such as Pneumocystis jirovecii pneumonia (often referred to as PCP)
• amphotericin or co-trimoxazole, for treating fungal and bacterial infections
• probenecid for treating gout and similar conditions, and administered with other antibiotics to enhance their effectiveness
• methadone used as a heroin substitute
• vincristine, vinblastine or doxorubicin for treating cancer. Inform your doctor if you are taking any of these medicines.

Some medicines interact with Combivir
These include:

• clarithromycin, an antibiotic. If you are taking clarithromycin, take your dose at least 2 hours before or after taking Combivir.
• phenytoin, for treating epilepsy. Inform your doctor if you are taking phenytoin. Your doctor may need to monitor you while you are taking Combivir.
• medicines (usually liquids) containing sorbitol and other sweeteners (such as xylitol, mannitol, lactitol or maltitol), if taken regularly.

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

Pregnancy
If you are pregnant, become pregnant, or are planning a pregnancy, discuss with your doctor the risks and benefits of taking Combivir for you and your baby.
Combivir and similar medicines may cause side effects in unborn children. If you have taken Combivir during pregnancy, your doctor may request regular blood tests and other diagnostic examinations to monitor your baby's development. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV has outweighed the risk of side effects.

Breast-feeding
Breast-feeding is not recommended for HIV-positive women, as HIV infection can be transmitted to the baby through breast milk.
A small amount of the components of Combivir may also pass into breast milk.
If you are breast-feeding or considering breast-feeding, you must discuss this with your doctor as soon as possible.

Driving and using machines
Combivir may cause dizziness and other side effects that may reduce alertness.
Do not drive or operate machinery unless you feel well.

Combivir contains sodium

• This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e. essentially "sodium-free".

3. How to take Combivir

Always take this medicine exactly as your doctor or pharmacist has instructed you.
Check with your doctor or pharmacist if you are unsure.
Swallow Combivir tablets with water. Combivir can be taken with or without food.
If you are unable to swallow the tablets whole, you may break them and mix them with a small amount of food or drink, and take the entire dose immediately.
Stay in regular contact with your doctor.
Combivir helps control your condition. You must take it every day to prevent your illness from worsening. You may still develop other infections and illnesses related to HIV infection.
Stay in contact with your doctor, and do not stop taking Combivir without consulting your doctor.

Dosage
Adults and adolescents weighing 30 kg or more
The usual dose of Combivir is one tablet twice daily.
Take the tablets at regular intervals, approximately 12 hours apart.

Children weighing between 21 kg and 30 kg
The usual starting dose of Combivir is half a tablet (½) in the morning and one whole tablet in the evening.

Children weighing between 14 kg and 21 kg
The usual starting dose of Combivir is half a tablet (½) in the morning and half a tablet (½) in the evening.

For children weighing less than 14 kg, lamivudine and zidovudine (the active substances in Combivir) should be taken separately.

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

If you forget to take Combivir
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 the missed dose.

4. Possible side effects

During HIV therapy, an increase in weight and in blood lipid and glucose levels may occur. This is partly related to the recovery of health status and lifestyle, and, in the case of blood lipids, sometimes to the HIV medicines themselves. Your doctor will monitor these changes.

Treatment with Combivir often causes loss of fat from the legs, arms, and face (lipoatrophy). This loss of body fat has been shown not to be completely reversible after discontinuation of zidovudine. Your doctor should monitor for signs of lipoatrofia. Inform your doctor if you notice any fat loss from your legs, arms, or face. If these signs occur, Combivir should be discontinued and HIV treatment changed.

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

During HIV treatment, it may be difficult to determine whether a symptom is an unwanted effect of Combivir or of other medicines you are taking, or an effect of HIV disease itself. For this reason, it is very important to inform your doctor about any changes in your health.

During combination antiretroviral therapy for HIV, both the side effects listed below for Combivir and other conditions may occur.

It is important to read the information elsewhere in this leaflet under 'Other possible side effects of combination antiretroviral therapy for HIV'.

Very common side effects
These may affect more than 1 in 10 patients:

• headache
• nausea

Common side effects
These may affect up to 1 in 10 patients:

• vomiting
• diarrhoea
• stomach pain
• loss of appetite
• dizziness
• tiredness, lack of energy
• fever (high temperature)
• general feeling of being unwell
• sleep disturbances (insomnia)
• muscle discomfort and pain
• joint pain
• cough
• irritation of nasal mucosa or runny nose
• skin rash
• hair loss (alopecia)

Common side effects that may be detected by blood tests include:

• low number of red blood cells (anaemia) or low number of white blood cells (neutropenia or leucopenia)
• increased liver enzymes
• increased levels of bilirubin in the blood (a substance produced by the liver), which may cause yellowing of the skin.

Uncommon side effects
These may affect up to 1 in 100 patients:

• shortness of breath
• flatulence
• itching
• muscle weakness

An uncommon side effect that may be detected by blood tests is:

• reduced number of cells involved in blood clotting (thrombocytopenia) or of all types of blood cells (pancytopenia).

Rare side effects
These may affect up to 1 in 1,000 patients:

• severe allergic reaction causing swelling of the face, tongue or throat, which may cause difficulty in swallowing or breathing
• liver disorders such as jaundice, enlarged liver or fatty liver, inflammation (hepatitis)
• lactic acidosis (excess lactic acid in the blood; see next section 'Other possible side effects of combination antiretroviral therapy for HIV')
• inflammation of the pancreas (pancreatitis)
• chest pain; heart muscle disease (cardiomyopathy)
• seizures
• anxiety or depression, difficulty concentrating, drowsiness
• indigestion, taste disturbances
• change in the colour of nails, skin, or mucous membranes inside the mouth
• flu-like feeling – chills and sweating
• tingling sensation in the skin (pins and needles)
• feeling of weakness in the limbs
• muscle tissue breakdown
• paraesthesia (altered sensation to touch)
• more frequent urination
• increased breast size in male patients

Rare side effects that may be detected by blood tests include:

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

Very rare side effects
These may affect up to 1 in 10,000 patients:
A very rare side effect that may be detected by blood tests is:

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

If you experience side effects
Tell your doctor or pharmacist if any of the side effects become severe or bothersome, or if you notice any side effect not listed in this leaflet.

Other possible side effects of combination antiretroviral therapy for HIV
Combination therapy such as Combivir may cause the development of other conditions during HIV treatment.

Old infections may flare up again
People with advanced HIV infection (Acquired Immunodeficiency Syndrome - AIDS) have a weakened immune system and are more likely to develop serious (opportunistic) infections. When such patients start treatment, previously hidden infections may flare up again, causing signs and symptoms of inflammation. These symptoms are likely due to the recovery of the immune system, so that the body starts fighting these infections.

In addition to opportunistic infections, autoimmune disorders (a condition occurring when the immune system attacks healthy body tissue) may also occur after you start taking medicines for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving towards the trunk of the body, palpitations, tremor or hyperactivity, inform your doctor immediately to receive necessary treatment.

If you notice any symptoms of infection while taking Combivir:
inform your doctor immediately. Do not take any other medicines for infection without medical advice.

Lactic acidosis is a rare but serious side effect
Some people taking Combivir develop a condition called lactic acidosis, together with an enlarged liver.

Lactic acidosis is caused by an increase in lactic acid in the body. It is a rare condition and, if it occurs, usually develops after several months of treatment. It can be life-threatening and may impair internal organs.

Lactic acidosis is more likely to occur in people with liver disease or in obese people (very overweight), especially women.

Signs of lactic acidosis include:

• difficult, deep and rapid breathing
• drowsiness
• weakness or numbness in the limbs
• nausea, vomiting
• stomach pain

During treatment, your doctor will monitor for signs of lactic acidosis. If you experience any of the symptoms listed above or any other symptom that concerns you:
contact your doctor as soon as possible.

You may have bone problems
Some people receiving combination antiretroviral therapy for HIV infection develop a condition called osteonecrosis. As a result of this condition, part of the bone tissue dies due to reduced blood supply to the bone. People may be more likely to develop this condition if they:

• have been on combination therapy for a long time
• are also taking anti-inflammatory medicines called corticosteroids
• consume alcoholic beverages
• have a very weak immune system
• are overweight.

Signs of osteonecrosis include:

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

If you notice any of these symptoms: inform your doctor.

Other effects may be detected by blood tests
Combination antiretroviral therapy for HIV infection may also cause:

• increased levels of lactic acid in the blood, which in rare cases may lead to lactic acidosis.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Combivir

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the container.
Do not store above 30°C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Combivir contains
The active substances are lamivudine and zidovudine. The excipients are:

• tablet core – microcrystalline cellulose, sodium starch glycolate (gluten-free), magnesium stearate, anhydrous colloidal silica.
• tablet coating – hypromellose, titanium dioxide, macrogol 400, polysorbate 80.

Description of the appearance of Combivir and contents of the pack
Combivir film-coated tablets are supplied in packs containing blisters or bottles with child-resistant closures. Each pack type contains 60 film-coated tablets. The tablets are divisible, capsule-shaped, white to off-white, with "GXFC3" printed on both sides.

Marketing Authorisation Holder and Manufacturer
Manufacturer Marketing Authorisation Holder
Delpharm Poznań Spółka Akcyjna ViiV Healthcare BV
ul. Grunwaldzka 189 Van Asch van Wijckstraat 55H
60-322 Poznan 3811 LP Amersfoort
Poland The Netherlands

For further information on this medicinal product, please contact the local representative of the Marketing Authorisation Holder.

België/Belgique/Belgien Lietuva
ViiV Healthcare srl/bv ViiV Healthcare BV
Tél/Tel: + 32 (0)10 85 65 00 Tel: + 370 80000334

България Luxembourg/Luxemburg
ViiV Healthcare BV ViiV Healthcare srl/bv
Teл.: + 359 80018205 Belgique/Belgien
Tél/Tel: + 32 (0)10 85 65 00

Česká republika Magyarország
GlaxoSmithKline s.r.o. ViiV Healthcare BV
Tel: + 420 222 001 111 Tel.: + 36 80088309
[email protected]

Danmark Malta
GlaxoSmithKline Pharma A/S ViiV Healthcare BV
Tlf: + 45 36 35 91 00 Tel: + 356 80065004
[email protected]

Deutschland Nederland
ViiV Healthcare GmbH ViiV Healthcare BV
Tel.: + 49 (0)89 203 0038-10 Tel: + 31 (0) 33 2081199
[email protected]

Eesti Norge
ViiV Healthcare BV GlaxoSmithKline AS
Tel: + 372 8002640 Tlf: + 47 22 70 20 00

Ελλάδα Österreich
GlaxoSmithKline Μονοπρόσωπη A.E.B.E. GlaxoSmithKline Pharma GmbH
Τηλ: + 30 210 68 82 100 Tel: + 43 (0)1 97075 0
[email protected]

España Polska
Laboratorios ViiV Healthcare, S.L. GSK Services Sp. z o.o.
Tel: + 34 900 923 501 Tel.: + 48 (0)22 576 9000

France Portugal
ViiV Healthcare SAS VIIVHIV HEALTHCARE, UNIPESSOAL, LDA.
Tél.: + 33 (0)1 39 17 6969 Tel: + 351 21 094 08 01
[email protected] [email protected]

Hrvatska România
ViiV Healthcare BV ViiV Healthcare BV
Tel: + 385 800787089 Tel: + 40 800672524

Ireland Slovenija
GlaxoSmithKline (Ireland) Limited ViiV Healthcare BV
Tel: + 353 (0)1 4955000 Tel: + 386 80688869

Ísland Slovenská republika
Vistor hf. ViiV Healthcare BV
Sími: +354 535 7000 Tel: + 421 800500589

Italia Suomi/Finland
ViiV Healthcare S.r.l. GlaxoSmithKline Oy
Tel: + 39 (0)45 7741600 Puh/Tel: + 358 (0)10 30 30 30

Κύπρος Sverige
ViiV Healthcare BV GlaxoSmithKline AB
Τηλ: + 357 80070017 Tel: + 46 (0)8 638 93 00
[email protected]

Latvija United Kingdom (Northern Ireland)
ViiV Healthcare BV ViiV Healthcare BV
Tel: + 371 80205045 Tel: + 44 (0)800 221441
[email protected]

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