Label: information for the user

Combivir 150 mg/300 mg film-coated tablets

lamivudine/zidovudine

Read this label carefully before starting to take this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribedonly to you, and you must notgive it to other people even if they have the same symptomsas you, as it may harm them.
• If you experience any adverse effects, consultyour doctor or pharmacist, even if they are not listed in this label. See section 4.

1.What is Combivir and how it is used

2.What you need to knowbefore starting to take Combivir

3.How to take Combivir

4.Adverse effects

5.Storage of Combivir

6.Contents of the package and additional information

Combivir is used in the treatment of the infection caused by the HIV (human immunodeficiency virus) in adults and children.

Combivir contains two active ingredients used for the treatment of the infection caused by the HIV: lamivudine and zidovudine. Both belong to a group of antiretroviral medications calledinhibitors of reverse transcriptase analogs of nucleosides(INSTIs).

Combivir 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 cellsare a type of white blood cell that plays an important role in helping your body fight infection.

Not everyone responds to Combivir treatment in the same way. Your doctor will monitor the effectiveness of your treatment.

Do not take Combivir

• if you areallergicto lamivudine, zidovudine, or any of the other ingredients inthis medication(including those listed in section 6)
• if you havea very low red blood cell count(anemia) ora very low white blood cell count(neutropenia).

Consult your doctorif you think you may have any of these conditions.

Be especially careful with Combivir

Some people who take Combivir or other combination treatments for HIV infection have a higher risk of serious side effects. You need to know that there is a higher risk:

• if you have ever hadliver disease, including hepatitis B or C (if you have hepatitis B, do not stop taking Combivir without consulting your doctor, as it may worsen)
• if you havekidney disease
• if you havesignificant obesity(especially if you are a woman).

Consult your doctor ifyou have any of these conditions.Your doctor will decide if the active ingredients are suitable for you.You may need additional tests, including blood tests, while taking this medication. For more information, see section 4.

Be aware of important symptoms

Some people who take HIV medications develop other disorders, which can be serious. You need to know what signs and symptoms to watch for while taking Combivir.

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

Other medications and Combivir

Inform your doctor or pharmacist if you are taking or have recently taken any other medication,including herbal medications and those purchased without a prescription.

Remember to inform your doctor or pharmacist if you start taking a new medication while taking Combivir.

The following medications should not be used with Combivir:

• other medications containing lamivudine, used to treatHIV infectionorhepatitis B
• emtricitabine, to treatHIV infection
• stavudine,to treatHIV infection
• ribavirin or ganciclovir injections, to treatviral infections
• high doses ofco-trimoxazole(trimethoprim and sulfamethoxazole combination), an antibiotic
• cladribine, used to treatacute lymphoblastic leukemia.

Inform your doctorif you are being treated with any of these medications.

Some medications may increase the risk of side effects, or make them worse.

These include:

• valproatesodium, to treatepilepsy
• interferon, to treatviral infections
• pyrimethamine, to treatmalariaand other parasitic infections
• dapsone, to preventpneumoniaand treat skin infections
• fluconazole or flucytosine, to treatfungal infectionssuch asCandida
• pentamidine or atovaquone, to treat parasitic infections such asPneumocystis jirovecii(often calledPCP)
• amphotericinor co-trimoxazole (trimethoprim and sulfamethoxazole combination), to treatfungal and bacterial infections
• probenecid, to treatgoutand similar conditions, and administered with some antibiotics to make them more effective
• methadone, used as aheroin substitute
• vincristine,vinblastine, ordoxorubicin, to treatcancer.

Inform your doctorif you are taking any of the above medications.

Some medications interact with Combivir

These include:

• clarithromycin, an antibiotic

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

• phenytoin, to treatepilepsy.

Inform your doctorif you are taking phenytoin. Your doctor may need to monitor you while you are taking Combivir.

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

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

Pregnancy

If you are pregnant, if you become pregnant, or if you are planning to become pregnanttalk to your doctor about the risks and benefits of taking Combivir for both you and your baby.

Combivir and similar medications may cause side effects in babies during pregnancy.

If you have been takingCombivirduring your pregnancy, your doctor may request periodic blood tests and other diagnostic tests to monitor your baby's development. In children whose mothers took INTIs during pregnancy, the benefit of HIV protection was greater than the risk of adverse effects.

Breastfeeding

Do not recommendthat women with HIV breastfeed, as the infection can be transmitted to the baby through breast milk.

A small amount of Combivir components may also pass into breast milk.

If you are breastfeeding or plan to breastfeed,you should consult your doctor as soon as possible.

Driving and operating machinery

Combivir may cause dizzinessand other side effects thatreduce your alertness.

Do not drive or operate machineryunless you feel well.

Combivir contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per tablet; it is essentially “sodium-free”.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult again with your doctor or pharmacist.

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

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

Maintain regular contact with your doctor

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

Remain in contact with your doctor and do not stop taking Combivirwithout first speaking with your doctor.

How much to take

Adults and adolescents weighing at least30 kgof weight

The usual dose of Combivir is one tablet twice a day.

Take the tablets at regular intervals of time, leaving approximately 12 hours between each tablet.

Children weighing between 21 and30 kgof weight

The usual starting doseis half a tablet(½)in the morning and one whole tablet at night.

Children weighing between 14 and21 kgof weight

The usual starting doseis half a tablet(½)in the morning andhalf a tablet(½)at night.

For children weighing less than14 kgof weight, lamivudine and zidovudine (the active ingredients of Combivir) must be taken separately.

If you take more Combivir than you should

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

If you forget to take Combivir

If you forget to take a dose, take it as soon as you remember and then continue with your usual treatment.Do not take a double dose to compensate for the missed doses.

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 recovery of health and lifestyle, and in the case of lipids in the blood, sometimes to the HIV medications themselves. Your doctor will monitor these changes.

Treatment with Combivir often causes a loss of fat from the legs, arms, and face (lipoatrophy). This loss of body fat has been shown not to be completely reversible after stopping zidovudine. Your doctor should monitor signs of lipoatrophy. If you notice any loss of fat in your legs, arms, and face, inform your doctor. When these symptoms occur, Combivir should be stopped and HIV treatment changed.Like all medicines,this medicinecan cause side effects, although not everyone will experience them.

When you are on HIV treatment, it may be difficult to distinguish if a symptom is a side effect of Combivir or of other medicines you are taking, or is due to an effect of the disease caused by HIV.Therefore, it is very important that you inform your doctor about any change in your health.

In addition to the side effects listed below for Combivir, other disorders may develop during combined HIV treatment.

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

Very common side effects

May affect more than 1 in 10 people:

• headache
• unwellness(nausea).

Common side effects

May affect up to 1 in 10 people:

• vomiting
• diarrhea
• stomach pain
• loss of appetite
• feeling of dizziness
• fatigue, lack of energy
• fever (elevated temperature)
• general feeling of unwellness
• difficulty falling asleep (insomnia)
• muscle pain and discomfort
• joint pain
• cough
• irritated or runny nose
• skin rash
• hair loss (alopecia).

The 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)
• increase in liver enzymes
• increase in the amount of 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 100 people:

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

The uncommon side effects that may appear in blood tests are:

• decrease in the number of cells involved in blood clotting (trombocytopenia) or in all types of blood cells (pancytopenia).

Rare side effects

May affect up to 1 in 1,000 people:

• severe allergic reaction that causes swelling of the face, tongue, or throat that can cause difficulty swallowing or breathing

• liver damage, such as jaundice, enlarged liver, fatty liver, inflammation (hepatitis)
• lactic acidosis (excess lactic acid in the blood, see the section below “Other possible side effects of combined HIV treatment”)
• pancreatitis (inflammation of the pancreas)(pancreatitis)
• chest pain, heart muscle disease (myocarditis)
• seizures (convulsions)
• feeling of depression or anxiety, difficulty concentrating, drowsiness
• indigestion, changes in taste
• changes in the color of the nails, skin, or mucous membranes inside the mouth
• feeling of flu — chills and sweating
• tingling sensation in the skin (pinpricks)
• weakness in the limbs
• muscle rupture
• numbness
• frequent urination
• enlargement of the breasts in men.

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

• increase in an enzyme calledamylase
• failure of the bone marrow to produce new red blood cells (aplastic anemia).

Very rare side effects

May affect up to 1 in 10,000 people:

A very rare side effect that may appear in blood tests is:

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

If you experience side effects

Inform your doctor or pharmacistif you consider that any of the side effects you experience are severe or if you notice any side effect not mentioned in this leaflet.

Other possible side effects of combined HIV treatment

Combined treatments,such as Combivir, may cause other disorders to develop during HIV treatment.

Exacerbation of old infections

People with advanced HIV infection (AIDS) have weakened immune systems and a higher risk of developing serious infections (opportunistic infections). When these people start treatment, they may find that old infections, which were previously hidden, 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.

In addition to opportunistic infections, other autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you have started taking medicines to treat your HIV infection. Autoimmune disorders may appear many monthsafter the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and rising to the body trunk, palpitations, tremors, or hyperactivity; inform your doctor immediately to receive the necessary treatment.

If you notice any symptoms of infection while taking Combivir:

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

Lactic acidosis is a rare but serious side effect

Some people taking Combivir develop a condition called lactic acidosis, along with an enlarged liver.

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 potentially fatal, causing organ failure. Lactic acidosis is more likely to develop in patients with liver disease or in obese people (with significant overweight), especially women.

The signs of lactic acidosis include:

• difficulty breathing, rapid and deep breathing
• drowsiness
• numbness or weakness of the limbs
• unwellness (nausea), vomiting
• stomach pain.

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

Visit your doctor as soon as possible.

You may have problems with your bones

Some people receiving combined HIV treatment may develop a bone disease calledosteonecrosis. With this disease, part of the bone tissue dies due to a reduction in blood supply to the bone. People are more likely to develop this disease:

• if they have been taking combined treatment for a long time
• if they also take anti-inflammatory medicines 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, and shoulder)
• difficulty moving.

If you notice any of these symptoms:

Inform your doctor.

Other effects that may appear in blood tests

Combined HIV treatment may also cause:

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

Communication of side effectsof side effects

If you experience any type of side effect, consult your doctor or pharmacist, evenif it is apossibleside effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medicine.

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

Do not use this medication after the expiration date that appears on the box..

Do not store at a temperature above 30 °C.

Medicines should not be disposed of through drains or in the trash.Ask your pharmacist how to dispose ofthe packaging and medications that you no longerneed.By doing so, you will help protect the environment.

Combivir Composition

The active ingredients are lamivudine and zidovudine. The other components are:

• tablet core : microcrystalline cellulose, sodium carboxymethyl starch (gluten-free), magnesium stearate, colloidal silicon dioxide
• • coating : hypromellose, titanium dioxide, macrogol 400, and polisorbate 80

Appearance of Combivir and packaging contents

Combivir film-coated tablets are supplied in cartons containing blister packs or a child-resistant bottle. Each type of packaging contains 60 film-coated tablets. These tablets are white to off-white, capsule-shaped, scored, and have the code GXFC3 embossed on both sides.

Marketing Authorization Holder and Responsible Person for Manufacturing

For more information about this medication, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:

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