Combivir (Lamivudine and Zidovudine)

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 ingredients used to treat HIV infection: lamivudine and zidovudine. Both belong to a group of antiretroviral medicines called nucleoside analogue reverse transcriptase inhibitors (NRTIs).

Combivir does not completely cure HIV infection. It reduces the amount of virus in your body and helps keep it at a low level. It also increases the CD4 cell count in your blood. CD4 cells are a type of white blood cell that help your body fight infection.

Not everyone responds to treatment with Combivir in the same way. Your doctor will monitor how well your treatment is working.

Before you take Combivir

Don't take Combivir:

• if you're allergic (hypersensitive) to lamivudine or zidovudine, or any of the other ingredients in Combivir tablets (listed in section 6)
• if you have a very low red blood cell count (anaemia) or a very low white blood cell count (neutropenia).

Check with your doctor if you think any of these apply to you.

Take special care with Combivir

Some people taking Combivir or other combination treatments for HIV have a higher risk of serious side effects. You need to be aware of these extra risks:

• if you have ever had liver disease, including hepatitis B or C (if you have hepatitis B infection, don't stop Combivir without your doctor's advice, as your hepatitis may come back)
• if you have kidney disease
• if you are seriously overweight (especially if you're a woman)
• if you're diabetic and using insulin.

Talk to your doctor if any of these apply to you. Your doctor will decide whether the active ingredients are suitable for you. You may need extra check-ups, including blood tests, while you're taking this medicine. See Section 4 for more information.

Look out for important symptoms

Some people taking medicines for HIV infection develop other conditions, which can be serious. You need to know which important signs and symptoms to watch for while you're taking Combivir.

Protect other people

HIV infection is spread through sexual contact with someone who has the infection, or through transfer of infected blood (for example, by sharing needles). Combivir will not stop you passing HIV infection on to other people. To help protect other people from becoming infected with HIV:

Use a condom when you have oral or penetrative sex.

Don't risk blood transfer - for example, don't share needles.

Other medicines and Combivir

Tell your doctor or pharmacist if you're taking any other medicines, or if you've taken any recently, including herbal medicines or medicines you bought without a prescription.

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

These medicines should not be used with Combivir:

• stavudine or zalcitabine, to treat HIV infection
• ribavirin, or injections of ganciclovir or foscarnet, to treat viral infections
• high doses of co-trimoxazole, an antibiotic.

Tell your doctor if you're being treated with any of these.

Some medicines can make side effects more likely, or make them worse.

These include:

• sodium valproate, to treat epilepsy
• interferon, to treat viral infections
• pyrimethamine, to treat malaria and other parasitic infections
• dapsone, to prevent pneumonia and treat skin infections
• fluconazole or flucytosine, to treat fungal infections such as Candida
• pentamidine or atovaquone, to treat parasitic infections such as PCP
• amphotericin or co-trimoxazole, to treat fungal and bacterial infections
• probenecid, to treat gout and 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 doctor if you're taking any of these.

Some medicines interact with Combivir

These include:

• clarithromycin, an antibiotic. If you're taking clarithromycin, take your dose at least 2 hours before or after taking Combivir.
• phenytoin, for treating epilepsy.

Tell your doctor if you're taking phenytoin. Your doctor may need to monitor you while you're taking Combivir.

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 Combivir.

Combivir and similar medicines may cause side effects in unborn babies. If you become pregnant while you're taking Combivir, your baby may need extra check-ups, including blood tests, to make sure they are developing normally.

Children whose mothers took NRTIs (medicines like Combivir) during pregnancy had a reduced risk of being infected with HIV. This benefit is greater than the risk of side effects.

Breast-feeding

Women who are HIV-positive must not breastfeed, because HIV infection can be passed on to the baby in breast milk.

If you're breastfeeding or thinking about breastfeeding:

Talk to your doctor straight away.

Driving and using machines

Combivir can make you dizzy and may cause other side effects that make you less alert. Don't drive or use machines unless you're feeling well.

How to take Combivir

Always take Combivir exactly as your doctor has told you to. Check with your doctor or pharmacist if you're not sure.

Swallow Combivir tablets with some water. Combivir can be taken with or without food.

If you cannot swallow the tablets whole, you may crush them and mix them with a small amount of food or drink, then take the full dose straight away.

Stay in regular contact with your doctor.

Combivir helps to control your condition. You need to keep taking it every day to stop your illness getting worse. You may still develop other infections and illnesses linked to HIV infection.

Keep in touch with your doctor, and don't stop taking Combivir without your doctor's advice.

How much to take

Adults and adolescents 30 kg or more

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

Take the tablets at regular times, leaving about 12 hours between each tablet.

Children who weigh between 21 and 30 kg

The usual starting dose of Combivir is half a tablet in the morning and one whole tablet in the evening.

Children who weigh between 14 and 21 kg

The usual starting dose of Combivir is half a tablet in the morning and half a tablet in the evening.

For children who weigh less than 14 kg, lamivudine and zidovudine (the ingredients of Combivir) should be taken separately.

If you take too much Combivir

If you accidentally take too much Combivir, tell your doctor or pharmacist, or contact your 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. Don't take a double dose to make up for a missed dose.

Possible side effects

Like all medicines, Combivir can cause side effects, although not everyone gets them.

When you're being treated for HIV, it can be hard to tell whether a symptom is a side effect of Combivir or other medicines you're taking, or an effect of HIV itself. That's why it's very important to talk to your doctor about any changes in your health.

As well as the side effects listed below for Combivir, other conditions can develop during combination therapy for HIV. It is important to read the information later in this section under 'Other possible side effects of combination therapy for HIV.'

Very common side effects

These may affect more than 1 in 10 people:

• headache
• feeling sick (nausea).

Common side effects

These may affect up to 1 in 10 people:

• being sick (vomiting)
• diarrhoea
• stomach pains
• loss of appetite
• feeling dizzy
• tiredness, lack of energy
• fever (high temperature)
• a general feeling of being unwell
• difficulty sleeping (insomnia)
• muscle pain and discomfort
• joint pain
• cough
• an irritated or runny nose
• skin rash
• hair loss (alopecia).

Common side effects that might show up in blood tests are:

• a low red blood cell count (anaemia) or low white blood cell count (neutropenia or leucopenia)
• an increase in the level of liver enzymes
• an increased amount of bilirubin in the blood (a substance produced in the liver), which may make your skin look yellow.

Uncommon side effects

These may affect up to 1 in 100 people:

• feeling breathless
• wind (flatulence)
• itching
• muscle weakness.

An uncommon side effect that may show up in a blood test is:

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

Rare side effects

These may affect up to 1 in 1000 people:

• a serious allergic reaction causing swelling of the face, tongue or throat, which may cause difficulty swallowing or breathing
• liver disorders, such as jaundice, enlarged liver or fatty liver, inflammation (hepatitis)
• lactic acidosis (see the next section, 'Other possible side effects of combination therapy for HIV')
• inflammation of the pancreas (pancreatitis)
• chest pain; disease of the heart muscle (cardiomyopathy)
• fits (convulsions)
• feeling depressed or anxious, not being able to concentrate, feeling drowsy
• indigestion, changes in taste
• changes in the colour of your nails, your skin, or the skin inside your mouth
• a flu-like feeling - chills and sweating
• tingling feelings in the skin (pins and needles)
• a feeling of weakness in the limbs
• breakdown of muscle tissue
• numbness
• passing urine more often
• enlarged breasts in men.

Rare side effects that may show up in blood tests are:

• an increase in an enzyme called amylase
• a 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 people:

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

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

If you get side effects

Tell your doctor or pharmacist if any side effects become severe or troublesome, or if you notice any side effects not listed in this leaflet.

Other possible side effects of combination therapy for HIV

Combination therapy such as Combivir may cause other conditions to develop during HIV treatment.

Old infections may flare up

People with advanced HIV infection (AIDS) have weak immune systems and are more likely to develop serious 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 caused by the body's immune system becoming stronger, so the body starts to fight these infections. If you get any symptoms of infection while you're taking Combivir:

Tell your doctor straight away. Don't take other medicines for the infection without your doctor's advice.

Your body shape may change

People taking combination therapy for HIV may notice changes in their body shape because of changes in fat distribution:

Fat may be lost from the legs, arms or face.

Extra fat may build up around the tummy (abdomen), or on the breasts or internal organs.

Fatty lumps (sometimes called buffalo hump) may appear on the back of the neck.

It is not yet known what causes these changes, or whether they have any long-term effects on your health. If you notice changes in your body shape, tell your doctor.

Lactic acidosis is a rare but serious side effect

Some people taking Combivir, or other medicines like it (NRTIs), develop a condition called lactic acidosis, together with an enlarged liver.

Lactic acidosis is caused by a build-up of lactic acid in the body. It is rare. If it happens, 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 people who have liver disease, or in obese (very overweight) people, especially women.

Signs of lactic acidosis include:

• deep, rapid, difficult breathing
• drowsiness
• numbness or weakness in the limbs
• feeling sick (nausea), being sick (vomiting)
• stomach pain.

During your treatment, your doctor will monitor you for signs of lactic acidosis. If you have any of the symptoms listed above, or any other symptoms that worry you:

See your doctor as soon as possible.

You may have problems with your bones

Some people taking combination therapy for HIV develop a condition called osteonecrosis. With this condition, parts of the bone tissue die because of reduced blood supply to the bone. People may be more likely to get this condition:

• if they have been taking combination therapy for a long time
• if they are also taking anti-inflammatory medicines called corticosteroids
• if they drink alcohol
• if their immune systems are very weak
• if they are overweight.

Signs of osteonecrosis include:

• stiffness in the joints
• aches and pains (especially in the hip, knee or shoulder)
• difficulty moving.

If you notice any of these symptoms, tell your doctor.

Other effects may show up in blood tests

Combination therapy for HIV can also cause:

1. increased levels of lactic acid in the blood, which on rare occasions can lead to lactic acidosis
2. increased levels of sugar and fats (triglycerides and cholesterol) in the blood
3. resistance to insulin (so if you're diabetic, you may have to change your insulin dose to control your blood sugar).

How to store Combivir

Keep Combivir out of the sight and reach of children.

Do not take Combivir after the expiry date shown on the carton.

Do not store above 30°C.

If you have any unwanted Combivir tablets, don't dispose of them in wastewater or household rubbish. Ask your pharmacist how to dispose of medicines you no longer need. These measures will help protect the environment.

Further information

What Combivir contains

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

• tablet core: microcrystalline cellulose, sodium starch glycollate (gluten free), magnesium stearate, colloidal silicon dioxide
• tablet film-coat: hypromellose, titanium dioxide, macrogol 400 and polysorbate 80.

What Combivir looks like and contents of the pack

Combivir film-coated tablets are supplied in tamper-evident blister packs containing 60 tablets. They are white to off-white, capsule-shaped scored tablets marked with the code GXFC3 on both sides.