Nevirapine

What Nevirapine is and what it is used for

This medicine belongs to a group of medicines called antiretrovirals, which are used to treat Human Immunodeficiency Virus (HIV-1) infection.

The active ingredient in this medicine is nevirapine. This is the substance that reduces the amount of virus in the blood, helping to improve your condition. It belongs to a class of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Reverse transcriptase is an enzyme that HIV needs in order to multiply. This medicine blocks reverse transcriptase. By stopping it from working, the medicine helps control HIV-1 infection.

You must take this medicine together with other antiretroviral medicines. Your doctor will recommend the best medicines for you.

Before you take this medicine

Do not take this medicine

• if you are allergic (hypersensitive) to nevirapine or any of the other ingredients in this medicine. See Section 6 of this leaflet for a list of the other ingredients
• if you have taken this medicine before and had to stop treatment because you developed:
• severe skin rash
• skin rash with other symptoms, for example:
• fever
• blistering
• mouth sores
• inflammation of the eye
• swelling of the face
• general swelling
• shortness of breath
• muscle or joint pain
• a general feeling of being unwell
• abdominal pain
• hypersensitivity (allergic) reactions
• inflammation of the liver (hepatitis)
• if you have severe liver disease
• if you have had to stop treatment in the past because of changes in your liver function
• if you are taking a medicine containing the herbal substance St John's Wort (Hypericum perforatum). This herbal substance may stop this medicine from working properly.

Take special care: During the first 18 weeks of treatment, it is very important that you and your doctor watch for signs of liver or skin reactions. These can become severe and even life-threatening. The risk is greatest during the first 6 weeks of treatment.

If you develop a severe rash or a hypersensitivity (allergic) reaction, which may appear as a rash, together with other side effects such as

• fever,
• blistering,
• mouth sores,
• inflammation of the eye,
• swelling of the face,
• general swelling,
• shortness of breath,
• muscle or joint pain,
• a general feeling of being unwell,
• or abdominal pain

you should stop taking this medicine and contact your doctor immediately, as these reactions can be life-threatening or lead to death. If you ever have only mild rash symptoms without any other reaction, tell your doctor straight away. They will advise you whether you should stop taking the medicine.

If you develop symptoms that suggest liver damage, such as

• loss of appetite,
• feeling sick (nausea),
• vomiting,
• yellow skin (jaundice),
• abdominal pain

you should stop taking the medicine and contact your doctor immediately.

If you develop severe liver, skin or hypersensitivity reactions while taking this medicine, never take it again without speaking to your doctor. You must take the dose exactly as prescribed by your doctor. This is especially important during the first 14 days of treatment.

The following patients are at increased risk of developing liver problems:

• women
• people infected with hepatitis B or C
• people with abnormal liver function tests
• treatment-naive patients with higher CD4 cell counts at the start of therapy (women more than 250 cells/mm³, men more than 400 cells/mm³)
• pre-treated patients with detectable HIV-1 plasma viral load and higher CD4 cell counts at the start of therapy (women more than 250 cells/mm³, men more than 400 cells/mm³)

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection (AIDS-defining illness), signs and symptoms of inflammation from previous infections may appear soon after anti-HIV treatment is started. These symptoms are thought to be due to an improvement in the body's immune response, allowing the body to fight infections that may have been present without obvious symptoms. If you notice any symptoms of infection, tell your doctor immediately.

Changes in body fat may occur in patients receiving combination antiretroviral therapy. Contact your doctor if you notice any changes in body fat.

Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). Length of combination antiretroviral therapy, use of corticosteroids, alcohol consumption, severe weakening of the immune system and a higher body mass index may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially in the hip, knee and shoulder) and difficulty moving. If you notice any of these symptoms, tell your doctor.

This medicine is not a cure for HIV infection. You may therefore continue to develop infections and other illnesses associated with HIV infection. You should therefore stay in regular contact with your doctor. In addition, this medicine does not prevent the risk of passing HIV to other people through blood or sexual contact. Use appropriate precautions to avoid passing HIV on to others. Please speak to your doctor.

Use in children

Tablets can be taken by:

• children aged 16 years or over
• children under 16 years of age who weigh 50 kg or more
• or who have a body surface area above 1.25 square metres.

For smaller children, an oral suspension is available.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription. Tell your doctor about all other medicines you are taking before you start treatment. Your doctor may need to check whether your other medicines are still working properly and adjust the doses. Carefully read the package leaflet for all other HIV medicines you are taking with this medicine.

It is particularly important that you tell your doctor if you are taking or have recently taken:

• St John's Wort (Hypericum perforatum, a medicine used to treat depression)
• rifampicin (a medicine used to treat tuberculosis)
• rifabutin (a medicine used to treat tuberculosis)
• macrolides, e.g. clarithromycin (a medicine used to treat bacterial infections)
• fluconazole (a medicine used to treat fungal infections)
• ketoconazole (a medicine used to treat fungal infections)
• itraconazole (a medicine used to treat fungal infections)
• methadone (a medicine used to treat opioid dependence)
• warfarin (a medicine used to reduce blood clotting)
• hormonal contraceptives (e.g. the "pill")
• atazanavir (another medicine used to treat HIV infection)
• lopinavir/ritonavir (another medicine used to treat HIV infection)
• fosamprenavir (another medicine used to treat HIV infection)
• efavirenz (another medicine used to treat HIV infection)

Your doctor will carefully monitor the effects of this medicine and any of these medicines if you are taking them together.

If you are having kidney dialysis, your doctor may consider adjusting your dose. This is because the active ingredient can be partly removed from your blood by dialysis.

Taking this medicine with food and drink

There are no restrictions on taking this medicine with food and drink.

Pregnancy and breast-feeding

Ask your doctor or pharmacist for advice before taking any medicine.

You should stop breast-feeding if you are taking this medicine. In general, it is recommended that you do not breast-feed if you have HIV infection because it is possible for your baby to become infected with HIV through your breast milk.

Driving and using machines

There have been no specific studies on the ability to drive and use machines. If you feel that your ability to drive or use machines may be affected, you should not drive or use machines.

Important information about some of the ingredients

Tablets contain lactose (milk sugar). If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

How to take this medicine

You should not use this medicine on its own. You must take it with at least two other antiretroviral medicines. Your doctor will recommend the best medicines for you.

Always take this medicine exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Only take the tablets by mouth. Do not chew the tablets. You may take this medicine with or without food.

Dosage

The dose is one 200 mg tablet per day for the first 14 days of treatment (the "lead-in" period). After 14 days, the usual dose is one 200 mg tablet twice a day.

It is very important that you take only one tablet a day for the first 14 days (the "lead-in" period). If you develop any rash during this period, do not increase the dose, but consult your doctor.

The 14-day "lead-in" period has been shown to lower the risk of skin rash.

As this medicine must always be taken together with other HIV antiretroviral medicines, you should follow the instructions for your other medicines carefully. These are supplied in the package leaflets for those medicines.

This medicine is also available as an oral suspension. This is particularly suitable if:

• you have problems swallowing tablets
• or you are a child weighing less than 50 kg
• or you are a child with a body surface area less than 1.25 square metres (your doctor will work out your body surface area).

You should continue treatment for as long as your doctor tells you to.

Your doctor will monitor you with liver tests or for side effects such as rash. Depending on the results, your doctor may decide to interrupt or stop treatment. Your doctor may then decide to restart treatment at a lower dose.

If you take more than you should

Do not take more than prescribed by your doctor and described in this leaflet. At present, there is little information on the effects of overdose. Consult your doctor if you have taken more than you should.

If you forget to take a dose

Try not to miss a dose. If you notice that you have missed a dose within 8 hours, take the next dose as soon as possible. If you notice it more than 8 hours later, take the next dose at the usual time.

If you stop taking this medicine

Taking all doses at the right times:

• greatly increases the effectiveness of your combination antiretroviral medicines
• reduces the chances of your HIV infection becoming resistant to your antiretroviral medicines.

It is important that you continue taking this medicine correctly, as described above, unless your doctor tells you to stop.

If you stop treatment for more than 7 days, your doctor will tell you to start the 14-day 'lead-in' period (described above) again before returning to the twice-daily dose.

If you have any further questions about the use of this product, ask your doctor or pharmacist.

Possible side effects

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

The most important side effects are severe and life-threatening skin reactions and serious liver damage. These reactions occur mainly in the first 18 weeks of treatment. This is therefore an important period that requires close monitoring by your doctor.

If you notice any rash symptoms at all, tell your doctor immediately.

When rash occurs, it is usually mild to moderate. However, in some patients a rash that appears as a blistering skin reaction can be severe or life-threatening (Stevens-Johnson syndrome and toxic epidermal necrolysis), and deaths have been recorded. Most cases of both severe rash and mild to moderate rash occur in the first six weeks of treatment.

If rash occurs and you also feel unwell, you must stop treatment and see your doctor immediately.

Hypersensitivity (allergic) reactions can occur. These reactions may appear in the form of anaphylaxis (a severe form of allergic reaction), with symptoms such as:

• rash
• swelling of the face
• difficulty breathing (bronchial spasm)
• anaphylactic shock

Hypersensitivity reactions can also occur as rash with other side effects such as:

• fever
• blistering of the skin
• mouth sores
• inflammation of the eye
• swelling of the face
• general swelling
• shortness of breath
• muscle or joint pain
• a reduction in the number of white blood cells (granulocytopenia)
• a general feeling of being unwell
• severe liver or kidney problems (liver or kidney failure)

Tell your doctor immediately if you develop a rash and any of the other side effects of a hypersensitivity (allergic) reaction. Such reactions can be life-threatening.

Abnormal liver function has been reported with the use of this medicine. This includes some cases of inflammation of the liver (hepatitis), which can be sudden and severe (fulminant hepatitis), and liver failure, which can be fatal.

Tell your doctor if you develop any of the following symptoms of liver damage:

• loss of appetite
• feeling sick (nausea)
• vomiting
• yellow skin (jaundice)
• abdominal pain

Side effects are grouped by how common they are, using the following categories:

The side effects described below have been reported in patients taking this medicine:

Very common:

• rash

Common:

• decreased numbers of white blood cells (granulocytopenia)
• allergic reactions (hypersensitivity)
• headache
• feeling sick (nausea)
• vomiting
• abdominal pain
• loose stools (diarrhoea)
• inflammation of the liver (hepatitis)
• muscle pain (myalgia)
• feeling tired (fatigue)
• fever
• abnormal liver function tests

Uncommon:

• drug rash with systemic symptoms (drug rash with eosinophilia and systemic symptoms)
• allergic reaction characterised by rash, swelling of the face, difficulty breathing (bronchial spasm) or anaphylactic shock
• decreased numbers of red blood cells (anaemia)
• yellow skin (jaundice)
• severe and life-threatening skin rashes (Stevens-Johnson syndrome/toxic epidermal necrolysis)
• hives (urticaria)
• fluid under the skin (angioedema)
• joint pain (arthralgia)

Rare:

• sudden and severe inflammation of the liver (fulminant hepatitis)

Combination antiretroviral therapy may cause changes in body shape due to changes in fat distribution. These may include loss of fat from the legs, arms and face, increased fat in the abdomen (tummy) and other internal organs, breast enlargement and fatty lumps on the back of the neck ('buffalo hump'). The cause and the long-term health effects of these conditions are not known at present. Combination antiretroviral therapy may also cause raised lactic acid and blood sugar, hyperlipaemia (increased fats in the blood) and resistance to insulin.

The following events have also been reported when this medicine has been used in combination with other antiretroviral agents:

• decreased numbers of red blood cells or platelets
• inflammation of the pancreas
• decreased or abnormal skin sensations. These events are commonly associated with other antiretroviral agents and may be expected to occur when this medicine is used in combination with other agents; however, it is unlikely that these events are due to this treatment.

Use in children

A reduction in white blood cells (granulocytopenia) can occur, which is more common in children. A reduction in red blood cells (anaemia), which may be related to treatment, is also more commonly seen in children. As with rash symptoms, tell your doctor about any side effects.

If any of the side effects becomes serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How to store this medicine

Keep out of the sight and reach of children.

Do not use after the expiry date stated on the carton and blister after "EXP". The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

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