Document: leaflet MAH GENERIC_PL 00289-2041 change

• leaflet MAH GENERIC_PL 00289-2040
• leaflet MAH GENERIC_PL 00289-2041

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NEVIRAPINE TEVA 400 mg PROLONGED-RELEASE TABLETS

PACKAGE LEAFLET: INFORMATION FOR THE USER

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

•    Keep this leaflet. You may need to read it again.

•    If you have any further questions, ask your doctor or pharmacist.

•    This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.

•    If you get any side effects talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET

1.    What Nevirapine Teva is and what it is used for

2.    What you need to know before you take Nevirapine Teva

3.    How to take Nevirapine Teva

4.    Possible side effects

5.    How to store Nevirapine Teva

6.    Contents of the pack and other information

OH What Nevirapine Teva is and what it is used for

Nevirapine Teva belongs to a group of medicines called antiretrovirals, used in the treatment of Human Immunodeficiency Virus (HIV-1) infection.

The active substance of your medicine is called nevirapine. Nevirapine 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. Nevirapine stops reverse transcriptase from working. By stopping reverse transcriptase from working, Nevirapine Teva helps control HIV-1 infection.

Nevirapine Teva is indicated for the treatment of HIV-1 infected adults, adolescents and children aged three years and above and able to swallow tablets. You must take Nevirapine Teva together with other antiretroviral medicines. Your doctor will recommend the best medicines for you.

Nevirapine Teva prolonged-release tablets should only be used after a two-week treatment with another type of nevirapine medicine (immediate-release tablets or suspension) unless you are currently on these medicines and are switching to the prolonged-release form.

©H What you need to know before you take Nevirapine Teva

Do NOT take Nevirapine Teva

•    if you are allergic to nevirapine or any of the other ingredients of this medicine (listed in section 6 'What Nevirapine Teva contains').

•    if you have taken nevirapine before and had to stop the treatment because you suffered from:

-    severe skin rash

-    skin rash with other symptoms for example: o fever

o blistering o mouth sores o inflammation of the eye o swelling of the face o general swelling o shortness of breath o muscle or joint pain o general feelings of illness o abdominal pain

-    hypersensitivity (allergic) reactions

-    inflammation of the liver (hepatitis)

•    if you have severe liver disease

•    if you have had to stop nevirapine 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 Nevirapine Teva from working properly.

Warnings and precautions

Talk to your doctor or pharmacist before taking

Nevirapine Teva.

During the first 18 weeks of treatment with Nevirapine Teva it is very important that you and your doctor watch out for signs of liver or skin reactions. These can become severe and even life-threatening. You are at greatest risk of such a reaction during the first 6 weeks of treatment.

If you experience severe rash or hypersensitivity (allergic reactions that may appear in the form of rash) accompanied by 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,

•    general feelings of illness,

•    or abdominal pain.

YOU SHOULD DISCONTINUE TAKING NEVIRAPINE TEVA AND YOU MUST CONTACT your doctor IMMEDIATELY be potentially life-threatening and lead to death. If you ever have only mild rash symptoms without any other reaction please inform your doctor immediately, who will advise you whether you should stop taking Nevirapine Teva.

If you experience symptoms suggesting damage of the liver, such as:

•    loss of appetite,

•    feeling sick (nausea),

•    vomiting,

•    yellow skin (jaundice),

•    abdominal pain,

you should discontinue taking Nevirapine Teva and must contact your doctor immediately.

If you develop severe liver, skin or hypersensitivity reactions whilst taking Nevirapine Teva, NEVER TAKE NEVIRAPINE TEVA again without referring to your doctor.

You must take the dose of nevirapine as prescribed by your doctor. This is especially important within the first 14 days of treatment (see more information in "How to take Nevirapine Teva").

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

•    women

•    infected with hepatitis B or C

•    abnormal liver function tests

•    treatment-naive patients with higher CD4 cell counts at the start of nevirapine 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 nevirapine therapy (women more than 250 cells/mmF, 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 occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body's immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please inform your doctor immediately.

In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection.

Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.

Changes of body fat may occur in patients receiving combination antiretroviral therapy. Contact your doctor if you notice changes in body fat (see section 4 'Possible side effects').

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). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe weakness of the immune system and 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 of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

If you are taking nevirapine and zidovudine concomitantly please inform your doctor since he might need to check your white blood cells.

Do NOT take Nevirapine Teva after an exposure to HIV unless you have been diagnosed with HIV and instructed to do so by your doctor.

Nevirapine is not a cure for HIV infection. Therefore, you may continue to develop infections and other illnesses associated with HIV infection. You should therefore remain in regular contact with your doctor. You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your doctor the precautions needed to avoid infecting other people.

Prednisone should not be used to treat a rash related to nevirapine.

If you are taking oral contraceptives (e.g. 'pill') or other hormonal methods of birth control during treatment with Nevirapine Teva, you should use a barrier contraception (e.g. condoms) in addition to prevent pregnancy and further HIV transmission.

If you are receiving post-menopausal hormone therapy, ask your doctor for advice before taking this medicine.

If you are taking or are prescribed rifampicin to treat tuberculosis, please inform your doctor before taking this medicine with Nevirapine Teva.

Some patients taking other nevirapine prolonged-release formulations have reported the occurrence of remnants in faeces which may resemble intact tablets. Based on the data available, this has not been shown to affect the therapeutic response of these other formulations.

Children and adolescents

Nevirapine Teva 400 mg prolonged-release tablets can be taken by children if they:

•    are > 8 years of age and weigh 43.8 kg or more

•    are older than 3 years of age and below 8 years of age and weigh 25 kg or more

•    have a body surface area of 1.17 square metres or above.

For smaller children lower dose prolonged-release tablets or an oral suspension liquid form may be available.

Other medicines and Nevirapine Teva

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. Inform your doctor about all other medicines you are taking before you start taking Nevirapine Teva. Your doctor might need to monitor whether your other medicines are still working and adjust doses. Carefully read the package leaflet of all other HIV medicines you are taking in combination with Nevirapine Teva.

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

•    St. John's wort (Hypericum perforatum, medicine to treat depression)

•    rifampicin (medicine to treat tuberculosis)

•    rifabutin (medicine to treat tuberculosis)

•    macrolides e.g. clarithromycin (medicine to treat bacterial infections)

•    fluconazole (medicine to treat fungal infections)

•    ketoconazole (medicine to treat fungal infections)

•    itraconazole (medicine to treat fungal infections)

•    methadone (medicine used for treatment of opiate addicts)

•    warfarin (medicine to reduce blood clotting)

•    hormonal contraceptives (e.g. the 'pill')

•    atazanavir (another medicine to treat HIV infection)

•    lopinavir/ritonavir (another medicine to treat HIV infection)

•    fosamprenavir (another medicine to treat HIV infection)

•    efavirenz (another medicine to treat HIV infection)

•    etravirine (another medicine to treat HIV infection)

•    rilpivirine (another medicine to treat HIV infection)

•    delavirdine (another medicine to treat HIV infection)

•    zidovudine (another medicine to treat HIV infection)

•    boceprevir (medicine to treat hepatitis C)

•    telaprevir (medicine to treat hepatitis C)

•    elvitegravir/cobicistat (another medicine to treat HIV infection).

Your doctor will carefully monitor the effect of Nevirapine Teva and any of these medicines if you are taking them together.

Taking Nevirapine Teva with food and drink

There are no restrictions on taking Nevirapine Teva with food and drink.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

You should stop breast-feeding if you are taking Nevirapine Teva. It is, in general, recommended that you do not breast-feed if you have HIV infection because it is possible that your baby can become infected with HIV through your breast milk.

Driving and using machines

You may experience fatigue when taking Nevirapine Teva. Use caution when engaging in activities such as driving, using any tools or machines. If you experience fatigue, you should avoid potentially hazardous tasks such as driving or using any tools or machines.

3 How to take Nevirapine Teva

You should not use Nevirapine Teva 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. Check with your doctor or pharmacist if you are not sure.

Dosage:

Adults:

The dose is one 200 mg nevirapine tablet per day for the first 14 days of treatment ("lead-in" period). After 14 days, the usual dose is one 400 mg prolonged-release tablet once a day.

It is very important that you take only one nevirapine 200 mg tablet a day for the first 14 days ("lead-in" period). If you have any rash during this period, do NOT start taking Nevirapine Teva prolonged-release tablets but consult your doctor.

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

Patients who are already on immediate-release tablets or oral suspension can switch to the prolonged-release tablets without the lead-in period.

As nevirapine 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.

If needed your doctor will check the availability of lower dose nevirapine prolonged-release tablets (for children 3 years old and above after the lead-in period) or the oral suspension (for all age groups).

You should continue to take Nevirapine Teva for as long as instructed by your doctor.

As explained in 'Warnings and precautions', above, your doctor will monitor you with liver tests or for undesirable effects such as rash. Depending on the outcome, your doctor may decide to interrupt or stop your nevirapine treatment. Your doctor might then decide to restart you on a lower dose.

If you have a renal or hepatic impairment of any

degree please use only nevirapine 200 mg tablets or nevirapine 50 mg/5 ml oral suspension. If they are needed your doctor will check for the availability of these additional forms.

Only take Nevirapine Teva prolonged-release tablets by mouth. Do not chew your prolonged-release tablets. You may take Nevirapine Teva with or without food.

If you take more Nevirapine Teva than you should

Do not take more Nevirapine Teva than prescribed by your doctor and described in this leaflet. There is at present little information on the effects of nevirapine overdose. Consult your doctor if you have taken more Nevirapine Teva than you should.

If you forget to take Nevirapine Teva

Try not to miss a dose. If you notice you missed a dose within 12 hours of when it was due, take the missed dose as soon as possible. If it has been more than 12 hours since the dose was due, only take the next dose at the usual time.

If you stop taking Nevirapine Teva

Taking all doses at the appropriate 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 Nevirapine Teva correctly, as described above, unless your doctor instructs you to stop.

If you stop taking Nevirapine Teva for more than 7 days, your doctor will instruct you to start the 14 day 'lead-in' period with nevirapine tablets (described above) once again, before returning to the once daily dose with Nevirapine Teva prolonged-release tablets.

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

^4 Possible side effects

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.

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

As mentioned in 'Warnings and precautions' above, the most important side effects of Nevirapine Teva are severe and life-threatening skin reactions and serious liver damage. These reactions occur mainly in the first 18 weeks of treatment with nevirapine. This is therefore an important period which requires close monitoring by your doctor.

If you ever observe any rash symptoms, inform your doctor immediately.

When rash occurs, it is normally mild to moderate. However, in some patients a rash, which 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 of the cases of both severe rash and mild/moderate rash occur in the first six weeks of treatment.

If rash occurs and you also feel sick, you must stop treatment and visit your doctor immediately.

Hypersensitivity (allergic) reactions can occur. Such 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 your skin

•    mouth sores

•    inflammation of the eye

•    swelling of the face

•    general swelling

•    shortness of breath

•    muscle or joint pain

•    a reduction in the numbers of your white blood cells (granulocytopenia)

•    general feelings of illness

•    severe problems with your liver or kidneys (liver or kidney failure).

Tell your doctor IMMEDIATELY

rash and any of the other side effects of a hypersensitivity (allergic) reaction. Such reactions can be life-threatening.

Abnormal liver functioning has been reported with the use of nevirapine. This includes some cases of inflammation of the liver (hepatitis), which can be sudden and intense (fulminant hepatitis), and liver failure, which can both be fatal.

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

•    loss of appetite

•    feeling sick (nausea)

•    vomiting

•    yellow skin (jaundice)

•    abdominal pain.

The side effects described below have been experienced by patients given nevirapine 200 mg tablets during the 14 day lead-in phase:

Common (may affect up to 1 in 10 people):

•    rash

•    fever

•    headache

•    abdominal pain

•    feeling sick (nausea)

•    loose stools (diarrhoea)

•    feeling tired (fatigue).

Uncommon (may affect up to 1 in 100 people):

•    allergic reactions (hypersensitivity)

•    allergic reaction characterised by rash, swelling of the face, difficulty breathing (bronchial

spasm) or anaphylactic shock

•    drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)

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

•    severe and life-threatening skin rashes (Stevens-Johnson syndrome/toxic epidermal necrolysis)

•    yellow skin (jaundice)

•    hives (urticaria)

•    fluid under the skin (angioneurotic oedema)

•    vomiting

•    muscle pain (myalgia)

•    joint pain (arthralgia)

•    decreased numbers of white blood cells (granulocytopenia)

•    abnormal liver function tests

•    decreased blood phosphorus

•    increased blood pressure.

Rare (may affect up to 1 in 1000 people):

•    inflammation of the liver (hepatitis)

•    decreased numbers of red blood cells (anaemia).

The side effects described below have been experienced by patients given nevirapine prolonged-release tablets once daily in the maintenance phase:

Common (may affect up to 1 in 10 people):

•    rash

•    headache

•    abdominal pain

•    feeling sick (nausea)

•    inflammation of the liver (hepatitis)

•    feeling tired (fatigue)

•    abnormal liver function tests

•    fever

•    vomiting

•    loose stools (diarrhoea).

Uncommon (may affect up to 1 in 100 people):

•    allergic reactions (hypersensitivity)

•    allergic reaction characterised by rash, swelling of the face, difficulty breathing (bronchial spasm) or anaphylactic shock

•    drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)

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

•    severe and life-threatening skin rashes (Stevens-Johnson syndrome/toxic epidermal necrolysis)

•    decreased numbers of red blood cells (anaemia)

•    decreased numbers of white blood cells (granulocytopenia)

•    yellow skin (jaundice)

•    hives (urticaria)

•    fluid under the skin (angioneurotic oedema)

•    muscle pain (myalgia)

•    joint pain (arthralgia)

•    decreased blood phosphorus

•    increased blood pressure.

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

•    decreased numbers of red blood cells or platelets

•    inflammation of the pancreas

•    decrease in or abnormal skin sensations.

These events are commonly associated with other antiretroviral agents and may be expected to occur when nevirapine is used in combination with other agents; however, it is unlikely that these events are due to treatment with nevirapine.

Additional side effects in children and adolescents

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 nevirapine therapy, is also more commonly observed in children. As with rash symptoms, please inform your doctor of any side effects.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard By reporting side effects you can help provide more information on the safety of this medicine.

How to store Nevirapine Teva

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

Do not use this medicine after the expiry date which is stated on the carton and on the blister strip or bottle label after EXP The expiry date refers to the last day of that month.

This medicinal product does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

Contents of the pack and other information

What Nevirapine Teva contains

•    The active substance is nevirapine.

Each prolonged-release tablet contains 400 mg nevirapine.

•    The other ingredients are cellulose microcrystalline, povidone, polyethylene oxide, silica, colloidal anhydrous and magnesium stearate.

What Nevirapine Teva looks like and contents of the pack

Nevirapine Teva are white to off-white, oval, biconvex tablets, approximately 20.5 mm long and 10 mm wide, marked '400' on one side and plain on the other.

They are available in blister packs of 10, 10x1,30, 30x1,60, 60x1, 90, 90x1, 100 and 100x1 and HDPE bottles of 30 prolonged-release tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

TEVA UK Limited, Eastbourne, BN22 9AG, UK

Manufacturer

TEVA Gyogyszergyar Zrt., Pallagi ut 13, Debrecen, 4042, Hungary

This leaflet was last revised in 04/2016

PL 00289/2041

TEVA UK LIMITED    83638-A