PACKAGE LEAFLET: INFORMATION FOR THE PATIENT

Nevirapine Zentiva 200 mg tablets

Nevirapine

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 Zentiva is and what it is used for

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

3.    How to take Nevirapine Zentiva

4.    Possible side effects

5.    How to store Nevirapine Zentiva

6.    Contents of the pack and other information

1. WHAT NEVIRAPINE ZENTIVA IS AND WHAT IT IS USED FOR

Nevirapine Zentiva 200 tablets belong 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 Zentiva helps control HIV-1 infection.

Nevirapine Zentiva 200 mg tablets are indicated for the treatment of HIV-1 infected adults, adolescents and children of any age. You must take Nevirapine Zentiva together with other antiretroviral medicines. Your doctor will recommend the best medicines for you.

If Nevirapine Zentiva has been prescribed for your child, please note that all information in this leaflet is addressed to your child (in this case please read “your child” instead of “you”).

2.    WHAT YOU NEED TO KNOW BEFORE YOU TAKE NEVIRAPINE

ZENTIVA

Do not take Nevirapine Zentiva if you are allergic to nevirapine or any of the other ingredients of this medicine (listed in section 6).

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

•    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

-    general feelings of illness

-    abdominal pain

•    hypersensitivity (allergic) reactions

•    inflammation of the liver (hepatitis)

•    if you have severe liver disease

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

Warnings and precautions

Talk to your doctor or pharmacist before taking Nevirapine Zentiva

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 Zentiva 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 Zentiva 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 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 Zentiva after an exposure to HIV unless you have been diagnosed with HIV and instructed to do so by your doctor. Nevirapine Zentiva 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. There is still a risk of passing HIV to others through blood or sexual contact or contamination with blood when taking Nevirapine Zentiva. Use appropriate precautions to prevent passing on HIV to other people. Please refer to your doctor.

Prednisone should not be used to treat a rash related to Nevirapine Zentiva

If you are taking oral contraceptives (e.g. ‘pill’) or other hormonal methods of birth control during treatment with Nevirapine Zentiva, 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 Zentiva

Children and adolescents

Nevirapine Zentiva tablets can be taken by:

•    children 16 years of age or older

•    children under 16 years of age who:

-    weigh 50 kg or more

-    or have a body surface area above 1.25 square metres.

For smaller children an oral suspension liquid form is available.

Other medicines and Nevirapine Zentiva

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 Zentiva. 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 medicinal products you are taking in combination with Nevirapine Zentiva

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

• St. John’s Wort (Hypericumperforatum, medicine to treat depression)

•    rifampicin, rifabutin (medicines to treat tuberculosis)

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

•    fluconazole, ketoconazole, itraconazole (medicines 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, lopinavir/ritonavir, fosamprenavir, efavirenz, zidovudine, etravirine, rilpivirine, delavirdine, elvitegravir/cobicistat (another medicines to treat HIV-infection)

•    boceprevir, telaprevir (medicine to treat hepatitis C)

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

If you are undergoing kidney dialysis, your doctor may consider a dose adjustment of Nevirapine Zentiva. This is because Nevirapine Zentiva can be partly washed out of your blood by dialysis.

Nevirapine Zentiva with food and drink

There are no restrictions on taking Nevirapine Zentiva 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 Zentiva. 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 Zentiva. 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 ZENTIVA

You should not use Nevirapine Zentiva 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.

Dose

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

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

As Nevirapine Zentiva 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.

Nevirapine is also available in the market in liquid form 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 having a body surface area less than 1.25 square metres (your doctor will work out your surface area).

You should continue to take Nevirapine Zentiva 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 Zentiva treatment. Your doctor might then decide to restart you on a lower dose.

Only take Nevirapine Zentiva tablets by mouth. Do not chew your tablets. You may take Nevirapine Zentiva with or without food.

The score line is only there to help you break the tablet if you have difficulty swallowing it whole.

If you take more Nevirapine Zentiva than you should

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

If you forget to take Nevirapine Zentiva

Try not to miss a dose. If you notice that you have missed a dose within 8 hours of when it was due, take the missed dose as soon as possible. If it has been more than 8 hours since the dose was due only take the next dose at the usual time.

If you stop taking Nevirapine Zentiva

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 Zentiva correctly, as described above, unless your doctor instructs you to stop.

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

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

4. POSSIBLE SIDE EFFECTS

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 Zentiva are severe and life-threatening skin reactions and serious liver damage. These reactions occur mainly in the first 18 weeks of treatment with Nevirapine Zentiva. 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 liver or kidneys (liver or kidney failure).

Tell your doctor immediately if you experience 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 Zentiva.

This includes some cases of inflammation of the liver (hepatitis), which can be sudden and intense (fulminant hepatitis), and liver failure, which can be both 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 Zentiva:

Very common (may affect more than 1 in 10 people):

•    rash

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

•    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)

•    feeling tired (fatigue)

•    fever

•    abnormal liver function tests Uncommon (may affect up to 1 in 100 people):

•    allergic reaction characterized 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)

•    muscle pain (myalgia)

•    decreased blood phosphorus

•    increased blood pressure

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

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

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

Combination antiretroviral therapy may cause changes in body shape due to changes in fat

8

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

The following events have also been reported when Nevirapine Zentiva 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 Zentiva is used in combination with other agents; however, it is unlikely that these events are due to treatment with Nevirapine Zentiva

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.

5. HOW TO STORE NEVIRAPINE ZENTIVA

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 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.

6. CONTENTS OF THE PACK AND OTHER INFORMATION What Nevirapine Zentiva contains

The active substance is nevirapine. Each tablet contains 200 mg nevirapine.

The other ingredients are: microcrystalline cellulose, croscarmellose sodium, maize starch, povidone (K30), sodium starch glycolate, colloidal anhydrous silica, magnesium stearate.

What Nevirapine Zentiva looks like and contents of the pack

Off-white to pale yellow coloured, capsule shaped, biconvex tablets, debossed with ‘H’ on one side and ‘7’ on the other side with breakline on both sides.

Nevirapine Zentiva tablets are supplied in blisters, with 14, 60 or 120 tablets per carton.

Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

The Manufacturer is Pharmadox Healthcare Ltd., KW20A Kordin Industrial Park, Paola, PLA 3000, Malta or S.C. ZENTIVA S.A. B-dul. Theodor Pallady nr. 50, district 3, Bucuresti, cod 032266, Romania

The Marketing Authorisation Holder is Zentiva, One Onslow Street, Guilford, Surrey, GUI 4YS, UK.

This medicinal product is authorised in the Member States of the EEA under the following names:__

Portugal, Italy	Nevirapina Zentiva
United Kingdom	Nevirapine Zentiva 200 mg

This leaflet was last revised in April 2014

10