Package Insert: Information for the User

Nevirapina KERN PHARMA 200 mg Tablets EFG

Read this package insert carefully before starting to take the medication.

• Keep this package insert, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medication has been prescribed to you and should not be given to others, even if they have the same symptoms, as it may harm them.
• If you consider any of the adverse effects you are experiencing to be severe or if you notice any adverse effect not mentioned in this package insert, inform your doctor or pharmacist.

1. What Nevirapina Kern Pharma is and for what it is used

2. Before taking Nevirapina Kern Pharma

3. How to take Nevirapina Kern Pharma

4. Possible adverse effects

5. Storage of Nevirapina Kern Pharma

6. Additional information

Nevirapina Kern Pharma belongs to a group of medicines called antiretrovirals, which are used in the treatment of Human Immunodeficiency Virus (HIV) infection.

The active ingredient of this medicine is called nevirapina. This active ingredient reduces the amount of virus in the blood, thereby improving the disease.

Nevirapina belongs to a class of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). The reverse transcriptase is an enzyme that HIV needs to multiply. Nevirapina prevents the functioning of the reverse transcriptase. By preventing the functioning of the reverse transcriptase, nevirapina helps control the HIV infection.

You should take Nevirapina Kern Pharma along with other antiretroviral medicines. Your doctor will indicate the suitable medicines for you.

Do not take Nevirapina Kern Pharma

• if you are allergic (hypersensitive) to nevirapina or to any of the other components of Nevirapina Kern Pharma. See section 6 of this leaflet for a list of the other components (“Composition of Nevirapina Kern Pharma”))
• if you have taken Nevirapina Kern Pharma before and had to stop treatment because you experienced:
• severe skin rash
• skin rash with other symptoms such as:
• fever
• blistering
• mouth ulcers
• inflammation of the eye
• swelling of the face
• general swelling
• difficulty breathing
• muscle or joint pain
• general feeling of being unwell
• abdominal pain

• hypersensitivity reactions (allergies)
• inflammation of the liver (hepatitis)
• if you have a serious liver disease
• if you have had to stop treatment with Nevirapina in the past due to changes in your liver function
• if you are using any medicine that contains St. John's Wort (Hypericum perforatum)

Be especially careful with Nevirapina Kern Pharma

During the first 18 weeks of treatment with Nevirapina, it is very important that you and your doctor monitor the appearance of liver or skin reactions. These reactions can be severe and even life-threatening. The risk of developing these reactions is higher during the first 6 weeks of treatment.

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

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

In some patients with advanced HIV (AIDS) infection and a history of opportunistic infections (defining AIDS disease), signs and symptoms of previous infections may appear shortly after starting antiretroviral treatment. It is believed that these symptoms are due to an improvement in the body's immune response, allowing it to fight off infections that were present without apparent symptoms. If you notice any symptoms of infection, please inform your doctor immediately.

Changes in body fat may occur in patients receiving combination antiretroviral therapy. Consult your doctor if you notice changes in body fat (see section 4 “POSSIBLE ADVERSE EFFECTS”).

In some patients receiving combination antiretroviral therapy, a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone) may develop. The duration of antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunodeficiency, and high body mass index may be some of the many risk factors for developing this disease. The symptoms of osteonecrosis are: joint stiffness, pain, and discomfort, especially in the hip, knee, and shoulder, and difficulty moving. If you notice any of these symptoms, inform your doctor.

Nevirapina Kern Pharma does not cure HIV infection. Therefore, you may still be experiencing infections and other diseases associated with HIV infection. You should therefore maintain regular contact with your doctor. Additionally, Nevirapina Kern Pharma does not prevent the risk of HIV transmission to others through blood or sexual contact. Use appropriate precautions to avoid HIV transmission to others. Please consult your doctor.

Use in children

Nevirapina Kern Pharma tablets can be used in:

• children aged 16 years or older
• children under 16 years:
• with a body weight of 50 kg or more
• or with a body surface area of 1.25 m2 or more.

Use of other medicines

Inform your doctor or pharmacist if you are using or have used recently other medicines, including those obtained without a prescription. Before starting treatment with Nevirapina Kern Pharma, inform your doctor of all other medicines you are taking. Your doctor may need to check if your other medicines are still working and make dose adjustments. Read the leaflet of all other HIV medicines you are taking in combination with Nevirapina Kern Pharma.

It is especially important to inform your doctor if you are using or have used recently:

• St. John's Wort (Hypericum perforatum, medicinal plant for the treatment of depression)
• rifampicin (medicine for the treatment of tuberculosis)
• rifabutin (medicine for the treatment of tuberculosis)
• macrolides, e.g. clarithromycin (medicine for the treatment of bacterial infections)
• fluconazole (medicine for the treatment of fungal infections)
• ketoconazole (medicine for the treatment of fungal infections)
• itraconazole (medicine for the treatment of fungal infections)
• methadone (medicine used for the treatment of opioid addiction)
• warfarin (medicine to reduce blood clotting)
• hormonal contraceptives (e.g. “the pill”)
• atazanavir (other medicine for the treatment of HIV infection)
• lopinavir/ritonavir (other medicine for the treatment of HIV infection)
• fosamprenavir (other medicine for the treatment of HIV infection)
• efavirenz (other medicine for the treatment of HIV infection)

Your doctor will carefully monitor the effect of Nevirapina Kern Pharma and any of these medicines if you are using them together.

If you are undergoing kidney dialysis, your doctor may need to adjust the dose of Nevirapina Kern Pharma, as nevirapina may be partially removed from the blood by dialysis.

Taking Nevirapina Kern Pharma with food and drinks

There are no restrictions on taking Nevirapina Kern Pharma with food and drinks.

Pregnancy and breastfeeding

Consult your doctor or pharmacist before using any medicine.

You should stop breastfeeding if you are taking Nevirapina Kern Pharma. In general, it is not recommended to breastfeed if you have HIV infection, as your baby may become infected with HIV through breast milk.

Driving and operating machines

There are no specific studies on the ability to drive vehicles and operate machines. If you believe your ability to drive and operate machines may be affected, do not drive or operate machines.

Do not use Nevirapina Kern Pharma on your own. You must use it with at least two other antiretroviral medications. Your doctor will recommend the appropriate medications for you.

Follow exactly the administration instructions for Nevirapina Kern Pharma as indicated by your doctor. Consult your doctor or pharmacist if you have any doubts.

Nevirapina Kern Pharma should only be taken orally. Do not chew the tablet. You can take Nevirapina Kern Pharma with or without food.

Dosage:

The usual dose is one 200 mg tablet per day for the first 14 days of treatment (initial period).

After 14 days, the usual dose is one 200 mg tablet twice a day.

It has been demonstrated that the initial 14-day period reduces the risk of skin rash.

Since Nevirapina Kern Pharma must always be taken in combination with other antiretroviral medications, you must carefully follow the instructions for your other medications. These are provided in the prospectuses for these medications.

Nevirapina is also available in a liquid oral suspension form. It is particularly suitable if:

• You have difficulty swallowing tablets.
• You are a child weighing less than 50 kg.
• You are a child with a body surface area less than 1.25 m² (your doctor will determine the body surface area).

You must continue taking Nevirapina Kern Pharma for as long as your doctor tells you to.

As explained earlier in the section ‘Be especially careful with Nevirapina Kern Pharma’, your doctor will monitor your liver function and watch for the appearance of adverse effects such as rash. Depending on the results, your doctor may decide to interrupt or discontinue treatment with Nevirapina Kern Pharma.

If you take more Nevirapina Kern Pharma than you should

Do not take more Nevirapina Kern Pharma than your doctor has prescribed and what is described in this prospectus. Currently, there is little information available on the effects of a nevirapina overdose.

Consult your doctor if you have taken more Nevirapina Kern Pharma than you should.

If you forget to take Nevirapina Kern Pharma

Make sure not to forget any dose. If you realize you have forgotten to take a dose within less than 8 hours, take the next dose as soon as possible. If you realize after 8 hours, take the next dose at the usual time.

Do not take a double dose to compensate for the missed doses.

If you interrupt treatment with Nevirapina Kern Pharma

Take the doses at the indicated times:

• This greatly increases the effectiveness of your antiretroviral medication combination.
• This reduces the likelihood that the HIV infection will become resistant to antiretroviral medications.

It is essential that you continue taking Nevirapina Kern Pharma correctly, as described above, unless your doctor tells you to discontinue treatment.

If you interrupt the administration of Nevirapina Kern Pharma for more than 7 days, your doctor will instruct you to start again with the initial 14-day period (as described above), before returning to taking two doses per day.

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

Like all medicines, Nevirapina Kern Pharma can cause side effects, although not everyone will experience them.

As mentioned in ‘Be especially careful with Nevirapina Kern Pharma’, the most important side effects of nevirapina are severe skin reactions and liver damage that pose a risk to life. These reactions mainly occur during the first 18 weeks of nevirapina treatment. This is an important period that requires close monitoring by your doctor.

If you notice any symptoms of a rash, inform your doctor immediately.

When a rash occurs, it is usually mild to moderate. However, in some patients, a vesicular skin reaction rash can appear, which can be severe or life-threatening (Stevens-Johnson syndrome and toxic epidermal necrolysis), and there have been reported fatalities. Most cases of both severe and mild/moderate rashes occur during the first six weeks of treatment.

If a rash appears and you also feel unwell, you should interrupt treatment and visit your doctor immediately.

Allergic reactions (hypersensitivity) can occur. These reactions can appear in the form of anaphylaxis (a severe type of allergic reaction) with symptoms such as:

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

Allergic reactions can also present as a rash with other side effects such as:

• fever
• blistering of the skin
• mouth sores
• inflammation of the eye
• swelling of the face
• general swelling
• difficulty breathing
• muscle or joint pain
• decrease in the number of white blood cells in the blood (granulocytopenia)
• general feeling of being unwell
• serious liver or kidney problems (liver or kidney failure)

If you experience a rash and any of the other side effects of an allergic reaction (hypersensitivity), inform your doctor immediately. These reactions can be fatal.

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

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

• loss of appetite
• general feeling of being unwell (nausea)
• vomiting
• yellowing of the skin (jaundice)
• abdominal pain.

The evaluation of side effects is based on the following frequencies:

The following side effects have been described in patients who received nevirapina:

Very common:

• rash

Common:

• decrease in the number of white blood cells in the blood (granulocytopenia)
• allergic reactions (hypersensitivity)
• headache
• general feeling of being unwell (nausea)
• vomiting
• abdominal pain
• diarrhea
• inflammation of the liver (hepatitis)
• muscle pain (myalgia)
• feeling tired (fatigue)
• fever
• abnormalities in liver function tests

Uncommon:

• drug rash with systemic symptoms (drug rash with eosinophilia and systemic symptoms)
• allergic reactions characterized by rash, facial inflammation, difficulty breathing (bronchospasm), or anaphylactic shock
• decrease in the number of red blood cells in the blood (anemia)
• yellowing of the skin (jaundice)
• severe and potentially life-threatening skin eruptions (Stevens-Johnson syndrome/toxic epidermal necrolysis)
• hives
• fluid under the skin (angioneuritic edema)
• joint pain (arthralgia)

Rare:

• intense and sudden liver inflammation (fulminant hepatitis)

Combination antiretroviral therapy can cause changes in body shape due to changes in fat distribution. These can include loss of fat from the legs, arms, and face, increased fat in the abdomen (belly) and other internal organs, increased breast size, and fatty lumps on the back of the neck (“buffalo hump”). The cause and long-term effects of these changes are currently unknown. Combination antiretroviral therapy can also cause increased lactic acid and blood sugar, hyperlipidemia (increased blood fats), and insulin resistance.

When nevirapina has been used in combination with other antiretroviral medications, the following events have also been reported:

• decrease in the number of red blood cells or platelets
• inflammation of the pancreas
• decrease or abnormalities in skin sensations.

These effects are generally associated with other antiretroviral agents and may occur when nevirapina is used in combination with other agents; however, it is unlikely that these effects are due to nevirapina treatment.

Use in children

A decrease in white blood cells (granulocytopenia) may occur, more frequently in children. Decrease in red blood cells (anemia), which may be related to nevirapina treatment, is also more frequent in children. As with symptoms of rash, inform your doctor of any side effects.

If you consider that any of the side effects you are experiencing are severe or if you notice any side effects not mentioned in this prospectus, inform your doctor or pharmacist.

Keep out of reach and sight of children.

Do not use Nevirapina Kern Pharma after the expiration date that appears on the packaging after “CAD”. The expiration date is the last day of the month indicated.

This medication does not require special conditions for conservation.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and the

medicines that you do not need at the SIGRE collection pointof the pharmacy. If in doubt, ask your pharmacist how to dispose of the packaging and the medicines that you do not need. In this way, you will help protect the environment.

Nevirapina Kern Pharma Composition

• The active ingredient is nevirapina. Each tablet contains 200 mg of nevirapina.
• The other components are: microcrystalline cellulose, sodium croscarmellose, pregelatinized cornstarch, povidone K-25, sodium starch glycolate, colloidal silicon dioxide, magnesium stearate.

Product Appearance and Packaging Contents

Nevirapina Kern Pharma 200 mg tablets are presented in blister-type packaging.

The tablets are white, round, with a single line on one side and marked with a “K” on the other.

Each standard package contains 14 or 60 tablets. Each clinical package contains 120 tablets.

Marketing Authorization Holder and Responsible Manufacturer

Kern Pharma, S.L.

Colón II Industrial Estate

Venus 72

08228 Terrassa (Barcelona)

This leaflet was approved in June 2011

Detailed and updated information on this medication is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/.