NEVIRAPINE TARBIS FARMA 400 mg PROLONGED-RELEASE TABLETS

2. What you need to know before you take Nevirapine Tarbis Farma

Do not take Nevirapine Tarbis Farma

• if you are allergic to nevirapine or any of the other ingredients of this medicine (listed in section 6)
• if you have previously taken nevirapine and had to stop treatment because you suffered from:
• • severe skin rash
  • skin rash with other symptoms such as:
  • • fever
    • blisters
    • mouth sores
    • eye inflammation
    • facial swelling
    • general swelling
    • difficulty breathing
    • muscle or joint pain
    • general feeling of being unwell
    • abdominal pain
  • hypersensitivity reactions (allergic reactions)
  • liver inflammation (hepatitis)
• if you have severe liver disease
• if you have had to stop treatment with nevirapine in the past due to changes in liver function
• if you are taking any medicine that contains St. John's Wort (Hypericum perforatum). This substance may prevent Nevirapine from working properly.

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Nevirapine Tarbis Farma 400 mg prolonged-release tablets EFG.

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

If you experience a severe rash or hypersensitivity (allergic reactions that can appear as a rash) along with other side effects such as

• fever,
• blisters,
• mouth sores,
• eye inflammation,
• facial swelling,
• general swelling,
• difficulty breathing,
• muscle or joint pain,
• general feeling of being unwell,
• or abdominal pain

YOU MUST STOP TAKING NEVIRAPINE AND CONTACT YOUR DOCTOR IMMEDIATELY, as these reactions can be life-threatening or cause death. If you only experience mild rashes without any other reaction, inform your doctor immediately, who will advise you whether to stop taking nevirapine.

If you experience symptoms that suggest liver damage, such as

• loss of appetite,
• nausea,
• vomiting,
• yellowing of the skin (jaundice),
• abdominal pain

you must stop taking nevirapine and contact your doctor immediately.

If you develop severe liver, skin, or hypersensitivity reactions while taking NEVIRAPINE, DO NOT TAKE NEVIRAPINE AGAIN without consulting your doctor first.

You must take your dose of nevirapine exactly as prescribed by your doctor. This is especially important during the first 14 days of treatment (see more information in “How to take Nevirapine Tarbis Farma”).

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

• women
• patients infected with hepatitis B or C
• abnormal liver function tests
• patients who have never received treatment before and have high CD4 cell counts when starting treatment with nevirapine (in women, more than 250 cells/mm³; in men more than 400 cells/mm³)
• pre-treated patients with detectable HIV-1 viral load in plasma and high CD4 cell counts when starting treatment with nevirapine (in women, more than 250 cells/mm³; in men more than 400 cells/mm³)

Soon after starting anti-HIV treatment, some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (AIDS-defining illnesses) may experience signs and symptoms of inflammation of previous infections. These symptoms are thought to be due to an improvement in the body's immune response, which enables it to fight off infections that may have been present without causing symptoms. If you notice any symptoms of infection, do not hesitate to inform your doctor.

In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you have started taking medicines to treat your HIV infection. Autoimmune disorders can occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up towards the trunk of the body, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive the necessary treatment.

Changes in body fat may occur in patients who are taking combined antiretroviral therapy. Consult your doctor if you notice changes in body fat (see section 4 “Possible side effects”).

In some patients who are taking combined antiretroviral therapy, a bone disease called osteonecrosis (death of bone tissue due to loss of blood supply to the bone) may develop. The duration of combined antiretroviral therapy, use of corticosteroids, consumption of alcohol, severe immune system weakness, 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.

If you are taking nevirapine and zidovudine together, inform your doctor because you may need to have your white blood cell count monitored.

Do not take Nevirapine after exposure to HIV, unless you have been diagnosed with HIV and your doctor has told you to do so.

Prednisone should not be used to treat rashes associated with Nevirapine.

If you are taking oral contraceptives (e.g., “the pill”) or other hormonal methods of birth control during treatment with Nevirapine, you should also use a barrier method of birth control (e.g., condoms) to prevent pregnancy and transmission of HIV. If you are receiving post-menopausal hormone replacement therapy, consult your doctor before taking this medicine.

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

The prolonged-release tablets of Nevirapine Tarbis or parts of the tablets may be eliminated and seen occasionally in the feces. These may look like whole tablets, but they have not been shown to affect the efficacy of nevirapine.

Children and adolescents

Nevirapine Tarbis Farma 400 mg prolonged-release tablets EFG may be used in children if:

• they are 8 years of age or older and weigh at least 43.8 kg
• they are between 3 and 8 years of age and weigh at least 25 kg
• they have a body surface area of at least 1.17 m²

For younger children, a liquid form of the medicine is available as an oral suspension.

Other medicines and Nevirapine

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Before you start taking Nevirapine, tell your doctor about all the other medicines you are taking. Your doctor may need to check that your other medicines are still working and adjust the doses. Read the package leaflet of all your other anti-HIV medicines carefully.

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

• St. John's Wort (Hypericum perforatum, a herbal remedy for depression)
• rifampicin (a medicine to treat tuberculosis)
• rifabutin (a medicine to treat tuberculosis)
• macrolides, e.g., clarithromycin (a medicine to treat bacterial infections)
• fluconazole (a medicine to treat fungal infections)
• ketoconazole (a medicine to treat fungal infections)
• itraconazole (a medicine to treat fungal infections)
• methadone (a medicine to treat opioid addiction)
• warfarin (a medicine to prevent blood clots)
• 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)
• zidovudine (another medicine to treat HIV infection)
• elvitegravir/cobicistat (another medicine to treat HIV infection)

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

Using Nevirapine with food and drink

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

Pregnancy and breast-feeding

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

It is not recommendedthat HIV-infected women breast-feed their babies because HIV infection can be passed to the baby through breast milk.

If you are breast-feeding or thinking of breast-feeding, you should consult your doctor as soon as possible.

Driving and using machines

Taking Nevirapine can cause fatigue. Be careful when performing activities such as driving or using tools or machines. If you experience fatigue, you should avoid hazardous tasks such as driving and using tools or machines.

Nevirapine Tarbis Farma 400 mg prolonged-release tablets EFG contains lactose

The prolonged-release tablets of Nevirapine Tarbis Farma 400 mg contain lactose (a type of sugar).

If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.

3. How to take Nevirapine Tarbis Farma

Do not use Nevirapine alone, but with at least two other antiretroviral medicines. Your doctor will recommend the medicines that are suitable for you.

Follow the instructions for administration of this medicine exactly as prescribed by your doctor. If you are unsure, consult your doctor or pharmacist again.

Dose:

Adults

The dose is one 200 mg nevirapine tablet per day for the first 14 days of treatment (the “lead-in” period). A separate lead-in pack with 200 mg nevirapine tablets is available for this 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 tablet per day during the first 14 days (the “lead-in” period). If you develop any rash during this period, do not start taking Nevirapine and consult your doctor.

The 14-day “lead-in” period has been shown to reduce the risk of skin rash.

Patients who are already taking immediate-release tablets or oral suspension may switch to prolonged-release tablets without the need for the lead-in period.

Since Nevirapine must always be taken in combination with other antiretroviral medicines, you must always follow the instructions for your other medicines carefully. You can find these instructions in the package leaflets of the respective medicines.

Nevirapine is also available as an oral suspension (for all age groups, weights, and body surface areas).

You must continue to take Nevirapine for as long as your doctor tells you to.

As already explained in the section ‘Warnings and precautions’, your doctor will monitor you through liver function tests and watch for side effects such as rash. Depending on the results, your doctor may decide to stop or interrupt treatment with Nevirapine Tarbis Farma 400 mg prolonged-release tablets EFG. After that, your doctor may decide to restart treatment with a lower dose.

If you have kidney or liver problems of any degree, you can only take nevirapine 200 mg tablets or nevirapine 50 mg/5 ml oral suspension.

Only take Nevirapine Tarbis Farma 400 mg prolonged-release tablets EFG by mouth. Never chew the prolonged-release tablets. Nevirapine can be taken with or without food.

If you take more Nevirapine Tarbis Farma than you should

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

In case of overdose or accidental ingestion, consult your doctor or pharmacist or call the Toxicological Information Service, telephone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Nevirapine Tarbis Farma

Try not to miss any dose. If you realize you have missed a dose within 12 hours of the scheduled time, take the missed dose as soon as possible. If more than 12 hours have passed since the scheduled time, only take the next dose at the usual time.

If you stop taking Nevirapine Tarbis Farma

Taking the doses when they are due:

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

It is important that you continue to take Nevirapine in the correct way, as described above, unless your doctor tells you to stop treatment.

If you stop taking Nevirapine for more than 7 days, your doctor will tell you to start again with the 14-day lead-in period with nevirapine tablets (as described above) before taking a daily dose of Nevirapine Tarbis Farma 400 mg prolonged-release tablets EFG.

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

4. Possible Adverse Effects

During HIV treatment, an increase in body weight and levels of glucose and lipids in the blood may occur. This may be related, in part, to the recovery of health and lifestyle, and in the case of increased blood lipids, it may sometimes be due to the HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication may produce adverse effects, although not all people will experience them.

As already mentioned in 'Warnings and Precautions',the most important adverse effects of Nevirapina Tarbis Farma 400 mg prolonged-release tablets EFG are severe and life-threatening skin reactions and severe liver damage. These reactions occur mainly during the first 18 weeks of treatment with nevirapine. This is, therefore, 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 develops, it is usually mild to moderate. However, in some patients, the rash can take the form of a blistering skin reaction that can be severe or life-threatening (Stevens-Johnson syndrome and toxic epidermal necrolysis), and there have even been reported fatalities. Most cases of rash, both severe and mild/moderate, occur during the first six weeks of treatment.

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

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

• rash
• facial swelling
• difficulty breathing (bronchospasm)
• anaphylactic shock

Hypersensitivity reactions can also present as a rash with other adverse effects such as:

• fever
• blisters on the skin
• mouth sores
• eye inflammation
• facial swelling
• generalized swelling
• difficulty breathing
• muscle or joint pain
• decrease in the number of white blood cells in the blood (granulocytopenia)
• general malaise
• severe liver or kidney problems (liver or kidney failure)

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

Abnormalities in liver function have been described with the use of Nevirapina. This includes some cases of liver inflammation (hepatitis), which can be sudden and severe (fulminant hepatitis), and liver failure. Both can be fatal.

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

• loss of appetite
• nausea
• vomiting
• yellowing of the skin (jaundice)
• abdominal pain

The following adverse effects have been reported in patients who received nevirapine 200 mg tablets during the initial 14-day phase:

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

• rash
• fever
• headache
• abdominal pain
• nausea
• diarrhea
• fatigue

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

• allergic reactions (hypersensitivity)
• allergic reactions characterized by rash, facial swelling, difficulty breathing (bronchospasm), or anaphylactic shock
• drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)
• sudden and severe liver inflammation (fulminant hepatitis)
• severe and potentially fatal skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis)

Yellowing of the skin (jaundice)

• hives
• fluid under the skin (angioedema)
• vomiting
• muscle pain (myalgia)
• joint pain (arthralgia)
• decrease in the number of white blood cells (granulocytopenia)
• abnormalities in liver function tests
• decrease in blood phosphorus
• increase in blood pressure

Rare (may affect up to 1 in 1,000 people):

• liver inflammation (hepatitis)
• decrease in the number of red blood cells (anemia)

The following adverse effects have been reported in patients who received nevirapine prolonged-release tablets once daily in the maintenance phase:

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

• rash
• headache
• abdominal pain
• nausea
• liver inflammation (hepatitis)
• fatigue
• abnormalities in liver function tests
• fever
• vomiting
• diarrhea

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

• allergic reactions (hypersensitivity)
• allergic reactions characterized by rash, facial swelling, difficulty breathing (bronchospasm), or anaphylactic shock
• drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)
• sudden and severe liver inflammation (fulminant hepatitis)
• severe and potentially fatal skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis)

Decrease in the number of red blood cells (anemia)

• decrease in the number of white blood cells (granulocytopenia)
• yellowing of the skin (jaundice)
• hives
• fluid under the skin (angioedema)
• muscle pain (myalgia)
• joint pain (arthralgia)
• decrease in blood phosphorus
• increase in blood pressure

With the use of nevirapine in combination with other antiretroviral medications, the following effects have also been reported:

• decrease in the number of red blood cells or platelets
• pancreatitis
• decrease or abnormalities in skin sensation

These effects are often associated with other antiretroviral agents and can be expected when Nevirapina is used in combination with other agents; however, it is unlikely that these effects are due to treatment with nevirapine.

Other Adverse Effects in Children and Adolescents

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

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that is not listed in this leaflet. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Nevirapina Tarbis Farma

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

Do not use this medication after the expiration date stated on the carton, bottle, or blister. The expiration date is the last day of the month indicated.

Nevirapina Tarbis Farma 400 mg prolonged-release tablets EFG should be used within 30 days of the initial opening of the bottle.

This medication does not require special storage conditions.

Medications should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medication in the pharmacy's SIGRE point. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Nevirapina Tarbis Farma 400 mg prolonged-release tablets EFG

• The active ingredient is nevirapine. Each tablet contains 400 mg of nevirapine (in anhydrous form).

The other ingredients are:

• hypromellose
• magnesium stearate

Appearance of the Product and Package Contents

The Nevirapina Tarbis Farma 400 mg prolonged-release tablets EFG are oval, biconvex, white to off-white in color, and are engraved with an "H" on one side and "N1" on the other. The prolonged-release tablet should not be broken.

Nevirapina Tarbis Farma 400 mg prolonged-release tablets EFG are available in PVC-Aluminum blisters of 30, 90, or 180 (2 packs of 90) prolonged-release tablets and in HDPE bottles of 30 prolonged-release tablets.

It is possible that only some pack sizes are marketed.

Marketing Authorization Holder

Tarbis Farma S.L.

Gran Vía Carlos III, 94

08028 Barcelona

Spain

Manufacturer

Pharmadox Healthcare Ltd.

KW20A Kordin Industrial Park

Paola, PLA 3000

Malta

Amarox Pharma B.V.

Rouboslaan 32

Voorschoten, 2252TR

Netherlands

This medication is authorized in the following EEA Member States under the following names:

Spain: Nevirapina Tarbis Farma 400 mg prolonged-release tablets EFG

Netherlands: Nevirapine Amarox 400 mg tabletten met verlengde afgifte

United Kingdom: Nevirapine Amarox 400 mg prolonged-release tablets

Date of Last Revision: January 2023

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