NEVIRAPINE 400 mg Tablets

Contents of the leaflet

1. Package Leaflet: Information for the Patient
2. Nevirapine Accord, 400 mg, prolonged-release tablets
   1. Read the package leaflet carefully before taking the medicine, as it contains important information for you.
   2. Table of Contents of the Package Leaflet:
3. What is Nevirapine Accord and what is it used for
4. Important information before taking Nevirapine Accord
   1. When not to take Nevirapine Accord
   2. Warnings and precautions
   3. Before taking Nevirapine Accord, tell your doctor or pharmacist.
   4. During the first 18 weeks of taking Nevirapine Accord, it is very important that you or your doctor monitor for signs of liver or skin reactions, as they can be severe or life-threatening. The greatest risk
   5. In case of severe rash or allergic reactions (which may occur in the form of rash) accompanied by other side effects, such as:
   6. STOP TAKING NEVIRAPINE ACCORD AND
   7. IMMEDIATELY
   8. CONTACT YOUR DOCTOR, as these reactions can be life-threatening or fatal.
   9. In case of mild rash without other reactions, you should immediately inform your doctor, who may decide to discontinue nevirapine treatment.
   10. In case of signs of liver damage, such as:
   11. In case of severe liver, skin, or allergic reactions during Nevirapine Accord treatment, NEVER TAKE NEVIRAPINE AGAIN without consulting your doctor.
   12. Take nevirapine doses as recommended by your doctor. This is especially important during the first 14 days of treatment (see section "How to take Nevirapine Accord").
   13. Children and adolescents
   14. Nevirapine Accord and other medicines
   15. Nevirapine Accord with food and drink
   16. Pregnancy and breastfeeding
   17. Driving and using machines
   18. Nevirapine Accord contains lactose
5. How to take Nevirapine Accord
   1. Taking more Nevirapine Accord than prescribed
   2. Missing a dose of Nevirapine Accord
   3. Stopping Nevirapine Accord treatment
6. Possible side effects
   1. As mentioned above in the "Warnings and precautions" section, the most important side effects of Nevirapine Accord are severe and life-threatening skin reactions and serious liver damage. These reactions
   2. Additional side effects in children and adolescents
   3. Reporting side effects
7. How to store Nevirapine Accord
8. Contents of the pack and other information
   1. What Nevirapine Accord contains
   2. What Nevirapine Accord looks like and contents of the pack
   3. Marketing authorization holder:
   4. Manufacturer/Importer:
   5. This medicinal product is authorized in the Member States of the European Economic Area under the following names:
   6. Date of last revision of the package leaflet: October 2022

Package Leaflet: Information for the Patient

Nevirapine Accord, 400 mg, prolonged-release tablets

Nevirapine

Read the package leaflet carefully before taking the medicine, as it contains important information for you.

• Keep this package leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience any side effects, including those not listed in this package leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Table of Contents of the Package Leaflet:

• 1. What is Nevirapine Accord and what is it used for
• 2. Important information before taking Nevirapine Accord
• 3. How to take Nevirapine Accord
• 4. Possible side effects
• 5. How to store Nevirapine Accord
• 6. Contents of the pack and other information

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

Nevirapine Accord belongs to a group of medicines called antiretrovirals and is used to treat infections caused by the Human Immunodeficiency Virus (HIV-1).
The active substance of the medicine is nevirapine. Nevirapine belongs to a group of HIV medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Reverse transcriptase is an enzyme that HIV needs to replicate. Nevirapine blocks the action of reverse transcriptase. By stopping the action of reverse transcriptase, Nevirapine Accord helps to control HIV-1 infection.
Nevirapine Accord is indicated for the treatment of adults, adolescents, and children aged 3 years and older infected with HIV-1 who can swallow tablets. Nevirapine must always be taken in combination with other antiretroviral medicines. Your doctor will decide which medicines are best for you.
Nevirapine Accord prolonged-release tablets should only be taken after a 2-week treatment with another form of nevirapine (immediate-release tablets or oral suspension), unless you are already taking nevirapine in such a form and want to switch to prolonged-release tablets.

2. Important information before taking Nevirapine Accord

When not to take Nevirapine Accord

• if you are allergic to nevirapine or any of the other ingredients of this medicine (listed in section 6);
• if in the past you had to stop taking Nevirapine Accord because of:
• severe skin rash,
• skin rash with other symptoms, such as:
• fever,
• blistering,
• herpes simplex,
• eye inflammation,
• facial swelling,
• generalized swelling,
• shortness of breath,
• muscle or joint pain,
• general feeling of being unwell,
• abdominal pain.
• allergic reactions,
• liver inflammation.
• if you have severe liver disease,
• if in the past you had to stop taking nevirapine because of changes in liver function,
• if you are taking products containing St. John's Wort (Hypericum perforatum). This herbal product may decrease the effectiveness of Nevirapine Accord.

Warnings and precautions

Before taking Nevirapine Accord, tell your doctor or pharmacist.

During the first 18 weeks of taking Nevirapine Accord, it is very important that you or your doctor monitor for signs of liver or skin reactions, as they can be severe or life-threatening. The greatest risk

of such reactions is during the first 6 weeks of treatment.

In case of severe rash or allergic reactions (which may occur in the form of rash) accompanied by other side effects, such as:

• - fever,
• - blistering of the skin,
• - herpes simplex,
• - eye inflammation,
• - facial swelling,
• - generalized swelling,
• - shortness of breath,
• - muscle or joint pain,
• - general feeling of being unwell,
• - or abdominal pain

STOP TAKING NEVIRAPINE ACCORD AND

IMMEDIATELY

CONTACT YOUR DOCTOR, as these reactions can be life-threatening or fatal.

In case of mild rash without other reactions, you should immediately inform your doctor, who may decide to discontinue nevirapine treatment.

In case of signs of liver damage, such as:

• - loss of appetite,
• - feeling of nausea (nausea),
• - vomiting,
• - yellowing of the skin (jaundice),
• - abdominal pain, you should stop taking Nevirapine Accord and immediately contact your doctor.

In case of severe liver, skin, or allergic reactions during Nevirapine Accord treatment, NEVER TAKE NEVIRAPINE AGAIN without consulting your doctor.

Take nevirapine doses as recommended by your doctor. This is especially important during the first 14 days of treatment (see section "How to take Nevirapine Accord").

The following patients are at increased risk of liver problems:

• women
• patients with hepatitis B or C
• patients with abnormal liver function test results
• untreated patients with a high CD4 cell count at the start of nevirapine treatment (more than 250 cells/mm^3 in women, more than 400 cells/mm^3 in men)
• previously treated patients with a detectable plasma HIV-1 level and a high CD4 cell count after starting nevirapine treatment (more than 250 cells/mm^3 in women, more than 400 cells/mm^3 in men).

In some patients with advanced HIV infection (AIDS), who have had an opportunistic infection (a disease that indicates AIDS) in the past, objective and subjective signs of inflammation caused by the previous infection may appear soon after starting anti-HIV treatment. It is believed that these symptoms result from the improvement of the body's ability to respond to infections that may have been present without visible symptoms. If you notice any signs of infection, you should immediately contact your doctor.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy tissues) may also occur after starting HIV treatment. Autoimmune disorders can occur months after starting treatment. If you notice any signs of infection or other symptoms, such as muscle weakness, weakness starting from the hands and feet and progressing towards the torso, heart palpitations, tremors, or hyperactivity, you should immediately inform your doctor.
In patients receiving combination antiretroviral therapy, changes in body fat may occur. If you notice changes in body fat, you should contact your doctor (see section 4 "Possible side effects").
In some patients undergoing combination antiretroviral therapy, a bone disease called osteonecrosis (death of bone tissue due to lack of blood supply to the bone) may occur. The duration of combination antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immune system weakness, and increased body mass index may be some of the risk factors for the development of the disease. Symptoms of osteonecrosis are joint stiffness, pain (especially in the hip, knee, and shoulder), and difficulty moving. If you notice any of these symptoms, you should contact your doctor.
You should inform your doctor about taking nevirapine and zidovudine, as it may be necessary to check your white blood cell count.
You should not take Nevirapine Accord after being exposed to HIV, unless you have been diagnosed with HIV infection and the medicine has been prescribed by your doctor. Nevirapine Accord does not cure HIV infection. Therefore, other infections and diseases related to HIV infection may still develop. You should regularly contact your doctor.
You can still transmit HIV to others while taking this medicine, despite effective antiretroviral therapy reducing this risk. You should discuss with your doctor the precautions necessary to avoid infecting others.
Prednisone should not be used to treat a rash caused by taking Nevirapine Accord.
To prevent pregnancy and prevent the transmission of HIV, women taking oral contraceptives ("the pill") or using other hormonal contraceptives during Nevirapine Accord treatment should also use a mechanical contraceptive method (e.g., condoms).
Postmenopausal women using hormone replacement therapy should consult their doctor before taking this medicine.
If you are taking rifampicin to treat tuberculosis, you should contact your doctor before taking this medicine with Nevirapine Accord.
Some patients taking other prolonged-release forms of nevirapine have reported the presence of tablet fragments in the stool, which may look like whole tablets.
Currently available data do not confirm that this affects the therapeutic response of these other pharmaceutical forms.

Children and adolescents

Nevirapine Accord 400 mg prolonged-release tablets may be taken by children if:

• the child is ≥ 8 years old and weighs 43.8 kg or more
• the child is over 3 years old and under 8 years old and weighs 25 kg or more
• the body surface area is 1.17 m^2 or more

For younger children, smaller doses of prolonged-release tablets or other available pharmaceutical forms (e.g., oral suspension) are used. You should check their availability.

Nevirapine Accord and other medicines

Tell your doctor or pharmacist about all the medicines you are taking, have recently taken, or might take.
Tell your doctor about all the medicines you are taking before starting Nevirapine Accord, as it may be necessary to monitor whether these medicines are still effective and make any necessary dose adjustments. You should carefully read the package leaflet of other HIV medicines that will be taken with Nevirapine Accord.
In particular, it is important to inform your doctor about taking the following medicines:

• St. John's Wort (Hypericum perforatum, medicines used to treat depression)
• rifampicin (a medicine used to treat tuberculosis)
• rifabutin (a medicine used to treat tuberculosis)
• macrolide antibiotics, 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 addiction)
• warfarin (a medicine that reduces blood clotting)
• hormonal contraceptives (e.g., "the pill")
• atazanavir (another medicine used to treat HIV infection)
• lopinavir and ritonavir (other medicines used to treat HIV infection)
• fosamprenavir (another medicine used to treat HIV infection)
• efavirenz (another medicine used to treat HIV infection)
• etravirine (another medicine used to treat HIV infection)
• rilpivirine (another medicine used to treat HIV infection)
• delavirdine (another medicine used to treat HIV infection)
• zidovudine (a medicine used to treat HIV infection)
• boceprevir (a medicine used to treat hepatitis C)
• telaprevir (a medicine used to treat hepatitis C)
• elvitegravir, cobicistat (another medicine used to treat HIV infection)

Your doctor will closely monitor the effect of Nevirapine Accord and all the above medicines if they are taken in combination with them.

Nevirapine Accord with food and drink

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

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant, or plan to have a baby, ask your doctor for advice before taking this medicine.
While taking Nevirapine Accord, you should stop breastfeeding. Some doctors also recommend stopping breastfeeding in case of HIV infection, as it is possible that the baby may become infected with HIV through breast milk.

Driving and using machines

While taking Nevirapine Accord, you may experience fatigue. You should be careful when performing tasks such as driving, using tools, or operating machinery. If you experience fatigue, you should avoid performing potentially hazardous tasks, such as driving or using tools or operating machinery.

Nevirapine Accord contains lactose

Nevirapine Accord prolonged-release tablets contain lactose (milk sugar).
If you have been diagnosed with an intolerance to some sugars, you should contact your doctor before taking this medicine.

3. How to take Nevirapine Accord

Do not take Nevirapine Accord alone. The medicine should be taken in combination with at least two other antiretroviral medicines. Your doctor will prescribe the appropriate medicines.
Always take this medicine exactly as your doctor has told you. If you are not sure, ask your doctor or pharmacist.
Dosage:
Adults
200 mg of nevirapine is taken once a day for the first 14 days of treatment (lead-in period). A separate starter pack containing 200 mg nevirapine tablets may be available on the market and is intended for use during the lead-in period. After 14 days, the usual dose is one 400 mg prolonged-release tablet once a day.
It is very important to take only one 200 mg nevirapine tablet per day for the first 14 days (lead-in period). If a rash occurs during this period, you should not start taking Nevirapine Accord prolonged-release tablets, but consult your doctor.
It has been shown that using a 14-day lead-in period reduces the risk of skin rash.
Patients who are already taking immediate-release tablets or oral suspension may switch to prolonged-release tablets without a lead-in period.
Nevirapine Accord must always be taken in combination with other antiretroviral medicines. You should follow the instructions for the other medicines. These instructions are available in the package leaflets of those medicines.
Nevirapine may also be available on the market in smaller doses of prolonged-release tablets (for children aged 3 years and older, after the lead-in period) or as an oral suspension (for all age groups).
You should continue taking Nevirapine Accord for as long as your doctor recommends.
As described in the "Warnings and precautions" section above, your doctor will monitor the effects of treatment by checking liver function test results or looking for signs of side effects, such as rash. Based on the results of this monitoring, your doctor may decide to stop or discontinue Nevirapine Accord treatment. Your doctor may then recommend taking a lower dose of the medicine.
If you have kidney or liver dysfunction, regardless of its severity, you should take only nevirapine 200 mg tablets or nevirapine 50 mg/5 ml oral suspension, which may be available on the market.
Nevirapine Accord should be taken orally only. Do not chew the prolonged-release tablets. Nevirapine Accord can be taken with or without food.

Taking more Nevirapine Accord than prescribed

Do not take more Nevirapine Accord than your doctor has prescribed and is described in this package leaflet. There is limited information available on the effects of overdosing with Nevirapine Accord.
If you have taken more Nevirapine Accord than prescribed, you should contact your doctor.

Missing a dose of Nevirapine Accord

Do not miss a dose. If it has been less than 12 hours since the scheduled dose, you should take the dose as soon as possible. If it has been more than 12 hours since the scheduled dose, you should take only the next dose at the scheduled time.

Stopping Nevirapine Accord treatment

Taking all doses at the right time:

• greatly increases the effectiveness of the prescribed combination of antiretroviral medicines
• reduces the development of resistance of the HIV virus to antiretroviral medicines.

It is important to take Nevirapine Accord exactly as prescribed, until your doctor decides to stop treatment.
If you stop taking Nevirapine Accord for more than 7 days, your doctor will recommend restarting treatment with a 14-day lead-in period with nevirapine tablets (described above) before returning to taking one Nevirapine Accord prolonged-release tablet per day.
If you have any doubts about taking this medicine, you should consult your doctor or pharmacist.

4. Possible side effects

During HIV treatment, you may experience an increase in body weight and levels of lipids and glucose in the blood. This is partly due to the improvement in your condition and lifestyle, and in the case of lipid levels in the blood, sometimes to the HIV treatment itself. Your doctor will check these changes.
Like all medicines, Nevirapine Accord can cause side effects, although not everybody gets them.

As mentioned above in the "Warnings and precautions" section, the most important side effects of Nevirapine Accord are severe and life-threatening skin reactions and serious liver damage. These reactions

mainly occur during the first 18 weeks of nevirapine treatment. This is therefore an important period during which you will need close monitoring by your doctor.
In case of any signs of rash, you should immediately inform your doctor.
If a rash occurs, it usually has a mild to moderate severity. However, in some patients, a severe or life-threatening rash may occur (Stevens-Johnson syndrome and toxic epidermal necrolysis), and there have been reports of deaths. Most cases of both severe and mild or moderate rash occur within the first 6 weeks of treatment.
In case of rash and feeling unwell, you should stop taking the medicine and immediately inform your doctor.
Allergic reactions (hypersensitivity) may occur. Such reactions may occur in the form of anaphylaxis (a severe form of allergic reaction) with symptoms such as:

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

Allergic reactions may also occur in the form of rash or other side effects, such as:

• fever
• blistering of the skin
• herpes simplex
• eye inflammation
• facial swelling
• generalized swelling
• shortness of breath
• muscle or joint pain
• decreased white blood cell count (granulocytopenia)
• general feeling of being unwell
• severe liver or kidney dysfunction (liver or kidney failure).

In case of rash or other signs of an allergic reaction, you should immediately inform your doctor, as these reactions can be life-threatening.
There have been reports of liver function disorders after taking nevirapine, including a few cases of liver inflammation, which can be sudden and severe (fulminant hepatitis) and lead to liver failure and death.
You should inform your doctor if you experience signs of liver damage, such as:

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

The following side effects have been reported in patients taking nevirapine 200 mg tablets for 14 days during the lead-in phase of treatment:
Common (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 reaction 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 life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• yellowing of the skin (jaundice)
• hives
• fluid under the skin (angioedema)
• vomiting
• muscle pain
• joint pain
• decreased white blood cell count (granulocytopenia)
• abnormal liver function test results
• decreased phosphorus levels in the blood
• increased blood pressure

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

• liver inflammation
• decreased red blood cell count (anemia)

The following side effects have been reported in patients taking nevirapine prolonged-release tablets once a day in maintenance treatment:
Common (may affect up to 1 in 10 people):

• rash
• headache
• abdominal pain
• nausea
• liver inflammation
• fatigue
• abnormal liver function test results
• fever
• vomiting
• diarrhea

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

• allergic reactions (hypersensitivity)
• allergic reaction 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 life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• decreased red blood cell count (anemia)
• decreased white blood cell count (granulocytopenia)
• yellowing of the skin (jaundice)
• hives
• fluid under the skin (angioedema)
• muscle pain
• joint pain
• decreased phosphorus levels in the blood
• increased blood pressure

In addition to the above side effects, the following have been reported in patients taking nevirapine in combination with other antiretroviral medicines:

• decreased red or white blood cell count
• pancreatitis
• numbness or abnormal sensations in the skin. These symptoms are usually related to the use of other antiretroviral medicines and can be expected to occur when taking Nevirapine Accord in combination with other medicines; however, it is unlikely that they are caused solely by Nevirapine Accord.

Additional side effects in children and adolescents

Decreased white blood cell count (granulocytopenia) may occur, which is more common in children. Decreased red blood cell count (anemia), which may be related to nevirapine treatment, also occurs more frequently in children. As with rash, you should inform your doctor about any side effects.

Reporting side effects

If you experience any side effects, including those not listed in this package leaflet, you should tell your doctor, pharmacist, or nurse.
Side effects can be reported directly to the Department of Drug Safety Monitoring of the Office for Registration of Medicinal Products, Medical Devices, and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
tel: +48 22 49 21 301
fax: +48 22 49 21 309
website: https://smz.ezdrowie.gov.pl
Side effects can also be reported to the marketing authorization holder.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Nevirapine Accord

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, bottle, and blister.
The expiry date refers to the last day of that month.
There are no special storage instructions for this medicine.
Nevirapine Accord should be used within 30 days of opening the bottle.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.
There are no special storage instructions for this medicine.

6. Contents of the pack and other information

What Nevirapine Accord contains

The active substance is nevirapine. Each tablet contains 400 mg of nevirapine.
The other ingredients are: lactose monohydrate, hypromellose 2910 (3 mPa*s), hypromellose 2208 (4000 mPa*s), magnesium stearate.

What Nevirapine Accord looks like and contents of the pack

Nevirapine Accord is a white or almost white, oval, biconvex prolonged-release tablet with approximate dimensions of 19.2 mm in length and 9.3 mm in width, with "H" engraved on one side and "N1" on the other. The tablets should not be divided.
Nevirapine Accord is packaged in PVC/Aluminum blisters containing 30x1 or 90x1 tablets or HDPE bottles with a PP cap, with a desiccant plug, with a child-resistant closure, containing 30 tablets.
Not all pack sizes may be marketed.

Marketing authorization holder:

Accord Healthcare Polska Sp. z o.o.
Taśmowa 7 Street
02-677 Warsaw

Manufacturer/Importer:

Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta
Accord Healthcare B.V.,
Winthontlaan 200,
3526 KV Utrecht,
Netherlands
Accord Healthcare Polska Sp. z o.o.
Lutomierska 50 Street
95-200 Pabianice

This medicinal product is authorized in the Member States of the European Economic Area under the following names:

Date of last revision of the package leaflet: October 2022