Nevirapine accord

Package leaflet: Information for the patient

Nevirapine Accord, 400 mg, extended-release tablets
Nevirapinum
Please read all of this leaflet carefully before taking this medicine, because it contains
important information for you.

• Keep this leaflet, as 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 personally. Do not pass it on to others. It may harm other people, even if their symptoms are the same as yours.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

Leaflet contents:

1. What Nevirapine Accord is and what it is used for
2. What you need to know 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 Nevirapine Accord is and what it is used for

Nevirapine Accord belongs to a group of medicines called antiretrovirals and is used to treat
infection with the human immunodeficiency virus (HIV-1).
The active substance in this medicine is nevirapine. Nevirapine belongs to a group of anti-HIV
medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). Reverse transcriptase
is an enzyme that the HIV virus needs to multiply. Nevirapine inhibits the action of reverse
transcriptase. By blocking reverse transcriptase, Nevirapine Accord helps control HIV-1 infection.
Nevirapine Accord is indicated for the treatment of HIV-1 infected adults, adolescents, and
children aged 3 years and older who are able to 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 in the form of extended-release tablets should only be taken after a 2-week
lead-in period with another formulation of nevirapine (immediate-release tablets or oral
suspension), unless you are already taking nevirapine in such a formulation and wish to switch
to the extended-release tablet form.

2. Important information before using Nevirapine Accord

When not to use Nevirapine Accord

• if the patient is allergic to nevirapine or any of the other ingredients of this medicine (listed in section 6 "What Nevirapine Accord contains");
• if treatment with Nevirapine Accord has previously been discontinued due to:
  • severe skin rash,
  • skin rash accompanied by other symptoms such as:
    • fever,
    • blistering,
    • oral mucosal lesions,
    • eye inflammation,
    • facial swelling,
    • generalized swelling,
    • shortness of breath,
    • muscle or joint pain,
    • general malaise,
    • abdominal pain.
• hypersensitivity reactions (allergic reactions),
• liver inflammation.
• if the patient has severe liver disease,
• if nevirapine has previously been discontinued due to abnormal liver function tests,
• if the patient is taking products containing St John's wort (Hypericum perforatum). This herbal product may reduce the effectiveness of Nevirapine Accord.

Warnings and precautions
Before starting to take Nevirapine Accord, consult a doctor or pharmacist.
During the first 18 weeks of treatment with Nevirapine Accord, it is very important that the
patient or the treating doctor remain vigilant for symptoms of liver problems or skin reactions,
as these may be severe or even life-threatening. The greatest risk of such reactions occurs
during the first 6 weeks of treatment.
If severe rash or hypersensitivity (allergic reactions that may present as rash) occurs,
accompanied by other adverse effects such as:

• fever,
• blistering of the skin,
• oral mucosal lesions,
• eye inflammation,
• facial swelling,
• generalized swelling,
• shortness of breath,
• muscle or joint pain,
• general malaise,
• or abdominal pain,
  YOU MUST STOP TAKING NEVIRAPINE ACCORD AND CONTACT YOUR DOCTOR IMMEDIATELY,
  as these reactions may be life-threatening or fatal.

If mild rash without other symptoms ever occurs, inform your doctor immediately, who may
decide to discontinue nevirapine.
If symptoms indicating liver damage occur, such as:

• loss of appetite,
• nausea,
• vomiting,
• yellowing of the skin (jaundice),
• abdominal pain,
  treatment with Nevirapine Accord must be discontinued and you must contact your doctor immediately.

If severe liver reactions, skin reactions, or hypersensitivity occur during treatment with
Nevirapine Accord, NEVER take nevirapine again without consulting your doctor.
Take nevirapine exactly as prescribed by your doctor. This is particularly important during
the first 14 days of treatment (for more information, see section How to take Nevirapine Accord).
The following patients are at increased risk of liver problems:

• women,
• patients with hepatitis B or C virus infection,
• patients with abnormal liver function test results,
• untreated patients with high CD4 cell counts at the start of nevirapine treatment (in women >250 cells/mm³, in men >400 cells/mm³),
• previously treated patients with detectable HIV-1 plasma viral load and high CD4 cell counts after starting nevirapine (women >250 cells/mm³, men >400 cells/mm³).

In some patients with advanced HIV infection (AIDS), who previously had opportunistic infections (AIDS-defining illnesses), objective and subjective inflammatory symptoms may appear shortly after starting antiretroviral therapy. These symptoms are believed to result from improved immune system function, enabling the body to fight infections that were previously subclinical. If any signs of infection occur, contact your doctor immediately.

In addition to opportunistic infections, autoimmune disorders (conditions in which the immune system attacks healthy tissues) may also occur after starting antiretroviral therapy for HIV infection. Autoimmune disorders may manifest several months after initiating treatment. If any infection symptoms or other symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk, palpitations, tremor, or hyperexcitability occur, contact your doctor immediately for appropriate management.

Patients receiving combination antiretroviral therapy may experience changes in body fat distribution. If changes in body fat distribution are noticed, contact your doctor (see section 4 "Possible side effects").

In some patients receiving combination antiretroviral therapy, a bone disease called osteonecrosis (death of bone tissue due to inadequate blood supply) may occur. Duration of antiretroviral therapy, corticosteroid use, alcohol consumption, severe immune deficiency, and high body mass index may be among the many risk factors for developing this condition. Symptoms of osteonecrosis include joint stiffness, pain (especially in the hip, knee, or shoulder), and difficulty moving. Patients experiencing any of these symptoms should consult their doctor.

Inform your doctor if you are taking nevirapine together with zidovudine, as white blood cell counts may need to be monitored.

Do not use Nevirapine Accord after exposure to HIV unless HIV infection has been diagnosed and the medicine has been prescribed by a doctor. Nevirapine Accord does not cure HIV infection. Therefore, other infections and HIV-related conditions may still develop. Regular medical follow-up is necessary.

Patients may still transmit HIV while taking this medicine, although effective antiretroviral therapy reduces this risk. Patients should discuss with their doctor the necessary precautions to avoid infecting others.

Do not use prednisone to treat rash associated with Nevirapine Accord.

To prevent pregnancy and transmission of HIV infection, women taking oral contraceptives ("the pill") or using other hormonal contraceptive methods during treatment with Nevirapine Accord should additionally use a mechanical contraceptive method (e.g., condoms).

Postmenopausal women using hormone replacement therapy should consult their doctor before taking this medicine.

If the patient is taking rifampicin for tuberculosis treatment, consult a doctor before using this medicine with Nevirapine Accord.

Some patients taking other extended-release formulations of nevirapine have reported finding tablet fragments in their stool, which may resemble intact tablets. Current data do not confirm that this affects the therapeutic response of these other formulations.

Children and adolescents
Nevirapine Accord 400 mg extended-release tablets may be taken by children if:

• the child is ≥8 years old and weighs ≥43.8 kg, or
• the child is older than 3 years and younger than 8 years and weighs ≥25 kg, or
• body surface area is ≥1.17 m².

Lower doses of extended-release tablets or other available formulations (e.g., oral suspension) should be used in younger children. Check availability.

Nevirapine Accord and other medicines
Tell your doctor or pharmacist about all medicines currently taken or recently taken, as well as any medicines planned for future use.

Inform your doctor about all medicines taken before starting Nevirapine Accord, as monitoring may be required to ensure these medicines remain effective, and dose adjustments may be necessary. Carefully read the package leaflets of other medicines used to treat HIV infection that will be taken concurrently with Nevirapine Accord.

It is particularly important to inform your doctor if you are currently or recently taking any of the following medicines:

• St John's wort (Hypericum perforatum, herbal products used to treat depression),
• rifampicin (used to treat tuberculosis),
• rifabutin (used to treat tuberculosis),
• macrolide antibiotics, e.g., clarithromycin (used to treat bacterial infections),
• fluconazole (used to treat fungal infections),
• ketoconazole (used to treat fungal infections),
• itraconazole (used to treat fungal infections),
• methadone (used to treat opioid addiction),
• warfarin (used to reduce 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 (used to treat HIV infection),
• boceprevir (used to treat hepatitis C virus infection),
• telaprevir (used to treat hepatitis C virus infection),
• elvitegravir, cobicistat (other medicines used to treat HIV infection).

Your doctor will closely monitor the effects of Nevirapine Accord and all the above medicines if they are used concomitantly.

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

Pregnancy and breastfeeding
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor before using this medicine.

Breastfeeding must be discontinued during treatment with Nevirapine Accord. Some doctors also recommend discontinuing breastfeeding in case of HIV infection, as the child may become infected with HIV through breast milk.

Driving and operating machinery
Fatigue may occur during treatment with Nevirapine Accord. Exercise caution when performing tasks such as driving, using tools, or operating machinery. If fatigue occurs, avoid potentially dangerous activities such as driving, using tools, or operating machinery.

Nevirapine Accord contains lactose
Nevirapine Accord extended-release tablets contain lactose (milk sugar). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before using this medicine.

3. How to use Nevirapine Accord

Do not take Nevirapine Accord on its own. This medicine must be taken together with at least two other antiretroviral medicines. Your doctor will prescribe the appropriate additional medicines.
Always take this medicine exactly as your doctor has instructed. If in doubt, consult your doctor or pharmacist.

Dosage:

Adults
A dose of 200 mg of nevirapine once daily is recommended for the first 14 days of treatment (lead-in period). A separate starter pack containing 200 mg nevirapine tablets may be available and is intended for use during the lead-in period. After 14 days, the usual dose is one 400 mg extended-release tablet once daily.

It is very important to take only one 200 mg nevirapine tablet per day during the first 14 days (lead-in period). If a rash occurs during this period, do not start taking Nevirapine Accord extended-release tablets but consult your doctor immediately.

A 14-day lead-in period has been shown to reduce the risk of developing skin rash.

Patients who are already taking immediate-release tablets or oral suspension may switch to the extended-release tablet formulation without repeating the lead-in period.

Nevirapine Accord must always be taken in combination with other antiretroviral medicines. Follow the instructions provided for these other medicines, which are available in their respective package leaflets.

Nevirapine may also be available on the market in lower-dose extended-release tablets (for children aged 3 years and older, after the lead-in period) or as an oral suspension (for all age groups).

Continue taking Nevirapine Accord for as long as your doctor recommends.

As described in section "Warnings and precautions" above, your doctor will monitor the effects of treatment by checking liver function tests and for signs of adverse effects such as rash. Based on these results, your doctor may decide to interrupt or discontinue treatment with Nevirapine Accord. Your doctor may then recommend taking a lower dose.

If you have kidney or liver impairment, regardless of severity, only use 200 mg nevirapine tablets or 50 mg/5 ml nevirapine oral suspension, which may be available on the market.

Nevirapine Accord is for oral use only. Do not chew the extended-release tablets. Nevirapine Accord can be taken with or without food.

Taking more Nevirapine Accord than prescribed
Do not take more Nevirapine Accord than prescribed by your doctor or described in this leaflet. Currently, there is limited information on the effects of overdose with Nevirapine Accord.
If you have taken more than the recommended dose, contact your doctor immediately.

If you miss a dose of Nevirapine Accord
Do not skip doses. If less than 12 hours have passed since the missed dose was due, take the missed dose as soon as possible. If more than 12 hours have passed, take only the next scheduled dose at the usual time. Do not double the dose to make up for a forgotten one.

Stopping Nevirapine Accord
Taking all doses at the correct times:

• greatly increases the effectiveness of the prescribed antiretroviral combination
• reduces the risk of HIV developing resistance to antiretroviral medicines.

It is important to take Nevirapine Accord strictly as described above, unless your doctor decides to stop treatment.

If you stop taking Nevirapine Accord for more than 7 days, your doctor will advise restarting treatment with a 14-day lead-in period using nevirapine tablets (as described above) before resuming once-daily Nevirapine Accord extended-release tablets.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

During treatment for HIV infection, increases in body weight and in blood levels of lipids and glucose may occur. This is partly related to improved health and lifestyle, and in the case of blood lipid levels, sometimes to the antiretroviral therapy itself. Your doctor will monitor these changes.

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

As mentioned above in the "Warnings and precautions" section, the most important adverse effects during treatment with Nevirapine Accord are severe and life-threatening skin reactions and serious liver damage. These effects occur mainly within the first 18 weeks of nevirapine treatment. This is therefore a critical period requiring close medical monitoring.

If any rash symptoms occur at any time, you must inform your doctor immediately.

Rash is usually mild to moderate in severity. However, in some patients, blistering rash may be severe or life-threatening (Stevens-Johnson syndrome and toxic epidermal necrolysis), and fatal cases have been reported. Most cases of both severe and mild or moderate rash occur within the first 6 weeks of treatment.

If rash and general malaise occur, treatment must be discontinued and your doctor must be informed immediately.

Hypersensitivity (allergic) reactions may occur. Such reactions may present as anaphylaxis (a severe allergic reaction) with symptoms such as:

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

Hypersensitivity reactions may also occur as rash or other adverse effects such as:

• fever
• blistering of the skin
• oral mucosal ulcers
• eye inflammation
• facial swelling
• generalized swelling
• shortness of breath
• muscle or joint pain
• decreased white blood cell count (granulocytopenia)
• general malaise
• severe liver or kidney dysfunction (liver or kidney failure).

If rash or other symptoms of hypersensitivity (allergic) reaction occur, you must inform your doctor immediately, as these reactions may be life-threatening.

There have been reports of liver function disorders following nevirapine administration, including several cases of hepatitis, which may be sudden and severe (fulminant hepatitis), and liver failure, which may lead to death.

You should inform your doctor if you experience symptoms indicating liver damage, such as:

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

The following adverse effects were observed in patients receiving nevirapine 200 mg tablets for 14 days during the initial treatment phase:

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

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

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

• allergic reactions (hypersensitivity)
• allergic reaction characterized by rash, facial swelling, breathing difficulties (bronchospasm) or anaphylactic shock
• drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)
• sudden and severe hepatitis (fulminant hepatitis)
• severe and life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• yellowing of the skin (jaundice)
• urticaria
• fluid under the skin (angioedema)
• vomiting
• muscle pain
• joint pain
• decreased white blood cell count (granulocytopenia)
• abnormal liver function tests
• decreased blood phosphorus levels
• increased blood pressure

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

• hepatitis
• decreased red blood cell count (anaemia)

The following adverse effects were observed in patients receiving once-daily extended-release nevirapine tablets in maintenance treatment:

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

• rash
• headache
• abdominal pain
• nausea
• hepatitis
• fatigue
• abnormal liver function tests
• fever
• vomiting
• loose stools (diarrhoea)

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

• allergic reactions (hypersensitivity)
• allergic reaction characterized by rash, facial swelling, breathing difficulties (bronchospasm) or anaphylactic shock
• drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)
• sudden and severe hepatitis (fulminant hepatitis)
• severe and life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• decreased red blood cell count (anaemia)
• decreased white blood cell count (granulocytopenia)
• yellowing of the skin (jaundice)
• urticaria
• fluid under the skin (angioedema)
• muscle pain
• joint pain
• decreased blood phosphorus levels
• increased blood pressure

When nevirapine is used in combination with other antiretroviral medicines, the following symptoms have also been reported:

• decreased number of red blood cells or platelets
• pancreatitis
• numbness or unusual skin sensations.

These symptoms are usually associated with other antiretroviral medicines, and may be expected when Nevirapine Accord is used in combination with other drugs; however, it is unlikely that they would be caused by Nevirapine Accord alone.

Additional adverse effects in children and adolescents

Decreased white blood cell count (granulocytopenia) may occur and is more frequent in children. Decreased red blood cell count (anaemia), which may be related to nevirapine treatment, is also more frequent in children. As with rash symptoms, any adverse effects should be reported to the doctor.

Reporting of adverse effects

If any adverse effects occur, including any not listed in this leaflet, tell your doctor, pharmacist, or nurse.

Adverse effects can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Phone: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl

Adverse effects can also be reported to the marketing authorization holder.

Reporting adverse effects helps to provide more information on the safety of the medicine.

5. How to store Nevirapine Accord

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, bottle, and blister pack.
The expiry date refers to the last day of the stated month.
No special storage conditions are required 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.
No special storage conditions are required 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: monohydrate lactose, 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 modified-release tablet with approximate dimensions of 19.2 mm in length and 9.3 mm in width, embossed with "H" on one side and "N1" on the other. The tablet must not be divided.

Nevirapine Accord is packed in PVC/Aluminium blisters containing 30x1 or 90x1 tablets, or in HDPE bottles with a PP cap, sealing insert, and child-resistant closure, containing 30 tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Accord Healthcare Polska Sp. z o.o.
Taśmowa 7 Street
02-677 Warsaw
Poland

Manufacturer/Importer:
Pharmadox Healthcare Limited
KW20A Kordin Industrial Park
Paola, PLA 3000
Malta

Accord Healthcare B.V.
Winthontlaan 200
3526 KV Utrecht
The Netherlands

Accord Healthcare Polska Sp. z o.o.
Lutomierska 50
95-200 Pabianice
Poland

This medicinal product is authorised in the European Economic Area countries under the following names: