Nevirapine accord

Package leaflet: Information for the patient

Nevirapine Accord, 200 mg, 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 a specific individual. Do not pass it on to others. It may harm them even if their symptoms are the same.
• If you experience any side effects, 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 belongs to a group of medicines called antiretrovirals and is used in the treatment of human immunodeficiency virus (HIV-1) infection.
The active substance in this medicine is nevirapine. Nevirapine belongs to a group of anti-HIV medicines called non-nucleoside reverse transcriptase inhibitors. Reverse transcriptase is an enzyme that the HIV virus needs to multiply. Nevirapine inhibits the action of reverse transcriptase. By blocking reverse transcriptase, nevirapine helps control HIV-1 infection.
Nevirapine is indicated for the treatment of HIV-1 infected individuals: adults, adolescents and children regardless of age. Nevirapine must always be taken in combination with other antiretroviral medicines. Your doctor will decide which medicines are best for you.
If nevirapine has been prescribed for a child, please remember that all information in this
leaflet applies to the child (in such cases, the word "patient" should be understood as "child").

2. 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 nevirapine has previously been discontinued due to:
  • severe skin rash,
• skin rash associated with other symptoms such as:
• fever,
• blistering,
• oral mucosal ulcers,
• 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 liver function abnormalities,
  • if the patient is taking products containing St John’s wort ( Hypericum perforatum ). This herbal product may reduce the effectiveness of nevirapine.

Warnings and precautions
Before starting nevirapine, consult a doctor or pharmacist.
During the first 18 weeks of taking nevirapine, it is very important that the patient or
the treating physician monitor for symptoms related to the liver or skin reactions, as
they may be severe or even life-threatening. The highest risk of such reactions occurs
within the first 6 weeks of treatment.
If a severe rash or hypersensitivity (allergic reactions
which may present as a rash) occurs, accompanied by other adverse effects such as:

• fever,
• skin blistering,
• oral mucosal ulcers,
• eye inflammation,
• facial swelling,
• generalized swelling,
• shortness of breath,
• muscle or joint pain,
• general malaise,
• or abdominal pain,

NEVIRAPINE MUST BE DISCONTINUED
AND THE PATIENT MUST CONTACT A DOCTOR IMMEDIATELY, as these reactions may
be life-threatening or fatal.
If mild rash symptoms occur at any time without other reactions,
the patient must immediately inform the doctor, who may decide to discontinue
nevirapine treatment.
If symptoms indicating liver damage occur, such as:

• loss of appetite,
• nausea,
• vomiting,
• yellowing of the skin (jaundice),
• abdominal pain, nevirapine must be discontinued and the patient must contact a doctor immediately.

If severe liver reactions, skin reactions, or hypersensitivity occur during nevirapine treatment,
NEVER TAKE NEVIRAPINE AGAIN WITHOUT CONSULTING A DOCTOR.
The patient must take nevirapine doses exactly as prescribed by the doctor. This is particularly important
during the first 14 days of treatment (for more information, see section How to use 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 higher 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 levels and higher CD4 cell counts after starting nevirapine (women >250 cells/mm³, men >400 cells/mm³).

In some patients with advanced HIV infection (AIDS), who have previously had opportunistic infections (AIDS-defining illnesses), objective and subjective inflammatory symptoms caused by prior infections may appear shortly after starting antiretroviral therapy. These symptoms are believed to result from improved immune response, enabling the body to fight infections that may have been present without obvious symptoms. If any signs of infection are noticed, contact a doctor immediately.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissues) may also occur after starting antiretroviral therapy for HIV infection. Autoimmune disorders may appear several months after starting treatment. If any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk, palpitations, tremor, or hyperexcitability are noticed, contact the treating physician immediately for necessary treatment.
Body fat redistribution may occur in patients receiving combination antiretroviral therapy. If changes in body fat distribution are noticed, contact a doctor (see section 4 " Possible side effects ").
In some patients receiving combination antiretroviral therapy, a bone disease called osteonecrosis (bone tissue death due to inadequate blood supply) may occur. Duration of combination 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 the doctor if the patient is taking nevirapine together with zidovudine, as white blood cell counts may need to be monitored.
Do not use nevirapine after exposure to HIV unless HIV infection has been diagnosed and the medicine has been prescribed by a doctor.
Prednisone should not be used to treat rash associated with nevirapine.
To prevent pregnancy and transmission of HIV infection, women taking oral contraceptives ("the pill") or using other hormonal contraceptive methods during nevirapine treatment 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, they should consult their doctor before using this medicine with nevirapine.

Children and adolescents
Nevirapine Accord may be used in:

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

For younger children, the medicine is administered as an oral suspension.

Nevirapine Accord and other medicines
Inform the doctor or pharmacist about all medicines currently or recently taken, as well as any medicines planned for future use.
Inform the doctor about all medicines taken before starting nevirapine, as monitoring may be required to ensure these medicines remain effective, and dosage adjustments may be necessary. Carefully read the package leaflet of other medicines used to treat HIV infection that will be taken concomitantly with nevirapine.
It is particularly important to inform the doctor if the patient is currently or has recently taken any of the following medicines:

• St John’s wort preparations ( Hypericum perforatum , 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 dependence)
• 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)
• zidovudine (used to treat HIV infection)
• elvitegravir, cobicistat (another medicine used to treat HIV infection)

The doctor will closely monitor the effects of nevirapine and all the above medicines when used concomitantly.
In case of renal dialysis, the doctor may decide to increase the dose of nevirapine, as nevirapine may be partially removed from the blood during dialysis.

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

Pregnancy and breastfeeding
If the patient is pregnant, suspects she may be pregnant, or is planning a pregnancy, she should consult a doctor before using this medicine.
Breastfeeding by women infected with HIV is not recommended , as the child may become infected with HIV through breast milk.
If the patient is breastfeeding or considering starting breastfeeding, she should discuss this with her doctor as soon as possible .

Driving and using machines
Fatigue may occur while taking nevirapine. Exercise caution when performing activities 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 sodium
Nevirapine Accord contains less than 1 mmol (23 mg) of sodium per tablet, meaning the product is considered "sodium-free".

3. How to take Nevirapine Accord

Do not take nevirapine alone. This medicine must always 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:
The usual dose is one 200 mg tablet once daily for the first 14 days of treatment (lead-in period). After 14 days, the usual dose is one 200 mg tablet twice 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 increase the dose and consult your doctor immediately.

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

Nevirapine must always be taken in combination with other antiretroviral medicines. Follow the instructions for these other medicines as provided in their respective package leaflets.

This is particularly relevant:

• if the patient has difficulty swallowing tablets
• for patients or children with body weight less than 50 kg
• for children with body surface area below 1.25 m² (your doctor will calculate the body surface area).

Continue taking nevirapine for the duration recommended by your doctor.
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 nevirapine treatment. Your doctor may then recommend taking a lower dose of the medicine.

Nevirapine Accord tablets are for oral use only. Do not chew the tablets. Nevirapine Accord may be taken with or without food.

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

Missed dose of nevirapine
Do not skip doses. If less than 8 hours have passed since the missed dose was due, take the missed dose as soon as possible. If more than 8 hours have passed since the scheduled time, skip the missed dose and take the next dose at the usual time.

Stopping nevirapine
Taking all doses at the correct times:

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

It is important to take nevirapine strictly according to the instructions above until your doctor decides to stop treatment.
If you stop taking nevirapine for more than 7 days, your doctor will advise restarting treatment with the 14-day lead-in period (described above) before returning to the twice-daily dosing regimen.

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

4. Possible side effects

During treatment for HIV infection, increases in body weight as well as 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 treatment itself. Your doctor will monitor these changes.

Like all medicines, this medicine can cause side effects, although not everybody will get them.

As mentioned above in the section "Warnings and precautions", the most important side effects with nevirapine are severe and life-threatening skin reactions and severe liver damage. These events occur mainly within the first 18 weeks of taking nevirapine. This is therefore a critical period during which the patient requires close medical supervision.

If a rash of any kind occurs, 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 cases of death have been reported. Most cases of both severe and mild or moderate rash occur within the first 6 weeks of treatment.

If a rash occurs together with feeling unwell, treatment must be stopped immediately and the doctor must be informed without delay.

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

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

Hypersensitivity reactions may also occur as rash or other side 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 use, 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 any symptoms indicating liver damage, such as:

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

The side effects listed below have been observed in patients taking nevirapine.

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

• rash

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

• decreased white blood cell count (granulocytopenia)
• allergic reactions (hypersensitivity)
• headache
• nausea
• vomiting
• abdominal pain
• diarrhoea
• hepatitis
• fatigue
• fever
• abnormal liver function tests

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

• allergic reaction presenting as rash, facial swelling, breathing difficulties (bronchospasm) or anaphylactic shock
• decreased red blood cell count (anaemia)
• yellowing of the skin (jaundice)
• severe and life-threatening skin rashes (Stevens-Johnson syndrome, toxic epidermal necrolysis)
• urticaria
• angioedema
• joint pain
• muscle pain
• decreased blood phosphorus levels
• increased blood pressure

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

• sudden and severe hepatitis (fulminant hepatitis)
• rash with systemic symptoms (drug reaction with eosinophilia and systemic symptoms – DRESS)

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

• decreased 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 is used in combination with them; however, it is unlikely that they would be caused solely by nevirapine.

Additional side 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, any side effects should be reported to the doctor.

Reporting of side effects

If any side effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions at 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.

Reporting side effects helps provide more information on the safety of the 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 stated on the carton and blister after EXP.
The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Contents of the pack and other information

What Nevirapine Accord contains
The active substance is nevirapine. Each tablet contains 200 mg of nevirapine (as anhydrous nevirapine).
The other ingredients are: microcrystalline cellulose, sodium croscarmellose, maize starch,
povidone (K30), sodium carboxymethyl starch (type A), colloidal anhydrous silica, magnesium stearate.

What Nevirapine Accord looks like and contents of the pack
Nevirapine Accord is almost white to pale yellow, biconvex, capsule-shaped tablets, with "H" engraved on one side and "7" on the other, and a score line on both sides.
Nevirapine Accord is packed in PVC/Aluminum blisters containing 14, 60 or 120 tablets in a cardboard box, or in perforated PVC/Aluminum blisters containing 60x1, 120x1 or 180x1 tablets in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder:
Accord Healthcare Polska Sp. z o.o.
ul. Taśmowa 7
02-677 Warszawa
Tel: + 48 22 577 28 00

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

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