Nevirapine Mylan: detailed information

Package leaflet: Information for the patient

Nevirapine Mylan 400 mg prolonged-release tablets

anhydrous nevirapine
Generic medicine
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any adverse reactions, including those not listed in this leaflet, contact your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Nevirapine Mylan is and what it is used for
What you need to know before taking Nevirapine Mylan
How to take Nevirapine Mylan
Possible side effects
How to store Nevirapine Mylan
Contents of the pack and other information

1. What Nevirapina Mylan is and what it is used for

Nevirapina Mylan belongs to a group of medicines called antiretrovirals, used in the treatment of human immunodeficiency virus (HIV-1) infection.
The active substance in this medicine is called nevirapine. Nevirapine belongs to a class of anti-HIV medicines known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). Reverse transcriptase is an enzyme that HIV needs in order to multiply. Nevirapine blocks the activity of reverse transcriptase. By blocking reverse transcriptase activity, Nevirapina Mylan helps control HIV-1 infection.
Nevirapina Mylan is indicated for the treatment of HIV-1 infected adults, adolescents, and children aged 3 years and older who are able to swallow tablets. Nevirapina Mylan must be taken in combination with other antiretroviral medicines. Your doctor will recommend the most appropriate medicines for you.
Nevirapina Mylan extended-release tablets should only be used after a two-week treatment period with another type of nevirapine formulation (immediate-release tablets or oral suspension), except when you are currently being treated with nevirapine and are switching to the extended-release formulation.
If Nevirapina Mylan has been prescribed for your child, all information in this leaflet refers to your child (in this case, read “your child” instead of “you”).

2. What you should know before taking Nevirapine Mylan

Do not take Nevirapine Mylan

if you are allergic to nevirapine or to 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 experienced:
severe skin rash,
skin rash accompanied by other symptoms, for example:
fever
blisters
mouth ulcers
eye inflammation
facial swelling
general swelling
shortness of breath
muscle or joint pain
general malaise
abdominal pain
hypersensitivity reactions (allergic reactions)
liver inflammation (hepatitis)
if you have severe liver disease
if you previously had to discontinue treatment with nevirapine due to liver function abnormalities
if you are taking a medicine containing St. John's wort (Hypericum perforatum). This substance may prevent Nevirapine Mylan from working properly.

Warnings and precautions
Talk to your doctor or pharmacist before taking Nevirapine Mylan.
During the first 18 weeks of treatment with Nevirapine Mylan, it is very important that you and your
doctor pay close attention to any signs of liver-related or skin reactions. These may become serious and even life-threatening. Your risk of such reactions is higher during the first 6 weeks of treatment.
If a severe skin rash or hypersensitivity (i.e. allergic reactions that may appear as a rash) occurs,
accompanied by other adverse effects such as
fever,
blisters,
mouth ulcers,
eye inflammation,
facial swelling,
general swelling,
shortness of breath,
muscle or joint pain,
general malaise,
or abdominal pain,
YOU MUST STOP TAKING NEVIRAPINE MYLAN AND CONTACT YOUR DOCTOR
IMMEDIATELY, as these reactions may be potentially life-threatening or fatal. If you have only a mild skin rash without any other reaction,
inform your doctor immediately anyway, who will advise you whether you should stop taking
Nevirapine Mylan.
If symptoms indicating liver damage occur, such as
loss of appetite,
feeling unwell (nausea),
vomiting,
yellowing of the skin or eyes (jaundice),
abdominal pain,
you must stop taking Nevirapine Mylan and contact your doctor immediately.
If you develop severe liver-related, skin, or hypersensitivity reactions while taking
Nevirapine Mylan, DO NOT TAKE NEVIRAPINE AGAIN without first consulting
your doctor. You must take only the dose of Nevirapine Mylan prescribed by your doctor.
This is particularly important during the first 14 days of treatment (see further
information in “How to take Nevirapine Mylan”).
The following patients are at increased risk of developing liver problems:

women
patients co-infected with hepatitis B or C
patients with abnormal liver function test results
treatment-naïve patients with higher CD4 cell counts at the start of nevirapine therapy (women >250 cells/mm³, men >400 cells/mm³)
previously treated patients with detectable HIV-1 viral load in the blood and higher CD4 cell counts at the start of nevirapine therapy (women >250 cells/mm³, men >400 cells/mm³).

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections
(infections defining AIDS), inflammatory signs and symptoms of previous infections may occur
shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved
immune response, enabling the body to fight infections that may have been present without obvious
symptoms. If you notice any signs of infection, please inform your doctor immediately.
In addition to opportunistic infections, autoimmune disorders (a condition in which the immune
system attacks healthy body tissue) may also occur after starting medicines for HIV infection.
Autoimmune disorders may occur several months after starting treatment. If you notice any signs of
infection or other symptoms such as muscle weakness, initial weakness in hands and feet spreading
upwards towards the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to
receive necessary treatment.
A change in body fat distribution may occur in patients treated with combination antiretroviral
therapy. Contact your doctor if you notice changes in body fat (see section 4 “Possible side effects”).
Some patients taking combination antiretroviral therapy may develop a bone disease called
osteonecrosis (death of bone tissue due to reduced blood supply to the bones). The duration of
combination antiretroviral therapy, use of corticosteroids, alcohol consumption, severe immune
deficiency, and higher body mass index may be among the many risk factors for developing this
condition. Signs of osteonecrosis include joint stiffness, discomfort, and pain (especially in hips,
knees, and shoulders), and difficulty moving. Contact your doctor if you notice any of these
symptoms.
If you are taking nevirapine together with zidovudine, inform your doctor, as you may need to have
your white blood cell levels monitored.
Do not take nevirapine after exposure to HIV virus if you have not been diagnosed with the disease
and it has not been prescribed by your doctor.
Nevirapine does not cure HIV infection. Therefore, you may continue to develop infections and
other illnesses associated with HIV infection. While on treatment, you should continue regular
medical check-ups. You may still transmit HIV while taking this medicine, although the risk is
reduced by the effect of antiretroviral therapy. Discuss with your doctor the necessary precautions
to avoid transmitting the infection to others.
Prednisone must not be used to treat a skin rash related to nevirapine intake.
If you are using oral contraceptives (e.g. "the pill") or other hormonal birth control methods during
treatment with nevirapine, you must also use a barrier contraceptive method (e.g. a condom) to
prevent pregnancy and further transmission of HIV.
If you are on post-menopausal hormone replacement therapy, consult your doctor before taking this
medicine.
If you are taking or have been prescribed rifampicin for tuberculosis treatment, inform your doctor
before taking this medicine with nevirapine.
Nevirapine prolonged-release tablets or parts of the tablets may occasionally be seen in the stools.
They may resemble whole tablets, but this has not been shown to affect the efficacy of nevirapine.
Inform your doctor if you notice tablet fragments in your stools.

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

they are ≥ 8 years old and weigh 43.8 kg or more
they are older than 3 years and younger than 8 years and weigh 25 kg or more
they have a body surface area of 1.17 m² or more.

Smaller prolonged-release tablets or the liquid oral suspension formulation are available for younger
children.

Other medicines and Nevirapine Mylan
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other
medicines. Inform your doctor about all medicines you are taking before starting treatment with
Nevirapine Mylan.
Your doctor may need to check whether the other medicines remain effective and adjust their doses.
Read carefully the package leaflet of all other HIV medicines you are taking in combination with
Nevirapine Mylan.
It is particularly important that you inform your doctor if you are taking or have recently taken:

St. John's wort (Hypericum perforatum, a herbal remedy for depression)
rifampicin (a medicine for treating tuberculosis)
rifabutin (a medicine for treating tuberculosis)
macrolides e.g. clarithromycin (a medicine for treating bacterial infections)
fluconazole (a medicine for treating fungal infections)
ketoconazole (a medicine for treating fungal infections)
itraconazole (a medicine for treating fungal infections)
metadone (a medicine for treating opioid dependence)
warfarin (a medicine to reduce blood clotting)
hormonal contraceptives (e.g. the “pill”)
atazanavir (another medicine for treating HIV)
lopinavir/ritonavir (another medicine for treating HIV)
fosamprenavir (another medicine for treating HIV)
efavirenz (another medicine for treating HIV)
etravirine (another medicine for treating HIV)
rilpivirine (another medicine for treating HIV)
delavirdine (another medicine for treating HIV)
zidovudine (another medicine for treating HIV)
boceprevir (a medicine for treating hepatitis C)
telaprevir (a medicine for treating hepatitis C)
elvitegravir/cobicistat (another medicine for treating HIV). Your doctor will carefully monitor the effect of Nevirapine Mylan and each of these medicines if you are taking them in combination.

Nevirapine Mylan with food and drink
There are no restrictions regarding taking Nevirapine Mylan with food or drink.

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, are planning to become pregnant, or are breastfeeding,
ask your doctor or pharmacist for advice before taking this medicine.
You must stop breastfeeding if you are taking Nevirapine Mylan. In general, breastfeeding is not
recommended in case of HIV infection because the baby may contract HIV through breast milk.

Driving and using machines
When taking Nevirapine Mylan, you may experience fatigue. Be cautious when performing activities such as driving or operating any tools or machinery. If you experience fatigue, you should avoid potentially dangerous activities such as driving or operating any tools or machinery.

Nevirapine Mylan contains lactose and sodium
Nevirapine Mylan prolonged-release tablets contain lactose (milk sugar).
If your doctor has informed you of an intolerance to certain sugars, contact him before taking this
medicine.
This medicine contains less than 1 mmol of sodium (23 mg) per tablet; that is, it is essentially “sodium-free”.

3. How to take Nevirapine Mylan

You must not take Nevirapine Mylan on your own. It must be taken in combination with at least two other antiretroviral medicines. Your doctor will prescribe the most appropriate medicines for you.
Take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor.

Dosage:
Adults
The recommended dose is one 200 mg nevirapine tablet daily for the first 14 days of treatment ("initial phase"). A separate pack containing 200 mg immediate-release nevirapine tablets is available for this initial phase. After 14 days, the usual dose is one 400 mg prolonged-release tablet of Nevirapine Mylan taken once daily.

It is very important that you take only one nevirapine tablet per day during the first 14 days ("initial phase"). If you develop any rash during this period, do not start taking the prolonged-release tablets of Nevirapine Mylan, but contact your doctor immediately.
The 14-day "initial phase" has been shown to reduce the risk of skin rash.

Patients already being treated with immediate-release tablets or oral suspension may switch directly to the prolonged-release tablets without undergoing the initial phase.

Since Nevirapine Mylan must always be taken together with other antiretroviral medicines, you must also carefully follow the instructions for those other medicines. These instructions are available in their respective package leaflets.

Use in children and adolescents
Nevirapine is also available as prolonged-release tablets with a lower strength (for children aged at least 3 years and after the initial phase), or as an oral suspension suitable for all age groups (not marketed by the marketing authorization holder, but available from other companies for all age groups).

You must continue taking Nevirapine Mylan for the duration prescribed by your doctor.
As explained in the section "Warnings and precautions" above, your doctor will perform periodic checks, including liver function tests, and monitor for adverse effects such as skin rash. Depending on the results, your doctor may decide to temporarily interrupt or stop treatment with Nevirapine Mylan. Your doctor may consider restarting the medicine at a lower dose.

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

Take Nevirapine Mylan prolonged-release tablets by mouth with a liquid. Do not chew or break the prolonged-release tablets. You may take Nevirapine Mylan with or without food.

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

If you forget to take Nevirapine Mylan
Try not to miss any doses. If you remember within 12 hours of missing a dose, take the missed dose as soon as possible. If more than 12 hours have passed, take only the next dose at the scheduled time. Do not take a double dose to make up for a forgotten dose.

If you stop taking Nevirapine Mylan
Taking all doses at the correct times:

greatly increases the effectiveness of your antiretroviral medicines
reduces the chance that your HIV infection will become resistant to the medicines you are taking.

It is important to continue taking Nevirapine Mylan correctly as described above, unless your doctor tells you to stop treatment.
If you stop taking Nevirapine Mylan for more than 7 days, your doctor will instruct you to restart the 14-day "initial phase" with nevirapine tablets (as described above) before resuming once-daily treatment with Nevirapine Mylan prolonged-release tablets.

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

4. Possible side effects

During HIV therapy, increases in weight, blood lipid levels, and blood glucose levels may occur. This is partly related to the recovery of health status and lifestyle, and in the case of blood lipids, sometimes to the HIV medications themselves. Your doctor will monitor these changes.

Like all medicines, this medicine can cause side effects, although not everyone experiences them.

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

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

When it occurs, skin rash is usually mild or moderate. However, in some patients, a rash appearing as a blistering skin eruption can 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/moderate skin rashes occurred within the first six weeks of treatment.

If you develop a skin rash and also feel unwell, you must stop treatment and seek immediate medical attention.

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

skin rash
facial swelling
difficulty breathing (bronchospasm)
anaphylactic shock

Hypersensitivity reactions may also present as skin rashes accompanied by other adverse effects such as:

fever
skin blisters
mouth ulcers
eye inflammation
facial swelling
general swelling
shortness of breath
muscle or joint pain
inflammation of internal organs
decreased white blood cell count (granulocytopenia)
general feeling of being unwell
severe liver or kidney problems (liver or kidney function failure).

Inform your doctor immediately if you develop a skin rash and any of the other adverse effects associated with hypersensitivity (allergy). These reactions can be life-threatening.

Liver function abnormalities have been reported with the use of nevirapine. These include some cases of liver inflammation (hepatitis), which may be sudden and severe (fulminant hepatitis), and liver function failure, both of which can be fatal.

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

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

The following side effects were reported in patients treated with nevirapine 200 mg tablets during the 14-day lead-in phase:

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

skin rash
fever
headache
abdominal pain
feeling unwell (nausea)
loss of bowel control (diarrhea)
feeling of tiredness (fatigue)

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

allergic reactions (hypersensitivity)
allergic reaction characterized by skin rash, facial swelling, breathing difficulty (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 rashes (Stevens-Johnson syndrome/toxic epidermal necrolysis)
yellowing of the skin (jaundice)
hives (urticaria)
fluid accumulation under the skin (angioneurotic edema)
vomiting
muscle pain (myalgia)
joint pain (arthralgia)
decreased levels of phosphorus in the blood
increased blood pressure

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

liver inflammation (hepatitis)
decreased number of red blood cells (anaemia)

The following side effects have also been reported when nevirapine has been used in combination with other antiretroviral agents:

decreased number of red blood cells or platelets
inflammation of the pancreas
reduced or abnormal skin sensitivity

These cases are commonly associated with other antiretroviral agents and may occur when Nevirapina Mylan is used in combination with other agents; however, it is unlikely that these changes are caused by treatment with Nevirapina Mylan.

Additional side effects in children and adolescents

A decrease in the number of white blood cells (granulocytopenia) may occur more commonly in children. A reduction in red blood cells (anaemia), which may be associated with nevirapine therapy, is also more commonly observed in children. As with skin rash symptoms, inform your doctor of any adverse effects.

Reporting of side effects

If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Nevirapine Mylan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton, blister or bottle, following “Exp.”. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
For bottle packs: once opened, use within 100 days.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Nevirapine Mylan contains

The active substance is nevirapine. Each prolonged-release tablet contains 400 mg of nevirapine.
The other components are monohydrate lactose (see section 2 "Nevirapine Mylan contains lactose"), hypromellose, and sodium stearilfumarate.

Description of the appearance of Nevirapine Mylan and contents of the pack
Nevirapine Mylan is available as oval-shaped, prolonged-release tablets, white to off-white in colour, with M engraved on one side of the tablet and N403 on the other side.
Nevirapine Mylan is available in PVC/Aluminum blisters containing 14, 30, 30x1 (unit-dose blisters), 60, 90, 100 and 120 prolonged-release tablets, and in white HDPE bottles with white opaque polypropylene screw caps, containing 30, 90, 250 and 500 prolonged-release tablets. The bottles also contain cotton wool.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milano, Italy

Manufacturers
Generics [UK] Ltd, Station Close, Potters Bar, Hertfordshire, EN6 1TL, United Kingdom
McDermott Laboratories Limited trading as Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland
Mylan Hungary Kft., H-2900, Komárom, Mylan útca. 1, Hungary
Mylan UK Healthcare Limited, Building 20, Station Close, Potters Bar, EN6 1TL, United Kingdom
Mylan Germany GmbH, Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1, Bad Homburg v. d. Hoehe, Hessen, 61352, Germany

This medicinal product is authorised in the following European Economic Area countries and in the United Kingdom (Northern Ireland):
Austria Nevirapine Mylan 400 mg
Belgium Nevirapine Mylan 400 mg tabletten met verlengde afgifte
Denmark Nevirapin Mylan
Finland Nevirapine Mylan
France Névirapine Viatris L.P 400 mg comprimé à libération prolongée
Germany Nevirapin Mylan 400 mg Retardtabletten
Italy Nevirapina Mylan
Luxembourg Nevirapine Mylan 400 mg comprimés à libération prolongée
Netherlands Nevirapine Mylan 400 mg, tabletten met verlengde afgifte
Portugal Nevirapina Mylan
United Kingdom Nevirapine Mylan 400 mg prolonged-release tablets
(Northern Ireland)