VIRAMUNE 50 mg/5 ml ORAL SUSPENSION

2. What you need to know before you take Viramune

Do not take Viramune

• if you are allergic to nevirapine or any of the other ingredients of this medicine (listed in section 6)

• if you have previously taken Viramune and had to stop taking it because you had:
• severe skin rash
• skin rash with other symptoms such as:

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

• allergic reactions
• liver inflammation (hepatitis)
• if you have severe liver disease
• if you have had to stop taking Viramune in the past due to changes in your liver function
• if you are taking any other medicine containing St John's Wort (Hypericum perforatum). This product may cause Viramune to stop working properly.

Warnings and precautions

Talk to your doctor or pharmacist before you start taking Viramune.

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

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

• women
• patients infected with hepatitis B or C
• abnormal liver function tests
• patients who have not previously taken antiretroviral treatment with higher CD4+ cell counts at the start of treatment with Viramune (women with more than 250 cells/mm³, men with more than 400 cells/mm³)
• patients who have previously taken antiretroviral treatment with detectable HIV-1 viral load in plasma and higher CD4+ cell counts at the start of treatment with Viramune (women with more than 250 cells/mm³, men with more than 400 cells/mm³)

In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (AIDS-defining illnesses), signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to an improvement in the body's immune response, enabling it to fight off infections that were present but not causing symptoms. If you notice any symptoms of infection, please inform your doctor immediately.

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

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

In some patients who are taking combined antiretroviral therapy, a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone) may occur. The duration of combined antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immune system suppression, and high body mass index may be some of the many risk factors for developing this disease. The symptoms of osteonecrosis are: joint stiffness, pain, and discomfort, especially in the hip, knee, and shoulder, and difficulty moving. If you notice any of these symptoms, inform your doctor.

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

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

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

If you are taking oral contraceptives (e.g., “the pill”) or other hormonal methods of birth control while taking Viramune, you should also use a barrier method of birth control (e.g., condoms) to prevent pregnancy and transmission of HIV.

If you are receiving hormone replacement therapy, talk to your doctor before taking this medicine.

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

Children and adolescents

Viramune oral suspension can be used in children of all ages. Follow the administration instructions given by your child's doctor exactly.

Viramune is also available as tablets. Viramune tablets can be used in:

• children aged 16 years or older
• children under 16 years:
• weighing 50 kg or more
• or with a body surface area of 1.25 m² or more.

Other medicines and Viramune

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Before you start taking Viramune, tell your doctor about all other medicines you are taking. Your doctor may need to check that your other medicines are still working and make dose adjustments. Read the leaflet that comes with all other anti-HIV medicines you are taking with Viramune.

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

• St John's Wort (Hypericum perforatum, a herbal remedy for depression)
• rifampicin (a medicine 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)
• methadone (a medicine used to treat addiction to opiates)
• warfarin (a medicine for reducing blood clot formation)
• hormonal contraceptives (e.g., “the pill”)
• atazanavir (another medicine for treating HIV infection)
• lopinavir/ritonavir (another medicine for treating HIV infection)
• fosamprenavir (another medicine for treating HIV infection)
• efavirenz (another medicine for treating HIV infection)
• etravirine (another medicine for treating HIV infection)
• rilpivirine (another medicine for treating HIV infection)
• zidovudine (another medicine for treating HIV infection)
• elvitegravir/cobicistat (another medicine for treating HIV infection)

Your doctor will carefully monitor the effect of Viramune and any of these medicines if you are taking them at the same time.

If you are having kidney dialysis, your doctor may consider it necessary to adjust the dose of Viramune, as Viramune can be partially removed from the blood by dialysis.

Taking Viramune with food and drink

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

Pregnancy and breastfeeding

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

It is recommended thatHIV-infected women do not breastfeedtheir babies because HIV can be passed on to the baby through breast milk.

If you are breastfeeding or thinking of breastfeeding, you must consult your doctoras soon as possible.

Driving and using machines

While taking Viramune, you may experience fatigue. You should be careful when performing activities such as driving or using machines. If you experience fatigue, you should avoid performing tasks that may be potentially hazardous, such as driving or using machines.

Viramune contains sucrose, sorbitol, methyl parahydroxybenzoate, propyl parahydroxybenzoate, and sodium

Viramune oral suspension contains 150 mg of sucrose per ml. This should be taken into account in patients with diabetes mellitus. If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine. It may be harmful to teeth.

Viramune oral suspension contains 162 mg of sorbitol per ml. Sorbitol is a source of fructose. If your doctor has told you that you (or your child) have an intolerance to some sugars, or have been diagnosed with hereditary fructose intolerance (HFI), a rare genetic disorder in which the patient cannot break down fructose, consult your doctor before taking this medicine.

Viramune oral suspension contains methyl parahydroxybenzoate and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

Viramune oral suspension contains less than 1 mmol of sodium (23 mg) per dose; this is essentially “sodium-free”.

3. How to take Viramune

Do not use Viramune on your own. You should use it with at least two other antiretroviral medications. Your doctor will recommend the appropriate medications for you.

Follow the administration instructions for this medication exactly as indicated by your doctor. If in doubt, consult your doctor or pharmacist again.

The usual dose is the same for all adults (20 ml).

Your child's doctor will calculate the dose for your child. The calculation will take into account your child's age and weight or body surface area. Make sure your child's doctor clearly informs you about the dose you should give to your child.

For adults

The dose for adults is 20 ml (200 mg) once a day for the first 14 days of treatment (the "initial" period). After 14 days, the usual dose is 20 ml (200 mg) twice a day.

It is very important that you take only 20 ml of Viramune per day during the first 14 days (the "initial" period). If you experience any rash during this period, do not increase the dose and consult your doctor.

Viramune is also available in the form of 200 mg tablets for adults (16 years of age and older).

For children

The dose for children is 4 mg/kg of body weight or 150 mg/m2 of body surface area once a day for the first 14 days of treatment (the "initial" period). From then on, your child's dose will be modified to a twice-daily dosing regimen, and your child's doctor will decide on the appropriate dose based on your child's weight or body surface area.

It is very important that your child takes Viramune only once a day during the first 14 days (the "initial" period). If your child experiences any rash during this period, do not increase the dose and consult your child's doctor.

Viramune is also available in the form of 200 mg tablets for older children, particularly adolescents, weighing over 50 kg or with a body surface area over 1.25 m2. Your child's doctor will indicate the correct dosage for your child. Your child's doctor will continuously monitor your child's weight or body surface area to ensure the correct dose.

If you are unsure, consult your child's doctor or pharmacist.

The oral suspension of Viramune should be shaken gently before administration. Measure the exact dose using a dosing syringe.

If you are an adult and wish to use another measuring device (e.g., a cup or spoon), make sure to take the complete dose, as some Viramune may remain in the cup or spoon. To do this, rinse the device you used with water and drink the contents.

The oral dosing syringe and dosing cup are not provided with the Viramune oral suspension. Ask your pharmacist for a syringe or cup if you do not have one.

It has been shown that the 14-day "initial" period reduces the risk of skin rash.

As Viramune should always be taken in combination with other antiretroviral medications, follow the instructions for your other medications carefully. These are provided in the package leaflets for these medications.

You must continue taking Viramune for as long as your doctor indicates.

As explained earlier in the "Warnings and precautions" section, your doctor will monitor you with liver tests and watch for adverse effects such as rash. Depending on the results, your doctor may decide to interrupt or discontinue treatment with Viramune. Similarly, your doctor may decide to restart treatment at a lower dose.

Viramune oral suspension is presented as a liquid suspension and should be taken only orally. Shake the bottle gently before using the medication.

If you take more Viramune than you should

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

If you forget to take Viramune

Try not to miss any dose. If you realize you have forgotten to take a dose within 8 hours of the scheduled time, take the next dose as soon as possible. If more than 8 hours have passed since the scheduled time, only take the next dose at the usual time.

If you interrupt treatment with Viramune

Taking the doses at the indicated times:

• greatly increases the effectiveness of your antiretroviral medication combination
• decreases the likelihood that the HIV infection will become resistant to antiretroviral medications

It is important that you continue taking Viramune correctly, as described above, unless your doctor indicates that you should interrupt treatment.

If you interrupt administration of Viramune for more than 7 days, your doctor will indicate that you should start again with the 14-day "initial" period (as described above) before returning to the twice-daily dose.

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

4. Possible side effects

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

Like all medications, this medication can cause side effects, although not everyone will experience them.

As mentioned earlier in 'Warnings and precautions',the most important side effects of Viramune are severe skin reactions and life-threatening liver damage. These reactions occur mainly during the first 18 weeks of treatment with Viramune. This is, therefore, an important period that requires close monitoring by your doctor.

If you observe any symptoms of rash, inform your doctor immediately.

When a rash occurs, it is usually mild to moderate. However, in some patients, a rash appears in the form of a blistering skin reaction that can be severe or life-threatening (Stevens-Johnson syndrome and toxic epidermal necrolysis), and fatalities have been reported. Most cases of rash, both severe and mild/moderate, occur during the first six weeks of treatment.

If a rash appears and you also feel unwell, you should interrupt treatment and see your doctor immediately. Pay special attention to any rash that may appear in your child. Although it may seem normal (e.g., diaper irritation), it could be a Viramune-related rash. If in doubt, consult your child's doctor.

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

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

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

• fever
• blistering of the skin
• mouth sores
• eye inflammation
• facial swelling
• generalized swelling
• difficulty breathing
• muscle or joint pain
• decrease in white blood cell count (granulocytopenia)
• general malaise
• serious liver or kidney problems (liver or kidney failure)

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

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

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

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

The following adverse effects have been reported in patients taking Viramune:

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

• rash

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

• decrease in white blood cell count (granulocytopenia)
• allergic reactions (hypersensitivity)
• headache
• general malaise (nausea)
• vomiting
• abdominal pain
• diarrhea
• liver inflammation (hepatitis)
• fatigue
• fever
• abnormalities in liver function tests

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

• allergic reactions characterized by rash, facial swelling, difficulty breathing (bronchospasm), or anaphylactic shock
• decrease in red blood cell count (anemia)
• yellowing of the skin (jaundice)
• severe and potentially fatal skin reactions (Stevens-Johnson syndrome/toxic epidermal necrolysis)
• hives
• fluid under the skin (angioedema)
• joint pain (arthralgia)
• muscle pain (myalgia)
• decrease in blood phosphorus levels
• increase in blood pressure

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

• sudden and severe liver inflammation (fulminant hepatitis)
• drug reaction with systemic symptoms (drug reaction with eosinophilia and systemic symptoms)

When Viramune is used in combination with other antiretroviral medications, the following events have also been reported:

• decrease in red blood cell or platelet count
• pancreatitis
• decrease or abnormalities in skin sensations

These effects are generally associated with other antiretroviral agents and may occur when Viramune is used in combination with other agents; however, it is unlikely that these effects are due to treatment with Viramune.

Other side effects in children and adolescents

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

Reporting of side effects

If you experience any side effects, consult your doctor or pharmacist, even if it is possible that they are not listed in this package leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of Viramune

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

Do not use this medication after the expiration date stated on the packaging and on the bottle after "EXP". The expiration date is the last day of the month indicated.

Viramune should be used within 6 months of opening the bottle.

This medication does not require special storage conditions.

Medications should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medications that are no longer needed. This will help protect the environment.

6. Package contents and further information

Composition of Viramune

• The active ingredient is nevirapine. Each 5 ml contains 50 mg of the active ingredient nevirapine (as hemihydrate).
• The other ingredients are:
  • carbomer
  • methyl parahydroxybenzoate
  • propyl parahydroxybenzoate
  • sorbitol
  • sucrose
  • polysorbate 80
  • sodium hydroxide
  • water

Appearance and package contents

Viramune oral suspension is a homogeneous, white or almost white suspension.

Viramune oral suspension is available in plastic bottles of oral suspension for oral use, with 240 ml of suspension per bottle.

Viramune is also available in tablets for children and adults.

Marketing authorization holder

Boehringer Ingelheim International GmbH

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

Manufacturer

Boehringer Ingelheim Pharma GmbH & Co. KG

Binger Strasse 173

55216 Ingelheim am Rhein

Germany

or

Boehringer Ingelheim France

100-104 avenue de France

75013 Paris

France

You can obtain further information on this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this package leaflet:{MM/AAAA}

Other sources of information

Detailed information on this medication is available on the European Medicines Agency website: http://www.ema.europa.eu.