DARUNAVIR MYLAN 800 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Darunavir Mylan 800 mg Film-Coated Tablets EFG

darunavir

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this 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 signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Package Leaflet

1. What is Darunavir Mylan and what is it used for
2. What you need to know before you take Darunavir Mylan
3. How to take Darunavir Mylan
4. Possible side effects
5. Storage of Darunavir Mylan
6. Contents of the pack and other information

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

What is Darunavir Mylan?

Darunavir Mylan contains the active substance darunavir. Darunavir is an antiretroviral medicine used to treat Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. Darunavir reduces the amount of HIV in your body. This will improve your immune system and reduce the risk of developing illnesses associated with HIV infection.

What is it used for?

Darunavir is used to treat adults and children (from 3 years of age and at least 40 kg body weight) who are infected with HIV and

• have not taken antiretroviral medicines before.
• have taken antiretroviral medicines before (your doctor will determine this).

Darunavir must be taken with a low dose of cobicistat or ritonavir and other HIV medicines. Your doctor will discuss with you which combination of medicines is best for you.

2. What you need to know before you take Darunavir Mylan

Do not take Darunavir Mylan

• if you are allergicto darunavir or any of the other ingredients of this medicine (listed in section 6) or cobicistat or ritonavir.
• if you have severe liver problems.Ask your doctor if you are not sure about the severity of your liver disease. You may need to have some additional tests.

Do not combine Darunavir Mylan with any of the following medicines

If you are taking any of these medicines, consult your doctor to change to another medicine.

Do not combine darunavir with products that contain St. John's Wort (Hypericum perforatum).

Warnings and precautions

Consult your doctor, pharmacist, or nurse before you start taking Darunavir Mylan.

Darunavir does not cure HIV infection. You can still transmit HIV when taking this medicine, although effective antiretroviral treatment reduces the risk. Consult your doctor about the precautions needed to avoid infecting others.

People taking darunavir may still develop other infections and diseases associated with HIV infection. You must keep regular contact with your doctor.

People taking darunavir may develop a skin rash. It is not common for the rash to be severe or life-threatening. However, if you develop a rash, please consult your doctor.

Patient taking darunavir and raltegravir (for HIV infection), may more frequently experience rash (generally mild or moderate) than patients taking either of these medicines separately.

Tell your doctor about your situation BEFORE and DURING treatment

Make sure you check the following points and tell your doctor if any of them apply to you.

• Tell your doctor if you have had liver disease, including infection with hepatitis B or C. Your doctor will assess the severity of your liver disease before deciding if you can take darunavir.
• Tell your doctor if you have diabetes.Darunavir may increase blood sugar levels.

• Tell your doctor immediately if you notice any symptoms of infection(for example, enlarged lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, 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 have been present without causing symptoms.
• 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 for the necessary treatment.
• Tell your doctor if you have haemophilia.Darunavir may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulphonamides(for example, used for the treatment of certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to loss of blood supply to the bone). The risk of osteonecrosis is increased if you are taking corticosteroids, have had a high level of alcohol intake, have a high level of immunosuppression, or have a high body mass index. Signs of osteonecrosis include joint pain or pain in your arms or legs, and difficulty walking. If you notice any of these symptoms, please consult your doctor.

Elderly population

Darunavir Mylan has only been used in a limited number of patients aged 65 years or older. If you belong to this age group, please consult your doctor to see if you can use Darunavir Mylan.

Children and adolescents

Darunavir Mylan 800 mg tablets should not be used in children under 3 years of age or weighing less than 40 kg.

Taking Darunavir Mylan with other medicines

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

Some medicines must not be takenwith darunavir. The list can be found under the section “Do not combine Darunavir Mylan with any of the following medicines:”

In most cases, darunavir can be taken with other HIV medicines that belong to other classes [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and fusion inhibitors]. Darunavir has not been tested with cobicistat or ritonavir and all protease inhibitors and should not be used with other protease inhibitors. In some cases, it may be necessary to change the dose of the other medicines. Therefore, if you are taking other anti-HIV medicines, always consult your doctor and carefully follow their instructions on which medicines can be combined.

The following products may reduce the effect of darunavir. Tell your doctor if you are taking:

• Phenobarbital, phenytoin (to prevent seizures).
• Dexamethasone (corticosteroid).
• Efavirenz (for HIV infection).
• Boceprevir (for hepatitis C infection).
• Rifapentine, rifabutin (medicines for treating some infections like tuberculosis).
• Saquinavir (for HIV infection).

Darunavir may also affect the action of other medicines. Tell your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, dabigatran etexilate, rivaroxaban, warfarin (to reduce blood clotting), as the therapeutic or adverse effects of these medicines may be altered; your doctor may perform blood tests.
• Hormonal contraceptives based on oestrogen and hormone replacement therapy. Darunavir may reduce their effect. For contraception, alternative non-hormonal methods are recommended.

• Ethinylestradiol/drospirenone. Darunavir Mylan may increase the risk of elevated potassium levels due to the effect of drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower blood cholesterol). There may be an increased risk of muscle damage. Your doctor will decide which treatment to lower your cholesterol is most suitable for you, depending on your personal circumstances.
• Clarithromycin (antibiotic).
• Ciclosporin, everolimus, tacrolimus, sirolimus (to suppress the immune system), as the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, such as betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye diseases, joint and muscle diseases, and other inflammatory diseases. If alternatives cannot be used, they can only be administered after a medical assessment and under close monitoring by your doctor to check for the occurrence of adverse effects of corticosteroids.
• Buprenorphine/naloxone (medicines for the treatment of opioid dependence).
• Salmeterol (medicine for the treatment of asthma).
• Artemether/lumefantrine (a combination of medicines for treating malaria).
• Dasatinib, everolimus, nilotinib, vinblastine, vincristine (for the treatment of cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung condition called pulmonary arterial hypertension).
• Simeprevir (for the treatment of hepatitis C infection).
• Fentanyl, oxycodone, tramadol (for the treatment of pain).

This is nota complete list of medicines. Tell your doctor about all the medicines you are taking.

Taking Darunavir Mylan with food and drink

See section 3 “How to take Darunavir Mylan”.

Pregnancy and breast-feeding

Tell your doctor immediately if you are pregnant, plan to become pregnant, or are breast-feeding. Pregnant or breast-feeding women should not take darunavir with ritonavir unless specifically advised to do so by their doctor. Pregnant or breast-feeding women should not take darunavir with cobicistat.

It is recommended that women infected with HIV do not breast-feed their babies, as there is a possibility that the baby may become infected with HIV through breast milk, and due to the unknown effects of the medicine on the baby.

Driving and using machines

Do not drive or operate machinery if you experience dizziness after taking darunavir.

Darunavir Mylan contains less than 1 mmol sodium (23 mg) per dose, i.e., it is essentially “sodium-free”.

3. How to take Darunavir Mylan

Follow the administration instructions for this medicine as described in this prospectus or as indicated by your doctor, pharmacist, or nurse. In case of doubt, ask your doctor, pharmacist, or nurse.

Do not stop taking darunavir or cobicistat or ritonavir without consulting your doctor first, even if you feel better.

After starting treatment, do not change the dose or interrupt treatment without your doctor's instructions.

Darunavir Mylan 800 mg tablets are used only for the 800 milligram once-daily regimen.

Dose for adults who have not taken antiretroviral medications before (to be determined by your doctor)

The normal dose of darunavir is 800 milligrams (2 tablets of 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) once a day. You should take darunavir every day and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. Darunavir does not work properly without cobicistat or ritonavir and food. Before taking darunavir and cobicistat or ritonavir, you should eat 30 minutes beforehand. The type of food is not important. Do not interrupt treatment with darunavir or cobicistat or ritonavir without consulting your doctor first, even if you feel better.

Instructions for adults

• Take one 800 milligram tablet at the same time, once a day, every day.
• Always take darunavir with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take darunavir with food.
• Swallow the tablet with a drink, which can be water or milk.
• Take the other HIV medications used in combination with darunavir and cobicistat or ritonavir as your doctor recommends.

Dose for adults who have taken antiretroviral medications before (to be determined by your doctor)

The dose is:

• 800 milligrams of darunavir (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) with 150 milligrams of cobicistat or 100 milligrams of ritonavir once a day.

Or

• 600 milligrams of darunavir (2 tablets containing 300 milligrams of darunavir or 1 tablet containing 600 milligrams of darunavir) with 100 milligrams of ritonavir twice a day.

Please talk to your doctor about which dose is correct for you.

Dose for children from 3 years of age, weighing more than 40 kilograms, who have not taken antiretroviral medications before (to be determined by your child's doctor)

• The usual dose of darunavir is 800 milligrams (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) with 100 milligrams of ritonavir once a day.

Dose for children from 3 years of age, weighing more than 40 kilograms, who have taken antiretroviral medications before (to be determined by your child's doctor)

The dose is:

• 800 milligrams of darunavir (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) with 100 milligrams of ritonavir once a day.

Or

• 600 milligrams of darunavir (2 tablets containing 300 milligrams of darunavir or 1 tablet containing 600 milligrams of darunavir) with 100 milligrams of ritonavir twice a day.

Please talk to your doctor about which dose is correct for you.

Instructions for children from 3 years of age, weighing more than 40 kilograms

• Take 800 milligrams of darunavir (2 tablets containing 400 milligrams of Darunavir Mylan or 1 tablet containing 800 milligrams of Darunavir Mylan) at the same time, once a day, every day.
• Always take darunavir with 100 milligrams of ritonavir.
• Take darunavir with food.
• Swallow the tablets with a liquid, such as water or milk.
• Take the other medications used in combination with darunavir and ritonavir as your doctor recommends.

If you take more Darunavir Mylan than you should

Inform your doctor, pharmacist, or nurse immediately.

If you forget to take Darunavir Mylan

If you realize within 12 hours, take the tablets immediately. Always take the dose with cobicistat or ritonavir and with food. If you realize after 12 hours, skip that dose and take the next one as usual. Do not take a double dose to make up for forgotten doses.

Do not stop taking Darunavir Mylan without talking to your doctor first

HIV medications can make you feel better. Even if you feel better, do not stop taking Darunavir Mylan. Consult your doctor first.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

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

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

Tell your doctor if you develop any of the following side effects.

There have been reports of liver problems that can occasionally be severe. Your doctor will perform a blood test before you start treatment with darunavir. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood tests, as there is a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin and the whites of the eyes, darkening (tea color) of the urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness in the right side below your ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. The skin rash is usually mild to moderate. A skin rash can also be a symptom of a rare and serious situation. Therefore, it is essential to talk to your doctor if you develop a rash. Your doctor will advise you on how to control the symptoms or if you should stop taking darunavir.

Other serious side effects were diabetes (frequent) and pancreatitis (uncommon).

Very common side effects (may affect more than 1 in 10 patients)

• diarrhea.

Common side effects (may affect up to 1 in 10 patients)

• vomiting, nausea, abdominal pain or distension, upper abdominal pain (dyspepsia), flatulence.
• headache, fatigue, dizziness, somnolence, numbness, tingling, or pain in the hands or feet, weakness, difficulty staying asleep.

Uncommon side effects (may affect up to 1 in 100 patients)

• chest pain, changes in the electrocardiogram, rapid heart rate.
• decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance.
• breathing difficulties, cough, nasal bleeding, throat irritation.
• stomach or mouth inflammation, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching.
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night.
• hives, severe skin swelling (mainly lips or eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail discoloration.
• muscle pain, muscle sensitivity or weakness, muscle cramps or weakness, pain in the limbs, osteoporosis.
• reduced thyroid gland function. This can be seen in a blood test.
• high blood pressure (increased blood pressure), flushing.
• red or dry eyes.
• fever, swelling of the lower limbs due to fluid retention, discomfort, irritability, pain.
• infection symptoms, herpes simplex.
• erectile dysfunction, breast enlargement.

• sleep disorders, somnolence, depression, anxiety, abnormal dreams, decreased sexual desire.

Rare side effects (may affect up to 1 in 1,000 patients)

• a reaction called DRESS (severe rash, which can be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils [a type of white blood cell], liver, kidney, or lung damage).
• heart attack, slow heart rate, palpitations.
• visual impairment.
• chills, strange sensation.
• a feeling of confusion or disorientation, altered mood, agitation.
• fainting, epileptic seizure, changes or loss of taste.
• mouth ulcers, vomiting blood, lip inflammation, dry lips, tongue with thrush.
• nasal discharge.
• skin lesions, dry skin.
• muscle stiffness or in the joints, joint pain with or without inflammation.
• changes in some blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: increase in some white blood cells.

Some side effects are typical of HIV medications that belong to the same family as darunavir. These are:

• muscle pain, sensitivity, or weakness. In rare cases, these muscle disorders can be severe.

Reporting side effects

If you experience side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospectus. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Darunavir Mylan

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

Do not use this medicine after the expiration date stated on the carton and blister or bottle, after EXP. The expiration date is the last day of the month indicated.

In the case of blisters with plastic on one side and aluminum on the other: Do not store above 25°C.

In the case of blisters with aluminum on both sides: This medicine does not require special storage conditions.

In the case of bottles: Once opened, use the product within 90 days. This medicine does not require special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medicine. This will help protect the environment.

6. Package contents and additional information

Composition of Darunavir Mylan

• The active ingredient is darunavir. Each tablet contains 800 milligrams of darunavir.

• The other ingredients are anhydrous colloidal silica, microcrystalline cellulose, crospovidone, sodium starch glycolate, hypromellose, magnesium stearate. The coating contains partially hydrolyzed polyvinyl alcohol, titanium dioxide, macrogol, and talc.

Appearance of Darunavir Mylan and package contents

Darunavir Mylan 800 mg film-coated tablets are white or almost white, oval, with two curved sides, marked with an "M" on one side and "DV8" on the other.

Darunavir Mylan 800 mg film-coated tablets are available in blisters containing 30 tablets and in plastic bottles containing 30, 60, and 90 tablets.

Not all pack sizes may be marketed.

Marketing authorization holder

Mylan S.A.S.

117 Allee des Parcs

69800 Saint Priest

France

Manufacturer

Mylan Hungary Kft

H-2900 Komárom, Mylan utca 1

Hungary

McDermott Laboratories Limited under the trade name Gerard Laboratories 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13 Ireland

You can obtain more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of last revision of this prospectus: {MM/YYYY}.

Other sources of information

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