DARUNAVIR MYLAN 600 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Darunavir Mylan 600 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 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 diseases 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 15 kg in weight who are infected with HIV and have already used other antiretroviral medicines.

Darunavir must be taken with a low dose of 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 to 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. While you are taking this medicine, you may still develop infections or other illnesses associated with HIV. Keep in regular contact with your doctor.

People taking darunavir may develop skin reactions. It is not common for the skin reaction to be severe or life-threatening. However, if you develop a skin reaction, please contact 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(e.g., enlarged lymph nodes, 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 starting in the hands and feet and moving up towards the trunk of the body, palpitations, tremor, or hyperactivity, inform your doctor immediately to seek necessary treatment.
• Tell your doctor if you have hemophilia.Darunavir may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides(e.g., used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems.Some patients using combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to lack of blood supply to the bone).

Some of the many risk factors for developing this disease include the duration of combination antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, and a higher body mass index. The signs of osteonecrosis are pain, discomfort, and stiffness in the joints (especially the hip, knees, and shoulders) and difficulty walking. If you notice any of these symptoms, inform 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.

Paediatric population

Darunavir is not used in children under 3 years of age or weighing less than 15 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 in the section "Do not combine Darunavir Mylan with any of the following medicines:"

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

The following products may reduce the effect of darunavir. Inform 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 certain infections like tuberculosis).
• Saquinavir (for HIV infection).

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

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disorders), 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 estrogens and hormone replacement therapy. The effect of darunavir may be reduced. For birth control, alternative non-hormonal contraceptive 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 reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine which cholesterol-reducing treatment is best for you based on your personal circumstances.
• Clarithromycin (antibiotic).
• Cyclosporine, 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, joint, and muscle disorders, and other inflammatory disorders. If alternatives cannot be used, they can only be administered after a medical evaluation and under close monitoring by your doctor to control 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 the treatment of malaria).
• Dasatinib, everolimus, nilotinib, vinblastine, vincristine (for the treatment of cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension).
• Simeprevir (for the treatment of hepatitis C infection).
• Fentanyl, oxycodone, tramadol (for the treatment of pain).

In certain cases, it may be necessary to modify the dose of some medicines because when combined, the therapeutic or adverse effects of these or darunavir may be affected.

Tell your doctor if you are taking:

• Alfentanil (a strong and short-acting injectable pain reliever used in surgical procedures).
• Digoxin (for the treatment of certain heart disorders).
• Clarithromycin (antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (for the treatment of fungal infections). Voriconazole can only be administered after a medical evaluation.
• Rifabutin (against bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation).

• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for the treatment of depression and anxiety).
• Maraviroc (for the treatment of HIV infection).
• Methadone (for the treatment of opioid dependence).
• Carbamazepine, clonazepam (to prevent seizures or to treat certain types of neuropathic pain).
• Colchicine (for the treatment of gout or familial Mediterranean fever).

• Bosentan (for the treatment of high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (for the treatment of psychiatric conditions).

This is nota complete list of medicines. Inform 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

Inform your doctor immediately if you are pregnant, plan to become pregnant, or are breast-feeding. Pregnant or breast-feeding women should not take Darunavir Mylan with ritonavir unless their doctor has specifically told them to do so. 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 because there is a possibility that the babies could be infected with HIV through their milk, and due to the unknown effects of the medicine on the baby.

Consult your doctor or pharmacist before using any medicine.

Driving and using machines

Do not drive or operate machines if you feel dizzy after taking Darunavir Mylan.

Darunavir Mylan contains less than 1 mmol of sodium (23 mg) per dose, which is essentially "sodium-free".

3. How to take Darunavir Mylan

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

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

Once treatment has started, the dose or form of the dose should not be changed, nor should treatment be interrupted without consulting a doctor.

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

You will require a different dose of darunavir, which cannot be administered with these 600-milligram tablets. Other doses of Darunavir Mylan are available.

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

The dose is:

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

Or

• 800 milligrams of darunavir (2 tablets containing 400 milligrams of darunavir or 1 tablet containing 800 milligrams of darunavir) along with 100 milligrams of ritonavir once a day. The 400-milligram and 800-milligram Darunavir Mylan tablets are used only to achieve the 800-milligram once-daily dose.

Talk to your doctor about which dose is correct for you.

Instructions for adults

• Take darunavir always with ritonavir. Darunavir cannot work properly without ritonavir.
• In the morning, take a 600-milligram tablet of darunavir along with 100 milligrams of ritonavir.
• In the evening, take a 600-milligram tablet of darunavir along with 100 milligrams of ritonavir.
• Take darunavir with food. Darunavir cannot work properly without food. The type of food does not matter.
• Swallow the tablets with a drink, which can be water or milk.
• The 75-milligram and 150-milligram Darunavir Mylan tablets and the 100-milligram-per-milliliter oral suspension have been developed for use in children, but in some cases, they may be used in adults.

Dose for children from 3 years of age, weighing at least 15 kilograms, who have not taken antiretroviral medications before (to be determined by your child's doctor)

The doctor will calculate the correct daily dose based on the child's weight (see the following table). This dose should not exceed the recommended adult dose, which is 800 milligrams of darunavir along with 100 milligrams of ritonavir once a day.

The doctor will inform you about what amount of Darunavir Mylan tablets and what amount of ritonavir (capsules, tablets, or solution) the child should take.

Oral solution of ritonavir: 80 milligrams per milliliter

Dose for children from 3 years of age, weighing at least 15 kilograms, who have taken antiretroviral medications before (to be determined by your child's doctor)

The doctor will establish the correct dose based on the child's weight (see the following table). The doctor will determine if the once-daily or twice-daily dose is appropriate for the child. This dose should not exceed the recommended adult dose, which is 600 milligrams of darunavir along with 100 milligrams of ritonavir twice a day or 800 milligrams of darunavir along with 100 milligrams of ritonavir once a day. The doctor will inform you about what amount of Darunavir Mylan tablets and what amount of ritonavir (capsules, tablets, or solution) the child should take. Lower-concentration tablets are available to achieve the appropriate dosing regimen. Other presentations of this medication may be more suitable for children; ask your doctor or pharmacist.

Dose twice a day

• The child's doctor will determine if the 800-milligram Darunavir Mylan once-daily dose can be used for children 12 years of age or older and weighing at least 40 kilograms. This dose cannot be administered with the 600-milligram tablets. Other doses of Darunavir Mylan are available.

Dose once a day

Instructions for children

• The child must take darunavir always with ritonavir. Darunavir cannot work properly without ritonavir.
• The child must take the appropriate dose of darunavir and ritonavir twice a day or once a day. If darunavir is prescribed twice a day, the child should take one dose in the morning and another in the evening. The child's doctor will determine the appropriate dosing regimen for your child.
• The child must take darunavir with food. Darunavir cannot work properly without food. The type of food does not matter.
• The child must swallow the tablets with a drink, such as water or milk.
• The 75-milligram and 150-milligram Darunavir Mylan tablets have been developed for use in children weighing less than 40 kilograms, but in some cases, they may be used in adults.

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 6 hours, take the missed dose immediately. Always take it with ritonavir and with food. If you realize after 6 hours, skip that dose and continue with the next dose as usual. Do not take a double dose to make up for missed 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 medication, ask your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV treatment, weight gain and increased lipid and glucose levels may occur. This is associated, in part, with the recovery of health and lifestyle, and in the case of blood lipids, sometimes due to the medications used to treat HIV. Your doctor will perform tests to detect these changes.

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

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

Liver problems have been reported, which can sometimes be severe. Your doctor will perform blood tests before starting treatment with darunavir. If you have chronic hepatitis B or C infection, your doctor will perform blood tests more frequently because you are more likely to develop liver problems. Talk to your doctor about the signs and symptoms of liver problems. These signs and symptoms can include, among others: yellowing of the skin or the whites of the eyes, dark urine (tea-colored), pale stools, nausea, vomiting, loss of appetite, or pain, itching, or discomfort in the right upper abdomen.

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 using darunavir.

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

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, nausea, dry mouth, abdominal discomfort, constipation, belching.
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night.
• hives, severe skin and tissue swelling (mainly lips or eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail discoloration.
• muscle pain, muscle sensitivity or weakness. In rare cases, these muscle disorders can be severe.
• 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 or joint stiffness, 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: increased 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 leaflet. 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 medication.

5. Storage of Darunavir Mylan

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the box and bottle, after EXP. The expiration date is the last day of the month indicated.

This medication does not require special storage conditions.

In the case of bottles: Once opened, use the product within 100 days.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any medication you no longer need. This will help protect the environment.

6. Package contents and additional information

Darunavir Mylan composition

• The active ingredient is darunavir. Each tablet contains 600 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

The 600-milligram Darunavir Mylan film-coated tablets are white or almost white, oval, with two curved sides, marked with an "M" on one face and "DV5" on the other.

The 600-milligram Darunavir Mylan film-coated tablets are available in blisters containing 30 and 60 tablets and in plastic bottles containing 30, 60, and 90 tablets.

Only some 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, trading as Gerard Laboratories, 35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13, Ireland

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

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

Other sources of information

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