Darunavir Mylan - patient leaflet, side effects, dosage

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

What is Darunavir Mylan?

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

What it is used for?

Darunavir is used to treat adults and children of 3 years of age and above, and at least 15 kilogram body weight who are infected by HIV and who have already used other antiretroviral medicines.

Darunavir must be taken in combination with a low dose of ritonavir and other anti-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 allergic to 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 unsure about the severity of your

liver disease. Some additional tests might be necessary.

Do not combine Darunavir Mylan with any of the following medicines

If you are taking any of these, ask your doctor about switching to another medicine.

Medicine	Purpose of the medicine
Avanafil	to treat erectile dysfunction

Astemizole or terfenadine	to treat allergy symptoms
Triazolam and oral (taken by mouth) midazolam	to help you sleep and/or relieve anxiety
Cisapride	to treat some stomach conditions
Colchicine (if you have kidney and/or liver problems)	to treat gout or familial Mediterranean fever
Lurasidone, pimozide, quetiapine or sertindole	to treat psychiatric conditions
Ergot alkaloids like ergotamine , dihydroergotamine , ergometrine and methylergonovine	to treat migraine headaches
Amiodarone, bepridil, dronedarone, ivabradine, quinidine, ranolazine	to treat certain heart disorders e.g. abnormal heart beat
Lovastatin simvastatin and lomitapide	to lower cholesterol levels
Rifampicin	to treat some infections such as tuberculosis
The combination product lopinavir/rito­navir	this anti-HIV medicine belongs to the same class as darunavir
Elbasvir/grazo­previr	to treat hepatitis C infection
Alfuzosin	to treat enlarged prostate
Sildenafil	to treat high blood pressure in the pulmonary circulation
Dabigatran, ticagrelor	to help stop the clumping of platelets in the treatment of patients with a history of a heart attack
Naloxegol	to treat opioid induced constipation
Dapoxetine	to treat premature ejaculation
Domperidone	to treat nausea and vomiting

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

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Darunavir Mylan.

Darunavir is not a cure for HIV infection. You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting other people.

People taking darunavir may still develop infections or other illnesses associated with HIV infection.

You must keep in regular contact with your doctor.

People taking darunavir may develop a skin rash. Infrequently a rash may become severe or potentially life-threatening. Please contact your doctor whenever you develop a rash.

In patients taking darunavir and raltegravir (for HIV infection), rashes (generally mild or moderate) may occur more frequently than in patients taking either medicine separately.

Tell your doctor about your situation BEFORE and DURING your treatment

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

• – Tell your doctor if you have had problems with your liver before, including hepatitis B or C infection. Your doctor may evaluate how severe your liver disease is before deciding if you can take darunavir.

• – Tell your doctor if you have diabetes. Darunavir might increase sugar levels in the blood.

• – 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 infection, 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 the body to fight infections that may have been present with no obvious symptoms.

• – In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start 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 beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.

• – Tell your doctor if you have haemophilia. Darunavir might increase the risk of bleeding.

• – Tell your doctor if you are allergic to sulphonamides (e.g. used to treat certain infections).

• – Tell your doctor if you notice any musculoskeletal problems. Some patients taking

combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Elderly

Darunavir has only been used in limited numbers of patients 65 years or older. If you belong to this age group, please discuss with your doctor if you can use Darunavir Mylan.

Children

Darunavir is not for use in children younger than 3 years of age or weighing less than 15 kilograms.

Other medicines and Darunavir Mylan

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

There are some medicines that you must not combine with darunavir. These are mentioned above under the heading ‘Do not combine Darunavir Mylan with any of the following medicines:’

In most cases, darunavir can be combined with anti-HIV medicines belonging to another class [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. Darunavir with ritonavir has not been tested with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases dosage of other medicines might need to be changed. Therefore always tell your doctor if you take other antiHIV medicines and follow your doctor’s instruc­tion carefully on which medicines can be combined.

The effects of darunavir might be reduced if you take any of the following products. Tell your doctor if you take:

• - Phenobarbital, phenytoin (to prevent seizures)

• - Dexamethasone (corticosteroid)

• - Efavirenz (HIV infection)

• - Rifapentine, rifabutin (medicines to treat some infections such as tuberculosis)

• - Saquinavir (HIV infection).

The effects of other medicines might be influenced if you take darunavir. Tell your doctor if you take: – Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine , propafenone , timolol, verapamil (for heart disease) as the therapeutic effect or side effects of these medicines may be increased.

• - Apixaban, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce clotting of the blood) as their therapeutic effect or side effects may be altered; your doctor may have to check your blood.

• – Oestrogen-based hormonal contraceptives and hormonal replacement therapy. Darunavir might

reduce its effectiveness. When used for birth control, alternative methods of non-hormonal contraception are recommended.

• – Ethinylestradi­ol/drospireno­ne. Darunavir might increase the risk for elevated potassium levels by drospirenone.

• - Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for your specific situation.

• - Clarithromycin (antibiotic)

– Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as the therapeutic effect or side effects of these medicines might be increased. Your doctor might want to do some additional tests.

• - Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory conditions of the skin, eyes, joints and muscles and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected or applied to the skin. If alternatives cannot be used, its use should only take place after medical evaluation and under close monitoring by your doctor for corticosteroid side effects.

• - Buprenorphine/na­loxone (medicines to treat opioid dependence)

• - Salmeterol (medicine to treat asthma)

• - Artemether/lu­mefantrine (a combination medicine to treat malaria)

• - Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)

• - Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder

called pulmonary arterial hypertension)

• - Glecaprevir/pi­brentasvir (to treat hepatitis C infection)

• - Fentanyl, oxycodone, tramadol (to treat pain)

• - Fesoterodine, solifenacin (to treat urologic disorders).

The dosage of other medicines might need to be changed since either their own or darunavir’s the­rapeutic effect or side effects may be influenced when combined.

Tell your doctor if you take:

• - Alfentanil (injectable strong and short-acting painkiller that is used for surgical procedures)

• - Digoxin (to treat certain heart disorders)

• - Clarithromycin (antibiotic)

• - Itraconazole, isavuconazole, fluconazole , posaconazole, clotrimazole (to treat fungal infections). Voriconazole should only be taken after 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 (to treat depression and anxiety)

• - Maraviroc (to treat HIV infection)

• - Methadone (to treat opiate dependence)

• - Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)

• - Colchicine (to treat gout or familial Mediterranean fe­ver)

• - Bosentan (to treat high blood pressure in the pulmonary circulation)

• - Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedative agents)

• - Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are 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, planning to become pregnant or if you are breastfeeding. Pregnant or breast-feeding mothers must not take darunavir with ritonavir unless specifically directed by the doctor. Pregnant or breast-feeding mothers should not take darunavir with cobicistat.

It is recommended that HIV infected women must not breast-feed their infants because of both the possibility of your baby becoming infected with HIV through your breast milk and because of the unknown effects of the medicine on your baby.

Driving and using machines

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

Darunavir Mylan contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’.

3. How to take Darunavir Mylan

Always use this medicine exactly as described in this leaflet or as your doctor, pharmacist or nurse has told you. Check with your doctor, pharmacist or nurse if you are not sure.

Even if you feel better, do not stop taking Darunavir Mylan and ritonavir without talking to your doctor.

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be stopped without instruction of the doctor.

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have not taken antiretroviral medicines before (your child’s doctor will determine this)

The doctor will work out the right once daily dose based on the weight of the child (see table below). This dose must not exceed the recommended adult dose, which is 800 milligram darunavir together with 100 milligram ritonavir once a day.

The doctor will inform you on how much Darunavir Mylan tablets and how much ritonavir (capsules, tablets or solution) the child must take.

Weight	One darunavir dose is	One ritonavir a dose is
between 15 and 30 kilograms	600 milligram	100 milligram
between 30 and 40 kilograms	675 milligram	100 milligram
more than 40 kilograms	800 milligram	100 milligram

a ritonavir oral solution: 80 milligram per milliliter

Dose for children of 3 years of age and above, weighing at least 15 kilograms who have taken antiretroviral medicines before (your child’s doctor will determine this)

The doctor will work out the right dose based on the weight of the child (see table below). The doctor will determine if once daily dosing or twice daily dosing is appropriate for the child. This dose must not exceed the recommended adult dose, which is 600 milligram darunavir together with 100 milligram ritonavir two times per day or 800 milligram darunavir together with 100 milligram ritonavir once a day.

The doctor will inform you on how many Darunavir Mylan tablets and how much ritonavir (capsules, tablets or solution) the child must take. Tablets of other strengths are available and your doctor may have prescribed a certain combination of tablets to construct the appropriate dosing regimen.

Other forms of this medicine may be more suitable for children: ask your doctor or pharmacist.

Twice daily dosing

Weight	One dose is
between 15 and 30 kilograms	375 milligram darunavir + 50 milligram ritonavir twice a day
between 30 and 40 kilograms	450 milligram darunavir + 60 milligram ritonavir twice a day
more than 40 kilograms*	600 milligram darunavir + 100 milligram ritonavir twice a day

* For children aged 12 or more and weighing at least 40 kilograms, your child’s doctor will determine if Darunavir Mylan 800 milligram once daily dosing may be used. This cannot be administered with these 75 milligram tablets. Other strengths of Darunavir Mylan are available.

Once daily dosing

Weight	One darunavir dose is	One ritonavir a dose is
between 15 and 30 kilograms	600 milligram	100 milligram
between 30 and 40 kilograms	675 milligram	100 milligram
more than 40 kilograms	800 milligram	100 milligram

Instructions for children

• – The child must take darunavir always together with ritonavir. Darunavir cannot work properly

without ritonavir.

• – The child must take the appropriate doses of darunavir and ritonavir two times per day or once a day. If prescribed darunavir twice daily the child must take one dose in the morning, and one dose in the evening. Your 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 is not important.

• – The child must swallow the tablets with a drink such as water or milk.

Dose for adults who have not taken antiretroviral medicines before (your doctor will determine this)

You will require a different dose of darunavir which cannot be administered with these 75 milligram tablets. Other strengths of Darunavir Mylan are available.

Dose for adults who have taken antiretroviral medicines before (your doctor will determine this) The dose is either:

• – 600 milligram darunavir (2 tablets containing 300 milligram of darunavir or 1 tablet containing

600 milligram of darunavir) together with 100 milligram ritonavir twice daily.

OR

• – 800 milligram darunavir (2 tablets containing 400 milligram of darunavir or 1 tablet containing

800 milligram of darunavir) together with 100 milligram ritonavir once daily. Darunavir Mylan 400 milligram and 800 milligram tablets are only to be used to construct the once daily 800 milligram regimen.

Please discuss with your doctor which dose is right for you.

Instructions for adults

• – Take darunavir always together with ritonavir. Darunavir cannot work properly without

ritonavir.

• – In the morning, take 600 milligram darunavir together with 100 milligram ritonavir.

• – In the evening, take 600 milligram darunavir together with 100 milligram ritonavir.

• – Take darunavir with food. Darunavir cannot work properly without food. The type of food is not

important.

• – Swallow the tablets with a drink such as water or milk.

• – Darunavir Mylan 75 milligram and 150 milligram tablets have been developed for use in children, but can also be used in adults in some cases.

If you take more Darunavir Mylan than you should Contact your doctor, pharmacist or nurse immediately.

If you forget to take Darunavir Mylan

If you notice within 6 hours , you must take the tablets immediately. Always take with ritonavir and food. If you notice after 6 hours , then skip the intake and take the next doses as usual. Do not take a double dose to make up for a forgotten dose.

If you vomit after taking Darunavir Mylan and ritonavir

If you vomit within 4 hours of taking the medicine, another dose of Darunavir Mylan and ritonavir should be taken with food as soon as possible. If you vomit more than 4 hours after taking the medicine, then you do not need to take another dose of Darunavir Mylan and ritonavir until the next regularly scheduled time.

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

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

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking darunavir. Talk to your doctor first.

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

4. Possible side effects

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for 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

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests before you start darunavir. If you have chronic hepatitis B or C infection, your doctor should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below your ribs.

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to moderate. A skin rash might also be a symptom of a rare severe situation. It is therefore important to talk to your doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether darunavir must be stopped.

Other severe side effects were diabetes (common), and inflammation of the pancreas (uncommon).

Very common side effects (may affect more than 1 in 10 people) – diarrhoea.

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

• – vomiting, nausea, abdominal pain or distension, dyspepsia, flatulence

• – headache, tiredness, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of

strength, difficulty falling asleep.

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

• – chest pain, changes in electrocardiogram, rapid heart beating

• – decreased or abnormal skin sensitivity, pins and needles, attention disturbance, loss of memory, problems with your balance

• – difficulty breathing, cough, nosebleed, throat irritation

• – inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the abdomen, constipation, belching

• – kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of urine, sometimes at night

• – urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails

• – muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis

• – slowing down of the thyroid gland function. This can be seen in a blood test.

• – high blood pressure, flushing

• – red or dry eyes

• – fever, swelling of lower limbs due to fluids, malaise, irritability, pain

• – symptoms of infection, herpes simplex

• – erectile dysfunction, enlargement of breasts

• – sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual drive

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

• – a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, swelling of the face or lymph glands, increase of eosinophils (type of white blood cells), effects on liver, kidney or lung]

• – heart attack, slow heart beating, palpitations

• – visual disturbance

• – chills, feeling abnormal

• – a feeling of confusion or disorientation, altered mood, restlessness

• – fainting, epileptic fits, changes or loss of taste

• – mouth sores, vomiting blood, inflammation of the lips, dry lips, coated tongue

• – running nose

• – skin lesions, dry skin

• – stiffness of muscles or joints, joint pain with or without inflammation

• – changes in some values of your blood cells or chemistry. These can be seen in the results of blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some white blood cells.

Some side effects are typical for anti-HIV medicines in the same family as darunavir. These are:

• – muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been serious.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed inBy reporting side effects you can help provide more information on the safety of this medicine.

5. How to store Darunavir Mylan

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

Do not use this medicine after the expiry date which is stated on the carton, blister and on the bottle after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

For bottles: Once opened, use within 100 days.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away any medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Darunavir Mylan contains

• – The active substance is darunavir. Each tablet contains 75 milligrams of darunavir.

• – The other ingredients are colloidal anhydrous silica, cellulose microcrystalline, crospovidone,

What Darunavir Mylan looks like and contents of the pack

Darunavir Mylan 75 mg film-coated tablets are white to off-white, oval shaped with two curved sides, marked with M on one side and DV1 on the other side.

Darunavir Mylan 75 mg film-coated tablets are available in blister packs containing 480 tablets and in plastic bottles containing 480 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Mylan Pharmaceuticals Limited

Damastown Industrial Park,

Mulhuddart, Dublin 15,

DUBLIN

Ireland

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

Mylan Germany GmbH

Zweigniederlassung Bad Homburg v. d. Hoehe, Benzstrasse 1

Bad Homburg v. d. Hoehe

Hessen, 61352

Germany

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Belgie/Belgiqu­e/Belgien Mylan bvba/sprl Tél/Tel: + 32 (0)2 658 61 00 Etnrapua Maw.iaH EOO4 Ten: +359 2 44 55 400 Česká republika Mylan Healthcare CZ s.r.o. Tel: + 420 222 004 400 Danmark Viatris ApS Tlf: +45 28 11 69 32 Deutschland Mylan Healthcare GmbH Tel: +49 800 0700 800 Eesti BGP Products Switzerland GmbH Eesti filiaal Tel: + 372 6363 052 EZZáSa Generics Pharma Hellas EnE Tql: +30 210 993 6410 España Mylan Pharmaceuticals, S.L Tel: + 34 900 102 712 France Mylan S.A.S Tel: +33 4 37 25 75 00 Hrvatska Mylan Hrvatska d.o.o. Tel: +385 1 23 50 599 Ireland Mylan Ireland Limited Tel: +353 1 8711600

Lietuva Mylan Healthcare UAB Tel: +370 5 205 1288 Luxembourg/Lu­xemburg Mylan bvba/sprl Tel: + 32 (0)2 658 61 00 (Belgique/Belgien) Magyarorszag Mylan EPD Kft Tel: + 36 1 465 2100 Malta V.J. Salomone Pharma Ltd Tel: + 356 21 22 01 74 Nederland Mylan BV Tel: +31 (0)20 426 3300 Norge Viatris AS Tel: + 47 66 75 33 00 Österreich Arcana Arzneimittel GmbH Tel: +43 1 416 2418 Polska Mylan Healthcare Sp. z o.o. Tel: + 48 22 546 64 00 Portugal Mylan, Lda. Tel: + 351 21 412 72 56 Romania BGP Products SRL Tel: +40 372 579 000 Slovenija Mylan Healthcare d.o.o. Tel: + 386 1 23 63 180

Kùnpoç

Varnavas Hadjipanayis Ltd

Tql: + 357 2220 7700

United Kingdom (Northern Ireland)

Mylan IRE Healthcare Limited

Tel: +353 18711600

This leaflet was last revised in {MM/YYYY}.

Other sources of information

Detailed information on this medicine is available on the European Medicines Agency web site: