PREZISTA 400 mg film-coated tablets

What is PREZISTA?

PREZISTA is an antiretroviral medicine used in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. PREZISTA 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?

PREZISTA 400 mg is used to treat adults who are infected by HIV and

• who have not used antiretroviral medicines before.
• in certain patients who have used antiretroviral medicines before (your doctor will determine this).

PREZISTA 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.

PREZISTA must be taken in combination with a low dose of ritonavir and other antiretroviral medicines. It is therefore important that you read the package leaflet that is provided with these medicines. If you have any questions about your medicines, please ask your doctor or pharmacist.

Do not take PREZISTA

• if you are allergic (hypersensitive) to darunavir, other ingredients of PREZISTA 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 PREZISTA 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 astemizole or terfenadine to treat allergy symptoms triazolam and oral taken by mouth midazolam to help you sleep andor relieve anxiety

cisapride to treat some stomach conditions pimozide or sertindole to treat psychiatric conditions to treat migraine and headaches ergot alkaloids like ergotamine, dihydroergotamine, ergonovine and methylergonovine amiodarone, bepridil, quinidine and systemic lidocaine to treat certain heart disorders e.g. abnormal heart beat lovastatin and simvastatin to lower cholesterol levels rifampicin to treat some infections such as tuberculosis the combination product lopinavirritonavir an anti-HIV medicine belonging to the same class as PREZISTA products that contain St Johns wort Hypericum perforatum alfuzosin to treat enlarged prostate sildenafil to treat high blood pressure in the pulmonary circulation

Take special care with PREZISTA

PREZISTA is not a cure for HIV infection. PREZISTA does not reduce the risk of passing HIV to others through sexual contact or blood contamination. Therefore, you must continue to use appropriate precautions.

People taking PREZISTA may still develop infections or other illnesses associated with HIV infection. You must keep in regular contact with your doctor.

People taking PREZISTA 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 PREZISTA and raltegravir, rashes (generally mild or moderate) may occur more frequently than in patients taking either drug separately.

PREZISTA 400 mg is not for use in children and adolescents, as it has not been studied in patients under 18 years.

PREZISTA 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 PREZISTA.

Tell your doctor about your situation BEFORE and DURING your treatment Make sure that you check the following seven 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. Your doctor may evaluate how severe your liver disease is before deciding if you can take PREZISTA.
• Tell your doctor if you have diabetes. PREZISTA might increase sugar levels in the blood.
• Tell your doctor immediately if you notice any symptoms of infection. 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.
• Tell your doctor if you notice changes in body fat. Redistribution, accumulation or loss of body fat may occur in patients receiving a combination of antiretroviral medicines.
• Tell your doctor if you have haemophilia. PREZISTA, might increase the risk of bleeding.
• Tell your doctor if you are allergic tosulphonamides (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.

Taking other medicines

PREZISTA might interact with other medicines. Please tell your doctor if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

There are some medicines that you must not combine with PREZISTA. These are mentioned above under the heading ?Do not combine PREZISTA with any of the following medicines:?

In most cases, PREZISTA 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)]. PREZISTA with ritonavir has not been tested with all PIs (protease inhibitors) and must not be used with some PIs. Therefore always tell your doctor if you take other anti-HIV medicines and follow your doctor?s instruction carefully on which medicines can be combined.

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

• phenobarbital, phenytoin (to prevent seizures)
• dexamethasone (steroid)
• efavirenz (HIV infection).

The effects of other medicines might be influenced if you take PREZISTA. Tell your doctor if you take:

• felodipine, nifedipine, nicardipine (for heart disease) as the therapeutic effect or unwanted side effects of these medicines may be increased.
• warfarin (to reduce clotting of the blood) as their therapeutic effect or unwanted side effects may be altered; your doctor may have to check your blood.
• estrogen-based hormonal contraceptives and hormonal replacement therapy. PREZISTA might reduce its effectiveness. When used for birth control, alternative methods of non-hormonal contraception are recommended.
• pravastatin, atorvastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle tissue disorder might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for your specific situation.
• clarithromycin (antibiotic)
• cyclosporin, tacrolimus, sirolimus (to treat your immune system) as the therapeutic effect or unwanted side effects of these medicines might be increased. Your doctor might want to do some additional tests.
• fluticasone, budesonide (to control asthma). 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 opiate dependence)
• salmeterol (medicine to treat asthma).

The dosage of other medicines might need to be changed since either their own or PREZISTA?s therapeutic effect or unwanted side effects may be influenced when combined.
Tell your doctor if you take:

• digoxin (to treat certain heart disorders)
• ketoconazole, itraconazole, clotrimazole (against 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)
• paroxetine, sertraline (to treat depression and anxiety)
• methadone
• sedative agents (e.g. midazolam administered by injection)
• carbamazepine (to prevent seizures or to treat certain types of nerve pain)
• colchicine (medicine to treat gout)
• bosentan (medicine to treat high blood pressure int the pulmonary circulation).

Taking PREZISTA with food and drink

See section 3 ?How to take PREZISTA.?

Pregnancy and breast-feeding

Tell your doctor immediately if you are pregnant or if you are breast-feeding. Pregnant or breast-feeding mothers must not take PREZISTA unless specifically directed by the doctor. 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 PREZISTA.

Important information about some of the ingredients of PREZISTA

PREZISTA tablets contain sunset yellow FCF (E110) which may cause allergic reactions.

Always use PREZISTA exactly as your doctor has told you. You must check with your doctor if you are not sure.
Even if you feel better, do not stop taking PREZISTA without talking to your doctor.

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

PREZISTA 400 milligram tablets are only to be used to construct the once daily 800 milligram regimen.

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

The usual dose of PREZISTA is 800 milligram (2 tablets containing 400 milligram of PREZISTA) once daily.
You must take PREZISTA every day and always in combination with 100 milligram of ritonavir and with
food. PREZISTA cannot work properly without ritonavir and food. You must eat a meal or a snack within 30 minutes prior to taking your PREZISTA and ritonavir. The type of food is not important. Even if you feel better, do not stop taking PREZISTA without talking to your doctor.

Instructions for adults

• Take two 400 milligram tablets at the same time, once a day, every day.
• Take PREZISTA always together with 100 milligram of ritonavir.
• Take PREZISTA with food.
• Swallow the tablets with a drink such as water or milk.
• Take your other HIV medicines used in combination with PREZISTA and ritonavir as recommended by your doctor.

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

• 800 milligram PREZISTA (2 tablets containing 400 milligram of PREZISTA) together with 100 milligram ritonavir once daily. OR
• 600 milligram (2 tablets containing 300 milligram of PREZISTA or 1 tablet containing 600 milligram of PREZISTA) together with 100 milligram ritonavir twice daily.

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

Dose for children of 6 years of age and above, weighing at least 20 kilograms
Children of 6 years of age and above, weighing at least 20 kilograms require a different dosing schedule and dose of PREZISTA, which cannot be administered with these 400 milligram tablets. Other strengths of PREZISTA are available.

Removing the child resistant cap

The plastic bottle comes with a child resistant cap and must be opened as follows Push the plastic screw cap down while turning it counter clockwise. Remove the unscrewed cap.

If you take more PREZISTA than you should

Contact your doctor or pharmacist immediately.

If you forget to take PREZISTA

If you notice within 12 hours, you must take the tablets immediately. Always take with ritonavir and food. If you notice after 12 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.

Do not stop using PREZISTA without talking to your doctor first

HIV therapy may increase your sense of well-being. Even when you feel better, do not stop taking PREZISTA. Talk to your doctor first.

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

Like all medicines, PREZISTA can cause side effects, although not everybody gets them. When treating HIV infection, it is not always easy to identify what side effects are caused by PREZISTA, which are caused by other medicines you are taking, or which are caused by the HIV infection itself.

The frequency of possible side effects listed below is defined using the following convention:

• very common: affects more than 1 user in 10
• common: affects 1 to 10 users in 100
• uncommon: affects 1 to 10 users in 1,000
• rare: affects 1 to 10 users in 10,000
• very rare: affects less than 1 user in 10,000
• not known: the frequency cannot be estimated from the available data.

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

Very common side effects

• diarrhoea.

Common side effects

• 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
• body changes associated with fat redistribution, changes in your blood tests such as cholesterol, decreased appetite
• 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 contact your doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether PREZISTA must be stopped.

Uncommon side effects

• heart attack, chest pain, changes in electrocardiogram, rapid or slow heart beating, palpitations
• fainting, epileptic fits, decreased or abnormal skin sensibility, pins and needles, changes or loss of taste, attention disturbance, loss of memory, problems with your balance
• difficulty breathing, cough, nosebleed, running nose, throat irritation
• inflammation of the pancreas, stomach, lips or mouth, mouth sores, heartburn, retching, vomiting blood, dry mouth or lips, discomfort of the abdomen, constipation, belching, coated tongue
• 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, dry or scaly skin, coloration of nails, skin lesions
• muscle pain, muscle cramps or weakness, stiffness of muscles or joints, joint pain with or without inflammation, pain in extremity, osteoporosis
• slowing down of the thyroid gland function. This can be seen in a blood test.
• diabetes, increased or decreased weight, increased appetite, increased thirst
• high blood pressure, flushing
• visual disturbance, red or dry eyes
• fever, swelling of lower limbs due to fluids, malaise, chills, feeling abnormal, irritability, pain
• symptoms of infection, herpes simplex
• liver problems such as hepatitis
• erectile dysfunction, enlargement of breasts
• sleeping problems, sleepiness, depression, a feeling of confusion or disorientation, anxiety, altered mood, abnormal dreams, decrease in sexual drive, restlessness
• changes in some values of your blood cells or chemistry. These can be seen in the results of blood tests. Your doctor will explain these to you. Examples are: low white or red blood cell count, low blood platelet count, high sugar levels, high levels of insulin.

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

• raised blood sugar and worsening of diabetes.
• muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been serious.
• changes in body shape due to fat redistribution. These may include loss of fat from legs, arms and face, increased fat in the abdomen (belly) and other internal organs, breast enlargement and fatty lumps on the back of the neck (buffalo hump). The cause and long-term health effects of these conditions are not known at this time.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor.

Keep out of the reach and sight of children.

Do not use PREZISTA after the expiry date which is stated on the box and on the bottle after the letters EXP. The expiry date refers to the last day of that month.

PREZISTA does not require any special storage conditions.

Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What PREZISTA contains

• The active substance is darunavir. Each tablet contains 400 mg of darunavir as ethanolate.
• The other ingredients are microcrystalline cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate. The film-coating contains poly(vinyl alcohol) - partially hydrolyzed, macrogol 3350, titanium dioxide (E171), talc, sunset yellow FCF (E110).

What PREZISTA looks like and contents of the pack

Film-coated, light orange, oval shaped tablet, mentioning TMC on one side, 400MG on the other side. 60 tablets in a plastic bottle.
PREZISTA is also available as 75 mg, 150 mg, 300 mg and 600 mg film-coated tablets.

Marketing Authorisation Holder

Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Manufacturer

Janssen-Cilag SpA, Via C. Janssen, 04010 Borgo San Michele, Latina, Italy

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

BelgiëBelgiqueBelgien TIBOTEC, een divisie van, une division de, eine Division der JANSSEN-CILAG NVSA Antwerpseweg 15-17 B-2340 Beerse TelTél 32 14 64 94 11 LuxembourgLuxemburg TIBOTEC, une division de, eine Division der JANSSEN-CILAG NVSA Antwerpseweg 15-17 B-2340 Beerse BelgiqueBelgien TélTel 32 14 64 94 11

Magyarország TIBOTEC, a JANSSEN-CILAG Kft. divíziója H-2045 Törökbálint, Tó Park Tel 36 23 513 800 TIBOTEC, Johnson Johnson, d.o.o. .. 4 , 4 1766 . 359 2 489 94 00

eská republika TIBOTEC, divize JANSSEN-CILAG s.r.o. Karla Englie 320106 CZ-150 00 Praha 5 - Smíchov Tel 420 227 012 222 Malta AM MANGION LTD. Mangion Building, Triq dida fi Triq Valletta MT-al-Luqa LQA 6000 Tel 356 2397 6000

Danmark TIBOTEC, en division af JANSSEN-CILAG AS Hammerbakken 19 DK-3460 Birkerød Tlf 45 45 94 82 82 Nederland TIBOTEC, een divisie van JANSSEN-CILAG B.V. Postbus 90240 NL-5000 LT Tilburg Tel 31 13 583 73 73

Deutschland JANSSEN-CILAG GmbH Johnson Johnson Platz 1 D-41470 Neuss Tel 49 2137 955-955 Norge TIBOTEC, en divisjon av JANSSEN-CILAG AS Drammensveien 288 N-0283 Oslo Tlf 47 24 12 65 00

Eesti TIBOTEC, JANSSEN-CILAG Polska Sp. z o.o. Eesti filiaal Lõõtsa 2 EE-11415 Tallinn Tel 372 617 7410 Österreich TIBOTEC, eine Division von JANSSEN-CILAG Pharma GmbH Pfarrgasse 75 A-1232 Wien Tel 43 1 610 300

TIBOTEC, JANSSEN-CILAG .... 56 GR-151 21 , T 30 210 80 90 000 Polska TIBOTEC, oddzia JANSSEN-CILAG Polska Sp. z o.o. ul. Iecka 24 PL-02-135 Warszawa Tel 48 22 237 60 00

España JANSSEN-CILAG, S.A. división TIBOTEC Paseo de las Doce Estrellas, 5-7 Campo de las Naciones E-28042 Madrid Tel 34 91 722 81 00 Portugal TIBOTEC, uma divisão da JANSSEN-CILAG FARMACÊUTICA, LDA. Estrada Consiglieri Pedroso, 69 A Queluz de Baixo PT-2734-503 Barcarena Tel 351 21 43 68 835

France TIBOTEC, une division de JANSSEN-CILAG 1, rue Camille Desmoulins, TSA 91003 F-92787 Issy Les Moulineaux, Cedex 9 Tél 0 800 25 50 75 33 1 55 00 44 44 România TIBOTEC, subsidiar a Janssen-Cilag, Johnson Johnson d.o.o. Strada Tipografilor nr. 11-15, Cldirea S-Park, corp A2, etaj 5 013714 Bucureti Tel 40 21 2 071 800

Ireland TIBOTEC, a division of JANSSEN-CILAG Ltd. 50-100 Holmers Farm Way High Wycombe Buckinghamshire HP12 4EG - UK Tel 44 1494 567 444 Slovenija TIBOTEC za Janssen-Cilag, del JohnsonJohnson d.o.o. martinska cesta 53 SI-1000 Ljubljana Tel 386 1 401 18 30

Slovenská republika TIBOTEC, divízia Johnson Johnson s.r.o. Plynárenská 7B SK-824 78 Bratislava Tel 421 233 552 600 Ísland TIBOTEC, deild hjá JANSSEN-CILAG co Vistor hf. Hörgatún 2 IS-210 Garðabær Sími 354 535 7000

Italia TIBOTEC, una divisione di JANSSEN-CILAG SpA Via M. Buonarroti, 23 I-20093 Cologno Monzese MI Tel 39 02 2510 1 SuomiFinland TIBOTEC JANSSEN-CILAG OY VaisalantieVaisalavägen 2 FI-02130 EspooEsbo PuhTel 358 207 531 300

, 7 CY-1060 357 22 755 214 Sverige TIBOTEC, en division inom JANSSEN-CILAG AB Box 7073 S-192 07 Sollentuna Tel 46 8 626 50 00

Latvija TIBOTEC, JANSSEN-CILAG Polska Sp. z o.o. filile Latvij Bauskas iela 58A-3 Rga, LV 1004 Tel 371 678 93561 United Kingdom TIBOTEC, a division of JANSSEN-CILAG Ltd. 50-100 Holmers Farm Way High Wycombe Buckinghamshire HP12 4EG - UK Tel 44 1494 567 444

Lietuva
UAB ?Johnson & Johnson?
Gele-inio Vilko g. 18A
LT-08104 Vilnius
Tel: +370 5 278 68 88

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