PREZISTA 400 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

PREZISTA 400 mg film-coated tablets

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.

• 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 pack and other information

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

1. What is PREZISTA and what is it used for

What is PREZISTA?

PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used in the treatment of infection by the Human Immunodeficiency Virus (HIV). It belongs to a group of medicines called protease inhibitors. PREZISTA reduces the amount of HIV in your body. This improves your immune system and reduces the risk of diseases associated with HIV infection.

What is it used for?

The 400 milligram PREZISTA tablet is used to treat adults and children (from 3 years of age and at least 40 kilograms in weight) infected with HIV and

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

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

2. What you need to know before you take PREZISTA

Do not take PREZISTA

• if you are allergicto darunavir or any of the other ingredients of this medicine (listed in section 6) or to 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 PREZISTA 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 PREZISTA with products that contain St. John's Wort (Hypericum perforatum)

perforatum).

Warnings and precautions

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

PREZISTA does not cure HIV infection. While you are taking this medicine, you can still transmit HIV to others, although effective antiviral treatment reduces this risk. Consult your doctor about the precautions needed to avoid infecting others.

People taking PREZISTA may develop other infections or diseases associated with HIV infection. You must remain under regular medical care.

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

Patients taking PREZISTA and raltegravir (for HIV infection) may develop rashes (usually mild or moderate) more frequently than patients taking either of the two 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 apply to you.

• Tell your doctor if you have 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 PREZISTA.

• Tell your doctor if you have diabetes. PREZISTA may cause an increase in blood sugar levels.

• Tell your doctor immediately if you notice any symptoms of infection(for example, swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, signs and symptoms of inflammation due to previous infections may appear shortly after starting HIV treatment.

It is believed that these symptoms are due to an improvement in the body's immune response, which allows it to fight off infections that were present without any apparent symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you start taking medicines for your HIV treatment. Autoimmune disorders can appear many months after starting 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, tremors, or hyperactivity, tell your doctor immediately to receive the necessary treatment.
• Tell your doctor if you have hemophilia. PREZISTA may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides(for example, 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 caused by lack of blood supply to the bone). Some of the many risk factors for 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 of the joints (especially the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please consult your doctor.

Elderly population

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

Children and adolescents

The 400 milligram PREZISTA tablet must not be used in children under 3 years of age or weighing less than 40 kilograms.

Taking PREZISTA with other medicines

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

Some medicines must not be combinedwith PREZISTA. The list can be found in the section “Do not combine PREZISTA with any of the following medicines:”

In most cases, PREZISTA can be combined with HIV medicines that belong to other classes [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA has not been tested with cobicistat or ritonavir with all HIV protease inhibitors and must not be used with other HIV 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 tell your doctor and follow their instructions carefully on which medicines can be combined.

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

• Phenobarbital, phenytoin(to prevent seizures)
• Dexamethasone(corticosteroid)
• Efavirenz(for HIV infection)
• Boceprevir(to treat hepatitis C infection)
• Rifapentine, rifabutin(medicines to treat certain infections such as tuberculosis)
• Saquinavir(for HIV infection).

PREZISTA may also affect the effects 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 disorders) because the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin(to reduce blood clotting) because 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. PREZISTA may reduce their effectiveness. For birth control, alternative non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. PREZISTA 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-lowering treatment is best for you based on your personal circumstances.
• Clarithromycin(antibiotic)
• Cyclosporin, everolimus, tacrolimus, sirolimus(to inhibit the immune system) because the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, including 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 conditions. If alternatives cannot be used, their use should only be done after a clinical evaluation and with close monitoring by your doctor to assess the 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 to treat malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine(for cancer treatment)
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension)

• Glecaprevir/pibrentasvir, simeprevir(to treat hepatitis C infection)
• Fentanyl, oxycodone, tramadol(to treat pain)
• Fesoterodine, solifenacin(to treat urological disorders).

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 PREZISTA may be affected.

Tell your doctor if you are taking:

• Alfentanil(a strong and short-acting injectable analgesic used in surgical procedures)
• Digoxin(for the treatment of certain heart disorders)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat 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(to treat depression andanxiety)
• Maraviroc(to treat HIV infection)
• Methadone(to treat narcotic dependence)
• Carbamazepine, clonazepam(to prevent epileptic 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, chlorazepate, diazepam, estazolam, flurazepam, midazolam when administered by injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes).

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

Taking PREZISTA with food and drinks

See section 3 “How to take PREZISTA.”

Pregnancy and breastfeeding

Tell your doctor immediately if you are pregnant, plan to become pregnant, or are breastfeeding. Pregnant or breastfeeding women must not take PREZISTA with ritonavir unless their doctor specifically instructs them to do so. Pregnant or breastfeeding women must not take PREZISTA with cobicistat.

It is recommended that women infected with HIV do not breastfeed their babies because there is a possibility that the babies may become infected with HIV through breast milk, as well as the unknown effects of the medicine on the babies.

Driving and using machines

Do not drive or use machines if you experience dizziness after taking PREZISTA.

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

3. How to Take PREZISTA

Follow the administration instructions for this medication exactly as stated in this leaflet or as indicated by your doctor, pharmacist, or nurse. If you have any doubts, ask your doctor, pharmacist, or nurse.

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

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

The 400-milligram PREZISTA tablets are used only to achieve the 800-milligram once-daily dosing regimen.

Dose for Adults Who Have Not Previously Taken Antiretroviral Medications (to be determined by your doctor)

The dose will be determined by your doctor)

The normal dose of PREZISTA is 800 milligrams (2 tablets of 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) once a day.

You must take PREZISTA every day and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. PREZISTA does not work properly without cobicistat or ritonavir and food. Before taking PREZISTA and cobicistat or ritonavir, you must eat 30 minutes before. The type of food is not important.

Do not interrupt treatment with PREZISTA or cobicistat or ritonavir without consulting your doctor first, even if you feel better.

Instructions for Adults

• Take two 400-milligram tablets at the same time, once a day, every day.
• Always take PREZISTA with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take PREZISTA with food.
• Swallow the tablets with a drink, which can be water or milk.

• Take the other HIV medications used in combination with PREZISTA and cobicistat or ritonavir as your doctor recommends.
• The 100-milligram-per-milliliter oral suspension of PREZISTA has been developed for use in children, but in some cases, it can also be used in adults.

Dose for Adults Who Have Previously Taken Antiretroviral Medications (to be determined by your doctor)

The dose is:

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

Or

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

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

Dose for Children 3 Years of Age and Older, Weighing More Than 40 Kilograms, Who Have Not Previously Taken Antiretroviral Medications (to be determined by your child's doctor)

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

Dose for Children 3 Years of Age and Older, Weighing More Than 40 Kilograms, Who Have Previously Taken Antiretroviral Medications (to be determined by your child's doctor)

The dose is:

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

Or

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

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

Instructions for Children 3 Years of Age and Older, Weighing More Than 40 Kilograms

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

Child-Resistant Cap Removal

If You Take More PREZISTA Than You Should

Inform your doctor, pharmacist, or nurse immediately.

If You Forget to Take PREZISTA

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 missed doses.

Do Not Stop Taking PREZISTA Without Talking to Your Doctor First

HIV medications can make you feel better. Even if you feel better, do not stop taking PREZISTA. 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, 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 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.

There have been reports of liver problems that can occasionally be severe. Your doctor will perform a blood test before you start treatment with PREZISTA. 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-colored) urine, pale stools, 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 PREZISTA.

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, belching, dry mouth, abdominal discomfort,
• constipation, belching
• kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• hives, severe swelling of the skin and other tissues (mainly the 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.
• hypertension (high 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]
• myocardial infarction, 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: an increase in some white blood cells.

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

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

Reporting Side Effects

If you experience any 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 PREZISTA

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

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

PREZISTA does not require special storage conditions.

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

Composition of PREZISTA

• The active ingredient is darunavir. Each tablet contains 400 milligrams of darunavir (as ethanolate).
• The other ingredients are microcrystalline cellulose, anhydrous colloidal silica, crospovidone, and magnesium stearate. The coating contains partially hydrolyzed poly(vinyl alcohol), macrogol 3350, titanium dioxide (E171), talc, and yellow sunset FCF (E110).
• This medication contains less than 1 mmol of sodium (23 mg) per unit dose; it is essentially "sodium-free".

Appearance of the Product and Package Contents

Film-coated tablet, oval, light orange in color, marked with TMC on one side and 400MG on the other side.

60 tablets in a plastic bottle.

PREZISTA is also available in 75-milligram, 150-milligram, 300-milligram, 600-milligram, and 800-milligram film-coated tablets and 100-milligram-per-milliliter oral suspension.

Marketing Authorization Holder

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

Manufacturer

Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy

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

Date of the Last Revision of this Leaflet:{MM/YYYY}.

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