Package Insert: Information for the User

PREZISTA 600 mg Film-Coated Tablets

darunavir

Read this package insert carefully before starting to take this medicine, because

it contains important information for you.

• Keep this package insert, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to others
• who have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this package insert. See section 4.

What is PREZISTA?

PREZISTA contains the active ingredient darunavir. PREZISTA is an antiretroviral medication used in the treatment of Human Immunodeficiency Virus (HIV) infection. It belongs to a group of medications called protease inhibitors. PREZISTA reduces the amount of HIV present in the body. This will improve the immune system and decrease the risk of developing diseases associated with HIV infection.

How is it used?

PREZISTA is used to treat adults and children aged 3 years or older and weighing at least 15 kilograms who are infected with HIV and have already used other antiretroviral medications.

PREZISTA should be taken in combination with a low dose of ritonavir and other HIV medications. Your doctor will explain the most suitable combination of medications for you.

Do not take PREZISTA

• if you areallergicto darunavir or to any of the other ingredients of this medicine (listed in section 6) or to ritonavir.
• if you havesevere liver problems. Ask your doctor if you are not sure how serious your liver disease is. You may need to have some additional tests.

Do not take PREZISTA with any of the following medicines

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

Do not take PREZISTA with products that contain St. John's Wort (Hypericum perforatum

).

Warnings and precautions

Ask your doctor, pharmacist or nurse before starting to take PREZISTA.

PREZISTA does not cure HIV infection. While you are taking this medicine, you may still be able to pass HIV to others, although effective antiviral treatment reduces the risk. Ask your doctor about the precautions you need to take not to infect others.

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

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

Patients taking PREZISTA and raltegravir (for HIV infection) may experience rashes (usually mild or moderate) more frequently than patients taking either of the two medicines separately.

Inform your doctor about your situation BEFORE and DURING treatment

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

• Inform your doctor if you have had anyliver disease, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding if you can take PREZISTA.

• Inform your doctor if you havediabetes. PREZISTA may cause an increase in blood sugar levels.

• Inform your doctor immediately if you notice anysymptoms 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 the body to fight off infections that were present without any apparent symptoms.

• Additionally, you may develop autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) after starting treatment for HIV infection. Autoimmune disorders may 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 rising to the trunk of the body, palpitations, tremors or hyperactivity, inform your doctor immediately to receive the necessary treatment.
• Inform your doctor if you havehaemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you areallergic to sulfonamides(for example, used to treat certain infections).
• Inform your doctor if you notice anybone or muscle problems. Some patients taking antiretroviral combination treatment may develop a bone disorder called osteonecrosis (death of bone tissue caused by a lack of blood supply to the bone). Some of the many risk factors for developing this disease, among others, are the duration of antiretroviral combination treatment, 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 hip, knee, and shoulder) and difficulty moving. If you notice any of these symptoms, please ask your doctor.

Older people

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

Children

PREZISTA is not used in children under 3 years of age or weighing less than 15 kg.

Taking PREZISTA with other medicines

Inform your doctor or pharmacist if you are taking or have recently taken any other medicine.

Some medicinesshould not be takenwith PREZISTA. The list can be found in the section “Do not take PREZISTA with any of the following medicines:”

In most cases, PREZISTA can be taken with medicines against HIV that belong to other classes [for example, NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists and IFs (fusion inhibitors)]. PREZISTA has not been tested with ritonavir with all protease inhibitors (PIs) and should not be used with other HIV protease inhibitors. In some cases, the dose of the other medicines may need to be changed. Therefore, if you are taking other HIV medicines, inform your doctor and follow their instructions carefully about which medicines can be taken together.

The following products may reduce the effectiveness of PREZISTA. Inform your doctor if you take:

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

PREZISTA may also affect the effects of other medicines. Inform your doctor if you take:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil(for heart problems) 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 need to do blood tests.
• Oral contraceptives based on estrogens and hormone replacement therapy. PREZISTA may reduce their effectiveness. For birth control, non-hormonal methods are recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of potassium levels rising 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 treatment to reduce cholesterol is best for you according to your personal circumstances.
• Clarithromycin(antibiotic)
• Ciclosporin, everolimus, tacrolimus, sirolimus(to inhibit the immune system) because the therapeutic or adverse effects of these medicines may be increased. Your doctor may need to do additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.These medicines are used to treat allergies, asthma, inflammatory bowel disease, eye, joint, and muscle inflammatory conditions, and other inflammatory conditions. If alternatives cannot be used, their use should only be made after a clinical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.
• Buprenorphine/naloxone(medicines for opioid dependence treatment)
• Salmeterol(medicine for asthma treatment)
• Artemether/lumefantrine(a combination of medicines for malaria treatment)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine(to treat cancer)
• Sildenafil, tadalafil, vardenafil(for erectile dysfunction or to treat a heart and lung condition called pulmonary hypertension)

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

In some cases, the dose of some medicines may need to be changed as they may be affected by PREZISTA or vice versa.

Inform your doctor if you take:

• Alfentanil(injection analgesic with strong and short action used in surgical procedures)
• Digoxin(to treat certain heart problems)
• Clarithromycin(antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole(to treat fungal infections). Voriconazole can only be administered after a medical evaluation.
• Rifabutin(to treat 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 opioid dependence)
• Carbamazepine, clonazepam(to prevent seizures or to treat certain types of neuropathic pain)
• Colchicine(to treat gout or familial Mediterranean fever)
• Bosentan(to treat 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).

Thisis not a complete list of medicines. Inform your doctor aboutallthe medicines you are taking.

Taking PREZISTA with food and drinks

See section 3 “How to take PREZISTA.”

Pregnancy and breastfeeding

Inform your doctor immediately if you are pregnant, planning to become pregnant or breastfeeding. Pregnant women or breastfeeding women should not take PREZISTA with ritonavir unless your doctor specifically tells you to.Pregnant women or breastfeeding women should not take PREZISTA with cobicistat.

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

Ask your doctor or pharmacist before using any medicine.

Driving and operating machines

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

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

Follow exactly the medication administration instructions contained in this leaflet or those indicated by your doctor, pharmacist, or nurse. If in doubt, ask your doctor, pharmacist, or nurse.

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

Once treatment has begun, do not change the dose or form of the dose or interrupt treatment without consulting your doctor.

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

You will require a different PREZISTA dose that cannot be administered with these 600 milligram tablets. Other PREZISTA concentrations are available.

Dosage for adults who have taken antiretroviral medications before (will be determined by your doctor)

The dosage is:

• 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.

Or

• 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. PREZISTA 400 milligram and 800 milligram tablets are used only to obtain the 800 milligram once-a-day dosing regimen.

Please speak with your doctor about what dose is correct for you.

Instructions for adults

• Take PREZISTA always along with ritonavir. PREZISTA does not act adequately without ritonavir.
• In the morning, take one 600 milligram PREZISTA tablet along with 100 milligrams of ritonavir.
• In the evening, take one 600 milligram PREZISTA tablet along with 100 milligrams of ritonavir.
• Take PREZISTA with food. PREZISTA does not act adequately without food. The type of food is not important.
• Swallow the tablets with a drink, which can be water or milk.

Tablets of 75 milligrams and 150 milligrams and an oral suspension of 100 milligrams per milliliter have been developed for use in children, but in some cases they may also be used in adults

Dosage for children aged 3 years or older, weighing at least 15 kilograms who have not taken antiretroviral medications before (will be determined by your child's doctor)

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

Your child's doctor will inform you about what amount of PREZISTA tablets and what amount of ritonavir (capsules, tablets, or solution) your child should take.

Dosage for children aged 3 years or older, weighing at least 15 kilograms who have taken antiretroviral medications before (will be determined by your child's doctor)

Your child's doctor will establish the correct dose based on the child's weight (see the table below). Your child's doctor will determine if a once-a-day or twice-a-day dose is appropriate for the child. This dose should not exceed the recommended adult dose, which is 600 milligrams of PREZISTA along with 100 milligrams of ritonavir twice a day or 800 milligrams of PREZISTA along with 100 milligrams of ritonavir once a day. Your child's doctor will inform you about how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) your child should take. Other PREZISTA concentrations are available to obtain the appropriate dosing regimen.

PREZISTA oral suspension is also available. Your child's doctor will tell you if PREZISTA tablets or oral suspension are suitable for your child.

Twice-a-day dosing

*Your child's doctor will determine if for children aged 12 years or older and weighing at least 40 kilograms, the 800 milligram once-a-day dose can be used. This dose cannot be administered with the 600 milligram tablets. Other PREZISTA concentrations are available.

Ritonavir oral solution: 80 milligrams per milliliter

Instructions for children

• Your child must take PREZISTA always along with ritonavir. PREZISTA cannot act adequately without ritonavir.
• Your child must take the correct dose of PREZISTA and ritonavir twice a day or once a day. If a twice-a-day dose has been prescribed, your 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.
• Your child must take PREZISTA with food. PREZISTA cannot act adequately without food. The type of food is not important.
• Your child must swallow the tablets with a drink, such as water or milk.
• Tablets of 75 milligrams and 150 milligrams and an oral suspension of 100 milligrams per milliliter have been developed for use in children weighing less than 40 kilograms, but in some cases they may also be used in adults

Removing the child-resistant cap

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 6 hours, take the missed dose immediately. Always with ritonavir and with food. If you realize more than 6 hours after the missed dose, omit that dose and continue with the usual dosing regimen. Do not take a double dose to compensate for the missed doses.

Do not stop taking PREZISTA without speaking with your doctor

Antiretroviral 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.

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

Like all medications, this medication can produce side effects, although not all people will experience them.

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

There have been reports of liver problems that may occasionally be severe. Your doctor will perform a blood test before starting treatment with PREZISTA. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood test results, as there is a higher probability of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin and white of the eyes, darkening (tea color) of the urine, pale stools (intestinal movements), nausea, vomiting, loss of appetite, or pain, feeling of pain or discomfort 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 severe condition. Therefore, it is essential to talk to your doctor if you present a rash. Your doctor will advise you on how to control symptoms or if you should discontinue PREZISTA.

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

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

• diarrhea.

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

• vomiting, nausea, abdominal pain or distension, upper abdominal pain (dyspepsia),
• flatulence
• headache, fatigue, dizziness, drowsiness, numbness,

• tingling, numbness, or pain in the hands or feet, loss of strength, difficulty falling asleep.

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

• chest pain, changes in the electrocardiogram, rapid heart movements
• decreased or abnormal sensitivity in the skin, numbness, attention disorder, memory loss, difficulty maintaining balance
• difficulty breathing, cough, nasal bleeding, throat irritation
• inflammation of the stomach or mouth, heartburn, nausea, dry mouth, abdominal discomfort,
• constipation, belching
• renal insufficiency, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (especially the lips or eyes), eczema,
• excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration
• muscle pain, muscle cramps, or weakness, joint pain, osteoporosis
• reduced thyroid function. This can be seen in a blood test.
• hypertension (increased blood pressure), flushing
• red or dry eyes
• fever, swelling of the lower extremities due to fluid retention, discomfort,
• irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction, breast enlargement
• difficulty falling asleep, drowsiness, depression, anxiety, abnormal dreams,
• decreased libido.

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

• a reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial swelling or lymph node enlargement, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage]
• myocardial infarction, slow heart movements, palpitations
• visual disturbances
• chills, strange sensation
• a feeling of confusion or disorientation, altered mood, agitation
• syncope, seizure, changes or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, tongue with plaque
• nasal secretion
• skin lesions, dry skin
• muscle stiffness 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. For example: increased levels of 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 type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medication.

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

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

PREZISTA does not require special storage conditions.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and any medication that you no longer need. This will help protect the environment.

Composition of PREZISTA

• The active ingredient is darunavir. Each tablet contains 600 milligrams of darunavir (as etanolate).
• - The other components 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 sunset yellow FCF (E110).
• - This medicine contains less than 1 mmol of sodium (23 mg) per unit dose; it is essentially "sodium-free".

Appearance of the product and contents of the package

Oval-shaped, orange-colored tablet with a film coating, marked with TMC on one side and 600MG on the other side.

60 tablets in a plastic bottle.

PREZISTA is also available in film-coated tablets of 75 milligrams, 150 milligrams, 300 milligrams, 400 milligrams, 800 milligrams, and oral suspension of 100 milligrams per milliliter.

Marketing Authorization Holder

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

Responsible for manufacturing

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

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last review date of this leaflet:{MM/YYYY}.

For detailed information about this medicine, please visit the website of the European Medicines Agency:http://www.ema.europa.eu.