Package Insert: Information for the User

PREZISTA 800 mg Film-Coated Tablets

darunavir

Read this package insert carefully before you start taking 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 for you only, and you must 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 your body. This will improve your immune system and decrease the risk of developing diseases associated with HIV infection.

For what it is used?

The PREZISTA 800 milligram tablet is used to treat adults and children (at least 3 years old, weighing at least 40 kilograms) infected with HIV and

• who have not used antiretroviral medications before.
• in certain patients who have used antiretroviral medications before (determined by your doctor).

PREZISTA must be taken with a low dose of cobicistat or 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 components of this medication (listed in section 6) or to cobicistat or to ritonavir.
• if you havesevere liver problems. Ask your doctor if you are unsure of the severity of your liver disease. You may need to have some additional tests.

Do not combine PREZISTA with any of the following medications

If you are taking any of these medications, consult your doctor to change to another medication.

Do not combine PREZISTA with products containing St. John's Wort (Hypericum perforatum

).

Warnings and precautions

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

PREZISTA does not cure HIV infection. While you are taking this medication, you may still be able to transmit HIV to others, although effective antiviral treatment reduces the risk. Consult your doctor about what precautions are necessary to avoid infecting others.

People taking PREZISTA may develop other infections or diseases associated with HIV infection. You should maintain 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 consult 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 medication separately.

Inform your doctor about your situation BEFORE and DURING treatment

Make sure to 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 observe 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 apparent symptoms.

• Additionally, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may develop after you start taking medications for HIV treatment. Autoimmune disorders may appear many months after treatment begins. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and ascending to the body trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you havehemophilia. 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 therapy may develop a condition called osteonecrosis (bone death caused by a lack of blood supply to the bone). Some risk factors for this condition include the duration of antiretroviral therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, and a higher body mass index. Signs of osteonecrosis include pain, discomfort, and stiffness in the joints (especially the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please consult your doctor.

Older adults

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

Children and adolescents

The 800 mg PREZISTA tablet should not be used in children under 3 years of age or weighing less than 40 kg.

Taking PREZISTA with other medications

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

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

In most cases, PREZISTA can be combined with HIV medications belonging to other classes [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and IFs (fusion inhibitors)]. PREZISTA has not been tested with cobicistat or ritonavir with all protease inhibitors (PIs) and should not be used with other protease inhibitors. In some cases, the dose of the other medications may need to be adjusted. Therefore, if you are taking other HIV medications, inform your doctor and carefully follow their instructions on which medications can be combined.

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(medications to treat some infections such as tuberculosis)
• Saquinavir(for HIV infection).

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

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil(for heart conditions) because the therapeutic or adverse effects of these medications may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin(to reduce blood coagulation) because the therapeutic or adverse effects of these medications may be altered; your doctor may require 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 elevated potassium levels due to the drospirenone effect.
• 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 individual circumstances.
• Clarithromycin(antibiotic)
• Ciclosporin, everolimus, tacrolimus, sirolimus(to inhibit the immune system) because the therapeutic or adverse effects of these medications may be increased. Your doctor may require additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.These medications are used to treat allergies, asthma, inflammatory bowel disease, eye, joint, and muscle inflammation, 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(medications for opioid dependence treatment)
• Salmeterol(medication for asthma treatment)
• Artemether/lumefantrine(a combination of medications 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 medications may need to be adjusted as they may be affected by the combination with PREZISTA or by PREZISTA itself.

Inform your doctor if you take:

• Alfentanil(injection analgesic with strong and short action used in surgical procedures)
• Digoxin(to treat certain heart conditions)
• 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 administered by injection, zolpidem(sedatives)
• Perphenazine, risperidone, thioridazine(to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes).

Thisis not a complete list of medications. Inform your doctor aboutallthe medications 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 mothers should not take PREZISTA with ritonavir unless specifically instructed by their doctor.Pregnant women or breastfeeding mothers should not take PREZISTA with cobicistat.

It is recommended that HIV-infected women 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 medication on children.

Driving and operating machinery

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 administration instructions of this medication contained in this leaflet or those indicated by your doctor, pharmacist, or nurse. In case of doubt, ask your doctor, pharmacist, or nurse.

Do not stop taking PREZISTA or cobicistat or ritonavir without consulting your doctor, 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.

PREZISTA 800 milligram tablets are used only for the 800 milligram once-a-day regimen.

Dose for adults who have not taken antiretroviral medications (certainly determined by your doctor)

determined by your doctor)

The usual 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 act adequately without cobicistat or ritonavir and food. Before taking PREZISTA and cobicistat or ritonavir, you must ingest food 30 minutes beforehand. The type of food is not important.

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

Instructions for adults

• Take one 800 milligram tablet at the same time, once a day, every day.
• Take PREZISTA always with 150 milligrams of cobicistat or 100 milligrams of ritonavir.
• Take PREZISTA with food.
• Swallow the tablet 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 oral suspension of PREZISTA 100 milligrams per milliliter has been developed for use in children, but in some cases, it may also be used in adults.

Dose for adults who have taken antiretroviral medications (certainly 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) 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) with 100 milligrams of ritonavir twice a day.

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

Dose for children from 3 years of age, with a weight of more than 40 kilograms who have not taken antiretroviral medications (the doctor of your child will determine)

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

Dose for children from 3 years of age, with a weight of more than 40 kilograms who have taken antiretroviral medications (the doctor of your child will determine)

The dose is:

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

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

Instructions for children from 3 years of age, with a weight of 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.
• Take PREZISTA always with 100 milligrams of ritonavir.
• Take PREZISTA with food.
• Swallow the tablets with a drink, such as water or milk.
• Take the other medications used in combination with PREZISTA and ritonavir as your doctor recommends.

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 12 hours, take the tablets immediately. Always take the dose with cobicistat or with ritonavir and with food. If you realize after 12 hours, omit that dose and make the next one in the usual way. Do not take a double dose to compensate for the missed doses.

Do not stop taking PREZISTA without talking to your doctor

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.

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 the HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication may 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 the 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 develop a rash. Your doctor will advise you on how to control the 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, tingling, 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 to you. 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 packaging 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 800 milligrams of darunavir (as etanolate).
• The other components are microcrystalline cellulose, anhydrous colloidal silica, crospovidone, magnesium stearate, hypromellose. The coating contains partially hydrolyzed poly(vinyl alcohol), macrogol 3350, titanium dioxide (E171), talc, and iron oxide red (E172).
• This medicinal product 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

Dark red, oval-shaped, film-coated tablet, marked with T on one side and 800 on the other side. 30 tablets in a plastic bottle. PREZISTA 800 milligrams tablets are available in packages containing one or three bottles.

Not all package sizes may be marketed.

PREZISTA is also available in film-coated tablets of 75 milligrams, 150 milligrams, 300 milligrams, 400 milligrams, and 600 milligrams, and oral suspension of 100 milligrams per milliliter.

Holder of the marketing authorization

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 medicinal product, please contact the local representative of the marketing authorization holder:

Last date of revision of this leaflet: {MM/YYYY}

The detailed information on this medicinal product is available on the website of the European Medicines Agency: http://www.ema.europa.eu