Prospecto: information for the user

PREZISTA 100 mg/ml oral suspension

darunavir

Read this prospect carefully before starting to take this medicine, because

it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist or nurse.
• This medicine has been prescribed to you alone, and you must not give it to others
• who may 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 prospect. 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 infected with HIV as well as children infected with HIV aged 3 years or older and weighing at least 15 kilograms (see How to take PREZISTA)

PREZISTA should 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 ingredients of this medicine (listed in section 6)cobicistat or to ritonavir.
• if you havesevere liver problems. Ask your doctor if you are unsure 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 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 medicine, you may still be able to pass 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 medicine 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(e.g. 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, tremor 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(e.g. used to treat certain infections).
• Inform your doctor if you notice anybone or muscle problems. Some patients taking antiretroviral combination therapy may develop a condition called osteonecrosis (bone death caused by a lack of blood supply to the bone). Some of the many risk factors for developing this condition, among others, are the duration of antiretroviral combination therapy, the use of corticosteroids, alcohol consumption, severe immunosuppression, and a higher body mass index. 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.

Older adults

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

Children

PREZISTA is not used in children under 3 years of age or with a weight of less than 15 kilograms.

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 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 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 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 carefully follow their instructions about which medicines 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(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 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.
• 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 treatment to reduce cholesterol levels 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 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, 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 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 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 because 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 disorders)
• 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).

• Metformin (to treat type 2 diabetes).

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 mothers should not take PREZISTA with ritonavir unless your doctor specifically instructs you to do so.Pregnant women or breastfeeding mothers should not take PREZISTA with cobicistat.

It is recommended that HIV-infected women do not breastfeed their babies because 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.

Driving and operating machinery

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

The oral suspension of PREZISTA contains sodium p-hydroxybenzoate. This ingredient may cause allergic reactions (some of which may be delayed).

Follow exactly the administration instructions of the medication 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 cobicistat 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.

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

Your 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 plus 100 milligrams of ritonavir once a day.

Your doctor will inform you about how much PREZISTA oral suspension and how much ritonavir (capsules, tablets or solution) your child should take.

Your child should take PREZISTA every day and always in combination with 100 milligrams of ritonavir and with food. PREZISTA cannot act properly without ritonavir or food. Your child should eat any type of food 30 minutes before taking PREZISTA and ritonavir. The type of food is not important.

Dose for children aged 3 years or older, weighing at least 15 kilograms who have taken antiretroviral medications before (your child's doctor will determine this)

Your doctor will establish the correct dose based on the child's weight (see the table below). Your doctor will determine if the 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 plus 100 milligrams of ritonavir twice a day or 800 milligrams of PREZISTA plus 100 milligrams of ritonavir once a day.

Your doctor will inform you about how much PREZISTA oral suspension and how much ritonavir (capsules, tablets or solution) your child should take.

Dose twice a day

Instructions for children

• Your child should take PREZISTA always with ritonavir. PREZISTA cannot act properly without ritonavir.
• Your child should take the correct dose of PREZISTA and ritonavir twice a day or once a day. If PREZISTA is given twice a day, your child should take one dose in the morning and one in the evening. Your child's doctor will determine the appropriate dosing schedule for your child.
• Your child should take PREZISTA with food. PREZISTA cannot act properly without food. The type of food is not important.

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

The usual dose of PREZISTA is 800 milligrams once a day.

You should take PREZISTA every day and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. PREZISTA cannot act properly without cobicistat or ritonavir and without food. Before taking PREZISTA and cobicistat or ritonavir, you should eat food 30 minutes beforehand. The type of food is not relevant. Even if you feel better, do not stop taking PREZISTA or cobicistat or ritonavir without consulting your doctor first.

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

The dose is:

• 600 milligrams of PREZISTA plus 100 milligrams of ritonavir twice a day.

Or

• 800 milligrams of PREZISTA plus 150 milligrams of cobicistat or 100 milligrams of ritonavir once a day.

Please consult your doctor about what dose is correct for you.

Instructions for adults

• Take PREZISTA always with cobicistat or ritonavir. PREZISTA cannot act properly without cobicistat or ritonavir.

• Take PREZISTA with food. PREZISTA cannot act properly without food. The type of food is not important.

Instructions for use

Use the dosing syringe included in the package to measure your dose exactly:

1. Shake the bottle well before each use.

2. Open the PREZISTA oral suspension bottle by pressing the cap down and turning it counterclockwise at the same time.

4. Pull the plunger up to the top of the line on the tube that marks the dose prescribed by your doctor.

5. Take the PREZISTA dose. Place the tip of the oral dosing syringe in your mouth. Press the plunger of the syringe towards your mouth, then swallow.

6. Close the bottle with the cap after use, and keep PREZISTA oral suspension as indicated below in section 5.

7. Remove the plunger from the tube of the syringe, rinse with water and let it air dry after each use.

8. After air drying, place the oral dosing syringe in its initial position and store it with the PREZISTA bottle.

Do not use the dosing syringe for other medications.

If you take more PREZISTA than you should

Inform your doctor, pharmacist or nurse immediately.

If you forget to take PREZISTA

If you take PREZISTA twice a day and realize within 6 hours, take the oral suspension immediately. Always with ritonavir and with food. If you realize after 6 hours, omit that dose and take the next one as usual. Do not take a double dose to compensate for the missed doses.

If you take PREZISTA once a day and realize within 12 hours, take the oral suspension immediately. Always with cobicistat or ritonavir and with food. If you realize after 12 hours, omit that dose and take the next one as usual. Do not take a double dose to compensate for the missed doses.

Do not stop taking PREZISTA without talking to 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 levels of glucose and lipids in the blood. This may be partly related to health recovery 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 produce side effects, although not all people will experience them.

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

Cases of liver problems have been reported, which 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 tests as there is a higher probability of developing liver problems. Discuss the signs and symptoms of liver problems with your doctor. 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 discuss with your doctor if you present 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, 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 on the safety of this medication.

Keep this medication out of the sight and reach 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.

Do not store above 86°F (30°C).

Do not refrigerate or freeze. Avoid excessive heat exposure.

Store in the original packaging.

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 milliliter contains 100 milligrams of darunavir (as etanolate).
• The other components are hydroxypropylcellulose, microcrystalline cellulose, and sodium carmellose, citric acid monohydrate, sucralose, strawberry flavor cream, flavor masker, sodium p-hydroxybenzoate (E219), hydrochloric acid (for pH adjustment), purified water.

• - This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; it is essentially "sodium-free".

Appearance of the product and contents of the package

White to off-white opaque oral suspension. Supplied in an amber glass bottle of 200 ml with a child-resistant polipropylene closure and a 6 ml low-density polyethylene (LDPE) pipette for oral administration with graduations of 0.2 ml. The neck of the bottle is filled with a low-density polyethylene fixer that holds the dosing pipette. Do not use the dosing pipette for other medicines.

PREZISTA is also available in film-coated tablets of 75 milligrams, 150 milligrams, 300 milligrams, 400 milligrams, 600 milligrams, and 800 milligrams.

Marketing Authorization Holder

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

Responsible for manufacturing

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

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

Last date of revision 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.