PREZISTA 75 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

PREZISTA 75 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, as 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 to treat 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?

PREZISTA is used to treat adults and children from 3 years of age and at least 15 kg body weight who are infected with HIV and have already used other antiretroviral medicines.

PREZISTA must be taken with a low dose of ritonavir and other HIV medicines. Your doctor will discuss the most suitable combination of medicines with 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 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 containing St. John's Wort (Hypericum 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 may still transmit HIV to others, although effective antiviral treatment reduces the risk. Consult your doctor about the precautions needed to avoid infecting other people.

People taking PREZISTA may develop other infections or diseases associated with HIV infection. You must 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 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 had any liver disease, including hepatitis B or C infection. 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 increase your blood sugar levels.

• Tell your doctor immediately if you notice any symptoms 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 soon after starting HIV treatment.

It is believed that these symptoms are due to an improvement in the body's immune response, which enables it to fight off infections that were present but not showing any 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 have started taking medicines for the treatment of your 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 towards the trunk of the body, palpitations, tremor, 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(e.g., used to treat certain infections).
• Tell your doctor if you notice any bone or muscle problems. Some patients using combined antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to lack of blood supply to the bone). Some of the many risk factors for developing this disease include the duration of combined 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 hip, knee, and shoulder) 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

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

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 takenwith 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 from 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 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 action 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-reducing treatment is best for you based on your personal circumstances.
• Clarithromycin(antibiotic)
• Ciclosporin, everolimus, tacrolimus, sirolimus(to suppress 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 disease, 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 the treatment of cancer)
• 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 and anxiety)
• 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(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).

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

Taking PREZISTA with food and drink

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 has specifically told 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 could be infected with HIV through breast milk, as well as the unknown effects of the medicine on the baby.

Driving and using machines

Do not drive or use machines if you feel dizzy after taking PREZISTA.

3. How to take PREZISTA

Follow the administration instructions for the medication contained in this prospectus or as indicated by your doctor, pharmacist, or nurse. In case of doubt, ask your doctor, pharmacist, or nurse.

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

Once treatment has started, the dose or form of the dose should not be changed or treatment interrupted without consulting a doctor.

Dose for children from 3 years of age, weighing at least 15 kilograms, who have not taken antiretroviral medications before (the child's doctor will determine this)

The doctor will calculate the correct daily dose based on the child's weight (see the 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.

The doctor will inform you about how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) the child should take.

Dose for children from 3 years of age, weighing at least 15 kilograms, who have taken antiretroviral medications before (the child's doctor will determine this)

The doctor will establish the correct dose based on the child's weight (see the table below). The doctor will determine if a once-daily or twice-daily 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. The doctor will inform you about how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Other concentrations of the tablets are available, and your doctor may prescribe a specific combination of tablets to achieve the appropriate dosage.

The oral suspension of PREZISTA is also available. Your doctor will tell you if PREZISTA tablets or the oral suspension are suitable for the child.

Dose twice a day

Instructions for children

• The child must take PREZISTA always along with ritonavir. PREZISTA cannot work properly without ritonavir.
• The child must take the appropriate dose of PREZISTA and ritonavir twice a day or once a day. If PREZISTA is prescribed twice a day, the child should take one dose in the morning and another at night. The child's doctor will determine the appropriate dosage schedule for the child.
• The child must take PREZISTA with food. PREZISTA cannot work properly without food. The type of food is not important.
• The child must swallow the tablets with a drink, such as water or milk.

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

You will require a different dose of PREZISTA that cannot be administered with these 75-milligram tablets. Other concentrations of PREZISTA are available.

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

The dose 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. The 400-milligram and 800-milligram PREZISTA tablets are used only to achieve the 800-milligram once-daily dosage.

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

Instructions for adults

• Take PREZISTA always along with ritonavir. PREZISTA does not work properly without ritonavir.
• In the morning, take 600 milligrams of PREZISTA along with 100 milligrams of ritonavir.
• In the evening, take 600 milligrams of PREZISTA along with 100 milligrams of ritonavir.
• Take PREZISTA with food. PREZISTA does not work properly without food. The type of food is not important.
• Swallow the tablets with a drink, which can be water or milk.
• The 75-milligram and 150-milligram PREZISTA tablets and the 100-milligram-per-milliliter oral suspension have been developed for use in children, but they can also be used in adults in some cases.

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 6 hours, take the tablets immediately. Always with ritonavir and with food. If you realize after 6 hours, skip that dose and proceed with the next dose 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 blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication can cause side effects, although not all people 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 greater likelihood 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 on the right side below the 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 present a rash. Your doctor will advise you on how to control the symptoms or if you should interrupt PREZISTA.

Other serious side effects were diabetes (frequent) and pancreatitis (uncommon).

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, simple herpes
• 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 may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils, 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, coated tongue
• nasal discharge
• skin lesions, dry skin
• muscle stiffness or joint pain, 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 it is a possible side effect not listed in this prospectus. 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 sight and reach of children.

Do not use this medication after the expiration date stated on the box and 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 75 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), and talc.
• This medication contains less than 1 mmol of sodium (23 mg) per dose; it is essentially "sodium-free".

Appearance of the product and package contents

Coated tablet, white, oblong, marked with TMC on one side and 75 on the other side.

480 tablets in a plastic bottle.

PREZISTA is also available in 150-milligram, 300-milligram, 400-milligram, 600-milligram, and 800-milligram coated tablets and a 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 prospectus:{MM/YYYY}.

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