Prezista

Package leaflet: Information for the user

PREZISTA 100 mg/ml oral suspension

darunavir
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effect, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What PREZISTA is and what it is used for

What PREZISTA is
PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used for the treatment of human immunodeficiency virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. PREZISTA works by reducing the amount of HIV in the body, improving the immune system, and reducing the risk of developing HIV-related diseases.
What PREZISTA is used for
PREZISTA is used to treat adults and children aged 3 years and older who weigh at least 15 kg (kilograms) and who are infected with HIV (see How to take PREZISTA).
PREZISTA must be taken in combination with a low dose of cobicistat or ritonavir and with other anti-HIV medicines. Your doctor will discuss with you the most appropriate combination of medicines for your treatment.

2. What you need to know before taking PREZISTA

Do not take PREZISTA

• If you are allergic to darunavir, or to any of the other ingredients of this medicine (listed in section 6), or to cobicistat or ritonavir.
• If you have severe liver problems. Consult your doctor if you are unsure about the severity of your liver disease. Additional tests may be required.

Inform your doctor about all the medicines you are taking, including medicines taken orally, inhaled,
injected, or applied to the skin.
Do not take PREZISTA with any of the following medicines
If you are currently taking any of these medicines, ask your doctor how to switch to another medicine.

Do not co-administer PREZISTA with products containing St John's wort (Hypericum perforatum).
Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking PREZISTA.
PREZISTA is not a cure for HIV infection.
People taking PREZISTA may still develop infections or other conditions associated with HIV infection. You should maintain regular contact with your doctor.
Patients taking PREZISTA may develop skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a rash.
In patients taking PREZISTA and raltegravir (for HIV infection), rashes (usually mild or moderate) may occur more frequently than in patients taking each medicine separately.
Inform your doctor about your medical condition BEFORE and DURING treatment
Please review the following points and inform your doctor if any of them apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe PREZISTA.
• Inform your doctor if you have diabetes. PREZISTA may increase blood sugar levels.
• Inform your doctor immediately if you notice any signs 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 from prior infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply). Several risk factors for developing this condition include duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, aches, and pain (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
PREZISTA has been administered to a limited number of patients aged 65 years or older.
If you belong to this age group, consult your doctor before taking PREZISTA.
Children
PREZISTA is not indicated for use in children under 3 years of age or weighing less than 15 kg (kilograms).
Other medicines and PREZISTA
Inform your doctor or pharmacist if you are taking, or have recently taken, any other medicines.
There are certain medicines that must not be co-administered with PREZISTA. These have been listed previously under the heading “Do not co-administer PREZISTA with any of the following medicines”.
In most cases, PREZISTA can be co-administered with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA in combination with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you may take.
The effects of PREZISTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking PREZISTA, and your doctor may require additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be increased.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
• Hormonal contraceptives containing oestrogen or hormone replacement therapy. PREZISTA may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will determine which cholesterol-lowering medicine is most appropriate for you.
• Clarithromycin (antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle conditions, and other inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under close monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (to treat asthma).
• 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 or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (to treat pain).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted, as the therapeutic effect and side effects of these medicines or of PREZISTA may be affected when co-administered. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable painkiller used during surgery).
• Digoxin (to treat certain heart conditions).
• Clarithromycin (antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
• Rifabutin (for bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for high blood pressure in the lung 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 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 lung circulation).
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
PREZISTA with food and drink
See section 3 “How to take PREZISTA”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant.
Pregnant women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant women should not take PREZISTA with cobicistat.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving PREZISTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking PREZISTA.
PREZISTA oral suspension contains sodium methyl parahydroxybenzoate. This ingredient may cause allergic reactions (sometimes delayed).
PREZISTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per ml, i.e., essentially “sodium-free”.

3. How to take PREZISTA

Take this medicine exactly as instructed by your doctor, pharmacist, or
nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
Even if you feel better, do not stop taking PREZISTA with cobicistat or ritonavir without
speaking to your doctor.
After starting treatment, do not change the dose, dosage form, or stop treatment without
instructions from your doctor.
Dose for children aged 3 years and older and weighing at least 15 kilograms who have not
previously received antiretroviral medicines (your child’s doctor will determine this condition)
The doctor will calculate the correct daily dose based on the child's body weight and age (see table below). This dose must not exceed the recommended adult dose, which is 800 milligrams of PREZISTA together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily.
Your doctor will inform you how much PREZISTA oral suspension and how much cobicistat (tablets) or ritonavir (capsules, tablets, or solution) the child should take.

The child must take PREZISTA every day and always in combination with 150 milligrams of
cobicistat or 100 milligrams of ritonavir and with food. PREZISTA may not work properly without
cobicistat or ritonavir and food. The child must consume a meal or snack within 30 minutes
before taking PREZISTA and cobicistat or ritonavir. The type of food is not important.
The child's doctor will determine whether PREZISTA should be taken with cobicistat or with ritonavir.
Dose for children aged 3 years and older and weighing at least 15 kg (kilograms) who have previously received antiretroviral medicines (this condition will be determined by the child's doctor)
The doctor will calculate the appropriate dose based on the child's weight and age (see table below). The doctor will decide whether once-daily or twice-daily dosing is appropriate for the child. This dose must not exceed the recommended adult dose, which is 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily or 800 milligrams of PREZISTA together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily.
The doctor will inform you how much PREZISTA oral suspension and how much cobicistat (tablets) or ritonavir (capsules, tablets or solution) the child should take.
Dose twice daily

Once-daily dose

Instructions for children

• The child must always take PREZISTA together with cobicistat or ritonavir. PREZISTA cannot work effectively without cobicistat or ritonavir.
• The child must take the appropriate doses of PREZISTA and ritonavir twice daily or once daily, or PREZISTA and cobicistat once daily. If PREZISTA is prescribed twice daily, the child must take one dose in the morning and one dose in the evening. The child's doctor will determine the appropriate dose for the child.
• The child must take PREZISTA with food. PREZISTA cannot work effectively without food. The type of food is not important.

Dose for adults who have never taken antiretroviral medicines before (to be determined by the doctor)
The usual dose of PREZISTA is 800 milligrams once daily.
You must take PREZISTA every day and always together with 150 milligrams of cobicistat or
100 milligrams of ritonavir and with food. PREZISTA cannot work optimally without cobicistat or
ritonavir and without food. You must eat a meal or a snack within 30 minutes before taking
PREZISTA and cobicistat or ritonavir. The type of food does not matter. Even if you feel better, do not stop
taking PREZISTA and cobicistat or ritonavir before speaking with your doctor.
Dose for adults who have previously taken antiretroviral medicines (to be determined by the doctor)
The doses are:

• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir, twice daily, or
• 800 milligrams of PREZISTA together with 150 milligrams of cobicistat or 100 milligrams of ritonavir, once daily.

Discuss with your doctor which dose is most appropriate.
Instructions for adults

• Take PREZISTA always with cobicistat or ritonavir. PREZISTA does not work adequately without cobicistat or ritonavir.
• Take PREZISTA with food. PREZISTA does not work adequately without food. The type of food taken is unimportant.

Instructions for use
Use the oral dosing syringe supplied with the package to accurately measure the dose:

1. Shake the bottle well before each use.
2. Open the PREZISTA oral suspension bottle by pushing down on the cap and turning it counterclockwise.
3. Insert the dosing syringe all the way to the bottom of the bottle.

4. Pull the plunger up to the mark indicating the dose (ml) prescribed by the doctor.
5. Take the dose of PREZISTA. Place the tip of the oral dosing syringe in the mouth. Push the plunger of the syringe toward the mouth while swallowing.
6. Close the bottle with the cap after use and store PREZISTA oral suspension as described in section 5 below.
7. Remove the plunger from the barrel of the syringe, rinse with water, and allow to air-dry after each use.
8. After air-drying, reassemble the syringe and store it with the PREZISTA bottle.

Do not use the dosing syringe with other medicines.
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 daily and realize you have missed a dose within 6 hours, you must
take the oral suspension immediately. Always take the oral suspension together with ritonavir
and food. If you realize after 6 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for the missed dose.
If you take PREZISTA once daily and realize you have missed a dose within 12 hours,
you must take the oral suspension immediately. Always take the oral suspension together with
cobicistat or ritonavir and food. If you realize after 12 hours, skip the missed dose and take the next dose
as usual. Do not take a double dose to make up for the missed dose.
In case of vomiting after taking PREZISTA and cobicistat or ritonavir
If vomiting occurs within 4 hours after taking the medicine, you must take another dose of
PREZISTA and cobicistat or ritonavir with food as soon as possible. If vomiting occurs more than 4 hours
after taking the medicine, you do not need to take another dose of PREZISTA and
cobicistat or ritonavir until the next scheduled dose.
Contact your doctor if you have any doubts about what to do if you miss a dose or vomit.
Do not stop treatment with PREZISTA without first consulting your doctor
Anti-HIV medicines can make you feel better. Do not stop taking PREZISTA, even if you
feel better. Consult your doctor first.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or
nurse.

4. Possible side effects

During HIV treatment, weight gain and increased levels of lipids and glucose in the blood may occur.
This is partly related to the recovery of health status and lifestyle, and in the case of blood lipids, sometimes also to the HIV medicines themselves. Your doctor will monitor these changes.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor if you develop any of the following side effects
Liver problems have been reported, which occasionally can be serious. Your doctor will need to carry out blood tests before starting PREZISTA. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark urine (tea-coloured), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.
Skin rashes (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to moderate in severity. A skin rash may also be a symptom of a more serious and rare condition. It is important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether PREZISTA should be discontinued.
Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).
Very common side effects (may affect more than 1 in 10 people)

• diarrhoea

Common side effects (may affect up to 1 in 10 people)

• vomiting, nausea, abdominal pain or bloating, dyspepsia (indigestion), flatulence
• headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon side effects (may affect up to 1 in 100 people)

• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, difficulty with balance
• difficulty breathing, cough, nosebleeds, sore throat
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
• reduced thyroid function. This can be detected through blood tests.
• high blood pressure, hot flushes
• red or dry eyes
• fever, leg swelling due to fluid retention, malaise, chills, abnormal sensations, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction (problems with erection), breast enlargement
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sex drive

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

• a reaction called DRESS [severe rash which may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cells in the blood), effects on the liver, kidneys or lungs]
• heart attack, slow heartbeat, palpitations
• vision disorders
• chills, feeling unwell
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, seizures, change or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• runny nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• deposition of darunavir crystals in the kidney leading to kidney disease.

Some side effects are typical of anti-HIV medicines belonging to the same class as PREZISTA.
These are:

• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PREZISTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
Do not store above 30°C.
Do not refrigerate or freeze. Avoid exposure to excessive heat.
Keep in the original packaging.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer used. This will help protect the environment.

6. Package contents and other information

What PREZISTA contains

• The active substance is darunavir. Each millilitre contains 100 milligrams of darunavir (as ethanolate).
• The other ingredients are hydroxypropyl cellulose, microcrystalline cellulose and sodium carmellose, citric acid monohydrate, sucralose, strawberry flavour, flavouring agent to mask the taste, sodium methyl hydroxybenzoate (E219), hydrochloric acid (for pH adjustment), purified water.

Description of the appearance of PREZISTA and contents of the pack
White to off-white oral suspension. Supplied in a 200 ml amber glass bottle with a child-resistant polypropylene closure and a graduated 6 ml oral dosing pipette with 0.2 ml graduations made of LDPE. The bottle neck contains a low-density polyethylene (LDPE) insert to hold the dosing pipette. Do not use the oral dosing pipette with other medicines.
PREZISTA is also available as film-coated tablets containing 75 milligrams, 150 milligrams, 400 milligrams, 600 milligrams, and 800 milligrams.
Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium
Manufacturer
Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
For further information about this medicine, contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]
България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]
Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]
Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]
Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]
Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]
Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300
España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]
France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]
Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]
Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: +353 1 800 709 122 Tel: +386 1 401 18 00
[email protected]
Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]
Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]
Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]
Latvija United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 Tel: +44 1 494 567 444
[email protected]
More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Patient Information Leaflet: Information for the User

PREZISTA 75 mg film-coated tablets

darunavir
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What PREZISTA is and what it is used for

What PREZISTA is
PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used for the treatment of human immunodeficiency virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. PREZISTA works by reducing the amount of HIV in the body, improving the immune system, and reducing the risk of developing HIV-related illnesses.
What it is used for
PREZISTA is used to treat adults and children aged 3 years and older who weigh at least 15 kg (kilograms) and who have already been treated with other antiretroviral medicines.
PREZISTA must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for your treatment.

2. What you should know before taking PREZISTA

Do not take PREZISTA

• If you are allergic to darunavir, or to any of the other ingredients of this medicine (listed in section 6), or to ritonavir.
• If you have severe liver problems. Ask your doctor for advice if you are unsure about the severity of your liver disease. You may need further tests.

Inform your doctor about all the medicines you are taking, including medicines taken orally, inhaled,
injected, or applied to the skin.
Do not take PREZISTA with any of the following medicines
If you are currently taking one of these medicines, ask your doctor how to switch to another medicine.

Do not co-administer PREZISTA with products containing St John’s wort (Hypericum perforatum).
Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking PREZISTA.
PREZISTA is not a cure for HIV infection.
People who take PREZISTA may still develop infections or other illnesses associated with HIV infection. You must remain in regular contact with your doctor.
Patients taking PREZISTA may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
In patients taking PREZISTA and raltegravir (for HIV infection), rashes (generally mild or moderate) may occur more frequently than in patients taking each medicine separately.
Inform your doctor about your medical condition 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 previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe PREZISTA.
• Inform your doctor if you have diabetes. PREZISTA may increase blood sugar levels.
• Inform your doctor immediately if you notice any signs 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 from prior infections may occur soon after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may occur many months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
• Inform your doctor if you notice any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Some of the many risk factors for developing this condition may include duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, pain, and aches (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
PREZISTA has been administered to a limited number of patients aged 65 years or older.
If you belong to this age group, consult your doctor before taking PREZISTA.
Children
PREZISTA is not indicated for use in children under 3 years of age or weighing less than 15 kg (kilograms).
Other medicines and PREZISTA
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines.
There are medicines that must not be co-administered with PREZISTA. These have been listed earlier under the heading “Do not co-administer PREZISTA with any of the following medicines”.
In most cases, PREZISTA can be co-administered with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA in combination with ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you may take.
The effects of PREZISTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking PREZISTA, and your doctor may require additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be altered.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
• Hormonal contraceptives containing oestrogens or hormone replacement therapy. PREZISTA may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
• Clarithromycin (antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle disorders, and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under careful monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (to treat asthma).
• 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 or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (to treat pain).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted, as the therapeutic effect and side effects of these medicines or of PREZISTA may be affected when co-administered. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
• Alfentanil (a potent, short-acting injectable painkiller used during surgery)
• Digoxin (to treat certain heart conditions)
• Clarithromycin (antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor
• Rifabutin (for bacterial infections)
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for 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 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, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives)
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions)

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
PREZISTA with food and drink
See section 3 “How to take PREZISTA”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant.
Pregnant women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant women should not take PREZISTA with cobicistat.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving PREZISTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking PREZISTA.
PREZISTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take PREZISTA

Take this medicine exactly as prescribed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Even if you feel better, do not stop taking PREZISTA and ritonavir without talking to your
doctor.
After starting treatment, do not change the dose, dosage form, or stop treatment without instructions from your doctor.
Dose for children aged 3 years and older and weighing at least
15 kilograms who have not previously taken antiretroviral medicines (this condition will be determined by the child's doctor)
The doctor will calculate the appropriate daily dose based on the child's body weight (see table below). This dose must not exceed the recommended dose for adults, which is 800 milligrams of PREZISTA together with 100 milligrams of ritonavir once daily.
The doctor will inform you how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) the child should take.

Dose for children aged 3 years and older and weighing at least 15 kg
(kilograms) who have previously taken antiretroviral medicines (this condition will be determined by the
child's doctor)
The doctor will calculate the appropriate dose based on the child's weight (see table below). The doctor will decide whether a once-daily or twice-daily dosing regimen is appropriate for the child. The dose must not exceed the recommended adult dose, which is 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily or 800 milligrams of PREZISTA together with 100 milligrams of ritonavir once daily.
The doctor will inform you how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Other dosage strengths of tablets are available, and the doctor may prescribe a combination of tablets to achieve the appropriate dosage regimen. PREZISTA oral suspension is also available. The doctor will decide whether PREZISTA tablets or oral suspension is suitable for the child.
Dose twice daily

*
Once daily dose

Instructions for children

• The child must always take PREZISTA together with ritonavir. PREZISTA cannot work effectively without ritonavir.
• The child must take the appropriate doses of PREZISTA and ritonavir twice daily or once daily. If PREZISTA is prescribed twice daily, the child should take one dose in the morning and one dose in the evening. The doctor will determine which regimen is most appropriate for the child.
• The child must take PREZISTA with food. PREZISTA cannot work effectively 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 never taken antiretroviral medicines (to be determined by the doctor)
Different doses of PREZISTA may be required that cannot be administered with
these 75 mg tablets. Other formulations of PREZISTA are available.
Dose for adults who have previously taken antiretroviral medicines (to be determined by the
doctor)
The doses are:

• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir, twice daily, or
• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 milligrams of ritonavir, once daily. The 400 milligram and 800 milligram PREZISTA tablets should only be used to construct the 800 milligram once-daily regimen.

Discuss with the doctor which dose is most appropriate.
Instructions for adults

• Take PREZISTA always with ritonavir. PREZISTA does not work adequately without ritonavir.
• In the morning, take 600 milligrams of PREZISTA together with 100 milligrams of ritonavir.
• In the evening, take 600 milligrams of PREZISTA together with 100 milligrams of ritonavir.
• Take PREZISTA with food. PREZISTA does not work adequately without food. The type of food taken is not important.
• Swallow the tablets with a drink such as water or milk.
• PREZISTA 75 milligram, 150 milligram tablets and 100 milligrams per milliliter oral suspension have been developed for use in children, but may be used in certain cases in adults as well.

Removing the child-resistant cap

The plastic bottle is supplied with a child-resistant cap and must be opened as follows:

• Press down on the plastic cap and turn it counterclockwise.
• Remove the unscrewed 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, you must take the tablets immediately. Always take the tablets together with ritonavir and food. If you realize after 6 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for a forgotten dose.
If vomiting occurs after taking PREZISTA and ritonavir
If vomiting occurs within 4 hours of taking the medicine, you must take another dose of PREZISTA and ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, you do not need to take another dose of PREZISTA and ritonavir until the next scheduled dose.
Contact your doctor if you have any doubts about what to do if you miss a dose or vomit.
Do not stop treatment with PREZISTA without first consulting your doctor
Anti-HIV medicines can make you feel better. Do not stop taking PREZISTA, even if you feel better. Consult your doctor first.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV therapy, an increase in weight and in blood lipid and glucose levels may occur.
This is partly related to the recovery of health status and lifestyle, and in the case of blood lipids, sometimes also to the HIV medicines themselves. Your doctor will monitor these changes.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor if you develop any of the following side effects.

Liver problems have been reported, which occasionally can be serious. Your doctor will carry out blood tests before starting PREZISTA. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to moderate in severity. A skin rash may also be a symptom of a more serious and rare condition. It is therefore important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether PREZISTA should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

Very common side effects (may affect more than 1 in 10 people):

• Diarrhea

Common side effects (may affect up to 1 in 10 people):

• Vomiting, nausea, abdominal pain or bloating, dyspepsia (digestive difficulties), flatulence
• Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of strength, difficulty falling asleep

Uncommon side effects (may affect up to 1 in 100 people):

• Chest pain, changes in electrocardiogram, rapid heartbeat
• Decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, difficulty with balance
• Breathing difficulties, cough, nosebleeds, sore throat
• Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• Hives, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• Muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
• Slowed thyroid function. This can be detected by blood tests.
• High blood pressure, hot flushes
• Red or dry eyes
• Fever, leg swelling due to fluid retention, malaise, chills, unusual sensations, irritability, pain
• Symptoms of infection, herpes simplex
• Erectile dysfunction (problems with erection), breast enlargement
• Sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

• A reaction called DRESS [severe rash that may be accompanied by fever, fatigue, facial or lymph node swelling, increased eosinophils (a type of white blood cell), effects on liver, kidneys or lungs]
• Heart attack, slow heartbeat, palpitations
• Vision disorders
• Chills, feeling unwell
• A sensation of confusion or disorientation, mood changes, restlessness
• Fainting, seizures, changes or loss of taste
• Mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• Runny nose
• Skin lesions, dry skin
• Stiffness of muscles or joints, joint pain with or without inflammation
• Changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• Crystallization of darunavir in the kidney leading to kidney disease

Some side effects are typical of anti-HIV medicines belonging to the same class as PREZISTA. These include:

• Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PREZISTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What PREZISTA contains

• The active substance is darunavir. Each tablet contains 75 milligrams of darunavir (as ethanolate).
• The other components are: microcrystalline cellulose, anhydrous colloidal silica, crospovidone, magnesium stearate. The film coating contains partially hydrolysed polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc.

Description of the appearance of PREZISTA and contents of the pack
White, film-coated, oval-shaped tablet marked "TMC" on one side and "75" on the other. 480 tablets in a plastic bottle.
PREZISTA is also available as film-coated tablets containing 150 milligrams, 400 milligrams, 600 milligrams, 800 milligrams and as an oral suspension of 100 milligrams/millilitre.

Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

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

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
[email protected]

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
[email protected]

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227

Danmark
Janssen-Cilag A/S
Tlf: +45 4594 8282
[email protected]

Deutschland
Janssen-Cilag GmbH
Tel: +49 2137 955 955
[email protected]

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
[email protected]

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
[email protected]

France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
[email protected]

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
[email protected]

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Ísland
Janssen-Cilag AB c/o Vistor hf.
Sími: +354 535 7000
[email protected]

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
[email protected]

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
[email protected]

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
[email protected]

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
[email protected]

Malta
AM MANGION LTD
Tel: +356 2397 6000

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
[email protected]

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
[email protected]

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00
[email protected]

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800
[email protected]

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
[email protected]

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
[email protected]

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
[email protected]

United Kingdom (Northern Ireland)
Janssen Sciences Ireland UC
Tel: +44 1 494 567 444

More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu/.

Package leaflet: information for the user

PREZISTA 150 mg film-coated tablets

darunavir
Please read this entire leaflet carefully before taking this medicine, as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What PREZISTA is and what it is used for

What PREZISTA is
PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine
used to treat human immunodeficiency virus (HIV) infection. It belongs to a group of medicines called
protease inhibitors. PREZISTA works by reducing the amount of HIV in the body, improving the immune system, and reducing the risk of developing HIV-related diseases.
What it is used for
PREZISTA is used to treat HIV infection in adults and children aged 3 years and older who weigh at least 15 kg (kilograms) and who have previously taken other antiretroviral medicines.
PREZISTA must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for your treatment.

2. What you need to know before taking PREZISTA

Do not take PREZISTA

• If you are allergic to darunavir, or to any of the other ingredients of this medicine (listed in section 6) or to ritonavir.
• If you have severe liver problems. Ask your doctor for advice if you are unsure about the severity of your liver disease. You may need further tests.

Inform your doctor about all the medicines you are taking, including medicines taken orally, inhaled,
injected, or applied to the skin.
Do not take PREZISTA with any of the following medicines
If you are currently taking one of these medicines, ask your doctor how to switch to another medicine.

Do not co-administer PREZISTA with products containing St. John’s Wort (Hypericum perforatum).
Warnings and precautions
Consult your doctor, pharmacist, or nurse before taking PREZISTA.
PREZISTA is not a cure for HIV infection.
People taking PREZISTA may still develop infections or other diseases associated with HIV infection. Regular follow-up with your doctor is necessary.
Patients taking PREZISTA may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor immediately if you develop a rash.
Skin rashes (generally mild or moderate) may occur more frequently in patients taking PREZISTA together with raltegravir (for HIV infection) than in patients taking each medicine separately.
Inform your doctor about your medical condition BEFORE and DURING treatment
Make sure to review the following points and inform your doctor if any of them apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe PREZISTA.
• Inform your doctor if you have diabetes. PREZISTA may increase blood sugar levels.
• Inform your doctor immediately if you notice any signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, inflammatory symptoms from prior infections may occur soon after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for HIV treatment. Autoimmune disorders may appear several months after treatment initiation. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet spreading toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (bone tissue death due to reduced blood supply to the bone). Several risk factors for developing this condition include long-term use of combination antiretrovirals, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, pain, and discomfort (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
PREZISTA has been administered to a limited number of patients aged 65 years or older.
If you belong to this age group, consult your doctor before taking PREZISTA.
Children
PREZISTA is not indicated for use in children under 3 years of age or weighing less than 15 kg (kilograms).
Other medicines and PREZISTA
Inform your doctor or pharmacist if you are taking, or have recently taken, any other medicines.
There are medicines that must not be co-administered with PREZISTA. These have been listed previously under the heading “Do not co-administer PREZISTA with any of the following medicines”.
In most cases, PREZISTA can be combined with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA in combination with ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines you can take.
The effects of PREZISTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking PREZISTA, and your doctor may require additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be altered.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both therapeutic effects and side effects may be altered.
• Hormonal contraceptives containing estrogens or hormone replacement therapy. PREZISTA may reduce their effectiveness. When hormonal therapy is used for contraception, use of additional non-hormonal contraceptive methods is recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will determine which cholesterol-lowering medicine is most suitable for you.
• Clarithromycin (antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle disorders, and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected, or applied to the skin. If alternative treatments are not possible, these medicines may only be taken after evaluation by your doctor and under careful monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (for the treatment of asthma).
• Artemether/lumefantrine (a combination of medicines for the treatment of malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (for pain treatment).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted, as the therapeutic effect and side effects of these medicines or of PREZISTA may be affected when co-administered. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable painkiller used during surgery).
• Digoxin (for the treatment of certain heart conditions).
• Clarithromycin (antibiotic).
• Itraconazole, posaconazole, isavuconazole, fluconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
• Rifabutin (for bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for high blood pressure in the pulmonary circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for the treatment of depression and anxiety).
• Maraviroc (for treating HIV infection).
• Methadone (for treating opioid dependence).
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain).
• Colchicine (for the treatment of gout or familial Mediterranean fever).
• Bosentan (for the treatment of high blood pressure in the pulmonary circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (for treating psychiatric conditions).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
PREZISTA with food and drinks
See section 3 “How to take PREZISTA”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant.
Pregnant women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant women should not take PREZISTA with cobicistat.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving PREZISTA.
Breastfeeding is not recommended in women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or planning to breastfeed, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking PREZISTA.
PREZISTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take PREZISTA

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Even if you feel better, do not stop taking PREZISTA and ritonavir without talking to your
doctor.
After starting treatment, do not change the dose, dosage form, or stop treatment without instructions from your doctor.
Dose for children aged 3 years and older and weighing at least 15 kilograms who have not previously taken antiretroviral medicines (your child’s doctor will determine this condition)
Your doctor will calculate the appropriate daily dose based on the child's body weight (see table below). This dose must not exceed the recommended dose for adults, which is 800 milligrams of PREZISTA together with 100 milligrams of ritonavir once daily.
Your doctor will inform you how many PREZISTA tablets and how much ritonavir (capsules, tablets or solution) the child should take.

Dose for children aged 3 years and older and weighing at least 15 kg
(kilograms) who have previously taken antiretroviral medicines (this condition will be
determined by the child's doctor)
The doctor will calculate the appropriate dose based on the child's weight (see table below). The doctor will decide whether a once-daily or twice-daily dosing regimen is appropriate for the child. The dose must not exceed the recommended adult dose, which is 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily or 800 milligrams of PREZISTA together with 100 milligrams of ritonavir once daily.
The doctor will inform you how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) the child should take. Other strengths of tablets are available, and the doctor may prescribe a combination of tablets to achieve the appropriate dosage regimen. PREZISTA oral suspension is also available. The doctor will decide whether PREZISTA tablets or oral suspension are suitable for the child.
Dose twice daily

*
Once daily dose

Instructions for children

• The child must always take PREZISTA together with ritonavir. PREZISTA cannot work effectively without ritonavir.
• The child must take the appropriate doses of PREZISTA and ritonavir twice daily or once daily. If PREZISTA is prescribed twice daily, the child must take one dose in the morning and one dose in the evening. The doctor will determine which regimen is most appropriate for the child.
• The child must take PREZISTA with food. PREZISTA cannot work effectively 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 never taken antiretroviral medicines (to be determined by the doctor)
Different doses of PREZISTA may be required that cannot be administered with these 150 mg tablets. Other formulations of PREZISTA are available.
Dose for adults who have previously taken antiretroviral medicines (to be determined by the doctor)
The doses are:

• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir, twice daily, or
• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 milligrams of ritonavir, once daily. The 400 milligram and 800 milligram tablets of PREZISTA must only be used to construct the 800 milligram once-daily regimen.
  Discuss with the doctor which dose is correct for you.

Instructions for adults

• Take PREZISTA always with ritonavir. PREZISTA does not work adequately without ritonavir.
• In the morning, take 600 milligrams of PREZISTA together with 100 milligrams of ritonavir.
• In the evening, take 600 milligrams of PREZISTA together with 100 milligrams of ritonavir.
• Take PREZISTA with food. PREZISTA does not work adequately without food. The type of food taken is not important.
• Swallow the tablets with a drink such as water or milk.
• PREZISTA 75 milligrams, 150 milligrams tablets and 100 milligrams per millilitre oral suspension have been developed for use in children, but may be used in some cases in adults as well.

Removing the child-resistant cap

The plastic bottle is equipped with a child-resistant cap and must be opened as follows:

• Push down the plastic cap and turn it counterclockwise.
• Remove the unscrewed cap.

If you take more PREZISTA than you should
Contact your doctor, pharmacist, or nurse immediately.
If you forget to take PREZISTA
If you realize within 6 hours, take the tablets immediately. Always take the tablets together with ritonavir and food. If you realize after 6 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for a forgotten dose.
If vomiting occurs after taking PREZISTA and ritonavir
If vomiting occurs within 4 hours of taking the medicine, take another dose of PREZISTA and ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, you do not need to take another dose of PREZISTA and ritonavir until the next scheduled dose.
Contact your doctor if you have any doubts about what to do if you miss a dose or vomit.
Do not stop treatment with PREZISTA without first talking to your doctor
Anti-HIV medicines can make you feel better. Do not stop taking PREZISTA, even if you feel better. Talk to your doctor first.
If you have any questions about using this medicine, talk to your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV treatment, weight gain and increased levels of lipids and glucose in the blood may occur.
This is partly related to the recovery of health status and lifestyle, and in the case of blood lipids, sometimes also to the HIV medications themselves. Your doctor will monitor these changes.
Like all medicines, this medicine can cause side effects, although not everybody experiences them.
Tell your doctor if you develop any of the following side effects
Liver problems have been reported, which occasionally can be serious. Your doctor will need to perform blood tests before starting PREZISTA. If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, as you have a higher risk of developing liver problems. Discuss with your doctor the signs and symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark-coloured urine (tea-coloured), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort under the right side of the ribs.
Skin rash (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to moderate in severity. A skin rash may also be a symptom of a more serious and rare condition. It is therefore important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether PREZISTA should be discontinued.
Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).
Very common side effects (may affect more than 1 in 10 people)

• diarrhoea

Common side effects (may affect up to 1 in 10 people)

• vomiting, nausea, abdominal pain or bloating, dyspepsia (digestive difficulties), flatulence
• headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon side effects (may affect up to 1 in 100 people)

• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, difficulty with balance
• difficulty breathing, cough, nosebleeds, throat irritation
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
• slowed thyroid function. This can be detected through blood tests.
• high blood pressure, hot flushes
• red or dry eyes
• fever, swelling of the legs due to fluid accumulation, malaise, chills, unusual sensations, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction (problems with erection), breast enlargement
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased libido

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

• a reaction called DRESS [severe rash which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), effects on the liver, kidneys or lungs]
• heart attack, slow heartbeat, palpitations
• vision disorders
• chills, feeling unwell
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, epileptic seizures, change or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• runny nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• deposition of darunavir crystals in the kidney leading to kidney disease.

Some side effects are typical of anti-HIV medicines belonging to the same class as PREZISTA.
These are:

• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist or nurse. You can also report side effects directly via the reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PREZISTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What PREZISTA contains

• The active substance is darunavir. Each tablet contains 150 milligrams of darunavir ethanolate.
• The other components are: microcrystalline cellulose, anhydrous colloidal silica, crospovidone, magnesium stearate. The coating contains partially hydrolyzed polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc.

Description of the appearance of PREZISTA and contents of the pack
White, film-coated oval tablet, marked with "TMC" on one side and "150" on the other.
240 tablets in a plastic bottle.
PREZISTA is also available as 75 milligram, 400 milligram, 600 milligram, and 800 milligram film-coated tablets, and as 100 milligram/millilitre oral suspension.

Marketing Authorization Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.B.E. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: +353 1 800 709 122 Tel: +386 1 401 18 00
[email protected]

Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]

Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]

Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

Latvija United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 Tel: +44 1 494 567 444
[email protected]

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

Package leaflet: information for the user

PREZISTA 400 mg film-coated tablets

darunavir
Please read this entire leaflet carefully before taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as you, because it may be harmful to them.
• If you experience any side effects, including those not listed in this leaflet, contact your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What PREZISTA is and what it is used for

What PREZISTA is
PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine
used for the treatment of human immunodeficiency virus (HIV) infection. It belongs to
a group of medicines called protease inhibitors. PREZISTA works by reducing the amount of
HIV in the body, improving the immune system, and reducing the risk of developing
HIV-related diseases.

What it is used for
PREZISTA 400 milligram tablets are used to treat adults and children (aged 3 years or older, and weighing at least 40 kilograms) with HIV infection who

• have not previously used other antiretroviral medicines, or
• in some patients who have previously used antiretroviral medicines (your doctor will determine to whom it should be given).

PREZISTA must be taken in combination with cobicistat or a low dose of ritonavir, and with other anti-HIV medicines. Your doctor will discuss with you the best combination of medicines for you.

2. What you should know before taking PREZISTA

Do not take PREZISTA

• If you are allergic to darunavir, or to any of the other ingredients of this medicine (listed in section 6), or to cobicistat or ritonavir.
• If you have severe liver problems. Ask your doctor for advice if you are unsure about the severity of your liver disease. You may need further tests.

Inform your doctor about all the medicines you are taking, including medicines taken orally, inhaled,
injected, or applied to the skin.
Do not take PREZISTA with any of the following medicines
If you are currently taking any of these medicines, ask your doctor how to switch to another medicine.

Do not co-administer PREZISTA with products containing St. John’s wort (Hypericum perforatum).
Warnings and precautions
Speak to your doctor, pharmacist, or nurse before taking PREZISTA.
PREZISTA is not a cure for HIV infection.
People taking PREZISTA may still develop infections or other illnesses associated with HIV infection. Regular contact with your doctor is necessary.
Patients taking PREZISTA may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
In patients taking PREZISTA and raltegravir (for HIV infection), rashes (generally mild or moderate) may occur more frequently than in patients taking each medicine separately.
Inform your doctor about your condition 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 previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe PREZISTA.

• Inform your doctor if you have diabetes. PREZISTA may increase blood sugar levels.

• Inform your doctor immediately if you notice any signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, inflammatory signs and symptoms from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may occur after starting medications for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.

• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.

• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).

• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Several risk factors for developing this condition include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint swelling, pain, and stiffness (especially in the hip, knee, and shoulders), and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly patients
PREZISTA has been administered to a limited number of patients aged 65 years and older.
If you belong to this age group, consult your doctor before taking PREZISTA.
Children and adolescents
PREZISTA 400 milligram tablets must not be used in children under 3 years of age or weighing less than 40 kilograms.
Other medicines and PREZISTA
Inform your doctor or pharmacist if you are taking or have recently taken any other medicine.
There are medicines that must not be co-administered with PREZISTA. These have been listed previously under the heading “Do not co-administer PREZISTA with any of the following medicines”.
In most cases, PREZISTA can be co-administered with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA in combination with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you can take.
The effects of PREZISTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking PREZISTA, and your doctor may require additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be altered.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), as both therapeutic effect and side effects may be altered.
• Hormonal contraceptives containing oestrogens or hormone replacement therapy. PREZISTA may reduce their effectiveness. When hormonal therapy is used for contraception, use of additional non-hormonal contraceptive methods is recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
• Clarithromycin (antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscular conditions, and other inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may be taken only after evaluation by your doctor and under close monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (to treat asthma).
• 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 for treating a heart or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (to treat pain).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted, as the therapeutic effect and side effects of these medicines or of PREZISTA may be affected when co-administered. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable painkiller used during surgery).
• Digoxin (to treat certain heart conditions).
• Clarithromycin (antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may be taken only after evaluation by your doctor.
• Rifabutin (to treat bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for 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 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, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
PREZISTA with food and drinks
See section 3 “How to take PREZISTA”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant.
Pregnant women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant women should not take PREZISTA with cobicistat.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving PREZISTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking PREZISTA.
PREZISTA tablets contain sunset yellow FCF (E110), which may cause allergic reactions.
PREZISTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free.”

3. How to take PREZISTA

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
Even if you feel better, do not stop taking PREZISTA and cobicistat or ritonavir without first talking to your doctor.
After treatment has been started, the dose or dosage form must not be changed, nor should treatment be stopped, without instructions from your doctor.
The 400 milligram tablets of PREZISTA should only be used to construct the 800 milligram once-daily regimen.

Dose for adults who have not previously taken antiretroviral medicines (your doctor will assess this)
The usual dose of PREZISTA is 800 milligrams (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) once daily.
You must take PREZISTA every day and always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. PREZISTA cannot work optimally without cobicistat or ritonavir and without food. You must eat a meal or snack within 30 minutes before taking PREZISTA and cobicistat or ritonavir. The type of food does not matter. Even if you feel better, do not stop taking PREZISTA and cobicistat or ritonavir before speaking with your doctor.

Instructions for adults

• Take two 400 milligram tablets at the same time each day
• Take PREZISTA always together with 150 milligrams of cobicistat or 100 milligrams of ritonavir
• Take PREZISTA with food
• Swallow the tablets with a drink such as water or milk
• Take any other HIV medicines used in combination with PREZISTA and cobicistat or ritonavir as directed by your doctor
• PREZISTA 100 milligrams per millilitre oral suspension was developed for use in children, but may be used in certain cases in adults as well.

Adults who have previously taken antiretrovirals (your doctor will assess this)
The dose is:

• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily, OR
• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily

Discuss with your doctor which dose is most appropriate.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (your child’s doctor will determine this condition)

• The usual dose of PREZISTA is 800 milligrams once daily (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 mg of ritonavir or 150 milligrams of cobicistat once daily.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (your child’s doctor will determine this condition)
The dose is either:

• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily, OR
• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is most appropriate.

Instructions for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms

• Take 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) at the same time each day.
• Take PREZISTA always together with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
• Take PREZISTA with food.
• Swallow the tablets with a drink such as water or milk.
• Take any other HIV medicines used in combination with PREZISTA and ritonavir or cobicistat as recommended by your doctor.

Removing the child-resistant cap

The plastic bottle is equipped with a child-resistant cap and should be opened as follows:

• Press down on the plastic cap and turn it counterclockwise.
• Remove the unscrewed cap.

If you take more PREZISTA than you should
Contact 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 tablets together with cobicistat or ritonavir and with food. If you realize after 12 hours, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for a missed dose.

If you vomit after taking PREZISTA and cobicistat or ritonavir
If you vomit within 4 hours of taking the medicine, you should take another dose of PREZISTA and cobicistat or ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, you do not need to take another dose of PREZISTA and cobicistat or ritonavir until the next scheduled dose.
Contact your doctor if you are unsure about what to do if you miss a dose or vomit.

Do not stop treatment with PREZISTA without first consulting your doctor
Anti-HIV medicines can make you feel better. Do not stop taking PREZISTA, even if you feel better. Speak to your doctor first.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor if you develop any of the following side effects

Liver problems have been reported, which occasionally can be serious. Your doctor will need to perform blood tests before starting PREZISTA. If you have chronic hepatitis B or C, your doctor must monitor your blood tests more frequently, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or the whites of the eyes, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to moderate in severity. A skin rash may also be a symptom of a rare but more serious condition. It is important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether PREZISTA should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

Very common side effects (may affect more than 1 in 10 people)

• Diarrhea

Common side effects (may affect up to 1 in 10 people)

• Vomiting, nausea, abdominal pain or bloating, dyspepsia (digestive difficulties), flatulence
• Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon side effects (may affect up to 1 in 100 people)

• Chest pain, changes in electrocardiogram, rapid heartbeat
• Decreased or abnormal skin sensitivity, tingling sensation, attention disorders, memory loss, balance difficulties
• Breathing difficulties, cough, nosebleeds, throat irritation
• Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• Hives, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• Muscle pain, muscle cramps or weakness, pain in the extremities, osteoporosis
• Slowed thyroid function. This can be detected by a blood test.
• High blood pressure, hot flushes
• Red or dry eyes
• Fever, leg swelling due to fluid retention, malaise, chills, abnormal sensations, irritability, pain
• Symptoms of infection, herpes simplex
• Erectile dysfunction (problems with erection), breast enlargement
• Sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

• A reaction called DRESS [severe rash which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), effects on the liver, kidneys or lungs]
• Heart attack, slow heartbeat, palpitations
• Vision disorders
• Chills, feeling unwell
• A sensation of confusion or disorientation, altered mood, restlessness
• Fainting, epileptic seizures, change or loss of taste
• Mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• Runny nose
• Skin lesions, dry skin
• Stiffness of muscles or joints, joint pain with or without inflammation
• Changes in certain blood cell or chemical values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• Darunavir crystal deposition in the kidney leading to kidney disease

Some side effects are typical of anti-HIV medicines belonging to the same class as PREZISTA. These are:

• Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects

If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly via the reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PREZISTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What PREZISTA Contains

• The active substance is darunavir. Each tablet contains 400 milligrams of darunavir ethanolate.
• The other components are: microcrystalline cellulose, anhydrous colloidal silica, crospovidone, magnesium stearate. The coating contains partially hydrolysed polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc, sunset yellow FCF (E110).

Description of the Appearance of PREZISTA and Package Contents
Orange, oval, film-coated tablet, marked TMC on one side and 400MG on the other.
60 tablets in a plastic bottle.
PREZISTA is also available as 75 milligram, 150 milligram, 600 milligram, and 800 milligram film-coated tablets, and as 100 milligram/millilitre oral suspension.

Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:

België/Belgique/Belgien
Janssen-Cilag NV
Tel/Tél: +32 14 64 94 11
[email protected]

България
„Джонсън & Джонсън България” ЕООД
Тел.: +359 2 489 94 00
[email protected]

Česká republika
Janssen-Cilag s.r.o.
Tel: +420 227 012 227
[email protected]

Danmark
Janssen-Cilag A/S
Tlf: +45 4594 8282
[email protected]

Deutschland
Janssen-Cilag GmbH
Tel: +49 2137 955 955
[email protected]

Eesti
UAB "JOHNSON & JOHNSON" Eesti filiaal
Tel: +372 617 7410
[email protected]

Ελλάδα
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε.
Tηλ: +30 210 80 90 000

España
Janssen-Cilag, S.A.
Tel: +34 91 722 81 00
[email protected]

France
Janssen-Cilag
Tél: 0 800 25 50 75 / +33 1 55 00 40 03
[email protected]

Hrvatska
Johnson & Johnson S.E. d.o.o.
Tel: +385 1 6610 700
[email protected]

Ireland
Janssen Sciences Ireland UC
Tel: +353 1 800 709 122

Ísland
Janssen-Cilag AB
c/o Vistor hf.
Sími: +354 535 7000
[email protected]

Italia
Janssen-Cilag SpA
Tel: 800.688.777 / +39 02 2510 1
[email protected]

Κύπρος
Βαρνάβας Χατζηπαναγής Λτδ
Τηλ: +357 22 207 700

Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]

Lietuva
UAB "JOHNSON & JOHNSON"
Tel: +370 5 278 68 88
[email protected]

Luxembourg/Luxemburg
Janssen-Cilag NV
Tél/Tel: +32 14 64 94 11
[email protected]

Magyarország
Janssen-Cilag Kft.
Tel.: +36 1 884 2858
[email protected]

Malta
AM MANGION LTD
Tel: +356 2397 6000

Nederland
Janssen-Cilag B.V.
Tel: +31 76 711 1111
[email protected]

Norge
Janssen-Cilag AS
Tlf: +47 24 12 65 00
[email protected]

Österreich
Janssen-Cilag Pharma GmbH
Tel: +43 1 610 300

Polska
Janssen-Cilag Polska Sp. z o.o.
Tel.: +48 22 237 60 00
[email protected]

Portugal
Janssen-Cilag Farmacêutica, Lda.
Tel: +351 214 368 600
[email protected]

România
Johnson & Johnson România SRL
Tel: +40 21 207 1800
[email protected]

Slovenija
Johnson & Johnson d.o.o.
Tel: +386 1 401 18 00
[email protected]

Slovenská republika
Johnson & Johnson, s.r.o.
Tel: +421 232 408 400

Sverige
Janssen-Cilag AB
Tfn: +46 8 626 50 00
[email protected]

Suomi/Finland
Janssen-Cilag Oy
Puh/Tel: +358 207 531 300
[email protected]

United Kingdom (Northern Ireland)
Janssen Sciences Ireland UC
Tel: +44 1 494 567 444

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

Package leaflet: Information for the user

PREZISTA 600 mg film-coated tablets

darunavir
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to others, even if they have the same symptoms as yours, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

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

1. What PREZISTA is and what it is used for

What PREZISTA is
PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used for the treatment of human immunodeficiency virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. PREZISTA works by reducing the amount of HIV in the body, improving the immune system, and reducing the risk of developing HIV-related illnesses.
What it is used for
PREZISTA is used to treat HIV infection in adults and children aged 3 years and older who weigh at least 15 kg (kilograms) and who have previously taken other antiretroviral medicines.
PREZISTA must be taken in combination with a low dose of ritonavir and other anti-HIV medicines. Your doctor will discuss with you the most appropriate combination of medicines for your treatment.

2. What you need to know before taking PREZISTA

Do not take PREZISTA

• If you are allergic to darunavir, or to any of the other ingredients of this medicine (listed in section 6), or to ritonavir.
• If you have severe liver problems (hepatic). Consult your doctor if you are unsure about the severity of your liver disease. Additional tests may be required.

Inform your doctor about all the medicines you are taking, including medicines taken orally, inhaled,
injected, or applied to the skin.
Do not take PREZISTA with any of the following medicines.
If you are currently taking one of these medicines, ask your doctor how to switch to an alternative medicine.

Do not co-administer PREZISTA with products containing St John's wort (Hypericum perforatum).
Warnings and precautions
Speak to your doctor, pharmacist or nurse before taking PREZISTA.
PREZISTA is not a cure for HIV infection.
People taking PREZISTA may still develop infections or other illnesses associated with HIV infection.
You must stay in regular contact with your doctor.
Patients taking PREZISTA may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
In patients taking PREZISTA and raltegravir (for HIV infection), rashes (generally mild or moderate) may occur more frequently than in patients taking each medicine separately.
Inform your doctor about your condition BEFORE and DURING treatment
Make sure you check the following points and inform your doctor if any of these apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to administer PREZISTA.
• Inform your doctor if you have diabetes. PREZISTA may increase blood sugar levels.
• Inform your doctor immediately if you notice any signs of infection (e.g. swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, inflammatory signs and symptoms from prior infections may arise soon after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, allowing the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition occurring when the immune system attacks healthy body tissue) may also occur after starting medications for the treatment of HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremor or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Several risk factors for developing this disease include duration of combined antiretroviral use, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint stiffness, pain and aches (particularly in the hip, knee and shoulders), and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly
PREZISTA has been administered to a limited number of patients aged 65 years and older.
If you belong to this age group, consult your doctor before taking PREZISTA.
Children
PREZISTA is not indicated for use in children under 3 years of age or weighing less than 15 kg (kilograms).
Other medicines and PREZISTA
Inform your doctor or pharmacist if you are taking or have recently taken any other medicines.
There are medicines that must not be co-administered with PREZISTA. These have been listed earlier under the heading “Do not co-administer PREZISTA with any of the following medicines”.
In most cases, PREZISTA can be co-administered with anti-HIV medicines belonging to another class [e.g. NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists and FIs (fusion inhibitors)]. PREZISTA in combination with ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines you may take.
The effects of PREZISTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking PREZISTA, and your doctor may require additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be altered.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
• Hormonal contraceptives containing oestrogens or hormone replacement therapy. PREZISTA may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
• Clarithromycin (an antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint and muscular conditions, and other inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may only be taken after evaluation by your doctor and under close monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (for the treatment of asthma).
• Artemether/lumefantrine (a combination of medicines for the treatment of malaria).
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer).
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (for pain treatment).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted, as the therapeutic effect and side effects of these medicines or of PREZISTA may be affected when co-administered. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable analgesic used during surgical procedures).
• Digoxin (for the treatment of certain heart conditions).
• Clarithromycin (an antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be taken after evaluation by your doctor.
• Rifabutin (for bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for high blood pressure in the lung circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for the treatment of depression and anxiety).
• Maraviroc (to treat HIV infection).
• Methadone (to treat opioid dependence).
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain).
• Colchicine (for the treatment of gout or familial Mediterranean fever).
• Bosentan (for the treatment of high blood pressure in the lung circulation).
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
PREZISTA with food and drink
See section 3 “How to take PREZISTA”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning a pregnancy.
Pregnant women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant women should not take PREZISTA with cobicistat.
Due to the possibility of adverse effects in infants, women should not breastfeed while receiving PREZISTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking PREZISTA.
PREZISTA tablets contain sunset yellow FCF (E110) which may cause allergic reactions.
PREZISTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take PREZISTA

Take this medicine exactly as directed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
Even if you feel better, do not stop taking PREZISTA and ritonavir without discussing it with your
doctor.
After starting treatment, do not change the dose, dosage form, or stop therapy without instructions from your doctor.

Dose for adults who have never taken antiretroviral medicines before (to be determined by the doctor)
Different doses of PREZISTA may be required that cannot be administered with these 600 mg tablets. Other formulations of PREZISTA are available.

Dose for adults who have previously taken antiretroviral medicines (to be determined by the doctor)
The doses are:

• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir, twice daily, or
• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 milligrams of ritonavir, once daily. The 400 mg and 800 mg PREZISTA tablets
  must only be used to construct the 800 mg once-daily regimen.
  Discuss with your doctor which dose is most appropriate.

Instructions for adults

• Always take PREZISTA with ritonavir. PREZISTA does not work adequately without ritonavir.
• In the morning, take 1 tablet of 600 milligrams of PREZISTA together with 100 milligrams of ritonavir.
• In the evening, take 1 tablet of 600 milligrams of PREZISTA together with 100 milligrams of ritonavir.
• Take PREZISTA with food. PREZISTA does not work adequately without food. The type of food consumed is not important.
• Swallow the tablets with a drink such as water or milk.
• PREZISTA 75 milligram, 150 milligram tablets, and 100 milligrams per millilitre oral suspension have been developed for use in children, but may be used in certain cases in adults as well.

Dose for children aged 3 years and older and weighing at least 15 kilograms who have not previously taken antiretroviral medicines (to be determined by the child's doctor)
The doctor will calculate the correct daily dose based on the child's body weight (see table below). This dose must not exceed the recommended adult dose, which is 800 milligrams of PREZISTA together with 100 milligrams of ritonavir once daily.
The doctor will inform you how many PREZISTA tablets and how much ritonavir (capsules, tablets, or solution) the child should take.

Dose for children aged 3 years and older and weighing at least 15 kg
(kilograms) who have previously taken antiretroviral medicines (this condition will be determined by the
child's doctor)
The doctor will calculate the appropriate dose based on the child's weight (see table below). The doctor
will decide whether a once-daily or twice-daily dosing regimen is appropriate for the child.
This dose must not exceed the recommended dose for adults, which is 600 milligrams of
PREZISTA together with 100 milligrams of ritonavir twice daily or 800 milligrams of
PREZISTA together with 100 milligrams of ritonavir once daily.
The doctor will inform you how many PREZISTA tablets and how much ritonavir (capsules, tablets, or
solution) the child should take.
Lower-dose tablets are available to achieve the appropriate dosing schedule.
PREZISTA oral suspension is also available. The doctor will decide whether PREZISTA tablets or
oral suspension are suitable for the child.
Dose twice daily

Once daily dose

Instructions for children

• The child must always take PREZISTA together with ritonavir. PREZISTA cannot work effectively without ritonavir.
• The child must take the appropriate doses of PREZISTA and ritonavir twice daily or once daily. If PREZISTA is prescribed twice daily, the child should take one dose in the morning and one dose in the evening. The doctor will determine which regimen is most appropriate for the child.
• The child must take PREZISTA with food. PREZISTA cannot work effectively without food. The type of food does not matter.
• The child should swallow the tablets with a drink such as water or milk.
• PREZISTA 75 milligram and 150 milligram tablets and 100 milligram/millilitre oral suspension have been developed for use in children weighing less than 40 kilograms but may also be used in other cases.

Removing the child-resistant cap

The plastic bottle comes with a child-resistant cap and must be opened as follows:

• Push the plastic cap down and turn it counterclockwise.
• Remove the unscrewed cap.

If you take more PREZISTA than you should
Contact your doctor, pharmacist, or nurse immediately.
If you forget to take PREZISTA
If you remember within 6 hours, take the missed dose immediately. Always take the tablets with ritonavir and food. If you remember after 6 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for the missed dose.
In case of vomiting after taking PREZISTA and ritonavir
If vomiting occurs within 4 hours of taking the medicine, take another dose of PREZISTA and ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, there is no need to take another dose of PREZISTA and ritonavir until the next scheduled dose.
Contact your doctor if you have any doubts about what to do if a dose is missed or if vomiting occurs.
Do not stop treatment with PREZISTA without first consulting your doctor
Anti-HIV medicines can make you feel better. Do not stop taking PREZISTA, even if you feel better. Consult your doctor first.
If you have any questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV therapy, weight gain and increased levels of lipids and glucose in the blood may occur.
This is partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to the HIV medications themselves.
Your doctor will monitor these changes.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Tell your doctor if you develop any of the following side effects

Liver problems have been reported, which occasionally can be serious. Your doctor will need to perform blood tests before starting PREZISTA.
If you have chronic hepatitis B or C, your doctor must check your blood tests more frequently, as you have a higher risk of developing liver problems.
Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark-coloured urine (like tea), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. These rashes are usually mild to moderate. A rash may also be a symptom of a more serious and rare condition. It is therefore important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage symptoms or whether PREZISTA should be discontinued.

Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).

Very common side effects (may affect more than 1 in 10 people)

• Diarrhoea

Common side effects (may affect up to 1 in 10 people)

• Vomiting, nausea, abdominal pain or bloating, dyspepsia (indigestion), flatulence
• Headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in hands or feet, loss of strength, difficulty falling asleep

Uncommon side effects (may affect up to 1 in 100 people)

• Chest pain, changes in electrocardiogram, rapid heartbeat
• Decreased or abnormal skin sensation, tingling sensation, attention disorders, memory loss, difficulty with balance
• Difficulty breathing, cough, nosebleeds, throat irritation
• Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• Kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• Hives, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• Muscle pain, muscle cramps or weakness, pain in extremities, osteoporosis
• Slowed thyroid function. This can be detected by blood test.
• High blood pressure, hot flushes
• Red or dry eyes
• Fever, leg swelling due to fluid accumulation, malaise, chills, unusual sensations, irritability, pain
• Symptoms of infection, herpes simplex
• Erectile dysfunction (problems with erection), breast enlargement
• Sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

• A reaction called DRESS [a severe rash which may be accompanied by fever, fatigue, facial or lymph node swelling, increased eosinophils (a type of white blood cell), effects on the liver, kidneys or lungs]
• Heart attack, slow heartbeat, palpitations
• Vision disorders
• Chills, feeling unwell
• A feeling of confusion or disorientation, altered mood, restlessness
• Fainting, seizures, change or loss of taste
• Mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• Runny nose
• Skin lesions, dry skin
• Stiffness of muscles or joints, joint pain with or without inflammation
• Changes in certain blood or urine test values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• Deposition of darunavir crystals in the kidney leading to kidney disease.

Some side effects are typical of anti-HIV medicines belonging to the same class as PREZISTA.
These include:

• Muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, please inform your doctor, pharmacist or nurse.
You can also report side effects directly via the reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store PREZISTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to
dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What PREZISTA contains

• The active substance is darunavir. Each tablet contains 600 milligrams of darunavir ethanolate.
• The other components are: microcrystalline cellulose, anhydrous colloidal silica, crospovidone, magnesium stearate. The coating contains partially hydrolyzed polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc, sunset yellow FCF (E110).

Description of the appearance of PREZISTA and contents of the pack
Orange, film-coated oval tablet, marked "TMC" on one side and "600MG" on the other.
60 tablets in a plastic bottle.
PREZISTA is also available as film-coated tablets of 75 milligrams,
150 milligrams, 400 milligrams, and 800 milligrams, and as an oral suspension of 100 milligrams/millilitre.

Marketing Authorization Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: +353 1 800 709 122 Tel: +386 1 401 18 00
[email protected]

Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]

Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]

Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

Latvija United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 Tel: +44 1 494 567 444
[email protected]

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

Package leaflet: Information for the user

PREZISTA 800 mg film-coated tablets

darunavir
Please read this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What PREZISTA is and what it is used for

What PREZISTA is
PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used for the treatment of human immunodeficiency virus (HIV) infection. It belongs to a group of medicines called protease inhibitors. PREZISTA works by reducing the amount of HIV in the body, improving the immune system, and reducing the risk of developing diseases associated with HIV infection.

What it is used for
PREZISTA 800 milligram tablets are used to treat HIV infection in adults and children (aged 3 years or older, and weighing at least 40 kilograms) who

• have not previously used other antiretroviral medicines, or
• in certain patients who have previously used antiretroviral medicines (your doctor will determine to whom it should be given).

PREZISTA must be taken in combination with cobicistat or a low dose of ritonavir, and with other anti-HIV medicines. Your doctor will discuss with you the most appropriate combination of medicines for your treatment.

2. What you need to know before taking PREZISTA

Do not take PREZISTA

• If you are allergic to darunavir, to any of the other ingredients of this medicine (listed in section 6), or to cobicistat or ritonavir.
• If you have severe liver problems. Ask your doctor for advice if you are unsure about the severity of your liver disease. Additional tests may be required.

Inform your doctor about all the medicines you are taking, including medicines taken orally, inhaled,
administered by injection, or applied to the skin.
Do not take PREZISTA with any of the following medicines
If you are currently taking one of these medicines, ask your doctor how to switch to another medicine.

Do not co-administer PREZISTA with products containing St. John's Wort (Hypericum perforatum).
Warnings and precautions
Consult your doctor, pharmacist, or nurse before taking PREZISTA.
PREZISTA is not a cure for HIV infection.
People taking PREZISTA may still develop infections or other diseases associated with HIV infection. Regular follow-up with your doctor is necessary.
Patients taking PREZISTA may develop a skin rash. Rarely, the rash may become severe or potentially life-threatening. Contact your doctor whenever you develop a skin rash.
In patients taking PREZISTA and raltegravir (for HIV infection), rashes (generally mild or moderate) may occur more frequently than in patients taking each medicine separately.
Inform your doctor about your medical condition BEFORE and DURING treatment
Please check the following points and inform your doctor if any of them apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe PREZISTA.

• Inform your doctor if you have diabetes. PREZISTA may increase blood sugar levels.

• Inform your doctor immediately if you notice any signs of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of opportunistic infections, inflammatory signs and symptoms from previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that may have been present without obvious symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting medications for HIV infection. Autoimmune disorders may occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.

• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.

• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).

• Inform your doctor if you experience any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Several risk factors for developing this condition include long-term use of combination antiretrovirals, corticosteroid use, alcohol consumption, severe immunosuppression, and high body mass index. Signs of osteonecrosis include joint swelling, pain, and stiffness (especially in the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Elderly patients
PREZISTA has been administered to a limited number of patients aged 65 years or older.
If you belong to this age group, consult your doctor before taking PREZISTA.
Children and adolescents
PREZISTA 800 milligram tablets must not be used in children under 3 years of age or weighing less than 40 kilograms.
Other medicines and PREZISTA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are medicines that must not be co-administered with PREZISTA. These have been listed previously under the heading “Do not co-administer PREZISTA with any of the following medicines”.
In most cases, PREZISTA can be co-administered with anti-HIV medicines belonging to another class [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA in combination with cobicistat or ritonavir has not been studied with all PIs (protease inhibitors) and must not be used with other HIV PIs. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you can take.
The effects of PREZISTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking PREZISTA, and your doctor may require additional blood tests. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be altered.
• Apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), because both the therapeutic effect and side effects may be altered.
• Hormonal contraceptives containing estrogens or hormone replacement therapy. PREZISTA may reduce their effectiveness. When hormonal therapy is used for contraception, use of alternative contraceptive methods other than hormonal therapy is recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most suitable for you.
• Clarithromycin (an antibiotic).
• Cyclosporine, everolimus, tacrolimus, sirolimus (to reduce immune system activity), as the therapeutic effect or side effects of these medicines may be increased.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle disorders, and other inflammatory conditions. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. If alternative treatments cannot be used, these medicines may be taken only after evaluation by your doctor and under close medical monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone (to treat opioid dependence).
• Salmeterol (to treat asthma).
• 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 for treating a heart or lung condition called pulmonary arterial hypertension).
• Glecaprevir/pibrentasvir (to treat hepatitis C infection).
• Fentanyl, oxycodone, tramadol (to treat pain).
• Fesoterodine, solifenacin (to treat urological disorders).

Your doctor may require additional blood tests and the dosage of other medicines may be adjusted, as the therapeutic effect and side effects of these medicines or of PREZISTA may be affected when co-administered. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting).
• Alfentanil (a potent, short-acting injectable painkiller used during surgery).
• Digoxin (to treat certain heart conditions).
• Clarithromycin (an antibiotic).
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may be taken only after evaluation by your doctor.
• Rifabutin (to treat bacterial infections).
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or for 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 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, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedatives).
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).
• Metformin (to treat type 2 diabetes).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.
PREZISTA with food and drinks
See section 3 “How to take PREZISTA”.
Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant or planning to become pregnant.
Pregnant women should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant women should not take PREZISTA with cobicistat.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving PREZISTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking PREZISTA.
PREZISTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take PREZISTA

Take this medicine exactly as prescribed by your doctor or pharmacist. If you
have any doubts, consult your doctor or pharmacist.
Even if you feel better, do not stop taking PREZISTA and cobicistat or ritonavir without
speaking to your doctor.
Once therapy has been started, the dose or dosage form should not be changed, nor should
treatment be stopped, without instructions from your doctor.
The 800 milligram PREZISTA tablets are intended for once-daily use only.

Dose for adults who have not previously taken antiretroviral medicines (your doctor
will assess this)
The usual dose of PREZISTA is 800 milligrams (2 tablets containing 400 milligrams of
PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) once daily.
You must take PREZISTA every day and always together with 150 milligrams of cobicistat or
100 milligrams of ritonavir and with food. PREZISTA cannot work optimally without cobicistat or
ritonavir and food. You must eat a meal or snack within 30 minutes before taking
PREZISTA and cobicistat or ritonavir. The type of food does not matter. Even if you feel better, do not
stop taking PREZISTA and cobicistat or ritonavir before speaking with your doctor.

Instructions for adults

• Take one 800 milligram tablet at the same time each day
• Take PREZISTA always with 150 milligrams of cobicistat or 100 milligrams of ritonavir
• Take PREZISTA with food
• Swallow the tablet with a drink such as water or milk
• Take any other HIV medicines used in combination with PREZISTA and cobicistat or ritonavir as directed by your doctor
• PREZISTA 100 milligrams per millilitre oral suspension was developed for use in children, but may be used in certain cases in adults as well.

Adults who have previously taken antiretrovirals (your doctor will assess this)
The dose is:

• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 150 milligrams of cobicistat or 100 milligrams of ritonavir once daily, or
• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily

Discuss with your doctor which dose is most appropriate.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (your child’s doctor will determine this condition)

• The usual dose of PREZISTA is 800 milligrams once daily (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 mg of ritonavir or 150 milligrams of cobicistat once daily.

Dose for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (your child’s doctor will determine this condition)
The dose is either:

• 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) together with 100 milligrams of ritonavir or 150 milligrams of cobicistat once daily, or
• 600 milligrams of PREZISTA together with 100 milligrams of ritonavir twice daily.

Discuss with your doctor which dose is most appropriate.

Instructions for children aged 3 years and older taking ritonavir and aged 12 years and older taking cobicistat, weighing more than 40 kilograms

• Take 800 milligrams of PREZISTA (2 tablets containing 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) at the same time each day.
• Take PREZISTA always together with 100 milligrams of ritonavir or 150 milligrams of cobicistat.
• Take PREZISTA with food.
• Swallow the tablets with a drink such as water or milk.
• Take any other HIV medicines used in combination with PREZISTA and ritonavir or cobicistat as recommended by your doctor.

Removing the child-resistant cap

The plastic bottle is equipped with a child-resistant cap and must be opened as follows:

• Press down on the plastic cap and turn it counterclockwise.
• Remove the loosened cap.

If you take more PREZISTA than you should
Inform your doctor, pharmacist, or nurse immediately.

If you forget to take PREZISTA
If you remember within 12 hours, take the missed dose immediately. Always take the tablets together with cobicistat or ritonavir and with food. If you remember after 12 hours, skip the missed dose and take the next dose at your usual time. Do not take a double dose to make up for the missed dose.

If you vomit after taking PREZISTA and cobicistat or ritonavir
If you vomit within 4 hours of taking the medicine, take another dose of PREZISTA and cobicistat or ritonavir with food as soon as possible. If vomiting occurs more than 4 hours after taking the medicine, you do not need to take another dose of PREZISTA and cobicistat or ritonavir until the next scheduled dose.
Contact your doctor if you have any doubts about what to do if you miss a dose or vomit.

Do not stop treatment with PREZISTA without first talking to your doctor
Anti-HIV medicines can make you feel better. Do not stop taking PREZISTA, even if you feel better. Talk to your doctor first.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

During HIV therapy, weight gain and increased levels of lipids and glucose in the blood may occur.
This is partly related to improved health status and lifestyle, and in the case of blood lipids, sometimes to the
HIV medicines themselves. Your doctor will monitor these changes.
Like all medicines, this medicine can cause side effects, although not everyone experiences them.
Tell your doctor if you develop any of the following side effects
Liver problems have been reported, which may occasionally be serious. Your doctor will need to perform blood
tests before starting PREZISTA. If you have chronic hepatitis B or C, your doctor must check your blood tests
more frequently, as you have a higher risk of developing liver problems. Talk to your doctor about the signs and
symptoms of liver problems. These may include yellowing of the skin or whites of the eyes, dark urine (tea-
coloured), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort
on the right side under the ribs.
Skin rashes (more frequent when used in combination with raltegravir), itching. These rashes are usually mild
to moderate in severity. A rash may also be a symptom of a rare but more serious condition. It is therefore
important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to
manage the symptoms or whether PREZISTA should be discontinued.
Other serious side effects included diabetes (common) and inflammation of the pancreas (uncommon).
Very common side effects (may affect more than 1 in 10 people)

• diarrhoea

Common side effects (may affect up to 1 in 10 people)

• vomiting, nausea, abdominal pain or bloating, dyspepsia (digestive difficulties), flatulence
• headache, fatigue, dizziness, drowsiness, numbness, tingling or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon side effects (may affect up to 1 in 100 people)

• chest pain, changes in electrocardiogram, rapid heartbeat
• decreased or abnormal skin sensitivity, tingling sensation, attention disturbances, memory loss, difficulty with balance
• difficulty breathing, cough, nosebleeds, throat irritation
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort, constipation, belching
• kidney failure, kidney stones, difficulty urinating, frequent or excessive urination, sometimes at night
• urticaria, severe swelling of the skin and other tissues (especially lips and eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, nail pigmentation
• muscle pain, muscle cramps or weakness, pain in the extremities, osteoporosis
• slowed thyroid function. This can be detected by a blood test.
• high blood pressure, hot flushes
• red or dry eyes
• fever, swelling of the legs due to fluid retention, malaise, chills, unusual sensations, irritability, pain
• symptoms of infection, herpes simplex
• erectile dysfunction (problems with erection), breast enlargement
• sleep disorders, drowsiness, depression, anxiety, altered dreams, decreased sexual desire

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

• a reaction called DRESS [a severe rash which may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell), effects on the liver, kidneys or lungs]
• heart attack, slow heartbeat, palpitations
• vision disorders
• chills, feeling unwell
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, seizures, change or loss of taste
• mouth ulcers, vomiting blood, inflammation of the lips, dry lips, coated tongue
• runny nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in certain blood or urine laboratory values. These may be seen in blood and/or urine tests. Your doctor will explain these results to you. Examples include: increase in certain white blood cells
• deposition of darunavir crystals in the kidney, leading to kidney disease.

Some side effects are typical of anti-HIV medicines in the same class as PREZISTA.
These are:

• muscle pain, fragility or weakness. In rare cases, these muscle disorders have been severe.

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or
nurse. You can also report side effects directly via the reporting system listed in Annex V. By reporting side
effects, you can help provide more information on the safety of this medicine.

5. How to store PREZISTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What PREZISTA contains

• The active substance is darunavir. Each tablet contains 800 milligrams of darunavir ethanolate.
• The other components are: microcrystalline cellulose, anhydrous colloidal silica, crospovidone, magnesium stearate, hypromellose. The coating contains partially hydrolyzed polyvinyl alcohol, macrogol 3350, titanium dioxide (E171), talc, iron oxide red (E172).

Description of the appearance of PREZISTA and contents of the pack
Dark red oval film-coated tablet, marked with T on one side and 800 on the other.
30 tablets in a plastic bottle. PREZISTA 800 milligram tablets are available in packs containing one bottle or three bottles per box.
Not all pack sizes may be marketed.
PREZISTA is also available as 75 milligram, 150 milligram, 400 milligram, and 600 milligram film-coated tablets, and as 100 milligram/millilitre oral suspension.

Marketing Authorization Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium

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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]

България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]

Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]

Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]

Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]

Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]

Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.Β.Ε. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300

España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]

France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]

Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]

Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: +353 1 800 709 122 Tel: +386 1 401 18 00
[email protected]

Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]

Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]

Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]

Latvija United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 Tel: +44 1 494 567 444
[email protected]

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