Prezista 400 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

PREZISTA 400 mg film-coated tablets

darunavir

Read all of this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the 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 adverse 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 is PREZISTA?

PREZISTA contains the active substance darunavir. PREZISTA is an antiretroviral medicine used to treat infection with the Human Immunodeficiency Virus (HIV). It belongs to a group of medicines called protease inhibitors. PREZISTA reduces the amount of HIV in your body. As a result, your immune system improves and the risk of developing HIV-related illnesses decreases.

What is it used for?

The PREZISTA 400 mg tablet is used to treat adults and children (from 3 years of age, weighing at least 40 kg) infected with HIV and who

• have not previously used antiretroviral medicines, or
• in certain patients who have previously used antiretroviral medicines (this will be determined by your doctor).

PREZISTA must be taken together with a low dose of cobicistat or ritonavir and other anti-HIV medicines. Your doctor will advise you on the most appropriate combination of medicines for you.

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. Ask your doctor if you are unsure about the severity of your liver disease. Additional tests may be needed.

Do not combine PREZISTA with any of the following medicines

If you are taking any of these drugs, consult your doctor to switch to another medicine.

Do not combine PREZISTA with products containing St. John’s wort (Hypericum perforatum).

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting PREZISTA.

PREZISTA does not cure HIV infection. While taking this medicine, you may still transmit HIV to others, although effective antiviral treatment reduces this risk. Ask your doctor about the necessary precautions to avoid infecting others.

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

People taking PREZISTA may develop a skin rash. It is uncommon for the rash to be severe or potentially life-threatening. Please consult your doctor if you develop a rash.

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

Inform your doctor about your condition BEFORE and DURING treatment

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

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

• Inform your doctor if you have diabetes. PREZISTA may cause an increase in 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 due to previous infections may appear shortly after starting HIV treatment.

These symptoms are believed to result from improved immune response, enabling the body to fight infections that were previously present without apparent symptoms.

• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you start taking medicines for your HIV infection. Autoimmune disorders may appear many months after starting treatment. If you notice any signs of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and moving up toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive appropriate treatment.
• Inform your doctor if you have haemophilia. PREZISTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Inform your doctor if you notice any bone or muscle problems. Some patients receiving combination antiretroviral therapy may develop a bone condition called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Risk factors for this condition include duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include joint pain, discomfort, and stiffness (especially in the hips, knees, and shoulders) and difficulty moving. If you notice any of these symptoms, please see your doctor.

Elderly population

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

Children and adolescents

The 400 mg PREZISTA tablet must not be used in children under 3 years of age or weighing less than 40 kg.

Taking PREZISTA with other medicines

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

Some medicines must not be combined with PREZISTA. The list can be found in the section “Do not combine PREZISTA with any of the following medicines.”

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

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

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

PREZISTA may also affect the effects of other medicines. 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 or adverse effects of these medicines may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin (to reduce blood clotting), as the therapeutic or adverse effects of these medicines may be altered; your doctor may perform blood tests.
• Hormonal contraceptives based on oestrogens and hormone replacement therapies. PREZISTA may reduce their effectiveness. For birth control, non-hormonal alternative contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to lower blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most suitable cholesterol-lowering treatment based on your individual circumstances.
• Clarithromycin (antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), as the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye, joint, and muscle conditions, and other inflammatory disorders. If alternatives cannot be used, their use should only occur after clinical evaluation and with close monitoring by your doctor for corticosteroid-related adverse effects.
• Buprenorphine/naloxone (medicines for opioid dependence treatment)
• Salmeterol (medicine for asthma treatment)
• Artemether/lumefantrine (a combination of medicines to treat malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (to treat cancer)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir, simeprevir (to treat hepatitis C infection)
• Fentanyl, oxycodone, tramadol (to treat pain)
• Fesoterodine, solifenacin (to treat urological disorders).

In certain cases, the dose of some medicines may need to be adjusted, as their therapeutic or adverse effects (or those of PREZISTA) may be affected when combined.

Inform your doctor if you are taking:

• Alfentanil (a potent, short-acting injectable analgesic used during surgical procedures)
• Digoxin (for the treatment of certain heart conditions)
• Clarithromycin (antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole may only be administered after medical evaluation.
• Rifabutin (for bacterial infections)
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or pulmonary hypertension)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
• Maraviroc (to treat HIV infection)
• Methadone (to treat narcotic dependence)
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine (to treat gout or familial Mediterranean fever)
• Bosentan (to treat high blood pressure in the pulmonary circulation)
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam when administered by injection, zolpidem (sedative agents)
• 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.

Taking PREZISTA with food and drink

See section 3 “How to take PREZISTA.”

Pregnancy and breastfeeding

Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant or breastfeeding mothers must not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant or breastfeeding mothers must not take PREZISTA with cobicistat.

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

Driving and using machines

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

PREZISTA tablets contain sunset yellow FCF (E110), which may cause allergic-type reactions.

3. How to take PREZISTA

Follow exactly the administration instructions for this medicine provided in this leaflet or those given by your doctor, pharmacist, or nurse. If in doubt, ask your doctor, pharmacist, or nurse.

Do not stop taking PREZISTA, nor cobicistat or ritonavir, without first consulting your doctor, even if you feel better.

After treatment has started, the dose or dosing regimen must not be changed or treatment interrupted without your doctor's instructions.

The 400-milligram PREZISTA tablets are used only to achieve the 800-milligram once-daily dosing regimen.

Dosage for adults who have not previously taken antiretroviral medicines (to be determined by your doctor)

The usual dose of PREZISTA is 800 milligrams (2 tablets of 400 milligrams of PREZISTA or 1 tablet containing 800 milligrams of PREZISTA) once daily.

You must take PREZISTA every day and always in combination with 150 milligrams of cobicistat or 100 milligrams of ritonavir and with food. PREZISTA does not work properly without cobicistat or ritonavir and food. You must eat a meal 30 minutes before taking PREZISTA and cobicistat or ritonavir. The type of food is not important.

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

Instructions for adults

• Take two 400-milligram tablets at once, once daily, every 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, which may be water or milk.

• Take the other HIV medicines used in combination with PREZISTA and cobicistat or ritonavir as your doctor has recommended.

• • The PREZISTA 100 milligrams per milliliter oral suspension has been developed for use in children, but in some cases may also be used in adults.

Dosage for adults who have previously taken antiretroviral medicines (to be determined by your doctor)

The dose is:

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

Or

• • 600 milligrams of PREZISTA (2 tablets containing 300 milligrams of PREZISTA or 1 tablet containing 600 milligrams of PREZISTA) together with 100 milligrams of ritonavir twice daily.

Please speak with your doctor about which dose is right for you.

Dosage for children aged 3 years and older, weighing more than 40 kilograms, who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

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

Dosage for children aged 3 years and older, weighing more than 40 kilograms, who have previously taken antiretroviral medicines (to be determined by your child's doctor)

The dose is:

• 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.

Or

• • 600 milligrams of PREZISTA (2 tablets containing 300 milligrams of PREZISTA or 1 tablet containing 600 milligrams of PREZISTA) together with 100 milligrams of ritonavir twice daily.

Please speak with your doctor about which dose is right for you.

Instructions for children aged 3 years and older, 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 once daily, every day.
• Take PREZISTA always together with 100 milligrams of ritonavir.
• Take PREZISTA with food.
• Swallow the tablets with a liquid such as water or milk.
• Take the other medicines used in combination with PREZISTA and ritonavir as directed by your doctor.

Removing the child-resistant 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 it within 12 hours , take the tablets immediately. Always take the dose with cobicistat or with ritonavir and with food. If you realize it after 12 hours , skip that dose and take the next one as usual. Do not take a double dose to make up for a missed dose.

Do not stop taking PREZISTA without first talking to your doctor

HIV medications can help you feel better. Even if you feel well, do not stop taking PREZISTA. Always consult your doctor first.

If you have any further questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible adverse effects

During HIV treatment, there may be an increase in weight and in blood glucose and lipid levels. This may be partly related to the recovery of health 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 adverse effects, although not everyone experiences them.

Tell your doctor if you develop any of the following adverse effects.

Cases of liver problems, which occasionally may be serious, have been reported. Your doctor will perform a blood test before you start treatment with PREZISTA. If you have a chronic infection caused by hepatitis B or C, your doctor will frequently check your blood tests, as 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 and whites of the eyes, darkening (tea-colored) of the urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under your ribs.

Skin rash (more frequent when used in combination with raltegravir), itching. Skin rash is usually mild to moderate. A skin rash may also be a symptom of a rare but serious condition. Therefore, it is important to talk to your doctor if you develop a rash. Your doctor will advise you on how to manage symptoms or whether to discontinue PREZISTA.

Other serious adverse effects included diabetes (frequent) and inflammation of the pancreas (uncommon).

Very common adverse effects (may affect more than 1 in 10 patients):

• Diarrhea

Common adverse effects (may affect up to 1 in 10 patients):

• Vomiting, nausea, abdominal pain or distension, upper abdominal pain (dyspepsia)
• Flatulence
• Headache, fatigue, dizziness, drowsiness, numbness sensation
• Numbness, tingling, or pain in the hands or feet, loss of strength, difficulty falling asleep

Uncommon adverse effects (may affect up to 1 in 100 patients):

• Chest pain, changes in electrocardiogram, rapid heartbeat
• Decreased or abnormal skin sensitivity, tingling, attention disorder, memory loss, difficulty maintaining balance
• Breathing difficulty, cough, nosebleed, throat irritation
• Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort
• Constipation, belching
• Renal failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• Urticaria, severe swelling of the skin and other tissues (especially lips or eyes), eczema
• Excessive sweating, night sweats, alopecia, acne, scaly skin, nail discoloration
• Muscle pain, muscle cramps or weakness, limb pain, osteoporosis
• Reduced thyroid gland function. This can be seen in a blood test.
• Hypertension (increased blood pressure), flushing
• Red or dry eyes
• Fever, swelling of the lower limbs due to fluid retention, malaise
• Irritability, pain
• Symptoms of infection, herpes simplex
• Erectile dysfunction, breast enlargement
• Difficulty falling asleep, drowsiness, depression, anxiety, abnormal dreams
• Decreased sex drive

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

• A reaction called DRESS [severe rash, which may be accompanied by fever, fatigue, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), liver, kidney, or lung damage]
• Myocardial infarction, slow heartbeat, palpitations
• Visual disturbance
• Chills, unusual sensation
• A feeling of confusion or disorientation, altered mood, agitation
• Fainting, epileptic seizure, changes or loss of taste
• Mouth ulcers, vomiting blood, lip inflammation, dry lips, coated tongue
• Nasal discharge
• Skin lesions, dry skin
• Muscle or joint stiffness, joint pain with or without inflammation
• Changes in certain blood cell or biochemical values. These changes can be seen in blood and/or urine tests. Your doctor will explain them to you. For example: increase in certain white blood cells.

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

• Muscle pain, tenderness, or weakness. In rare cases, these muscle disorders may be serious.

Reporting of adverse effects

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of 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, following EXP. The expiry date is the last day of the month indicated.

PREZISTA does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging no longer required. This will help protect the environment.

6. Contents of the container and other information

Composition of PREZISTA

• The active substance is darunavir. Each tablet contains 400 milligrams of darunavir (as ethanolate).
• • The other components are microcrystalline cellulose, colloidal anhydrous silica, crospovidone, and magnesium stearate. The coating contains poly(vinyl alcohol) – partially hydrolysed, macrogol 3350, titanium dioxide (E171), talc, and sunset yellow FCF (E110).
• • This medicine contains less than 1 mmol of sodium (23 mg) per dose unit; this is essentially "sodium-free".

Appearance of the product and contents of the container

Film-coated tablet, oval-shaped, light orange in colour, marked with TMC on one side and 400MG on the other side.

60 tablets in a plastic bottle.

PREZISTA is also available as film-coated tablets of 75 milligrams, 150 milligrams, 300 milligrams, 600 milligrams, and 800 milligrams, and as oral suspension of 100 milligrams per millilitre.

Marketing Authorisation Holder

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

Manufacturer

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

For more information about this medicine, you may contact the local representative of the Marketing Authorisation Holder:

Date of the most recent review of this leaflet: {MM/YYYY}.

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