Prezista 800 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

PREZISTA 800 mg film-coated tablets

darunavir

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

• Keep this leaflet, as 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 may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if such effects are not listed in this leaflet. See section 4.

Leaflet contents

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 is PREZISTA?

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

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

PREZISTA must be taken together with a low dose of cobicistat or ritonavir and other 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 required.

Do not combine PREZISTA with any of the following medicines

If you are taking any of these drugs, consult your doctor to switch to an alternative 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. Consult your doctor about which precautions are necessary to avoid infecting others.

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

People taking PREZISTA may develop a skin rash. It is 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 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 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, allowing 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 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 upward 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 disorder 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 discuss with your doctor whether you can use PREZISTA.

Children and adolescents

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

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 from other classes [e.g., NRTIs (nucleoside reverse transcriptase inhibitors), NNRTIs (non-nucleoside reverse transcriptase inhibitors), CCR5 antagonists, and FIs (fusion inhibitors)]. PREZISTA has not been tested with cobicistat or ritonavir in combination with all protease inhibitors (PIs) and must not be used with other 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 carefully follow their instructions 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), because the therapeutic or adverse effects of these medicines may be increased.
• Apixaban, edoxaban, rivaroxaban, warfarin (to reduce blood clotting), because the therapeutic or adverse effects of these medicines may be altered; your doctor may perform blood tests.
• Hormonal contraceptives based on oestrogens and hormone replacement therapies. PREZISTA may reduce their effectiveness. For birth control, non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. PREZISTA may increase the risk of elevated potassium levels due to drospirenone.
• Atorvastatin, pravastatin, rosuvastatin (to reduce blood cholesterol). There may be an increased risk of muscle damage. Your doctor will determine the most appropriate cholesterol-lowering treatment based on your individual circumstances.
• Clarithromycin (antibiotic)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), because the therapeutic or adverse effects of these medicines may be increased. Your doctor may perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel 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 for treating malaria)
• Dasatinib, everolimus, irinotecan, nilotinib, vinblastine, vincristine (for treating cancer)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or for treating a heart and lung condition called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir, simeprevir (for treating hepatitis C infection)
• Fentanyl, oxycodone, tramadol (for treating pain)
• Fesoterodine, solifenacin (for treating 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 in surgical procedures)
• Digoxin (for treating certain heart conditions)
• Clarithromycin (antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (for treating fungal infections). Voriconazole may only be administered after medical evaluation.
• Rifabutin (for bacterial infections)
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for treating depression and anxiety)
• Maraviroc (for treating HIV infection)
• Methadone (for treating narcotic dependence)
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine (for treating gout or familial Mediterranean fever)
• Bosentan (for treating high blood pressure in the pulmonary circulation)
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, midazolam administered by injection, zolpidem (sedative agents)
• Perphenazine, risperidone, thioridazine (for treating psychiatric conditions)
• Metformin (for treating 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 drinks

See section 3 “How to take PREZISTA.”

Pregnancy and breastfeeding

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

It is recommended that HIV-infected women do not breastfeed their infants, due to the risk of HIV transmission through breast milk and the unknown effects of the medicine on infants.

Driving and using machines

Do not operate tools or 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, cobicistat, or ritonavir without first consulting your doctor, even if you feel better.

After starting treatment, do not change the dose or dosing schedule or interrupt treatment without your doctor's instructions.

The 800 mg PREZISTA tablets are only to be used for the 800 mg once-daily regimen.

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

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

You must take PREZISTA every day and always in combination with 150 mg of cobicistat or 100 mg of ritonavir and with food. PREZISTA does not work properly without cobicistat or ritonavir and food. You should 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 one 800 mg tablet at the same time each day.

• Take PREZISTA always together with 150 mg of cobicistat or 100 mg of ritonavir.

• Take PREZISTA with food.

• Swallow the tablet with a drink, which may be water or milk.

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

• • The oral suspension of PREZISTA 100 mg per millilitre 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 mg of PREZISTA (2 tablets containing 400 mg of PREZISTA or 1 tablet containing 800 mg of PREZISTA) together with 150 mg of cobicistat or 100 mg of ritonavir once daily.

Or

• • 600 mg of PREZISTA (2 tablets containing 300 mg of PREZISTA or 1 tablet containing 600 mg of PREZISTA) together with 100 mg 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 kg, who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

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

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

The dose is:

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

Or

• • 600 mg of PREZISTA (2 tablets containing 300 mg of PREZISTA or 1 tablet containing 600 mg of PREZISTA) together with 100 mg 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 kg

• Take 800 mg of PREZISTA (2 tablets containing 400 mg of PREZISTA or 1 tablet containing 800 mg of PREZISTA) at the same time each day.
• Take PREZISTA always together with 100 mg 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 remember within 12 hours , take the tablets immediately. Always take the dose with cobicistat or with ritonavir and with food. If you remember after 12 hours , skip that dose and take the next one at your usual time. 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 medicines can make you feel better. Even if you feel better, do not stop taking PREZISTA. Talk to your doctor first.

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

4. Possible side 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 side effects, although not everybody gets them.

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

Cases of liver problems, occasionally severe, 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 check your blood tests frequently, as there is 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, dark (tea-colored) urine, 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. 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 the symptoms or whether you should stop taking PREZISTA.

Other serious side effects included diabetes (frequent) 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, upper abdominal pain (dyspepsia)
• Flatulence
• Headache, fatigue, dizziness, somnolence, feeling of numbness
• 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 sensation, tingling, attention disorder, memory loss, difficulty maintaining balance
• Breathing difficulty, cough, nosebleed, sore throat
• Inflammation of the stomach or mouth, heartburn, retching, dry mouth, abdominal discomfort
• Constipation, belching
• Kidney 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 discolouration
• 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, somnolence, depression, anxiety, abnormal 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, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), damage to the liver, kidney or lung]
• 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 side 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 severe.

Reporting of side effects

If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the national reporting system listed in Appendix V. By reporting side 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, after EXP. The expiry date refers to 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 pack and other information

Composition of PREZISTA

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

Film-coated tablet, oval-shaped, dark red in colour, marked with T on one side and 800 on the other side. 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 film-coated tablets of 75 milligrams, 150 milligrams, 300 milligrams, 400 milligrams and 600 milligrams, and as an 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

Further information on this medicine is available upon request to the local representative of the Marketing Authorisation Holder:

Date of the latest revision of this leaflet: {MM/YYYY}.

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