Prezista 100 mg/ml oral suspension

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

PREZISTA 100 mg/ml oral suspension

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 could harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if these are effects 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 will improve and the risk of developing HIV-related illnesses will decrease.

What is it used for?

PREZISTA is used to treat HIV-infected adults as well as HIV-infected children aged 3 years and older who weigh at least 15 kilograms (see How to take PREZISTA).

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), 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. 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 ever 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 anti-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 upward 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 (e.g., used to treat certain infections).
• Inform your doctor if you notice any bone or muscle problems. Some patients using combination antiretroviral therapy may develop a bone condition called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). Among many risk factors for this condition are duration of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, and higher body mass index. Signs of osteonecrosis include pain, discomfort, and stiffness in joints (especially 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

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

Taking PREZISTA with other medicines

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

Some medicines must not be 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 anti-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 has not been tested with cobicistat or ritonavir in combination 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 disorders), 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 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), 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 treatment of certain heart disorders)
• 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 high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
• Maraviroc (to treat HIV infection)
• Methadone (to treat narcotic dependence)
• Carbamazepine, clonazepam (to prevent epileptic seizures or to treat certain types of neuropathic pain)
• Colchicine (to treat gout or familial Mediterranean fever)
• Bosentan (to treat high blood pressure in the pulmonary circulation)
• Buspirone, 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 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 should not take PREZISTA with ritonavir unless specifically instructed by their doctor. Pregnant or breastfeeding women should not take PREZISTA with cobicistat.

HIV-infected women are advised not to breastfeed their infants due to the risk of transmitting HIV through breast milk, as well as the 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 oral suspension contains sodium methyl parahydroxybenzoate. This ingredient may cause allergic reactions (sometimes delayed).

3. How to take PREZISTA

Follow exactly the dosing instructions 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.

Once treatment has started, the dose or dosing regimen must not be changed or treatment interrupted without consulting your doctor.

Dosage for children aged 3 years and older, weighing at least 15 kilograms, who have not previously taken antiretroviral medicines (to be determined by your child's doctor)

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

Your doctor will inform you of the amount of PREZISTA oral suspension and the amount of ritonavir (capsules, tablets, or solution) your child should take.

The child must take PREZISTA every day and always in combination with 100 milligrams of ritonavir and food. PREZISTA cannot work properly without ritonavir and food. The child must eat any type of food 30 minutes before taking PREZISTA and ritonavir. The type of food does not matter.

Dosage for children aged 3 years and older, weighing at least 15 kilograms, who have previously taken antiretroviral medicines (to be determined by your child's doctor)

The doctor will determine the correct 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 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.

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

Twice-daily dosing

Instructions for children

• The child must always take PREZISTA together with ritonavir. PREZISTA cannot work properly without ritonavir.
• The child must take the appropriate dose of PREZISTA and ritonavir either twice daily or once daily. If PREZISTA is prescribed twice daily, the child must take one dose in the morning and one in the evening. Your child's doctor will determine the appropriate dosing schedule for your child.
• The child must take PREZISTA with food. PREZISTA cannot work properly without food. The type of food does not matter.

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

The usual dose of PREZISTA is 800 milligrams 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 cannot work properly without cobicistat or ritonavir and food. You must eat food 30 minutes before taking PREZISTA and cobicistat or ritonavir. The type of food is not relevant. Even if you feel better, do not stop taking PREZISTA, cobicistat, or ritonavir without first consulting your doctor.

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

The dose 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.

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

Instructions for adults

• Take PREZISTA always together with cobicistat or ritonavir. PREZISTA does not work properly without cobicistat or ritonavir.

• Take PREZISTA with food. PREZISTA does not work properly without food. The type of food is not important.

Instructions for use

Use the dosing syringe provided in the package to accurately measure your dose:

1. Shake the bottle well before each use.
2. Open the PREZISTA oral suspension bottle by pressing down on the cap and turning it counterclockwise at the same time.

1. Pull the plunger up to the top of the line on the syringe tube indicating the dose prescribed by your doctor.
2. Take the dose of PREZISTA. Place the tip of the oral dosing syringe into the mouth. Press the syringe plunger to deliver the dose into the mouth, then swallow.
3. Close the bottle with the cap after use, and store the PREZISTA oral suspension as instructed below in section 5.
4. Remove the plunger from the syringe tube, rinse with water, and allow it to air dry after each use.
5. After air drying, return the oral dosing syringe to its original position and keep it with the PREZISTA bottle.

Do not use the dosing syringe for other medications.

If you take more PREZISTA than you should

Inform your doctor, pharmacist, or nurse immediately.

If you forget to take PREZISTA

If you take PREZISTA twice daily and remember within 6 hours, take the oral suspension immediately. Always take it with ritonavir and food. If you remember after 6 hours, skip that dose and take the next one as usual. Do not take a double dose to make up for missed doses.

If you take PREZISTA once daily and remember within 12 hours, take the oral suspension immediately. Always take it with cobicistat or ritonavir and food. If you remember after 12 hours, skip that dose and take the next one as usual. Do not take a double dose to make up for missed doses.

Do not stop taking PREZISTA without first talking to your doctor

HIV medicines may 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 will experience them.

Inform your doctor if you develop any of the following adverse 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 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 speak with your doctor if you develop a rash. Your doctor will advise you on how to manage the symptoms or whether to discontinue PREZISTA.

Other serious adverse effects include 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 bloating, 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
• Kidney failure, kidney stones, difficulty urinating, excessive or frequent urination, sometimes at night
• Hives, 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 swelling, 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. Rarely, these muscle disorders may be severe.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if they are possible adverse effects not listed in this leaflet. You may also report them directly through the national reporting system detailed 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 on the bottle, after EXP. The expiry date is the last day of the month indicated.

Do not store above 30°C.

Do not refrigerate or freeze. Avoid exposure to excessive heat.

Keep in the original container.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicines and their containers. This will help protect the environment.

6. Contents of the pack and other information

Composition of PREZISTA

• The active substance is darunavir. Each millilitre contains 100 milligrams of darunavir (as ethanolate).

• The other components are hydroxypropylcellulose, microcrystalline cellulose and sodium carboxymethylcellulose, citric acid monohydrate, sucralose, strawberry flavour cream, flavour masker, sodium methylparahydroxybenzoate (E219), hydrochloric acid (for pH adjustment), purified water.

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

Nature of the product and contents of the pack

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

PREZISTA is also available as film-coated tablets containing 75 mg, 150 mg, 300 mg, 400 mg, 600 mg, and 800 mg.

Marketing Authorisation Holder

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

Manufacturer

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

For more information about this medicine, please 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 website of the European Medicines Agency: http://www.ema.europa.eu.