Prezista 150 mg film-coated tablets – patient leaflet, side effects, dosage

1What PREZISTA is and what it is used for

■■ What is PREZISTA?

PREZISTA contains the active substance darunavir.

PREZISTA is an antiretroviral medicine used in 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 your body. This will improve

your immune system and reduces the risk of

developing illnesses linked to HIV infection.

■■ What it is used for?

PREZISTA is used to treat adults and children of 3 years of age and above, and at least 15 kilogram body weight who are infected by HIV and who have already used 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 which combination of medicines is best for you.

2What you need to know before you take PREZISTA

■■ Do not take PREZISTA

• if you are allergic to darunavir or any of the other

  ingredients of this medicine (listed in section 6)

  or to ritonavir.

  • if you have severe liver problems. Ask your doctor if you are unsure about the severity of your liver disease. Some additional tests might be necessary.

■■ Do not combine PREZISTA with any of the following medicines

If you are taking any of these, ask your doctor about switching to another medicine.

Medicine Purpose of the medicine

Avanafil to treat erectile dysfunction

Astemizole or terfenadine to treat allergy symptoms

Triazolam and oral (taken by mouth) midazolam to help you sleep and/or relieve anxiety

Cisapride to treat some stomach conditions

Colchicine (if you have kidney and/or liver problems) to treat gout or familial Mediterranean fever

Lurasidone, pimozide, quetiapine or sertindole to treat psychiatric conditions

Ergot alkaloids like ergotamine, dihydroergotamine,

ergometrine and methylergonovine

to treat migraine headaches

Amiodarone, bepridil, dronedarone, ivabradine,

quinidine, ranolazine

to treat certain heart disorders e.g. abnormal heart beat

Lovastatin, simvastatin and lomitapide to lower cholesterol levels

Rifampicin to treat some infections such as tuberculosis

The combination product lopinavir/ritonavir this anti‑HIV medicine belongs to the same class as PREZISTA

Elbasvir/grazoprevir to treat hepatitis C infection

Alfuzosin to treat enlarged prostate

Sildenafil to treat high blood pressure in the pulmonary circulation

Dabigatran, ticagrelor to help stop the clumping of platelets in the treatment of patients with a history of a heart attack

Naloxegol to treat opioid induced constipation

Dapoxetine to treat premature ejaculation

Domperidone to treat nausea and vomiting

Do not combine PREZISTA with products that contain 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. You can

still pass on HIV when taking this medicine,

although the risk is lowered by effective

antiretroviral therapy. Discuss with your physician

the precautions needed to avoid infecting other

people.

People taking PREZISTA may still develop

infections or other illnesses associated with HIV

infection. You must keep in regular contact with

your doctor.

People taking PREZISTA may develop a skin rash.

Infrequently a rash may become severe or

potentially life‑threatening. Please contact your

doctor whenever you develop a rash.

In patients taking PREZISTA and raltegravir (for

HIV infection), rashes (generally mild or moderate)

may occur more frequently than in patients taking

either medicine separately.

■■ Tell your doctor about your situation

BEFORE and DURING your treatment

Make sure that you check the following points and

tell your doctor if any of these apply to you.

• Tell your doctor if you have had problems with

  your liver before, including hepatitis B or C

  infection. Your doctor may evaluate how severe

  your liver disease is before deciding if you can

  take PREZISTA.

• Tell your doctor if you have diabetes. PREZISTA

  might increase sugar levels in the blood.

• Tell your doctor immediately if you notice any

  symptoms of infection (for example enlarged

  lymph nodes and fever). In some patients with

  advanced HIV infection and a history of

  opportunistic infection, signs and symptoms of

  inflammation from previous infections may occur

  soon after anti‑HIV treatment is started. It is

  believed that these symptoms are due to an

  improvement in the body’s immune response,

  enabling the body to fight infections that may

  have been present with no obvious symptoms.

• In addition to the opportunistic infections,

  autoimmune disorders (a condition that occurs

  when the immune system attacks healthy body

  tissue) may also occur after you start taking

  medicines for the treatment of your HIV infection.

  Autoimmune disorders may occur many months

  after the start of treatment. If you notice any

  symptoms of infection or other symptoms such

  as muscle weakness, weakness beginning in the

  hands and feet and moving up towards the trunk

  of the body, palpitations, tremor or hyperactivity,

  please inform your doctor immediately to seek

  necessary treatment.

• Tell your doctor if you have haemophilia.

  PREZISTA might increase the risk of bleeding.

• Tell your doctor if you are allergic to

  sulphonamides (e.g. used to treat certain

  infections).

• Tell your doctor if you notice any musculoskeletal

  problems. Some patients taking combination

  antiretroviral therapy may develop a bone disease

  called osteonecrosis (death of bone tissue

  caused by loss of blood supply to the bone).

  The length of combination antiretroviral therapy,

  corticosteroid use, alcohol consumption, severe

  immunosuppression, higher body mass index,

  among others, may be some of the many risk

  factors for developing this disease. Signs of

  osteonecrosis are joint stiffness, aches and

  pains (especially of the hip, knee and shoulder)

  and difficulty in movement. If you notice any of

  these symptoms please inform your doctor.

  ■■ Elderly

PREZISTA has only been used in limited numbers

of patients 65 years or older. If you belong to this

age group, please discuss with your doctor if you

can use PREZISTA.

■■ Children

PREZISTA is not for use in children younger than

3 years of age or weighing less than 15 kilograms.

■■ Other medicines and PREZISTA

Tell your doctor or pharmacist if you are taking

or have recently taken any other medicines.

There are some medicines that you must not

combine with PREZISTA. These are mentioned

above under the heading ‘Do not combine

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 with ritonavir has

not been tested with all PIs (protease inhibitors)

and must not be used with other HIV PIs. In some

cases dosage of other medicines might need to be

changed. Therefore always tell your doctor if you

take other anti‑HIV medicines and follow your

doctor’s instruction carefully on which medicines

can be combined.

The effects of PREZISTA might be reduced if you

take any of the following products. Tell your doctor

if you take:

• Phenobarbital, phenytoin (to prevent seizures)
• Dexamethasone (corticosteroid)
• Efavirenz (HIV infection)

• Rifapentine, rifabutin (medicines to treat some

  infections such as tuberculosis)

• Saquinavir (HIV infection).

  The effects of other medicines might be influenced if you take PREZISTA. Tell your doctor if you take:

  • Amlodipine, diltiazem, disopyramide, carvedilol, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nifedipine, nicardipine, propafenone, timolol, verapamil (for heart disease) as the therapeutic effect or side effects of these medicines may be increased.
  • Apixaban, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce clotting of the blood) as their therapeutic effect or side effects may be altered; your doctor may have to check your blood.
  • Oestrogen‑based hormonal contraceptives and hormonal replacement therapy. PREZISTA might reduce its effectiveness. When used for birth control, alternative methods of non‑hormonal contraception are recommended.
  • Ethinylestradiol/drospirenone. PREZISTA might increase the risk for elevated potassium levels by drospirenone.
  • Atorvastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for your specific situation.
  • Clarithromycin (antibiotic)
  • Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as the therapeutic effect or side effects of these medicines might be increased. Your doctor might want to do some additional tests.
  • Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory conditions of the eyes, joints and muscles and other inflammatory conditions. If alternatives cannot be used, its use should only take place after medical evaluation and under close monitoring by your doctor for corticosteroid side effects.
  • Buprenorphine/naloxone (medicines to treat opioid dependence)
  • Salmeterol (medicine to treat asthma)
  • Artemether/lumefantrine (a combination medicine 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 (to treat hepatitis C infection)
  • Fentanyl, oxycodone, tramadol (to treat pain)
  • Fesoterodine, solifenacin (to treat urologic disorders).

The dosage of other medicines might need to be changed since either their own or PREZISTA’s therapeutic effect or side effects may be influenced when combined.

Tell your doctor if you take:

• Alfentanil (injectable strong and short‑acting painkiller that is used for surgical procedures)
• Digoxin (to treat certain heart disorders)
• Clarithromycin (antibiotic)
• Itraconazole, isavuconazole, fluconazole, posaconazole, clotrimazole (to treat fungal infections). Voriconazole should only be taken after medical evaluation.
• Rifabutin (against bacterial infections)
• Sildenafil, vardenafil, tadalafil (for erectile dysfunction or high blood pressure in the pulmonary circulation)
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
• Maraviroc (to treat HIV infection)
• Methadone (to treat opiate dependence)
• Carbamazepine, clonazepam (to prevent seizures or to treat certain types of nerve pain)

• Colchicine (to treat gout or familial

  Mediterranean fever)

• Bosentan (to treat high blood pressure in the pulmonary circulation)
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, midazolam when used as injection, zolpidem (sedative agents)
• Perphenazine, risperidone, thioridazine (to treat psychiatric conditions).

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are taking.

■■ PREZISTA with food and drink

See section 3 ‘How to take PREZISTA.’

■■ Pregnancy and breast‑feeding

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast‑feeding. Pregnant or breast‑feeding mothers should not take PREZISTA with ritonavir unless specifically directed by the doctor. Pregnant or breast‑feeding mothers should not take PREZISTA with cobicistat.

It is recommended that HIV infected women must not breast‑feed their infants because of both the possibility of your baby becoming infected with HIV through your breast milk and because of the unknown effects of the medicine on your baby.

■■ Driving and using machines

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

■■ PREZISTA contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium‑free’.

3How to take PREZISTA

Always use this medicine exactly as described in

this leaflet or as your doctor, pharmacist or nurse

has told you. Check with your doctor, pharmacist

or nurse if you are not sure.

Even if you feel better, do not stop taking PREZISTA

and ritonavir without talking to your doctor.

After therapy has been initiated, the dose or dosage form must not be changed or therapy must not be stopped without instruction of the doctor. © J‑C 2021 GB ‑ AW_177487 R © J‑C 2021 GB ‑ AW_177487 V

■■ Dose for children of 3 years of age and above, weighing at least 15 kilograms who have not taken antiretroviral medicines before (your child’s doctor will determine this)

The doctor will work out the right once daily dose based on the weight of the child (see table below). This dose must not exceed the recommended adult dose, which is 800 milligram PREZISTA together with 100 milligram ritonavir once a day. The doctor will inform you on how much PREZISTA tablets and how much ritonavir (capsules, tablets or solution) the child must take.

^a ritonavir oral solution: 80 milligram per milliliter

■■ Dose for children of 3 years of age and above, weighing at least 15 kilograms who have taken antiretroviral medicines before (your child’s doctor will determine this)

The doctor will work out the right dose based on the weight of the child (see table below). The doctor will determine if once daily dosing or twice daily dosing is appropriate for the child. This dose must not exceed the recommended adult dose, which is 600 milligram PREZISTA together with 100 milligram ritonavir two times per day or 800 milligram PREZISTA together with 100 milligram ritonavir once a day. The doctor will inform you on how many PREZISTA tablets and how much ritonavir (capsules, tablets or solution) the child must take. Tablets of other strengths are available and your doctor may have prescribed a certain combination of tablets to construct the appropriate dosing regimen.

PREZISTA oral suspension is also available. Your doctor will determine whether PREZISTA tablets or oral suspension is right for the child.

Twice daily dosing

* For children aged 12 or more and weighing at least 40 kilograms, your child’s doctor will determine if PREZISTA 800 milligram once daily dosing may be used. This cannot be administered with these 150 milligram tablets. Other strengths of PREZISTA are available.

Once daily dosing

^a ritonavir oral solution: 80 milligram per milliliter

■■ Instructions for children

• The child must take PREZISTA always together with ritonavir. PREZISTA cannot work properly without ritonavir.
• The child must take the appropriate doses of PREZISTA and ritonavir two times per day or once a day. If prescribed PREZISTA twice daily the child must take one dose in the morning, and one dose in the evening. Your child’s doctor will determine the appropriate dosing regimen for your child.
• The child must take PREZISTA with food. PREZISTA cannot work properly without food. The type of food is not important.

• The child must swallow the tablets with a drink such as water or milk.

  ■■ Dose for adults who have not taken antiretroviral medicines before (your doctor will determine this)

  You will require a different dose of PREZISTA which cannot be administered with these 150 milligram tablets. Other strengths of PREZISTA are available.

  ■■ Dose for adults who have taken antiretroviral medicines before (your doctor will determine this)

  The dose is either:

  • 600 milligram PREZISTA together with 100 milligram ritonavir twice daily.

OR

• 800 milligram PREZISTA (2 tablets containing 400 milligram of PREZISTA or 1 tablet containing 800 milligram of PREZISTA) together with 100 milligram ritonavir once daily. PREZISTA 400 milligram and 800 milligram tablets are only to be used to construct the once daily 800 milligram regimen.

Please discuss with your doctor which dose is right for you.

■■ Instructions for adults

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

■■ Removing the child resistant cap

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

• Push the plastic screw cap down while turning it counter clockwise.
• 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 notice within 6 hours, you must take the tablets immediately. Always take with ritonavir and food. If you notice after 6 hours, then skip the intake and take the next doses as usual. Do not take a double dose to make up for a forgotten dose.

■■ If you vomit after taking PREZISTA and ritonavir

If you vomit within 4 hours of taking the medicine, another dose of PREZISTA and ritonavir should be taken with food as soon as possible. If you vomit more than 4 hours after taking the medicine, then you do not need to take another dose of PREZISTA and ritonavir until the next regularly scheduled time.

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

■■ Do not stop taking PREZISTA without talking to your doctor first

Anti‑HIV medicines may make you feel better. Even when you feel better, do not stop taking PREZISTA. Talk to your doctor first.

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

4Possible side effects

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for 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 that may occasionally be severe have been reported. Your doctor should do blood tests before you start PREZISTA. If you have chronic hepatitis B or C infection, your doctor should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea coloured) urine, pale coloured stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below your ribs.

Skin rash (more often when used in combination with raltegravir), itching. The rash is usually mild to moderate. A skin rash might also be a symptom of a rare severe situation. It is therefore important to talk to your doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether PREZISTA must be stopped.

Other severe side effects were 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 distension, dyspepsia, flatulence
• headache, tiredness, 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 heart beating
• decreased or abnormal skin sensibility, pins and needles, attention disturbance, loss of memory, problems with your balance
• difficulty breathing, cough, nosebleed, throat irritation
• inflammation of the stomach or mouth, heartburn, retching, dry mouth, discomfort of the abdomen, constipation, belching

• kidney failure, kidney stones, difficult discharge of urine, frequent or excessive passage of urine, sometimes at night

  • urticaria, severe swelling of the skin and other tissues (most often the lips or the eyes), eczema, excessive sweating, night sweats, hair loss, acne, scaly skin, colouration of nails
  • muscle pain, muscle cramps or weakness, pain in extremity, osteoporosis
  • slowing down of the thyroid gland function. This can be seen in a blood test.
  • high blood pressure, flushing
  • red or dry eyes
  • fever, swelling of lower limbs due to fluids, malaise, irritability, pain
  • symptoms of infection, herpes simplex
  • erectile dysfunction, enlargement of breasts
  • sleeping problems, sleepiness, depression, anxiety, abnormal dreams, decrease in sexual 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 glands, increase of eosinophils (type of white blood cells), effects on liver, kidney or lung]
• heart attack, slow heart beating, palpitations
• visual disturbance
• chills, feeling abnormal
• a feeling of confusion or disorientation, altered mood, restlessness
• fainting, epileptic fits, changes or loss of taste
• mouth sores, vomiting blood, inflammation of the lips, dry lips, coated tongue
• running nose
• skin lesions, dry skin
• stiffness of muscles or joints, joint pain with or without inflammation
• changes in some values of your blood cells or chemistry. These can be seen in the results of blood and/or urine tests. Your doctor will explain these to you. Examples are: increase in some white blood cells.

Some side effects are typical for anti‑HIV medicines in the same family as PREZISTA. These are:

• muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been serious.

  ■■ Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.You can also report side effects directly via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

5How 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 on the bottle after EXP. The expiry date refers to the last day of that month.

PREZISTA does not require any special storage conditions.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away any medicines you no longer use. These measures will help protect the environment.

6Contents of the pack and other information

What PREZISTA contains

• The active substance is darunavir. Each tablet contains 150 milligram of darunavir (as ethanolate).
• The other ingredients are microcrystalline cellulose, colloidal anhydrous silica, crospovidone, magnesium stearate. The film‑coating contains poly(vinyl alcohol) ‑ partially hydrolysed, macrogol 3350, titanium dioxide (E171), talc.

What PREZISTA looks like and contents of the pack

Film‑coated, white, oval shaped tablet, mentioning TMC on one side, 150 on the other side. 240 tablets in a plastic bottle.

PREZISTA is also available as 75 milligram, 400 milligram, 600 milligram and 800 milligram film‑coated tablets and 100 milligram per milliliter oral suspension.

Marketing Authorisation Holder

Janssen‑Cilag Ltd., 50‑100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK

Manufacturer

Janssen‑Cilag SpA, Via C. Janssen,

Borgo San Michele, 04100 Latina, Italy

For information in large print, tape, CD or Braille, telephone 0800 7318450 This leaflet was last revised in January 2021. 3How to take PREZISTA (continued)