Rezolsta

Package leaflet: Information for the user

REZOLSTA 800 mg/150 mg film-coated tablets

darunavir/cobicistat
Please 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. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

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

1. What REZOLSTA is and what it is used for

What is REZOLSTA?
REZOLSTA contains the active substances darunavir and cobicistat. Darunavir belongs to a group of
HIV medicines called "protease inhibitors" that work by reducing the amount of HIV in the body to
very low levels. It is given together with cobicistat, which increases the amount of darunavir in the
blood. Treatment with REZOLSTA will improve the immune system (the body's natural defenses) and
reduce the risk of developing HIV-related illnesses, but REZOLSTA is not a cure for HIV infection.
What is it used for?
REZOLSTA 800 mg/150 mg (darunavir/cobicistat) is used to treat adults and paediatric patients weighing
at least 40 kilograms who have HIV infection (see section 3. How to take REZOLSTA in this leaflet).
REZOLSTA must be taken in combination with other HIV medicines. Your doctor will discuss with you
the best combination of medicines for your treatment.

2. What you need to know before taking REZOLSTA

Do not take REZOLSTA

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

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking REZOLSTA.
People who take REZOLSTA may still develop infections or other illnesses associated with HIV infection. You must stay in regular contact with your doctor.
People taking REZOLSTA may develop a skin rash. Sometimes the rash can become severe or potentially life-threatening. Contact your doctor whenever a rash develops.
Skin rashes (generally mild or moderate) may occur more frequently in patients taking REZOLSTA and raltegravir (for HIV infection) than in patients taking each medicine separately.
REZOLSTA has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor before taking REZOLSTA.
Make sure to check the following points and inform your doctor if any of them apply to you.

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

Children and adolescents
REZOLSTA 800 mg/150 mg (darunavir/cobicistat) must not be used in children weighing less than 40 kilograms.
REZOLSTA is also available as a 675 mg/150 mg film-coated tablet with a score line for children aged 6 years and older with a body weight of at least 25 kg and less than 40 kg (see the separate package leaflet for REZOLSTA 675 mg/150 mg film-coated tablets).

Other medicines and REZOLSTA
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are certain medicines that must not be taken together with REZOLSTA. These have been listed earlier under the heading “Do not take REZOLSTA with any of the following medicines”.
REZOLSTA must not be used with other antivirals containing a booster or with other antivirals that require a booster. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you can take.
The effects of REZOLSTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

• Bosentan (to treat heart conditions)
• Dexamethasone (injectable) (a corticosteroid)
• Efavirenz, etravirine, nevirapine (to treat HIV infection)
• Rifapentine, rifabutin (to treat bacterial infections)

The effects of other medicines may be affected by taking REZOLSTA, and your doctor may need to perform additional blood tests. Inform your doctor if you are taking:

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

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

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
• Alfentanil (a strong, short-acting injectable painkiller used during surgical procedures).
• Digoxin (for treating certain heart conditions).
• Clarithromycin (an antibiotic).
• Clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole (for fungal infections). Voriconazole must be taken only after evaluation by your doctor.
• Rifabutin (for bacterial infections).
• Tadalafil, sildenafil, vardenafil (for erectile dysfunction or for high blood pressure in the lung circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (for treating depression and anxiety).
• Maraviroc (for treating HIV infection).
• Colchicine (for treating gout or familial Mediterranean fever). If you have impaired renal and/or hepatic function, see section “Do not take REZOLSTA with any of the following medicines”.
• Bosentan (for treating high blood pressure in the lung circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as injection (medicines for treating sleep disorders and/or anxiety).
• Metformin (for treating type 2 diabetes).
• Fentanyl, oxycodone, tramadol (for pain treatment).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Pregnant women should not take REZOLSTA.
Due to the potential for adverse effects in infants, women must not breastfeed while taking REZOLSTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or planning to breastfeed, discuss this with your doctor as soon as possible.

Driving and using machines
Do not operate machinery or drive if you feel dizzy after taking REZOLSTA.

REZOLSTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take REZOLSTA

Take this medicine exactly as prescribed by your doctor, pharmacist, or nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
You must take REZOLSTA every day and always with food. REZOLSTA cannot work properly without food. You must eat a meal or a snack within the 30 minutes before taking REZOLSTA. The type of food is not important.

• Swallow the tablet whole with a drink such as water or milk. If you have difficulty swallowing REZOLSTA, inform your doctor. The tablet may be divided using a tablet cutter. The full dose (both halves) must be taken immediately after dividing the tablet, with a drink such as water or milk.
• Take any other anti-HIV medicines you are using in combination with REZOLSTA as recommended by your doctor.

Child-resistant cap removal

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

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

If you take more REZOLSTA than you should
Inform your doctor, pharmacist, or nurse immediately.
If you forget to take REZOLSTA
If you remember within 12 hours, take the tablet immediately. Always take the tablets with food. If you remember after 12 hours, skip the missed dose and take the next dose at the usual time. Do not take a double dose to make up for the missed dose.
If you vomit after taking REZOLSTA
If you vomit within 4 hours of taking the medicine, you must take another dose of REZOLSTA with food as soon as possible. If you vomit more than 4 hours after taking the medicine, you do not need to take another dose of REZOLSTA until the next scheduled dose.
Contact your doctor if you are unsure about what to do if you miss a dose or vomit.
Do not stop treatment with REZOLSTA without first consulting your doctor
Once treatment has started, it must not be stopped without your doctor's instructions.
Anti-HIV medicines may make you feel better. Do not stop taking REZOLSTA, even if you feel well. Talk to your doctor first.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

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

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

Other serious side effects observed in up to 1 in 10 patients included diabetes. Inflammation of the pancreas (pancreatitis) has been reported in 1 in 100 patients.

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

• Headache
• Diarrhoea, nausea

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

• Allergic reactions such as itching
• Decreased appetite
• Abnormal dreams
• Vomiting, stomach pain or bloating, indigestion, flatulence
• Muscle pain
• Fatigue
• Abnormal blood test results, such as certain liver or kidney tests. Your doctor will explain these to you
• Weakness

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

• Symptoms of infection or autoimmune disorders (immune reconstitution inflammatory syndrome)
• Osteonecrosis (bone tissue death caused by reduced blood flow to the bone)
• Breast enlargement
• Abnormal blood test results, such as certain tests for the pancreas, elevated blood sugar levels, abnormal lipid (fat) levels. Your doctor will explain these to you
• Allergic reactions such as hives, severe swelling of the skin and other tissues (especially lips or eyes)
• Severe skin rash with blisters and peeling of the skin, particularly around the mouth, nose, eyes, and genitals

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), and effects on the liver, kidneys, or lungs]
• Crystallisation of darunavir in the kidney, leading to kidney disease

Side effects with unknown frequency: a rash may become severe or potentially life-threatening

• Rash with blisters and peeling of the skin over much of the body
• Red rash covered with small pustules that may spread over the body, sometimes with fever

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

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

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

5. How to store REZOLSTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
Do not use this medicine more than 6 weeks after first opening the bottle.
REZOLSTA does not require any special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What REZOLSTA contains

• The active substances are darunavir and cobicistat. Each tablet contains 800 mg of darunavir (as ethanolate) and 150 mg of cobicistat.
• The other components are: hypromellose, colloidal silicon dioxide, silicified microcrystalline cellulose, crospovidone, magnesium stearate. The coating contains: polyvinyl alcohol – partially hydrolysed, titanium dioxide (E 171), polyethylene glycol (macrogol), talc, red iron oxide (E 172), black iron oxide (E 172).

Description of the appearance of REZOLSTA and contents of the pack
Pink, film-coated, oval-shaped tablet, printed with "TG" on one side and "800" on the other.
30 tablets in a plastic bottle.
Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Manufacturer
Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy
For further information about this medicinal product, contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]
България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]
Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]
Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf.: +45 4594 8282 Tel: +356 2397 6000
[email protected]
Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: 0800 086 9247 / +49 2137 955 6955 Tel: +31 76 711 1111
[email protected] [email protected]
Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]
Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Janssen-Cilag Pharma GmbH
Α.Ε.Β.Ε. Tel: +43 1 610 300
Tηλ: +30 210 80 90 000
España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]
France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]
Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]
Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: 1 800 709 122 Tel: +386 1 401 18 00
[email protected] [email protected]
Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor ehf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]
Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]
Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]
Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu.

Package leaflet: Information for the user

REZOLSTA 675 mg/150 mg film-coated tablets

darunavir/cobicistat
Please read this leaflet carefully before taking (or before your child takes) this
medicine, as it contains important information for you.

• Keep this leaflet. You or your child may need to read it again.
• If you or your child has any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you or your child only. Do not give it to others, even if their symptoms are the same as yours (or your child's), as it could be harmful.
• If any side effect occurs, including those not listed in this leaflet, consult your doctor, pharmacist, or nurse (or your child's). See section 4.
• The information contained in this leaflet is intended for you or your child; generally, the pronoun "you" will be used throughout this leaflet.

Contents of this leaflet:

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

1. What REZOLSTA is and what it is used for

What REZOLSTA is
REZOLSTA contains the active substances darunavir and cobicistat.
Darunavir belongs to a group of HIV medicines called "protease inhibitors" that work by reducing the amount of HIV in the body to very low levels. It is given together with cobicistat, which increases the amount of darunavir in the blood.
Treatment with REZOLSTA will improve the immune system (the body's natural defenses) and reduce the risk of developing HIV-related illnesses, but REZOLSTA is not a cure for HIV infection.
What it is used for
REZOLSTA 675 mg/150 mg (darunavir/cobicistat) is used to treat children aged 6 years and older, weighing at least 25 kg and less than 40 kilograms, who are infected with HIV (see How to take REZOLSTA in this leaflet).
REZOLSTA must be taken in combination with other HIV medicines. Your doctor will evaluate with you the most appropriate combination of medicines for your treatment.

2. What you need to know before taking REZOLSTA

Do not take REZOLSTA

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

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

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking REZOLSTA.
People who take REZOLSTA may also develop infections or other illnesses associated with HIV infection. You should maintain regular contact with your doctor.
People who take REZOLSTA may develop a rash. Sometimes the rash can become severe or potentially life-threatening. Contact your doctor whenever a rash develops.
Skin rashes (generally mild or moderate) may occur more frequently in patients taking REZOLSTA and raltegravir (for HIV infection) compared to patients taking each medicine separately.
Please check the following points and inform your doctor if any of them apply to you.

• Inform your doctor if you have previously had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of your liver disease before deciding whether to prescribe REZOLSTA.
• Inform your doctor if you have kidney problems. Your doctor will carefully evaluate whether to treat you with REZOLSTA.
• Inform your doctor if you have diabetes. REZOLSTA may increase blood sugar levels.
• Inform your doctor immediately if you notice any symptoms of infection (e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of unusual infections due to weakened immune system (opportunistic infections), signs and symptoms of inflammation from previous infections may occur shortly after starting HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without causing obvious symptoms.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after you start taking medicines for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in hands and feet and moving up toward the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive necessary treatment.
• Inform your doctor if you have haemophilia. REZOLSTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (used to treat certain infections).
• Inform your doctor if you notice any musculoskeletal problems. Some patients taking a combination of antiretroviral medicines may develop a bone disease called osteonecrosis (bone tissue death caused by reduced blood supply to the bone). This may be more likely with long-term HIV treatment, more severe immune system damage, being overweight, or use of alcohol or other medicines called corticosteroids. Signs of osteonecrosis include joint swelling, pain and stiffness (especially in the hip, knee, and shoulders), and difficulty moving. If you notice any of these symptoms, inform your doctor immediately.

Children and adolescents
This medicine must not be used in children under 6 years of age or weighing less than 25 kg.
REZOLSTA is also available as 800 mg/150 mg tablets for adolescents weighing at least 40 kg (see the separate package leaflet for REZOLSTA 800 mg/150 mg film-coated tablets).

Other medicines and REZOLSTA
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are medicines that must not be taken together with REZOLSTA. These have been listed earlier under the heading “Do not take REZOLSTA with any of the following medicines”.
REZOLSTA must not be used with other antivirals that require boosting or with other antivirals that require boosting. In some cases, the dose of other medicines may need to be adjusted. Therefore, always inform your doctor if you are taking other anti-HIV medicines and carefully follow your doctor’s instructions regarding which medicines can be taken together.
The effects of REZOLSTA may be reduced if you take any of the following medicines. Inform your doctor if you are taking:

• Bosentan (to treat heart conditions)
• Dexamethasone (injectable) (corticosteroid)
• Efavirenz, etravirine, nevirapine (to treat HIV infection)
• Rifapentine, rifabutin (to treat bacterial infections)

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

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

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

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
• Alfentanil (a strong, short-acting injectable painkiller used during surgery).
• Digoxin (to treat certain heart conditions).
• Clarithromycin (an antibiotic).
• Clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole (for fungal infections). Voriconazole must only be taken after evaluation by your doctor.
• Rifabutin (for bacterial infections).
• Tadalafil, sildenafil, vardenafil (for erectile dysfunction or high blood pressure in the lung circulation).
• Amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety).
• Maraviroc (to treat HIV infection).
• Colchicine (to treat gout or familial Mediterranean fever). If you have kidney and/or liver impairment, see section “Do not take REZOLSTA with any of the following medicines”.
• Bosentan (to treat high blood pressure in the lung circulation).
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as an injection (medicines to treat sleep disorders and/or anxiety).
• Metformin (to treat type 2 diabetes).
• Fentanyl, oxycodone, tramadol (to treat pain).

This is not a complete list of medicines. Inform your doctor about all medicines you are taking.

Pregnancy and breastfeeding
Inform your doctor immediately if you are pregnant, suspect you may be pregnant, or are planning a pregnancy. Women who are pregnant should not take REZOLSTA.
Due to the potential for adverse effects in infants, women must not breastfeed while receiving REZOLSTA.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.

Driving and using machines

• Do not operate machinery or drive if you feel dizzy after taking REZOLSTA.

REZOLSTA contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take REZOLSTA

Take this medicine exactly as instructed by your doctor, pharmacist, or
nurse. If you have any doubts, consult your doctor, pharmacist, or nurse.
You must take REZOLSTA every day and always with food. REZOLSTA cannot work
properly without food. You must eat a meal or snack within the 30 minutes before
taking REZOLSTA. The type of food is not important.

• Swallow the tablet whole with a drink such as water or milk. If you have difficulty swallowing REZOLSTA, inform your doctor. The tablet with a score line can be divided manually into two halves. The score line is provided specifically to facilitate tablet splitting. The full dose (both halves) must be swallowed immediately after splitting the tablet, to ensure complete dosing.
• Take any other anti-HIV medicines you are using in combination with REZOLSTA as recommended by your doctor.

Removing the child-resistant cap

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

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

If you take more REZOLSTA than you should
Inform your doctor, pharmacist, or nurse immediately.
If you forget to take REZOLSTA
If you remember within 12 hours, take the tablet immediately. Always take the tablets with food. If you remember after 12 hours, skip the missed dose and take the next dose as usual. Do not take a double dose to make up for a forgotten dose.
If you vomit after taking REZOLSTA
If you vomit within 4 hours of taking the medicine, you must take another dose of REZOLSTA with food as soon as possible. If you vomit more than 4 hours after taking the medicine, you do not need to take another dose of REZOLSTA until the next scheduled dose.
Contact your doctor if you have any doubts about what to do if you miss a dose or vomit.
Do not stop treatment with REZOLSTA without first talking to your doctor
After treatment has started, it must not be stopped without your doctor's instructions.
Anti-HIV medicines may make you feel better. Do not stop treatment with REZOLSTA, even if you feel better, without first consulting your doctor.
If you have any questions about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

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

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

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

Other serious side effects, observed in up to 1 in 10 patients, included diabetes. Inflammation of the pancreas (pancreatitis) has been reported in 1 in 100 patients.

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

• headache
• diarrhoea, nausea

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

• allergic reactions such as itching
• loss of appetite
• abnormal dreams
• vomiting, stomach pain or bloating, indigestion, flatulence
• muscle pain
• fatigue
• abnormal blood test results such as certain liver or kidney tests. Your doctor will explain these to you
• weakness

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

• symptoms of infection or autoimmune disorders (immune reconstitution inflammatory syndrome)
• osteonecrosis (death of bone tissue caused by loss of blood supply to the bone)
• breast enlargement
• abnormal blood test results such as certain tests for the pancreas, elevated blood sugar, abnormal lipid (fat) levels; your doctor will explain these to you
• allergic reactions such as hives, severe swelling of the skin and other tissues (especially lips or eyes)
• severe skin rash with blistering and peeling of the skin, particularly around the mouth, nose, eyes, and genitals

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

• a reaction called DRESS [severe rash which may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell), and effects on the liver, kidneys, or lungs]
• deposition of darunavir crystals in the kidney leading to kidney disease

Side effects with unknown frequency: a skin rash may become severe or potentially life-threatening:

• rash with blistering and peeling of the skin over large areas of the body
• red rash covered with small pustules that may spread over the body, sometimes with fever

Some side effects are typical of HIV medicines in the same class as REZOLSTA. These include:

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

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

5. How to store REZOLSTA

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and bottle after
Exp. The expiry date refers to the last day of that month.
Do not use this medicine more than 8 weeks after first opening the bottle.
REZOLSTA requires no special storage conditions.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What REZOLSTA contains

• The active substances are darunavir and cobicistat. Each tablet contains 675 mg of darunavir (as ethanolate) and 150 mg of cobicistat.
• The other components are: colloidal silicon dioxide, microcrystalline cellulose, sodium croscarmellose and magnesium stearate. The coating contains: yellow iron oxide (E 172), black iron oxide (E 172), polyethylene glycol (macrogol), polyvinyl alcohol (partially hydrolysed), talc and titanium dioxide (E 171).

Description of the appearance of REZOLSTA and contents of the pack
Green to dark green, film-coated oval tablet, with a score line, printed with "TG" on one side and "675" on the other.
30 tablets in a plastic bottle.
Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Manufacturer
Janssen Pharmaceutica NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]
България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]
Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]
Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf.: +45 4594 8282 Tel: +356 2397 6000
[email protected]
Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: 0800 086 9247 / +49 2137 955 6955 Tel: +31 76 711 1111
[email protected] [email protected]
Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]
Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Μονοπρόσωπη Janssen-Cilag Pharma GmbH
Α.Ε.Β.Ε. Tel: +43 1 610 300
Tηλ: +30 210 80 90 000
España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]
France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]
Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]
Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: 1 800 709 122 Tel: +386 1 401 18 00
[email protected] [email protected]
Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor ehf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]
Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]
Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]
Latvija
UAB "JOHNSON & JOHNSON" filiāle Latvijā
Tel: +371 678 93561
[email protected]
More detailed information on this medicinal product is available on the European Medicines Agency website: https://www.ema.europa.eu.