PProspect: information for the user

REZOLSTA 800 mg/150 mg - film-coated tablets

darunavir/cobicistat

Read this prospect carefully before starting to take this medicine, as it contains important information for you.

• Keep this prospect, as you may need to read it again.
• If you have any doubts, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this prospect. See section 4.

1. How to take REZOLSTA
2. Possible adverse effects
3. Storage of REZOLSTA
4. Contents of the pack and additional information

What is REZOLSTA?

REZOLSTA contains the active principles darunavir and cobicistat.

Darunavir belongs to a group of medications for HIV called “protease inhibitors”, which act by reducing the amount of HIV in your body to a very low level. Darunavir is administered with cobicistat, which increases the amount of darunavir in your blood.

Treatment with REZOLSTA will improve your immune system (your body's natural defenses) and reduce the risk of developing diseases related to HIV infection, although REZOLSTA is not a cure for HIV infection.

How is it used?

REZOLSTA is used to treat adults and adolescents 12 years of age and older who weigh at least 40 kilograms and are infected with HIV (see How to take REZOLSTA).

REZOLSTA should be taken in combination with other HIV medications. Your doctor will explain the most suitable combination of medications for you.

Do not take REZOLSTA

• if you areallergicto darunavir, cobicistat, or any of the other components of this medication (listed in section 6).
• if you have hadserious liver problems. Ask your doctor if you are unsure about the severity of your liver disease. You may need to have some additional tests.

Do not combine REZOLSTA with any of the following medications

If you are taking any of these medications, consult your doctor to change to another medication.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take REZOLSTA.

You may still be able to transmit HIV, although the risk is reduced with effective antiretroviral treatment. Consult your doctor about the precautions you need to take to avoid infecting others.

People taking REZOLSTA may be more susceptible to infections and other diseases associated with HIV infection. You should maintain regular contact with your doctor.

People taking REZOLSTA may develop skin rash. In rare cases, a rash can be severe or potentially life-threatening. Please consult your doctor if you experience a rash.

In patients treated with REZOLSTA and raltegravir (for HIV infection), skin rash may occur more frequently (usually mild or moderate) than in patients taking either of these medications separately.

REZOLSTA has been used in a limited number of patients aged 65 or older. If you belong to this age group, please consult your doctor before taking REZOLSTA.

Check the following points and inform your doctor if you find yourself in any of these situations.

• Inform your doctor if you have had anyliver diseasepreviously, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding whether you can take REZOLSTA.
• Inform your doctor if you have hadkidney problems. Your doctor will carefully consider whether you should be treated with REZOLSTA.
• Inform your doctor if you havediabetes. REZOLSTA may increase blood sugar levels.
• Inform your doctor immediately if you experience anysymptoms of infection(e.g., swollen lymph nodes and fever). In some patients with advanced HIV infection and a history of rare infections due to a weakened immune system (opportunistic infections), symptoms of inflammation may occur shortly after starting HIV treatment. It is believed that these symptoms are due to the improvement of the body's immune response, allowing it to fight off infections that may have been present but not evident.
• Additionally, it is possible that you may developautoimmune disorders(a situation that occurs when the immune system attacks healthy body tissues) after starting HIV treatment. Autoimmune disorders can occur many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and progressing to the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately and they can administer the necessary treatment.
• Inform your doctor if you havehemophilia. REZOLSTA may increase the risk of bleeding.
• Inform your doctor if you areallergic to sulfonamides(e.g., to treat certain infections).
• Inform your doctor if you experience anymusculoskeletal problems. Some patients receiving combination antiretroviral therapy may develop a bone disease called osteonecrosis (bone tissue destruction caused by interruption of blood supply to the bone). This is more likely with long-term HIV treatment, severe immune system damage, obesity, or use of other medications called corticosteroids. Signs of osteonecrosis include joint stiffness, pain, and difficulty moving (especially in the hips, knees, and shoulders). If you experience any of these symptoms, inform your doctor.

Children and adolescents

REZOLSTA should not be used in children under 12 years of age or weighing less than 40 kg.

Taking REZOLSTA with other medications

Inform your doctor or pharmacist if you are using or have recently used other medications.

Some other medicationsshould not be combinedwith REZOLSTA. These medications are listed later in the section titled 'Do not combine REZOLSTA with any of the following medications:.'

REZOLSTA should not be used with any other antiviral medication that contains a booster or another antiviral that requires a booster. In some cases, the dose of other medications may need to be adjusted. Therefore, always inform your doctor if you are taking other HIV medications and follow your doctor's instructions carefully about which medications can be combined.

The effects of REZOLSTA may be reduced if you take any of the following medications. Inform your doctor if you take:

• Bosentan(to treat heart disease)
• Dexamethasone (injectable) (corticosteroid)
• Efavirenz, etravirine, nevirapine(to treat HIV infection)

• Rifapentine, rifabutin(to treat bacterial infections).

REZOLSTA may also affect the effects of other medications. Inform your doctor if you take:

• Amlodipine, carvedilol, diltiazem, disopyramide, felodipine, flecainide, lidocaine, metoprolol, mexiletine, nicardipine,nifedipine, propafenone,timolol, verapamil(to treat heart disease) as the therapeutic effect or side effects of these medications may increase.
• Apixaban, edoxaban, rivaroxaban, warfarin(to reduce blood clotting), as it may alter the therapeutic effect or side effects; your doctor may need to perform regular blood tests.
• Clonazepam(to prevent seizures).
• Oral contraceptives and hormone replacement therapy. REZOLSTA may reduce their effectiveness. When used for birth control, alternative non-hormonal methods are recommended.
• Etinilestradiol/drospirenona. REZOLSTA may increase the risk of elevated potassium levels due to the drospirenona effect.
• Atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin(to lower cholesterol levels). There may be an increased risk of muscle damage. Your doctor will assess which cholesterol-lowering regimen is best for your individual situation.
• Ciclosporin, everolimus, tacrolimus, sirolimus(to suppress your immune system) as the therapeutic effect or side effects of these medications may increase. Your doctor may want to perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone.These medications are used to treat allergies, asthma, inflammatory bowel disease, eye, joint, and muscle inflammation, and other inflammatory conditions. If alternatives cannot be used, their use should only be made after a clinical evaluation and with close monitoring by your doctor to assess the adverse effects of corticosteroids.
• Buprenorphine/naloxone,methadone(medications for opioid dependence treatment)
• Salmeterol(medications for asthma treatment)
• Artemether/lumefantrine(a combination of medications for malaria treatment)
• Dasatinib, irinotecan, nilotinib, vinblastine, vincristine(medications for cancer treatment)
• Perphenazine, risperidone, thioridazine(psychiatric medications)
• Chlorazepate, diazepam, estazolam, flurazepam(medications for sleep disorders or anxiety)
• Sildenafil, tadalafil, vardenafil(to treat erectile dysfunction or a heart and lung disorder called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir(to treat hepatitis C infection)
• Fesoterodine, solifenacin(to treat urological disorders).

You may need to adjust the dosage of other medications if their therapeutic effects or side effects are affected by taking REZOLSTA. Inform your doctor if you take:

• Alfentanil(injectable analgesic, with strong and short action used for surgical procedures)
• Digoxin(to treat certain heart rhythm disorders)
• Clarithromycin(antibiotic)
• Clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole(against fungal infections).Voriconazoleshould only be taken after a patient evaluation.
• Rifabutin(against bacterial infections)
• Tadalafil, sildenafil, vardenafil(to treat 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)
• Colchicine(to treat gout or familial Mediterranean fever). If you have kidney or liver problems, see the section 'Do not combine REZOLSTA with any of the following medications:.'
• Bosentan(to treat high blood pressure in the pulmonary circulation)
• Buspirone, chlorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as an injection(medications for sleep disorders and/or anxiety)
• Metformin(to treat type 2 diabetes)
• Fentanyl, oxycodone, tramadol(to treat pain).

Thisis not a complete list of medications. Inform your doctorof allthe medications you are taking.

Pregnancy and breastfeeding

Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant women or breastfeeding women should not take REZOLSTA. It is recommended that HIV-infected women do not breastfeed their children, both due to the risk of transmitting the infection through breast milk and the unknown effects of this medication on the child.

Driving and operating machinery

Do not operate machinery or drive if you experience dizziness after taking REZOLSTA.

Follow exactly the administration instructions for this medication as indicated by your doctor, pharmacist or nurse. In case of doubt, consult your doctor, pharmacist or nurse again.

You must take REZOLSTA daily and always with food. REZOLSTA cannot work properly without food. You must take a meal or snack within 30 minutes prior to taking REZOLSTA. The type of food is not important.

• Swallow the tablet whole with a drink that can be water or milk. If you have difficulty swallowing REZOLSTA, tell your doctor. The tablet can be split using a tablet splitter. After splitting the tablet, the entire dose (both halves) must be taken immediately with a drink that can be water or milk.

• Take your other HIV medications that are used in combination with REZOLSTA as recommended by your doctor.

Removing the child-resistant cap

If you take more REZOLSTA than you should

Inform your doctor, pharmacist or nurse immediately.

If you forget to take REZOLSTA

If you realize within 12 hours, take the tablet immediately. Take it always with food. If you realize after 12 hours, omit that dose and take the next dose as usual. Do not take a double dose to compensate for the missed dose.

If you vomit after taking REZOLSTA

If you vomitwithin less than 4 hoursafter taking the medication, you must take another dose of REZOLSTA with food as soon as possible. If you vomit when more than4 hourshave passed since you took the medication, you do not need to take another dose of REZOLSTA until the next scheduled dose.

Contact your doctorif you have doubtsabout what to do if you miss a dose or vomit.

Do not stop taking REZOLSTA without first talking to your doctor

Once treatment has started, do not stop it without your doctor's instructions.

Antiretroviral medications can make you feel better. Even if you feel better, do not stop taking REZOLSTA. Consult your doctor first.

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

During HIV treatment, there may be an increase in weight and blood glucose and lipid levels. This may be partly related to health recovery and lifestyle, and in the case of blood lipids, sometimes to HIV medications themselves. Your doctor will monitor these changes.

Like all medications, this medication may produce side effects, although not all people will experience them.

Inform your doctor if you experience any of the following side effects.

There have been reports of liver problems that may be occasionally severe. Your doctor should perform blood tests before starting treatment with REZOLSTA. If you have chronic hepatitis B or C virus infection, your doctor should repeat blood tests more frequently, as you may have a higher probability of experiencing liver problems. Discuss liver problem signs and symptoms with your doctor. They may include yellowing of the skin or white of the eyes, dark-colored urine (like dark tea), pale-colored stools (deposits), nausea, vomiting, loss of appetite, or pain, discomfort, or pain and discomfort in the right side below the ribs.

A frequent side effect of REZOLSTA is skin rash (more frequent when used in combination with raltegravir), itching. The rash is usually mild or moderate. Skin rash may also be a symptom of a rare severe disorder. Therefore, it is essential to discuss your symptoms with your doctor if you experience a rash. Your doctor will instruct you on how to act on your symptoms and whether you should stop taking REZOLSTA.

Other severe side effects, seen in up to 1 in 10 patients, were diabetes. Pancreatitis (inflammation of the pancreas) has been reported in up to 1 in 100 patients.

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

• headache
• diarrhea, nausea.

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

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

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

• symptoms of infection or autoimmune disorders (inflammatory reconstitution syndrome)
• osteonecrosis (bone tissue death caused by loss of blood supply to the bone)
• breast enlargement
• altered blood test results, such as some pancreatic tests, high sugar levels, altered lipid levels (fats). Your doctor will explain these results
• allergic reactions such as urticaria, severe skin and tissue inflammation (more frequent in the lips or eyes)
• severe skin rash with blisters and peeling, especially 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 lymph node swelling, increased eosinophils (a type of white blood cell), liver, kidney, or lung effects].

Side effects with unknown frequency: a rash may become severe or potentially fatal:

• skin rash with blisters and peeling on most of the body
• red rash covered with small pus-filled blisters that may spread across the body, sometimes with fever.

Some side effects are typical of HIV medications that belong to the same family as REZOLSTA. These are:

• weakness or muscle pain. In rare cases, these muscle disorders may be severe.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is a possible side effect that does not appear in this prospectus. You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

Keep this medication out of the sight and reach of children.

Do not use this medication after the expiration date that appears on the box and on the bottle after CAD. The expiration date is the last day of the month indicated.

Do not use this medication after 6 weeks following the first opening of the bottle.

REZOLSTA does not require special conditions for conservation.

Medications should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. In this way, you will help protect the environment.

Composition of REZOLSTA

• The active ingredients are darunavir and cobicistat. Each tablet contains 800 mg of darunavir (as etanolate) and 150 mg of cobicistat.
• The other components are hypromellose, microcrystalline cellulose, colloidal silicon dioxide, crospovidone, and magnesium stearate. The coating film contains partially hydrolyzed polyvinyl alcohol, titanium dioxide, polyethylene glycol (macrogol), talc, red iron oxide, and black iron oxide.
• This medicine contains less than 1 mmol of sodium (23 mg) per unit dose; it is essentially "sodium-free".

Appearance of the product and contents of the pack

Pink, oval-shaped, film-coated tablet, engraved with "TG" on one side and "800" on the other. 30 tablets in a plastic bottle.

Marketing Authorization HolderJanssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Manufacturer

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

For more information about this medicine, please contact the local representative of the marketing authorization holder:

Last update of this leaflet: {MM/AAAA}.

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