REZOLSTA 800 MG/150 MG FILM-COATED TABLETS

Introduction

Prospect: information for the user

REZOLSTA 800 mg/150 mg - film-coated tablets

darunavir/cobicistat

Read the entire prospectus carefully before starting to take this medication, as it contains important information for you.

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

Contents of the prospectus

1. What is REZOLSTA and what is it used for
2. What you need to know before taking REZOLSTA

1. How to take REZOLSTA
2. Possible side effects
3. Storage of REZOLSTA
4. Package contents and additional information

1. What is REZOLSTA and what is it used for

What is REZOLSTA?

REZOLSTA contains the active ingredients darunavir and cobicistat.

Darunavir belongs to a group of HIV medications called "protease inhibitors", which reduce 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 suffering from diseases related to HIV infection, although REZOLSTA is not a cure for HIV infection.

What is it used for?

REZOLSTA is used to treat adults and adolescents from 12 years of age 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.

2. What you need to know before taking REZOLSTA

Do not take REZOLSTA

• if you are allergicto darunavir, cobicistat, or any of the other components of this medication (listed in section 6).
• if you have had severe liver problems. Ask your doctor if you have doubts about the severity of your liver disease. You may need to undergo 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.

When receiving this medication, you can still transmit HIV, although the risk is reduced with effective antiretroviral treatment. Consult your doctor about the necessary precautions to avoid infecting others.

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

People taking REZOLSTA may develop a skin rash. In rare cases, a rash can become 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 rashes (usually mild or moderate) may occur more frequently 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, talk to your doctor before taking REZOLSTA.

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

• Tell your doctor if you have had any liver diseasein the past, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding whether you can take REZOLSTA.
• Tell your doctor if you have had kidney problems. Your doctor will carefully consider whether to treat you with REZOLSTA.
• Tell your doctor if you have diabetes. REZOLSTA may increase your blood sugar levels.
• Tell your doctor immediately if you experience any symptoms 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 due to previous infections may appear 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 infections that may not have shown obvious symptoms.
• In addition to opportunistic infections, you may experience autoimmune disorders(a situation where the immune system attacks healthy body tissues) after starting HIV treatment. Autoimmune disorders can occur 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 moving towards the trunk, palpitations, tremors, or hyperactivity, inform your doctor immediately so that they can provide the necessary treatment.
• Tell your doctor if you have hemophilia. REZOLSTA may increase the risk of bleeding.
• Tell your doctor if you are allergic to sulfonamides(e.g., to treat certain infections).
• Tell your doctor if you notice any musculoskeletal problems. Some patients receiving combined antiretroviral therapy may develop a bone disease called osteonecrosis (destruction of bone tissue caused by interrupted blood flow to the bone). This is more likely with long-term HIV treatment, more severe immune system damage, overweight, or consumption of alcohol or other medications called corticosteroids. Signs of osteonecrosis are joint stiffness, discomfort, and pain (especially in the hip, knee, and shoulder) and difficulty moving. If you notice 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 kilograms.

Taking REZOLSTA with other medications

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

Some other medications should not be combinedwith REZOLSTA. These medications are listed below in the section "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 their instructions strictly regarding 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(for 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 their therapeutic effect or side effects; your doctor may need to perform blood tests to monitor you.
• Clonazepam(to prevent seizures).
• Hormonal contraceptives and hormone replacement therapy. REZOLSTA may reduce their effectiveness. When used for birth control, alternative non-hormonal contraceptive methods are recommended.
• Ethinylestradiol/drospirenone. REZOLSTA may increase the risk of elevated potassium levels due to the effect of drospirenone.
• Atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin(to reduce cholesterol levels). There may be a higher risk of muscle damage. Your doctor will assess which cholesterol-reducing regimen is best for your 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 diseases, inflammatory eye, joint, and muscle disorders, and other inflammatory conditions. If alternatives cannot be used, their use should only be done after a clinical evaluation and 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)
• Clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as an injection(medications for sleep disorders and/or anxiety)
• Sildenafil, tadalafil, vardenafil(for 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).

It may be necessary to adjust the dosage of other medications if their therapeutic or adverse effects or those of REZOLSTA are affected when administered together. Inform your doctor if you take:

• Alfentanil(a strong, short-acting injectable analgesic used for surgical procedures)
• Digoxin(to treat certain heart disorders)
• Clarithromycin(an antibiotic)
• Clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole(against fungal infections). Voriconazoleshould only be taken after medical evaluation of the patient.
• Rifabutin(against bacterial infections)
• Tadalafil, sildenafil, vardenafil(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)
• Colchicine(to treat gout or familial Mediterranean fever). If you have kidney and/or liver failure, see the section "Do not combine REZOLSTA with any of the following medications."
• Bosentan(to treat high blood pressure in the pulmonary circulation)
• Buspirone, clorazepate, 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).

This is nota complete list of medications. Inform your doctor of allthe medications you are taking.

Pregnancy and breastfeeding

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

Driving and using machines

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

3. How to take REZOLSTA

Follow the administration instructions of this medication exactly 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 before 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 cut using a tablet cutter. After cutting 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 following the recommendations of 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 hoursafterwards, take the tablet immediately. Always take it with food. If you realize after 12 hours, skip that dose and take the next dose as usual. Do not take a double dose to make up for the forgotten dose.

If you vomit after taking REZOLSTA

If you vomit 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 than 4 hourshave passed since you took the medication, it is not necessary to take another dose of REZOLSTA until the next scheduled administration time.

Contact your doctor if you have doubtsabout what to do if you forget a dose or vomit.

Do not stop taking REZOLSTA without talking to your doctor

Once treatment is started, it should not be suspended without the doctor's instructions.

HIV 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.

4. Possible side effects

During HIV treatment, there may be an increase in weight and glucose and lipid levels in the blood. This may be partly related to the recovery of health 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 can cause side effects, although not all people experience them.

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

Liver problems have been described, which can occasionally be serious. Your doctor should perform blood tests before you start treatment with REZOLSTA. If you have chronic hepatitis B or C infection, your doctor should repeat blood tests more frequently, as you may have a higher risk of liver problems. Talk to your doctor about the signs and symptoms of liver problems. They may include yellowing of the skin or the whites of the eyes, dark-colored urine (like dark tea), pale-colored stools (bowel movements), nausea, vomiting, loss of appetite, or pain, discomfort, or pain and discomfort in the right side below the ribs.

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

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

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

• headache
• diarrhea, nausea

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

• allergic reactions such as itching
• loss of appetite
• abnormal dreams
• vomiting, abdominal pain or swelling, indigestion, flatulence
• muscle pain
• fatigue
• altered blood test results, such as some liver or kidney tests. Your doctor will explain these results
• 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
• altered blood test results, such as some tests related to the pancreas, high sugar levels, altered "lipid" (fat) levels. Your doctor will explain these results
• allergic reactions such as hives, severe skin and tissue inflammation (more frequent in the lips or eyes)
• severe rash with blisters and peeling of the skin, 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 can be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cell), effects on the liver, kidney, or lung]

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

• rash with blisters and peeling of the skin over a large part of the body
• red rash covered with small blisters filled with pus that can spread throughout 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 can be serious

Reporting side effects

If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are possible side effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can help provide more information on the safety of this medication.

5. Storage of REZOLSTA

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the carton and on the bottle after EXP. The expiration date is the last day of the month indicated.

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

REZOLSTA does not require special storage conditions.

Medications should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medications you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of REZOLSTA

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

Appearance and package contents

Film-coated tablet, pink, oval, engraved with TG on one side, 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

You can request more information about this medication by contacting the local representative of the marketing authorization holder:

Date of last revision of this leaflet: {MM/AAAA}.

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