Rezolsta 800 mg/150 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

REZOLSTA 800 mg/150 mg - film-coated tablets

darunavir/cobicistat

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

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

Leaflet contents

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", which work by reducing the amount of HIV in your body to a very low level. Darunavir is given 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 HIV-related illnesses, although REZOLSTA is not a cure for HIV infection.

What is it used for?

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

REZOLSTA must be taken in combination with other HIV medicines. Your doctor will explain the most appropriate combination of medicines for you.

2. What you need to know before starting 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 had severe liver problems. Ask your doctor if you are unsure about the severity of your liver disease. You may need additional tests.

Do not combine REZOLSTA with any of the following medicines

If you are taking any of these medicines, consult your doctor to switch to an alternative treatment.

Warnings and precautions

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

While taking this medicine, you may still transmit HIV, although the risk is reduced with effective antiretroviral therapy. Please consult your doctor about the necessary precautions to avoid infecting others.

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

People taking REZOLSTA may develop a skin rash. Rarely, a rash may become severe or potentially life-threatening. Please consult your doctor if you develop 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 medicines separately.

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

Check the following points and inform your doctor if any of these situations apply to you.

• Inform your doctor if you have previously had any liver disease, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding whether you can take REZOLSTA.
• Inform your doctor if you have had kidney problems. Your doctor will carefully consider whether REZOLSTA treatment is appropriate for you.
• Inform your doctor if you have diabetes. REZOLSTA may increase blood sugar levels.
• Inform your doctor immediately if you experience any signs of infection (for example, 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 from previous infections may appear shortly after starting HIV treatment. These symptoms are believed to result from improved immune response, enabling the body to fight infections that were previously present but asymptomatic.
• In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissues) may occur after starting medications for HIV infection. Autoimmune disorders may 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 toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately so appropriate treatment can be provided.
• Inform your doctor if you have haemophilia. REZOLSTA may increase the risk of bleeding.
• Inform your doctor if you are allergic to sulfonamides (e.g., used to treat certain infections).
• Inform your doctor if you notice any musculoskeletal problems. Some patients receiving combination antiretroviral therapy may develop a bone condition called osteonecrosis (bone tissue destruction caused by interrupted blood supply to the bone). This is more likely with long-term HIV treatment, more severe immune system damage, overweight, or use of alcohol or other medicines called corticosteroids. Signs of osteonecrosis include joint stiffness, discomfort, pain (especially in the hip, knee, or shoulder), and difficulty moving. If you notice any of these symptoms, inform your doctor.

Children and adolescents

REZOLSTA must not be used in children under 12 years of age, or who weigh less than 40 kilograms.

Taking REZOLSTA with other medicines

Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Some other medicines must not be combined with REZOLSTA. These medicines are listed later in the section titled ‘Do not combine REZOLSTA with any of the following medicines:’.

REZOLSTA must not be used with any other antiviral medicine containing a booster or another antiviral requiring 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 HIV medicines, and strictly follow your doctor’s instructions regarding which medicines can be combined.

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

• Bosentan (for heart disease)
• Dexamethasone (injectable) (corticosteroid)
• Efavirenz, etravirine, nevirapine (for treating HIV infection)
• Rifapentine, rifabutin (for treating bacterial infections)

REZOLSTA may also affect the effects of other medicines. 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 medicines may increase.
• Apixaban, edoxaban, rivaroxaban, warfarin (to reduce blood clotting), as their therapeutic effect or side effects may be altered; your doctor may need to perform blood tests to monitor your condition.
• Clonazepam (to prevent seizures).
• Estrogen-containing hormonal contraceptives and hormone replacement therapy. REZOLSTA may reduce their effectiveness. When used for birth control, use of alternative non-hormonal contraceptive methods is recommended.
• Ethinylestradiol/drospirenone. REZOLSTA may increase the risk of elevated potassium levels caused by drospirenone.
• Atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin (to reduce cholesterol levels). There may be an increased risk of muscle damage. Your doctor will evaluate which cholesterol-lowering regimen is best suited to your individual situation.
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress your immune system), as the therapeutic effect or side effects of these medicines may increase. Your doctor may wish to perform additional tests.
• Corticosteroids, including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory eye, joint, and muscle conditions, and other inflammatory disorders. If alternative treatments are not available, their use should only occur after clinical evaluation and with close monitoring by your doctor for corticosteroid-related adverse effects.
• Buprenorphine/naloxone, methadone (medicines for opioid dependence treatment)
• Salmeterol (medicine for asthma treatment)
• Artemether/lumefantrine (a combination of medicines for treating malaria)
• Dasatinib, irinotecan, nilotinib, vinblastine, vincristine (medicines for cancer treatment)
• Perphenazine, risperidone, thioridazine (psychiatric medicines)
• Chlordiazepoxide, diazepam, estazolam, flurazepam (medicines for treating 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)

Dosage adjustments of other medicines may be necessary if their therapeutic or adverse effects or those of REZOLSTA are affected when taken together. Inform your doctor if you take:

• Alfentanil (a potent, short-acting injectable analgesic used during surgical procedures)
• Digoxin (to treat certain heart conditions)
• Clarithromycin (antibiotic)
• Clotrimazole, fluconazole, itraconazole, isavuconazole, posaconazole (for fungal infections). Voriconazole should only be taken after medical evaluation of the patient.
• Rifabutin (for 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 renal and/or hepatic impairment, see section “Do not combine REZOLSTA with any of the following medicines”.
• Bosentan (to treat high blood pressure in the pulmonary circulation)
• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as an injection (medicines to treat sleep problems 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 of all medicines you are taking.

Pregnancy and breastfeeding

Inform your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant or breastfeeding women must not take REZOLSTA. Women with HIV infection are advised not to breastfeed their infants, both due to the risk of transmitting the infection through breast milk and because of the unknown effects this medicine may have on the infant.

Driving and using machines

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

3. How to take REZOLSTA

Follow exactly the administration instructions for this medicine as indicated by your doctor, pharmacist, or nurse. If in 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 eat a meal or snack within 30 minutes before taking REZOLSTA. The type of food is not important.

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

• Take your other HIV medicines used in combination with REZOLSTA according to your doctor's instructions.

Removing the child-resistant cap

If you take more REZOLSTA than you should

Contact your doctor, pharmacist, or nurse immediately.

If you forget to take REZOLSTA

If you remember within 12 hours, take the missed dose immediately. Always take it with food. If you remember after 12 hours, skip that dose and take the next dose at your usual time. Do not take a double dose to make up for the forgotten dose.

If you vomit after taking REZOLSTA

If you vomit within 4 hours after taking the medicine, 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 your 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 taking REZOLSTA without first talking to your doctor

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

HIV medicines can make you feel better. Even if you feel better, do not stop taking REZOLSTA. Always consult your doctor first.

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

4. Possible adverse effects

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

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

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

Liver problems have been reported, which may occasionally be serious. Your doctor will perform blood tests before you start 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 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-colored urine (like strong tea), pale-colored stools (faeces), nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness on the right side under the ribs.

A common adverse effect of REZOLSTA is skin rash (more common when used in combination with raltegravir), and itching. The rash is usually mild or moderate. Skin rash may also be a symptom of a rare but serious disorder. Therefore, it is important to speak with your doctor if you develop a rash. Your doctor will advise you on how to manage your symptoms and whether you should stop taking REZOLSTA.

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

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

• headache
• diarrhoea, nausea

Common adverse 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 some tests related to your liver or kidneys. Your doctor will explain these results to you
• weakness

Uncommon adverse 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)
• enlargement of the breasts
• abnormal blood test results, such as some tests related to your pancreas, high blood sugar levels, altered levels of “lipids” (fats). Your doctor will explain these results to you
• allergic reactions such as hives, severe swelling of the skin and other tissues (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 adverse 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]

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

• rash with blisters and peeling of the skin over large areas of the body
• red rash covered with small pustule-filled blisters that may spread over the body, sometimes with fever

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

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

Reporting of adverse effects

If you experience any type of adverse effect, talk to your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of REZOLSTA

Keep this medicinal product out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and the bottle after "EXP". The expiry date refers to the last day of that month.

Store the bottle in the outer carton. Keep the bottle tightly closed to protect the medicinal product from moisture.

Do not use this medicine if you notice any signs of deterioration.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

Keep the bottle tightly closed and store it in the original packaging to protect from moisture.

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

Do not use this medicine after the expiry date stated on the carton and on the bottle after EXP. The expiry date refers to the last day of the month indicated.

Do not use this medicine more than 6 weeks after first opening the bottle.

REZOLSTA does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and containers you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of REZOLSTA

• 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, silicified microcrystalline cellulose, colloidal silicon dioxide, crospovidone and magnesium stearate. The film-coating contains partially hydrolysed 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 dose unit; that is, essentially "sodium-free".

Appearance of the product and contents of the pack

Film-coated tablet, pink in colour, oval-shaped, engraved 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, 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 Authorisation Holder:

Date of the most recent review of this leaflet: {MM/YYYY}.

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