Symtuza 800 mg/150 mg/200 mg/10 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Symtuza 800 mg/150 mg/200 mg/10 mg film-coated tablets

darunavir/cobicistat/emtricitabine/tenofovir alafenamide

This medicine is under additional monitoring, which will allow quicker identification of new safety information. You can help by reporting any side effects you may experience. Section 4, towards the end, includes information on how to report side effects.

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

• Keep this leaflet, as 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 and must not be given to other people, even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Symtuza is and what it is used for

Symtuza is an antiretroviral medicine used to treat infection with human immunodeficiency virus type 1 (HIV-1). It is used in adults and adolescents 12 years of age and older, weighing at least 40 kilograms. Symtuza contains four active substances:

• darunavir, an HIV medicine known as a protease inhibitor
• cobicistat, a booster (enhancer) of darunavir
• emtricitabine, an HIV medicine known as a nucleoside reverse transcriptase inhibitor
• tenofovir alafenamide, an HIV medicine known as a nucleotide reverse transcriptase inhibitor

Symtuza reduces the amount of HIV-1 in your body, thereby improving your immune system (your body's natural defences) and reducing the risk of developing HIV-related illnesses, although Symtuza is not a cure for HIV infection.

2. What you need to know before starting to take Symtuza

Do not take Symtuza

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

Do not combine Symtuza with any of the following medicines

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

Warnings and precautions

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

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

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

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

Talk to your doctor before taking Symtuza. Inform your doctor immediately if you are in any of the following situations.

• If you have had liver problems, including hepatitis B or C infection. Your doctor will assess the severity of your liver disease before deciding whether you can take Symtuza.

• If you have hepatitis B, your liver problems may worsen when you stop taking Symtuza. It is important not to stop taking Symtuza without first talking to your doctor.

• If you have had kidney problems. Your doctor will consider whether Symtuza is suitable for you.

• If you have diabetes. Symtuza may increase blood sugar levels.

• If you notice any signs of infection (e.g., swollen lymph nodes and fever). Some patients with advanced HIV infection and a history of unusual infections due to a weakened immune system (opportunistic infections) may experience signs and symptoms of inflammation from previous infections shortly after starting HIV treatment. These symptoms are believed to result from the improvement in the body's immune response, allowing it to fight infections that may have been present but without evident symptoms.

• If you notice symptoms such as muscle weakness, weakness starting in the hands and feet and progressing toward the trunk, palpitations, tremor, or hyperactivity, tell your doctor immediately. In addition to opportunistic infections, you may also develop autoimmune disorders (when the immune system attacks healthy body tissues) due to the improvement in immune response after starting medications for HIV infection. Autoimmune disorders may occur many months after starting treatment.

• If you have haemophilia. Symtuza may increase the risk of bleeding.

• If you are allergic to sulfonamides (used, for example, to treat certain infections).

• If you notice any muscle or bone problems. Some patients receiving HIV medications may develop a bone disease called osteonecrosis (damage to bone tissue caused by reduced blood supply to the bones). This is more likely with long-term HIV treatment, more severe immune system damage, obesity, or with alcohol use or corticosteroid medications. Signs of osteonecrosis include joint stiffness, discomfort, and pain (especially in the hip, knee, or shoulder) and difficulty moving. If you experience any of these symptoms, speak with your doctor.

Elderly patients

Symtuza has been used in only a limited number of patients aged 65 years or older. If you belong to this age group, talk to your doctor to determine whether you can use Symtuza.

Children and adolescents:

Symtuza must not be used in children under 12 years of age or weighing less than 40 kg, as it has not been studied in children under 12 years of age.

Other medicines and Symtuza

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

Some medicines must not be combined with Symtuza. These medicines are listed earlier in the section titled «Do not combine Symtuza with any of the following medicines:»

Symtuza must not be used with other antiviral medicines containing a booster or with other antivirals that require boosting. In some cases, it may be necessary to adjust the dose of other medicines. Therefore, always inform your doctor if you are taking any other HIV medicines and strictly follow your doctor's instructions regarding which medicines can be combined.

In addition, you must not take Symtuza with medicines containing tenofovir disoproxil (such as fumarate, phosphate, or succinate), lamivudine or adefovir dipivoxil, or with medicines that require boosting with ritonavir or cobicistat.

The effects of Symtuza may be reduced if you take any of the following products. Inform your doctor if you are taking:

• Bosentan (to treat high blood pressure in the pulmonary circulation)
• Dexamethasone (injection) (corticosteroid)
• Rifapentine, rifabutin (to treat bacterial infections)
• Oxcarbazepine (to prevent seizures).

Symtuza may also affect the effects of other medicines. Inform your doctor if you are taking:

• Amlodipine, diltiazem, disopyramide, felodipine, flecainide, mexiletine, nicardipine, nifedipine, propafenone, lidocaine, verapamil (for heart conditions), as the therapeutic effect or side effects of these medicines may be increased.

• Bosentan (to treat high blood pressure in the pulmonary circulation)

• Apixaban, edoxaban, rivaroxaban, clopidogrel (to reduce blood clotting), as the therapeutic effect or adverse effects may be altered.

• Clonazepam (to prevent seizures).

• Hormonal contraceptives based on oestrogens and hormone replacement therapy. Symtuza may reduce their effectiveness. When used as contraceptives, the use of alternative non-hormonal contraceptive methods is recommended.

• Ethinylestradiol/drospirenone. Symtuza may increase the risk of elevated potassium levels due to drospirenone.

• Budesonide, fluticasone (to control asthma). These should only be used after medical evaluation and under close medical supervision due to the risk of corticosteroid-related adverse effects.

• Buprenorphine/naloxone, methadone (medicines for opioid dependence treatment)

• Salmeterol (medicine for treating asthma)

• Artemether/lumefantrine (a combination of medicines for treating malaria)

• Dasatinib, irinotecan, nilotinib, vinblastine, vincristine (medicines for treating cancer)

• Prednisone (corticosteroid)

• Sildenafil, tadalafil, vardenafil (to treat erectile dysfunction or a heart and lung disorder called pulmonary arterial hypertension)

• Glecaprevir/pibrentasvir (to treat hepatitis C virus infection).

• Fentanyl, oxycodone, tramadol (to treat pain).

• Fesoterodine, solifenacin (to treat urological disorders).

Dosage adjustments of other medicines may be necessary, as their therapeutic or adverse effects or those of Symtuza may be affected when administered together. Inform your doctor if you are taking:

• Alfentanil (a potent, short-acting injectable analgesic used during surgical procedures)

• Carvedilol, metoprolol, timolol (for heart conditions)

• Warfarin (to reduce blood clotting), as the therapeutic effect or adverse effects may be altered; your doctor may need to perform blood tests.

• Digoxin (to treat certain heart disorders)

• Clarithromycin (antibiotic)

• Clotrimazole, fluconazole, isavuconazole, itraconazole, posaconazole (to treat fungal infections). Voriconazole should only be taken after medical evaluation of the patient.*

• Atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin (to reduce cholesterol levels). There may be an increased risk of muscle injury. Your doctor will evaluate which cholesterol-lowering regimen is best for your individual situation.

• Rifabutin (to combat 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)

• Perphenazine, risperidone, thioridazine (psychiatric medicines)

• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), as the therapeutic effect or adverse effects of these medicines may be increased. Your doctor may wish to perform additional tests.

• Colchicine (anti-gout medicine). If you have kidney or liver problems, see the section «Do not combine Symtuza with any of the following medicines*»* .

• Buspirone, chlordiazepoxide, diazepam, estazolam, flurazepam, zolpidem, midazolam when used by injection (medicines used to treat sleep problems or anxiety)

• Metformin (to treat type 2 diabetes)

This list of medicines is not exhaustive. Inform your healthcare provider 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 Symtuza.

Women with HIV are advised not to breastfeed their babies due to the risk of transmitting HIV through breast milk and because the medicine may affect the infant.

Driving and using machines

Symtuza may cause dizziness. Do not operate machinery or drive if you experience dizziness after taking Symtuza.

Symtuza contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

3. How to take Symtuza

Symtuza must be taken exactly as prescribed by your doctor.

• Take Symtuza once daily with food.
• Swallow the tablets whole with water. Do not chew, crush, or split the tablets.
• Take Symtuza at the same time each day, with or without other antiretroviral medications.
• Continue taking Symtuza for as long as your doctor recommends, even if you feel well. Stopping treatment may lead to worsening of your condition and increase the risk of developing resistance to antiretroviral drugs.

If you have any questions about how to take Symtuza, speak with your doctor or pharmacist.

Follow exactly the instructions for administering this medication as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

The recommended dose in adults and adolescents aged 12 years and older weighing at least 40 kg is one tablet once daily with food.

You must take Symtuza daily and always with food. You should eat a meal or snack within the 30 minutes before taking Symtuza. The type of food is not important.

• The tablet must not be crushed; instead, it should be swallowed whole. The tablet may be taken with a drink, such as water, milk, or a nutritional beverage. Take Symtuza around the same time each day.

How to open the child-resistant cap

If you take more Symtuza than you should

Contact your doctor or the nearest emergency department immediately and ask for help. Take the container with you so you can show what you have taken.

If you forget to take Symtuza

It is important that you do not miss a dose of Symtuza.

If you miss a dose:

• If you remember within 12 hours after the time you usually take Symtuza, take the tablet immediately with food. Then take the next dose at your usual time.
• If you remember 12 hours or more after the time you usually take Symtuza, do not take the missed dose and take the next doses at your usual time, with food. Do not take a double dose to make up for the missed dose.

If you vomit within 1 hour of taking the medicine, you should take another dose of Symtuza with food as soon as possible. If you vomit more than 1 hour after taking the medicine, you do not need to take another dose of Symtuza until the next scheduled time.

Contact your doctor if you have any doubts about what to do if you miss a dose or vomit.

Do not stop taking Symtuza without first talking to your doctor

HIV medicines can make you feel better. Even if you feel well, do not stop taking Symtuza. Talk to your doctor first.

When you are running low on Symtuza, contact your doctor or pharmacist for a new supply. This is very important because the amount of virus may start to increase if you stop taking the medicine, even for a short period of time. The disease would then be more difficult to treat.

If you have both HIV infection and hepatitis B, it is very important that you do not stop taking Symtuza without first talking to your doctor. You may need to have blood tests for several months after stopping treatment with Symtuza. In some patients with advanced liver disease or cirrhosis, hepatitis may worsen after stopping treatment, which could potentially be fatal.

Tell your doctor as soon as possible if you experience any new or unusual symptoms after stopping treatment, especially symptoms related to hepatitis B infection.

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

4. Possible adverse effects

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

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

Liver problems have been reported, which may sometimes be serious. Your doctor should carry out blood tests before you start treatment with Symtuza. If you have chronic hepatitis B or C virus infection, your doctor will need to 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 tea), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, discomfort, or tenderness on the right side under the ribs.

A skin rash may occur in more than 1 in 10 patients treated with Symtuza. Although most rashes are mild and resolve over time even if treatment continues, they may sometimes be severe or potentially life-threatening. It is important that you 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 Symtuza.

Other serious adverse effects observed in up to 1 in 10 patients included diabetes, increased blood fat levels, and symptoms of infection. Pancreatitis (inflammation of the pancreas) has been reported in up to 1 in 100 patients.

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

• headache
• diarrhea
• skin rash

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

• low red blood cell count (anemia)

• allergic reactions, such as hives, itching

• decreased appetite (anorexia)

• abnormal dreams

• vomiting, stomach pain or bloating, indigestion, flatulence (gas)

• abnormal blood test results, such as certain kidney tests. Your doctor will explain these to you.

• dizziness

• joint pain

• muscle pain, cramps, or muscle weakness

• weakness

• tiredness (fatigue)

• feeling unwell (nausea)

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

• severe inflammation of the skin and other tissues (more frequent in lips or eyes)

• symptoms of infection or autoimmune disorders (immune reconstitution inflammatory syndrome)

• enlargement of the breasts

• osteonecrosis (bone tissue damage caused by loss of blood supply to the bones)

• abnormal blood test results, such as certain pancreatic tests. Your doctor will explain these to you.

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, facial swelling or swollen lymph nodes, increased eosinophils (a type of white blood cell), and effects on the liver, kidneys, or lungs].

Some adverse effects are typical of HIV medicines similar to Symtuza. These include:

• increased blood sugar levels and worsening of diabetes
• muscle pain, tenderness, or weakness. In rare cases, these muscle disorders have been severe.
• immune reconstitution inflammatory syndrome. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (infections that are uncommon due to weakened immune system), signs and symptoms of inflammation from previous infections may appear shortly after starting HIV treatment, including Symtuza. In addition to opportunistic infections, you may develop an autoimmune disorder (a condition in which the immune system attacks healthy body tissues) after starting medications for HIV infection. Autoimmune disorders may occur many months after starting treatment.

If you experience any of these symptoms, inform your doctor.

During HIV treatment, weight gain and increased levels of lipids and glucose in the blood may occur. This is partly related to improved health and lifestyle changes, and in the case of blood lipids, sometimes to the HIV medicines themselves.

Your doctor will perform tests to detect these changes.

Reporting of adverse effects

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

5. Storage of Symtuza

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 the month indicated.

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

Store in the original container to protect from moisture. Keep the bottle tightly closed. Tablets may be kept outside the original container for up to 7 days and must be discarded if not taken within this time. Tablets stored outside the original container must not be returned to it.

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

6. Contents of the pack and other information

Composition of Symtuza

The active substances are darunavir, cobicistat, emtricitabine and tenofovir alafenamide. Each film-coated tablet contains 800 mg of darunavir (as ethanolate), 150 mg of cobicistat, 200 mg of emtricitabine and 10 mg of tenofovir alafenamide (as fumarate).

Other components are:

Tablet core:

The tablet core contains croscarmellose sodium, magnesium stearate, microcrystalline cellulose and colloidal silicon dioxide.

Tablet coating:

The film coating contains polyethylene glycol (macrogol), polyvinyl alcohol (partially hydrolysed), talc, titanium dioxide and yellow iron oxide.

Appearance of the product and contents of the pack

Film-coated tablet, capsule-shaped, ranging from yellow to brownish yellow, marked with the inscription «8121» on one side and «JG» on the other.

Symtuza is available in bottles containing 30 tablets (with silica gel as a desiccant, which should be kept in the bottle to help protect the tablets). The silica gel desiccant is included in a separate sachet or reservoir and must not be ingested.

Symtuza tablets are available in packs containing one or three bottles per carton.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, 2340 Beerse, Belgium

Manufacturer responsible for manufacturing
Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy

More information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorisation Holder:

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

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