Product Information for the User

Symtuza 800 mg/150 mg/200 mg/10 mg Film-Coated Tablets

darunavir/cobicistat/emtricitabina/tenofovir alafenamida

This product is subject to additional monitoring, which will facilitate the detection of new information about its safety. You can contribute by reporting any adverse effects you may experience. The final part of section 4 includes information on how to report these adverse effects.

Read this entire product information carefully before starting to take this product, because

it contains important information for you.

• Keep this product information, as you may need to refer to it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This product has been prescribed to you alone, and you must not give it to other people

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 product information. See section 4.

1. What you need to know before starting to take Symtuza
2. How to take Symtuza
3. Possible adverse effects

1. Storage of Symtuza
2. Contents of the pack and additional information

Symtuza is an antiretroviral medication used to treat human immunodeficiency virus type 1 (HIV-1) infection. It is used in adults and adolescents aged 12 years and older, with a minimum weight of 40 kilograms. Symtuza contains four active ingredients:

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

Symtuza reduces HIV-1 in your body, which will improve your immune system (natural defenses of the body) and reduce the risk of developing diseases related to HIV infection, although Symtuza is not a cure for HIV infection.

Do not take Symtuza

• if you areallergic(hypersensitive) to darunavir, cobicistat, emtricitabina, tenofovir alafenamida, or any of the other components of this medication (listed in section 6).
• if you havesevere liver problems. Ask your doctor if you have any doubts about the severity of your liver disease. You may need to have some additional tests.

Do not combine Symtuza with any of the following medications

If you are taking any of them, consult your doctor about the possibility of changing to another medication.

Warnings and precautions

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

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

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

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

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

• if you have hadliver 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 havehepatitis B, your liver problems may worsen when you stop taking Symtuza. It is essential to not stop taking Symtuza without consulting your doctor.
• if you have hadkidney problems. Your doctor will consider whether Symtuza is suitable for you.
• if you havediabetes. Symtuza may increase blood sugar levels.

• if you observe anysigns of infection(e.g., swollen lymph nodes and fever). Some patients with advanced HIV infection and who had unusual infections due to a weakened immune system (opportunistic infection) may experience signs and symptoms of inflammation due to previous infections 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 not have shown obvious symptoms.
• if you observe 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. In addition to opportunistic infections, you may also experienceautoimmune disorders(when the immune system attacks healthy body tissues) due to the improvement of the body's immune response after starting HIV treatment. Autoimmune disorders can appear many months after starting treatment.

• if you havehemophilia. Symtuza may increase the risk of bleeding.

• if you areallergic to sulfonamides(used, e.g., to treat certain infections).
• if you observe anymuscle and bone problems. Some patients receiving HIV medications may experience a bone disorder called osteonecrosis (bone tissue damage caused by loss of blood supply to the bones). This is more likely with long-term HIV treatment, when there is more severe immune system damage, obesity, or the use of alcohol or corticosteroid medications. Signs of osteonecrosis include joint stiffness, pain, and difficulty moving (especially in the hips, knees, and shoulders). If you experience any of these symptoms, consult your doctor.

Older adults

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

Children and adolescents:

Symtuza should 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 medications and Symtuza

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

Some medicationsshould not be combinedwith Symtuza. These medications are listed earlier in the section titled «Do not combine Symtuza with any of the following medications:»

Symtuza should not be used with other antiviral medications that contain a booster or with other antivirals that require boosting. In some cases, the dose of the other medications may need to be adjusted. Therefore, always inform your doctor if you are taking any other HIV medication and strictly follow your doctor's instructions on which medications can be combined.

Additionally, do not take Symtuza with medications that contain tenofovir disoproxil (such as fumarate, phosphate, or succinate), lamivudine, or adefovir dipivoxil, or with medications 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)(corticosteroid)
• Rifapentine, rifabutin(to treat bacterial infections)
• Oxcarbazepine(to prevent seizures).

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

• Amlodipine, diltiazem, disopyramide, felodipine, flecainide, mexiletine, nicardipine, nifedipine, propafenone, lidocaine, verapamil(for heart disease), as the therapeutic effect or side effects of these medications 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 side effects may be modified.
• Clonazepam(to prevent seizures).

• hormonal contraceptives based onestrogensand hormone replacement therapy. Symtuza may reduce their effectiveness. When used as contraceptives, alternative non-hormonal methods of contraception are recommended.

• Etinilestradiol/drospirenona. Symtuza may increase the risk of elevated potassium levels due to the drospirenone effect.
• Budesonide, fluticasone(to control asthma). It should only be used after a medical evaluation and under close monitoring by your doctor, in case you experience adverse effects of corticosteroids.

• Buprenorphine/naloxone, methadone(medications for opioid dependence treatment)
• Salmeterol(medication for asthma treatment)
• Artemether/lumefantrine(a combination of medications for malaria treatment)
• Dasatinib, irinotecan, nilotinib, vinblastine, vincristine(medications for cancer treatment)
• 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).

You may need to adjust the dosage of other medications as their therapeutic effects or side effects, or those of Symtuza, may be affected when taken together. Inform your doctor if you are taking:

• Alfentanil(injection, potent analgesic with short action, used in surgical interventions)
• Carvedilol, metoprolol, timolol(for heart disease)

• Warfarin(to reduce blood clotting), as the therapeutic effect or side effects may be modified; 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 used after a medical evaluation of the patient.

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

• Rifabutin(to combat 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)
• Perphenazine, risperidone, thioridazine(psychiatric medications)

• Ciclosporin, everolimus, tacrolimus, sirolimus(to suppress the immune system), as it may increase the therapeutic effect or side effects of these medications. Your doctor may want to perform additional tests.
• Colchicine(gout medication). If you have kidney or liver problems, see the section «Do not combine Symtuza with any of the following medications:»
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam(when used in injection, medications used to treat sleep problems or anxiety)
• Metformin(to treat type 2 diabetes)

This list of medicationsis notexhaustive. Inform your healthcare professional aboutallthe 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 mothers should not take Symtuza.

It is recommended that women with HIV not breastfeed their babies, due to the risk of the baby becoming infected with HIV through breast milk and because the medication may affect the baby.

Driving and operating machinery

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

Symtuza contains sodium

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

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

The recommended dose in adults and adolescents 12 years of age and older, weighing at least 40 kg, is one tablet once a day with food.

You must take Symtuza daily and alwayswith food. You must take a meal or a snack in the 30 minutes prior to taking Symtuza. The type of food is not important.

• The tablet should not be crushed; instead, it should be swallowed whole. The tablet can be taken with a drink, which can be water, milk, or a nutritional drink. Take Symtuza around the same time every day.

How to remove the child-resistant cap

If you take more Symtuza than you should

Get in touch with your doctor or the nearest emergency service immediately and seek help. Bring the bottle with you so they can see what you have taken.

If you forget to take Symtuza

It is very important not to miss a dose of Symtuza.

If you miss a dose:

• If you realize within less than 12 hoursafter the time you normally take Symtuza,take the tablet immediately with some food. Then take the next dose at the usual time.
• If you realize 12 hours or moreafter the time you normally take Symtuza,do not take the missed dose and take the next doses at the usual time, with some food. Do not take a double dose to make up for the missed doses.

If you vomit within the hour after taking the medication, you should take another dose of Symtuza with food as soon as possible. If you vomit more than 1 hour after taking the medication, you will 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

Antiretroviral medications can make you feel better. Although you may feel better, do not stop taking Symtuza. Consult your doctor first.

When you have little Symtuza left,ask your doctor or pharmacist for more. This is veryimportant because the amount of virus can start to increase if you stop taking the medication, even for a short period of time. The disease would then be more difficult to treat.

If you have both HIV and hepatitis B infection,it is very important that you do not stop takingSymtuza 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, there may be a worsening of hepatitis after stopping treatment, which can be potentially fatal.

Inform your doctor as soon as possibleif you experience any new or unusual symptoms after stoppingthe treatment, especially symptoms related to hepatitis B infection.

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

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

Liver problems have been described, which may be severe in some cases. Your doctor must perform blood tests before starting treatment with Symtuza. If you have a chronic hepatitis B or C virus infection, your doctor will need to repeat the blood tests more frequently, as you may be at a higher risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. They may include yellowing of the skin or the white part of the eyes, dark urine (like tea), light-colored stools, nausea, vomiting, loss of appetite, or pain, discomfort, or sensitivity in the right side below the ribs.

A skin rash may appear in more than 1 in 10 patients treated with Symtuza. Although most rashes are mild and disappear over time, even if treatment continues, they can be severe or potentially life-threatening in some cases. It is essential to talk to your doctor if you experience a rash. Your doctor will instruct you on how to manage your symptoms and whether you should stop taking Symtuza.

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

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

• Headache
• Diarrhea
• Skin rash

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

• Anemia (low red blood cell count)
• Allergic reactions, such as urticaria, itching
• Loss of appetite (anorexia)
• Abnormal dreams
• Vomiting, stomach pain, bloating, indigestion, flatulence (gas)
• Abnormal blood test results, such as some kidney function tests. Your doctor will explain this to you.
• Dizziness

• Joint pain
• Muscle pain, cramps, or weakness
• Weakness
• Fatigue (tiredness)
• Unpleasant feeling (nausea)

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

• Inflammation of the skin and other tissues (more common on the lips or eyes)
• Symptoms of infection or autoimmune disorders (inflammatory reconstitution syndrome)
• Enlargement of the breasts

• Osteonecrosis (bone tissue damage caused by loss of blood supply to the bones)
• Abnormal blood test results, such as some pancreas function tests. Your doctor will explain this to you.

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

• A reaction called DRESS (severe rash that may be accompanied by fever, fatigue, swelling of the face or lymph nodes, increased eosinophils, liver, kidney, or lung effects).

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

• Increased blood sugar and worsening of diabetes
• Muscle pain, weakness, or sensitivity. In rare cases, these muscle disorders have been severe.
• Inflammatory reconstitution syndrome. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (infrequent infections due to a weakened immune system), symptoms and signs of inflammation due to previous infections may appear shortly after starting HIV treatment, including Symtuza. In addition to opportunistic infections, you may develop an autoimmune disorder (disease that occurs when the immune system attacks healthy body tissues) after starting HIV treatment. Autoimmune disorders can appear many months after starting treatment.

Inform your doctor if you experience any of these symptoms.

During HIV treatment, you may experience weight gain and increased levels of lipids and glucose in the blood. This is related in part to the recovery of health and lifestyle habits, and in the case of lipid blood tests, sometimes to the HIV medicines themselves.

Your doctor will perform tests to detect these changes.

Reporting side effects

If you experience any type of side effect, consult your doctor, pharmacist, or nurse, even if it is not listed in this prospectus. You can also report them directly through thenational notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information about the safety of this medicine.

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.

Store in the original packaging to protect it from moisture.Keep the bottle perfectly closed.The tablets can be stored outside the original packaging for up to 7 days and must be discarded after that time if not taken. Tablets stored outside the original packaging should not be placed back in the packaging.

Medications should not be thrown down the drains or in the trash. Ask your pharmacist how to dispose of the containers and medications that you no longer need. This will help protect the environment.

Composition of Symtuza

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

The other components are:

Core of the tablet:

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

Coating of the tablet:

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

Appearance of the product and contents of the package

Film-coated tablet, with a capsule-shaped form, yellow to yellow-brown in color, with the inscription "8121" on one side and "JG" on the other.

Symtuza is presented in bottles of 30 tablets (with silica gel as a desiccant that must be kept in the bottle to help protect the tablets). The silica gel desiccant is included in a separate bag or container and should not be ingested.

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

Only some package sizes may be marketed.

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

Responsible for manufacturing

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.