Symtuza

Package leaflet: Information for the user

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

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide
Please read all of this leaflet carefully before taking this medicine because it contains
important information for you.

• Keep this leaflet. 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. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. See section 4.

Contents of this 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 human immunodeficiency virus type 1 (HIV-1) infection. It is used in adults and adolescents aged 12 years and older who weigh at least 40 kg. Symtuza contains four active substances:

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

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

2. What you should know before taking Symtuza

Do not take Symtuza

• if you are allergic (hypersensitive) to darunavir, cobicistat, emtricitabine, tenofovir alafenamide, or to any of the other ingredients of Symtuza (listed in section 6);
• if you have severe liver problems. Consult your doctor if you are unsure about the severity of your liver disease. Additional tests may be required.

Inform your doctor about all the medicines you are taking, including oral, inhaled,
injected, or topical medications.
Do not take Symtuza with any of the following medicines
If you are currently taking any of these medicines, ask your doctor how to switch to another medicine.

Consult your doctor, pharmacist, or nurse before taking Symtuza.
People taking Symtuza may still develop infections or other illnesses associated with HIV infection.
Regular follow-up with your doctor is necessary.
People taking Symtuza may develop a skin rash. Sometimes the rash may become severe or potentially life-threatening. Contact your doctor whenever a skin rash develops.
Kidney problems may occur during long-term use of Symtuza.
Talk to your doctor before taking Symtuza. Inform your doctor immediately if any of the following apply to you.

• If you have had liver problems, including hepatitis B or C infection. Your doctor may assess the severity of liver disease before deciding whether you should take Symtuza.
• If you have hepatitis B infection, liver problems may worsen once you stop taking Symtuza. It is important not to discontinue Symtuza without first discussing it with your doctor.
• If you have had kidney disease or if tests have shown kidney problems before or during treatment. Before starting and during treatment with Symtuza, your doctor may order blood tests to monitor kidney function. Your doctor will evaluate whether Symtuza is the right medicine 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). In some patients with advanced HIV infection and a history of unusual infections due to weakened immune system (opportunistic infections), signs and symptoms of inflammation from previous infections may occur soon after starting HIV treatment. These symptoms are thought to be due to an improved immune response.

allowing the body to fight infections that may have been present without obvious symptoms.

• If you notice symptoms such as muscle weakness, initial weakness in hands and feet spreading toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately. In addition to opportunistic infections, autoimmune disorders (when the immune system attacks healthy body tissue) may also occur after starting medications for HIV treatment, due to an improved immune response. 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 taking anti-HIV medicines may develop a bone disease called osteonecrosis (bone damage caused by reduced blood supply to the bone). This is more likely with long-term HIV treatment, more severe immune system damage, being overweight, or use of alcohol or medicines called corticosteroids. Signs of osteonecrosis include swelling, pain, and stiffness in the joints (especially the hip, knee, and shoulders) and difficulty moving. If you notice any of these symptoms, inform your doctor.

Elderly
Symtuza has been administered to a limited number of patients aged 65 years or older. If you belong to this age group, consult your doctor to determine whether you can use Symtuza.
Children and adolescents
Symtuza is not intended for use 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, have recently taken, or might take any other medicines.
There are certain medicines that must not be taken together with Symtuza. These have been listed earlier under the heading “Do not take 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 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 anti-HIV medicines and follow your doctor’s instructions carefully regarding which medicines you can take together.
Symtuza must not be taken with medicines containing tenofovir disoproxil (e.g., 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 medicines. Inform your doctor if you are taking:

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

The effects of other medicines may be affected by taking Symtuza, and your doctor may require additional blood tests. 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, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, clopidogrel (to reduce blood clotting), as both the therapeutic effect and side effects may be altered;
• Clonazepam (to prevent seizures)
• Estrogen-containing hormonal contraceptives or hormone replacement therapy. Symtuza may reduce their effectiveness. When hormonal therapy is used for contraception, use of additional non-hormonal contraceptive methods is recommended.
• Ethinylestradiol/drospirenone. Symtuza may increase the risk of elevated potassium levels caused by drospirenone.
• Corticosteroids including betamethasone, budesonide, fluticasone, mometasone, prednisone, triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory skin, eye, joint, and muscle conditions, and other inflammatory disorders. These medicines are generally taken orally, by inhalation, by injection, or applied to the skin. Use of these medicines should only occur after evaluation by your doctor and under close medical monitoring for corticosteroid-related side effects.
• Buprenorphine/naloxone, methadone (medicines to treat opioid dependence)
• Salmeterol (for the treatment of asthma)
• Artemether/lumefantrine (a combination of medicines for the treatment of malaria)
• Dasatinib, irinotecan, nilotinib, vinblastine, vincristine (medicines to treat cancer)
• Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat a heart and lung condition called pulmonary arterial hypertension)
• Glecaprevir/pibrentasvir (to treat hepatitis C virus infection)
• Fentanyl, oxycodone, tramadol (for pain treatment)
• Fesoterodine, solifenacin (to treat urological disorders)

Your doctor may require additional blood tests and may adjust the dose of other medicines because the therapeutic effect and side effects of these medicines or of Symtuza may be affected when used together. Inform your doctor if you are taking:

• Dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
• Alfentanil (a strong, fast-acting injectable painkiller used during surgical procedures)
• Carvedilol, metoprolol, timolol (for heart conditions)
• Digoxin (to treat certain heart disorders)
• Clarithromycin (an antibiotic)
• Clotrimazole, fluconazole, isavuconazole, itraconazole, posaconazole (to treat fungal infections). Voriconazole should only be taken after evaluation by your doctor.
• Atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. Your doctor will evaluate which cholesterol-lowering medicine is most appropriate for your specific condition.
• 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 (for treatment of depression and anxiety)
• Perphenazine, risperidone, thioridazine (psychotropic medicines)
• Cyclosporine, everolimus, tacrolimus, sirolimus (to suppress the immune system), as the therapeutic effect or side effects of these medicines may be increased.
• Colchicine (for gout). If you have kidney or liver problems, consult the section “Do not take Symtuza with any of the following medicines”.
• Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when administered by injection (medicines to treat sleep disorders or anxiety)
• Metformin (to treat type 2 diabetes)

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, suspect you may be pregnant, or are planning a pregnancy. Women who are pregnant should not take Symtuza.
Due to the potential for adverse effects in infants, women should not breastfeed while receiving Symtuza.
Breastfeeding is not recommended for women with HIV infection, as the infection can be transmitted to the infant through breast milk. If you are breastfeeding or considering breastfeeding, discuss this with your doctor as soon as possible.
Driving and using machines
Symtuza may cause dizziness. Do not operate machinery or drive if you feel dizzy after taking Symtuza.
Symtuza contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take Symtuza

Take this medicine exactly as prescribed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.
The recommended dose for adults and adolescents aged at least 12 years, weighing at least 40 kg, is one tablet daily taken with food.
You must take Symtuza every day and always with food. You should eat a meal or a snack within 30 minutes before taking Symtuza. The type of food is not important.
The tablet must not be crushed, but swallowed whole. The tablet may be taken with a drink such as water, milk, or a nutritional beverage. Take Symtuza at approximately the same time each day.

Removing the child-resistant cap

The plastic bottle comes with a child-resistant cap and must be opened as follows:

• Press down on the plastic cap and turn it counterclockwise.
• Remove the unscrewed cap.

If you take more Symtuza than you should
Contact your doctor or the nearest emergency department immediately. Take the bottle of tablets with you so you can show what has been taken.

If you forget to take Symtuza
It is important not to miss any doses of Symtuza.
If you miss a dose:

• If you remember within 12 hours of your usual dosing time, take the tablet immediately with food, then take the next dose at your usual time.
• If you remember 12 hours or more after your usual dosing time, skip 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 after taking the tablet, take another dose of Symtuza as soon as possible with food. If you vomit more than 1 hour after taking the tablet, do not take another dose of Symtuza until your next scheduled dose.
Contact your doctor if you have any questions about what to do if you miss a dose or if you vomit.

Do not stop treatment with Symtuza without first talking to your doctor.
Anti-HIV medicines can make you feel better. Do not stop taking Symtuza, even if you feel better. Discuss this first with your doctor.

When your supply of Symtuza starts to run low, obtain a new supply from your doctor or pharmacist. This is very important because the amount of virus may start to increase if the medicine is stopped, even for a short time. The disease may become more difficult to treat.

If you have both HIV infection and hepatitis B, it is very important not to stop treatment with Symtuza without first discussing it with your doctor. Blood tests may need to be repeated for several months after stopping treatment with Symtuza. In some patients with advanced liver disease or cirrhosis, stopping treatment may lead to worsening of hepatitis, which can be life-threatening.

Contact your doctor immediately if you notice any new or unusual symptoms after stopping treatment, especially symptoms normally associated with hepatitis B infection.

If you have any questions about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Tell your doctor if you develop any of the following side effects.

Liver problems have been reported, which occasionally may be serious. Your doctor will need to perform blood tests before starting Symtuza. If you have chronic hepatitis B or C, your doctor will need to monitor your blood tests more frequently, as you 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 the whites of the eyes, dark urine (tea-colored), pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, tenderness, or discomfort on the right side under the ribs.

Skin rash may occur in more than 1 in 10 patients treated with Symtuza. Although most rashes are mild and resolve over time while continuing treatment, some may be severe and life-threatening. It is important that you consult your doctor if you develop a skin rash. Your doctor will advise you on how to manage the symptoms or whether Symtuza should be discontinued.

Other serious side effects observed in up to 1 in 10 patients include diabetes, increased levels of fats in the blood, and symptoms of infection. Inflammation of the pancreas (pancreatitis) has been reported in up to 1 in 100 patients.

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

• headache
• diarrhoea
• skin rash

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

• low red blood cell count (anaemia)
• 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 the results to you in detail
• dizziness
• joint pain
• muscle pain, muscle cramps, or muscle weakness
• weakness
• tiredness (fatigue)
• feeling unwell (nausea)

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

• severe swelling of the skin and other tissues (especially lips and eyes)
• symptoms of infection or autoimmune disorders (immune reconstitution inflammatory syndrome)
• breast enlargement
• osteonecrosis (bone damage caused by loss of blood supply to the bone)
• abnormal blood test results, such as certain tests of the pancreas. Your doctor will explain the results to you in detail.

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, swelling of the face or lymph nodes, increased eosinophils (a type of white blood cells), effects on the liver, kidneys, or lungs]
• severe skin rash with blisters and peeling skin, particularly around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome)
• deposition of darunavir crystals in the kidney leading to kidney disease

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

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

Some side effects are typical of anti-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 (unusual infections due to a weakened immune system), signs and symptoms of inflammation from previous infections may occur shortly after starting HIV treatment, including with Symtuza. In addition to opportunistic infections, autoimmune disorders (a condition in which the immune system attacks healthy body tissue) may also occur after starting treatment for HIV infection. Autoimmune disorders may occur several months after starting treatment.
  If you notice any of these symptoms, tell your doctor.

During HIV treatment, increases in weight and in blood lipid and blood sugar levels may occur. This is partly related to recovery of health and lifestyle, and, in the case of blood lipids, sometimes related to the HIV medicines themselves. Your doctor will monitor these changes.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. You can also report side effects directly through the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store 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 that month.
Do not use this medicine after 6 months from the first opening of the bottle.
Store in the original packaging to protect from moisture. Keep the bottle tightly closed.
The tablets may be stored outside the original container for a maximum of 7 days and must be discarded after this period if not taken. Tablets stored outside the original container must not be returned to it.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Symtuza contains
The active substances are darunavir, cobicistat, emtricitabine and tenofovir alafenamide. Each film-coated tablet (tablet) contains 800 mg of darunavir (as ethanolate), 150 mg of cobicistat, 200 mg of emtricitabine and 10 mg of tenofovir alafenamide (as fumarate).
The other components are
Tablet core:
The tablet core contains sodium croscarmellose, magnesium stearate, microcrystalline cellulose and colloidal silicon dioxide (refer to section 2 “Symtuza contains sodium”).
Film coating:
The film coating contains polyethylene glycol (macrogol), polyvinyl alcohol (partially hydrolysed), talc, titanium dioxide (E171) and yellow iron oxide (E172).
Description of the appearance of Symtuza and the contents of the pack
Film-coated tablet, yellow to yellowish-brown, capsule-shaped, marked “8121” on one side and “JG” on the other side.
Symtuza is supplied in bottles containing 30 tablets (with a silica gel desiccant, which must remain in the bottle to protect the tablets). The silica gel desiccant is contained in a separate sachet or container and must not be ingested.
Symtuza tablets are available in packs containing one bottle or three bottles per carton. Not all pack sizes may be marketed.
Marketing Authorisation Holder
Janssen-Cilag International NV, Turnhoutseweg 30, B-2340 Beerse, Belgium
Manufacturer
Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy
For further information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
België/Belgique/Belgien Lietuva
Janssen-Cilag NV UAB "JOHNSON & JOHNSON"
Tel/Tél: +32 14 64 94 11 Tel: +370 5 278 68 88
[email protected] [email protected]
България Luxembourg/Luxemburg
„Джонсън & Джонсън България” ЕООД Janssen-Cilag NV
Тел.: +359 2 489 94 00 Tél/Tel: +32 14 64 94 11
[email protected] [email protected]
Česká republika Magyarország
Janssen-Cilag s.r.o. Janssen-Cilag Kft.
Tel: +420 227 012 227 Tel.: +36 1 884 2858
[email protected]
Danmark Malta
Janssen-Cilag A/S AM MANGION LTD
Tlf: +45 4594 8282 Tel: +356 2397 6000
[email protected]
Deutschland Nederland
Janssen-Cilag GmbH Janssen-Cilag B.V.
Tel: +49 2137 955 955 Tel: +31 76 711 1111
[email protected] [email protected]
Eesti Norge
UAB "JOHNSON & JOHNSON" Eesti filiaal Janssen-Cilag AS
Tel: +372 617 7410 Tlf: +47 24 12 65 00
[email protected] [email protected]
Ελλάδα Österreich
Janssen-Cilag Φαρμακευτική Α.Ε.B.E. Janssen-Cilag Pharma GmbH
Tηλ: +30 210 80 90 000 Tel: +43 1 610 300
España Polska
Janssen-Cilag, S.A. Janssen-Cilag Polska Sp. z o.o.
Tel: +34 91 722 81 00 Tel.: +48 22 237 60 00
[email protected]
France Portugal
Janssen-Cilag Janssen-Cilag Farmacêutica, Lda.
Tél: 0 800 25 50 75 / +33 1 55 00 40 03 Tel: +351 214 368 600
[email protected]
Hrvatska România
Johnson & Johnson S.E. d.o.o. Johnson & Johnson România SRL
Tel: +385 1 6610 700 Tel: +40 21 207 1800
[email protected]
Ireland Slovenija
Janssen Sciences Ireland UC Johnson & Johnson d.o.o.
Tel: 1 800 709 122 Tel: +386 1 401 18 00
[email protected] [email protected]
Ísland Slovenská republika
Janssen-Cilag AB Johnson & Johnson, s.r.o.
c/o Vistor hf. Tel: +421 232 408 400
Sími: +354 535 7000
[email protected]
Italia Suomi/Finland
Janssen-Cilag SpA Janssen-Cilag Oy
Tel: 800.688.777 / +39 02 2510 1 Puh/Tel: +358 207 531 300
[email protected] [email protected]
Κύπρος Sverige
Βαρνάβας Χατζηπαναγής Λτδ Janssen-Cilag AB
Τηλ: +357 22 207 700 Tfn: +46 8 626 50 00
[email protected]
Latvija United Kingdom (Northern Ireland)
UAB "JOHNSON & JOHNSON" filiāle Latvijā Janssen Sciences Ireland UC
Tel: +371 678 93561 Tel: +44 1 494 567 444
[email protected] [email protected]
More detailed information on this medicinal product is available on the website of the European Medicines Agency, http://www.ema.europa.eu.