Symtuza - patient leaflet, side effects, dosage

1. What Symtuza is and what it is used for

Symtuza is an antiretroviral medicine used to treat infection with human immunodeficiency virus 1 (HIV-1). 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 (enhancer) 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 and this will improve your immune system (your body’s natural defences) and reduce the risk of developing illnesses linked to HIV infection but Symtuza is not a cure for HIV infection.

2. What you need to know before you take Symtuza

Do not take Symtuza

• – if you are allergic (hypersensitive) to darunavir, cobicistat, emtricitabine, tenofovir

alafenamide, or any of the other ingredients of Symtuza (listed in section 6).

• – if you have severe liver problems. Ask your doctor if you are unsure about the severity of your

liver disease. Some additional tests might be necessary.

Tell your doctor about all medicines you take including medicines taken orally, inhaled, injected or applied to the skin.

Do not combine Symtuza with any of the following medicines

If you are taking any of these, ask your doctor about switching to another medicine.

Medicine	Purpose of the medicine
Alfuzosin	to treat enlarged prostate
Amiodarone, dronedarone, ivabradine, quinidine, or ranolazine	to treat certain heart disorders ( e.g. abnormal heart rhythm)
Carbamazepine, phenobarbital and phenytoin	to prevent seizures
Colchicine (if you have kidney/liver problems)	to treat gout
The combination product lopinavir/rito­navir	anti-HIV medicine
Rifampicin	to treat some infections such as tuberculosis
Pimozide , lurasidone, quetiapine or sertindole	to treat psychiatric conditions
Ergot alkaloids like ergotamine , dihydroergotamine , ergometrine and methylergonovine	to treat migraine headaches
St. John’s Wort (Hypericum perforatum)	a herbal product used for depression
Elbasvir/grazo­previr	to treat hepatitis C infection
Lovastatin, simvastatin and lomitapide	to lower cholesterol levels
Triazolam or midazolam (taken by mouth)	to help you sleep and/or relieve anxiety
Sildenafil	to treat a heart and lung disorder called pulmonary arterial hypertension. There are other uses for sildenafil. Please see section ‘Other medicines and Symtuza’.
Avanafil	to treat erectile dysfunction
Dabigatran, ticagrelor	to help stop the clumping of platelets in the treatment of patients with a history of a heart attack
Naloxegol	to treat opioid induced constipation
Dapoxetine	to treat premature ejaculation
Domperidone	to treat nausea and vomiting

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Symtuza.

You can still pass on HIV when taking this medicine, although the risk is lowered by effective antiretroviral therapy. Discuss with your physician the precautions needed to avoid infecting other people.

People taking Symtuza may still develop infections or other illnesses associated with HIV infection. You must keep in regular contact with your doctor.

People taking Symtuza may develop a skin rash. Infrequently a rash may become severe or potentially life-threatening. Please contact your doctor whenever you develop a rash.

Although kidney problems have not been observed with Symtuza, there is a possibility that you may experience kidney problems when taking Symtuza over a long period of time.

Talk to your doctor before taking Symtuza. Tell your doctor immediately, if any of these apply to you.

• if you have had problems with your liver, including hepatitis B or C infection. Your doctor

may evaluate how severe your liver disease is before deciding if you can take Symtuza.

• if you have hepatitis B infection, your liver problems may become worse after you stop taking

Symtuza. It is important not to stop taking Symtuza without talking to your doctor first.

• if you have had kidney disease or if tests have shown problems with your kidneys, before or

during treatment. Before starting treatment and during treatment with Symtuza, your doctor may order blood tests to monitor how your kidneys work. Your doctor will consider if Symtuza is the right medicine for you.

• if you have diabetes. Symtuza might increase sugar levels in the blood.
• if you notice any symptoms of infection (e.g. swollen lymph nodes and fever). In some patients

with advanced HIV infection and who had unusual infections due to a weakened immune system (opportunistic infection), signs and symptoms of inflammation from previous infections may occur soon after you start HIV treatment. It is believed that these symptoms are due to an improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms.

• if you notice symptoms such as muscle weakness, weakness beginning in the hands and feet and

moving up towards the trunk of the body, palpitations, tremor or hyperactivity, tell your doctor immediately. In addition to the opportunistic infections, autoimmune disorders (when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection, due to an improvement in the body’s immune response. Autoimmune disorders may occur many months after the start of treatment.

• if you have haemophilia. Symtuza might increase the risk of bleeding.
• if you are allergic to sulphonamides (e.g. used 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 loss of blood supply to the bone). This may be more likely with long-term HIV treatment, more severe damage to the immune system, being overweight, or the use of alcohol or medicines called corticosteroids. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms tell your doctor.

Elderly

Symtuza has only been used in limited numbers of patients 65 years or older. If you belong to this age group, please discuss with your doctor if you can use Symtuza.

Children and adolescents

Symtuza is not for use in children younger than 12 years, or weighing less than 40 kg , as it has not been studied in children under 12 years.

Other medicines and Symtuza

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

There are some medicines that you must not combine with Symtuza. These are mentioned above under the heading ‘Do not combine Symtuza with any of the following medicines’.

Symtuza must not be used with another antiviral medicine that contains a booster or another antiviral that requires boosting. In some cases dosage of other medicines might need to be changed. Therefore, always tell your doctor if you take other anti-HIV medicines and follow your doctor’s instruc­tion carefully on which medicines can be combined.

You should also not take Symtuza with medicines that contain tenofovir disoproxil (e.g. as fumarate, phosphate, or succinate), lamivudine or adefovir dipivoxil, or medicines that require boosting with ritonavir or cobicistat.

The effects of Symtuza might be reduced if you take any of the following products. Tell your doctor if you take:

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

• - Dexamethasone (injection) (corticosteroid)

• - Rifapentine, rifabutin (to treat bacterial infections)

• - Oxcarbazepine (to prevent seizures).

The effects of other medicines might be influenced if you take Symtuza. Tell your doctor if you take:

• - Amlodipine, diltiazem, disopyramide, felodipine, flecainide, mexiletine, nicardipine, nifedipine,

propafenone, lidocaine, verapamil (for heart disease) 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 clotting of the blood) as their

therapeutic effect or side effects may be altered.

• - Clonazepam (to prevent seizures).

• - Oestrogen -based hormonal contraceptives and hormone replacement therapy. Symtuza might

reduce its effectiveness. When used for birth control, non-hormonal contraception methods are recommended.

• - Ethinylestradi­ol/drospireno­ne. Symtuza might increase the risk for elevated potassium levels by

drospirenone.

• - Corticosteroids including betamethasone,bu­desonide, fluticasone, mometasone, prednisone,

triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammatory conditions of the skin, eyes, joints and muscles and other inflammatory conditions. These medicines are generally taken orally, inhaled, injected or applied to the skin. If alternatives cannot be used, its use should only take place after medical evaluation and under close monitoring by your doctor for corticosteroid side effects.

• - Buprenorphine/na­loxone, methadone (medicines to treat opioid dependence)

• - Salmeterol (medicine to treat asthma)

• - Artemether/lu­mefantrine (a combination medicine to treat malaria)

• - Dasatinib, irinotecan, nilotinib, vinblastine, vincristine (medicines to treat cancer)

• - Sildenafil, tadalafil, vardenafil (for erectile dysfunction or to treat 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 urologic disorders).

The dosage of other medicines might need to be changed since either their own or Symtuza’s the­rapeutic effect or side effects may be influenced when combined.

Tell your doctor if you take:

• - Alfentanil (injectable, strong and short-acting, painkiller that is used for surgical procedures)

• - Carvedilol, metoprolol, timolol (for heart disease)

• - Warfarin (to reduce clotting of the blood) as its therapeutic effect or side effects may be altered;

your doctor may have to check your blood.

• - Digoxin (to treat certain heart disorders)

• - Clarithromycin (antibiotic)

• - Clotrimazole, fluconazole, isavuconazole, itraconazole, posaconazole (for treating fungal

infections). Voriconazole should only be taken after medical evaluation.

• - Atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin (to lower cholesterol levels).

The risk of muscle damage might be increased. Your doctor will evaluate which cholesterol lowering regimen is best for your specific situation.

• - 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)

• - Perphenazine, risperidone, thioridazine (psychiatric medicines)

• - Ciclosporin, everolimus, tacrolimus, sirolimus (for dampening down your immune system) as

the therapeutic effect or side effects of these medicines might be increased. Your doctor might want to do some additional tests.

• - Colchicine (antigout). If you have kidney or liver problems see section ‘Do not combine

Symtuza with any of the following medicines’.

• - Buspirone, clorazepate, diazepam, estazolam, flurazepam, zolpidem, midazolam when used as

an injection (medicines to treat trouble with sleeping or anxiety)

• - Metformin (to treat type 2 diabetes)

This is not a complete list of medicines. Tell your healthcare provider about all medicines that you are taking.

Pregnancy and breast-feeding

Tell your doctor immediately if you are pregnant, planning to become pregnant or if you are breast-feeding. Pregnant or breast-feeding mothers should not take Symtuza.

It is recommended that women with HIV do not breast-feed their infants because of the possibility of the baby becoming infected with HIV through breast milk and because the medicine may affect the baby.

Driving and using machines

Symtuza can cause dizziness. Do not operate machines or drive if you feel dizzy after taking Symtuza.

Symtuza contains sodium

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

3. How to take Symtuza

Always take Symtuza exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose for adults and adolescents 12 years of age and older, who weigh at least 40 kg is one tablet each day with food.

You must take Symtuza every day and always with food. You must eat a meal or a snack within

30 minutes before taking your Symtuza. The type of food is not important.

• The tablet should not be crushed, but swallowed whole. The tablet can be taken with a drink

such as water, milk or any nutritional drink. Take Symtuza at around 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: Push the plastic screw cap down while turning it counter clockwise.
• Remove the unscrewed cap.

If you take more Symtuza than you should

Contact your doctor or nearest emergency department immediately for advice. Keep the tablet bottle with you so that you can show what you have taken.

If you forget to take Symtuza

It is important not to miss a dose of Symtuza.

If you do miss a dose:

• If you notice within 12 hours of the time you usually take Symtuza, you must take the tablet

immediately, with food. Then take the next dose at your usual time.

• If you notice 12 hours or more after the time you usually take Symtuza, then do not take the

missed dose and take the next doses with food at your usual time. Do not take a double dose to make up for a forgotten dose.

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

Contact your doctor if you are uncertain about what to do if you miss a dose or vomit.

Do not stop taking Symtuza without talking to your doctor first

Anti-HIV medicines may make you feel better. Even when you feel better, do not stop taking Symtuza. Talk to your doctor first.

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

If you have both HIV infection and hepatitis B, it is very important not to stop taking Symtuza without talking to your doctor first. You may require blood tests 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 may be life-threatening.

Tell your doctor immediately about new or unusual symptoms after you stop treatment, particularly symptoms you associate with hepatitis B infection.

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

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

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

Liver problems that may occasionally be severe have been reported. Your doctor should do blood tests before you start Symtuza. If you have chronic hepatitis B or C infection, your doctor should check your blood tests more often because you have an increased chance of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may include yellowing of your skin or whites of your eyes, dark (tea coloured) urine, pale-coloured stools (bowel movements), nausea, vomiting, loss of appetite, or pain, aching, or pain and discomfort on your right side below your ribs.

Skin rash may affect more than 1 in 10 patients receiving Symtuza. Although most rashes are mild and disappear after a while as treatment is continued, a rash can occasionally be severe or potentially life-threatening. It is important to talk to your doctor if you develop a rash. Your doctor will advise you how to deal with your symptoms or whether Symtuza must be stopped.

Other severe side effects, seen up to 1 patient in 10, were diabetes, increased blood fat levels and symptoms of infection. Inflammation of the pancreas (pancreatitis) has been reported in up to 1 patient in 100.

• Very common side effects (may affect more than 1 in 10 people) headache
• diarrhoea
• rash

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

• low red blood cell count (anaemia)
• allergic reactions such as nettle rash (urticaria), itching, decreased appetite (anorexia)
• abnormal dreams
• vomiting, pain or swelling of the belly, indigestion, flatulence (wind)
• abnormal blood test results such as some tests for your kidney. Your doctor will explain these to

you.

• dizziness
• joint pain
• muscle pain, muscle cramps or weakness
• weakness
• tiredness (fatigue)
• feeling sick (nausea)

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

• severe swelling of the skin and other tissues (most often the lips or the eyes)
• symptoms of infection or of autoimmune disorders (immune reconstitution inflammatory

syndrome)

• enlargement of breasts
• osteonecrosis (bone damage caused by loss of blood supply to the bone)
• abnormal blood test results such as some tests for your pancreas. Your doctor will explain these

to you.

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 glands, increase of eosinophils (type of white blood cells), effects on liver, kidney or lung].

Some side effects are typical for anti-HIV medicines similar to Symtuza. These are:

• – raised blood sugar and worsening of diabetes

• – muscle pain, tenderness or weakness. On rare occasions, these muscle disorders have been

serious.

• – immune reconstitution inflammatory syndrome. In some patients with advanced HIV infection

5. How to store Symtuza

Keep Symtuza out of the sight and reach of children.

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

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

Store in the original package in order to protect from moisture. Keep the bottle tightly closed. Tablets may be stored outside of the original container for up to 7 days and should be discarded after that time if not taken. Tablets stored outside of the original container should not be placed back into the container.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away any medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack and other information

What Symtuza contains

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

The other ingredients are

Tablet core:

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

Film coating:

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

What Symtuza looks like and contents of the pack

Yellow to yellowish-brown capsule shaped film-coated tablet, mentioning “8121” on one side and “JG” on the other side.

Symtuza comes in bottles of 30 tablets (with a silica gel desiccant that must be kept in the bottle to help protect your tablets). The silica gel desiccant is contained in a separate sachet or canister and should not be swallowed.

The 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, 2340 Beerse, Belgium

Manufacturer

Janssen-Cilag SpA, Via C. Janssen, Borgo San Michele, 04100 Latina, Italy

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

België/Belgiqu­e/Belgien

Janssen-Cilag NV

Tel/Tél: +32 14 64 94 11

Efc^rapufl

„^>KOHCbH & ^>KOHCbH Ebirapub' EOOfl

Ten.: +359 2 489 94 00

Česká republika

Janssen-Cilag s.r.o.

Tel: +420 227 012 227

Danmark Janssen-Cilag A/S Tlf: +45 4594 8282	Malta AM MANGION LTD Tel: +356 2397 6000
Deutschland Janssen-Cilag GmbH Tel: +49 2137 955 955	Nederland Janssen-Cilag B.V. Tel: +31 76 711 1111
Eesti UAB „JOHNSON & JOHNSON“ Eesti filiaal Tel: +372 617 7410	Norge Janssen-Cilag AS Tlf: +47 24 12 65 00
EXÀàôa Janssen-Cilag OappaKsuTiK^ A.E.B.E. Tql: +30 210 80 90 000	Österreich Janssen-Cilag Pharma GmbH Tel: +43 1 610 300
España Janssen-Cilag, S.A. Tel: +34 91 722 81 00	Polska Janssen-Cilag Polska Sp. z o.o. Tel.: +48 22 237 60 00
France Janssen-Cilag Tél: 0 800 25 50 75 / +33 1 55 00 40 03	Portugal Janssen-Cilag Farmacêutica, Lda. Tel: +351 214 368 600
Hrvatska Johnson & Johnson S.E. d.o.o. Tel: +385 1 6610 700	România Johnson & Johnson România SRL Tel: +40 21 207 1800
Ireland Janssen Sciences Ireland UC Tel: +353 1 800 709 122	Slovenija Johnson & Johnson d.o.o. Tel: +386 1 401 18 00
Ísland Janssen-Cilag AB c/o Vistor hf. Sími: +354 535 7000	Slovenská republika Johnson & Johnson, s.r.o. Tel: +421 232 408 400
Italia Janssen-Cilag SpA Tel: 800.688.777 / +39 02 2510 1	Suomi/Finland Janssen-Cilag Oy Puh/Tel: +358 207 531 300
Kùnpoç Bapváßaç XaTZnnavaY^ç Ató Tip.: +357 22 207 700	Sverige Janssen-Cilag AB Tfn: +46 8 626 50 00

Latvija

UAB „JOHNSON & JOHNSON“ filiäle Latvijä

Tel: +371 678 93561

This leaflet was last revised in {MM/YYYY}.

Detailed information on this medicine is available on the European Medicines Agency web site:.

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