800 mg/150 mg/200 mg/10 mg film-coated tablets
darunavir/cobicistat/emtricitabine/tenofovir alafenamide
What Symtuza is and what it is used for
Symtuza is an antiretroviral medicine used to treat infection with the human immunodeficiency virus 1 ( HIV -1 ). It is used in adults and adolescents aged 12 years or older with a body weight of at least 40 kg. Symtuza contains four active substances:
- darunavir, an anti – HIV medicine called a protease inhibitor
- cobicistat, a ‘booster’ for darunavir
- emtricitabine, an anti – HIV medicine called a nucleoside reverse transcriptase inhibitor.
- tenofovir alafenamide, an anti – HIV medicine called a nucleotide reverse transcriptase inhibitor.
Symtuza reduces HIV -1 in your body and this strengthens your immune system (your body’s natural defenses) and reduces the risk of developing diseases associated with HIV infection, but Symtuza is not a cure for HIV infection.
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. Talk to your doctor if you are unsure about the severity of your liver disease. Additional tests may need to be performed.
Tell your doctor about all the medicines you take, including medicines you take by mouth, inhale, inject or apply to your skin.
Do not combine Symtuza with any of the following medicines
If you are taking any of these medicines, ask your doctor if you should switch to another.
| Drug | The purpose of the medicine |
| Alfuzosin | to treat enlarged prostate |
| Amiodarone , dronedarone, ivabradine , quinidine or ranolazine | to treat certain heart conditions (e.g. abnormal heart rhythm) |
| Carbamazepine, phenobarbital and phenytoin | to prevent seizures |
| Colchicine (if you have kidney/liver problems) | to treat gout |
| The combination drug lopinavir/ritonavir | anti – HIV drugs |
| Rifampicin | to treat certain infections such as tuberculosis |
| Pimozide , lurasidone, quetiapine or sertindole | to treat psychiatric conditions |
| Ergot alkaloids such as ergotamine , dihydroergotamine , ergometrine and methylergonovine | to treat migraine headaches |
| St. John’s wort (Hypericum perforatum) | a natural remedy used for depression |
| Elbasvir/grazoprevir | to treat infection with hepatitis C |
| Lovastatin, simvastatin and lomitapide | to lower cholesterol levels |
| Triazolam or medazolam ( taken by mouth ) | to be able to sleep and/or relieve anxiety |
| Sildenafil | to treat a heart and lung disease called pulmonary arterial hypertension. Sildenafil has other uses. See the section “Other medicines and Symtuza”. |
| Avanafil | to treat erectile dysfunction |
| Tiggers | to prevent platelets from clumping together when treating patients who have had a heart attack |
| Naloxegol | to treat constipation caused by opioids |
| 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 transmit HIV while taking this medicine, although the risk is reduced with effective antiretroviral therapy. Discuss with the doctor what precautions you must take to avoid infecting others.
People taking Symtuza can still develop an infection or other diseases associated with HIV infection. You must have regular contact with a doctor.
People taking Symtuza may develop a rash. In rare cases, the rash can be severe or potentially life-threatening. Contact your doctor if 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 for a long time.
Talk to your doctor before taking Symtuza. Tell your doctor immediately if any of the following apply to you:
- if you have had an impaired liver function, including hepatitis B or C infection. The doctor assesses the severity of your liver disease before deciding whether you can take Symtuza.
- if you have a hepatitis B infection, your liver problems may get worse when you stop taking Symtuza. It is important not to stop taking Symtuza without first talking to your doctor.
- if you have kidney disease or if tests have shown that you have problems with the kidneys, before or during treatment. Before starting treatment and during treatment with Symtuza, doctors may order blood tests to check how your kidneys are working. Your doctor will consider whether Symtuza is suitable for you
- if you have diabetes. Symtuza can raise blood sugar levels.
- if you notice any symptoms of infection (eg swollen lymph nodes or fever). In some patients with advanced HIV infection who have previously had unusual infections due to a weakened immune system ( opportunistic infection ), signs and symptoms of inflammation from the previous infection may appear shortly after starting HIV treatment. It is believed that these symptoms are due to an improvement in the body’s immune response, which enables the body to fight infection that may have existed without giving clear symptoms.
- if you notice any symptoms of muscle weakness, a weakness that starts in the hands or feet and moves to the trunk, palpitations, tremors, or hyperactivity, tell your doctor right away. In addition to opportunistic infections, autoimmune diseases (when the immune system attacks healthy body tissue) can also occur because your immune system improves after you start taking drugs to treat your HIV infection. Autoimmune disorders may appear many months after treatment has begun.
- if you have hemophilia. Symtuza may increase the risk of bleeding.
- if you are allergic to sulphonamides (used for example to treat certain infections ).
- if you get problems in muscles and bones. Some patients taking anti – HIV medicines can develop a bone disease called osteonecrosis (bone tissue damage due to the reduced blood supply to the bone tissue). This may be more likely with long-term treatment against HIV, serious damage to the immune system, obesity, or the use of alcohol or medicines called corticosteroids. Signs of osteonecrosis are stiff and aching joints (especially in the hip, knee, and shoulder) and difficulty moving. If you notice any of these symptoms, tell your doctor.
Older
Symtuza has only been used in a limited number of patients who are 65 years of age or older. If you belong to this age group, discuss with your doctor whether you can use Symtuza.
Children and young people
Symtuza should not be used in children younger than 12 years of age, or who weigh less than 40 kg, as it has not been studied in children under 12 years of age.
Other medicines and Symtuza
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
There are certain medicines that you must not combine with Symtuza. These are listed 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 medicine that requires boosting. In some cases, the dose of one of the other medicines may need to be changed. Therefore, always tell your doctor if you are taking another anti – HIV medicine and carefully follow the doctor’s instructions about which medicines can be combined.
You should also not take Symtuza with medicines containing tenofovir disoproxil (as fumarate, phosphate, or succinate), lamivudine, or adefovir dipivoxil, or medicines that require boosting with ritonavir or cobicistat.
The effects of Symtuza may be reduced if you are taking any of the following medicines. Talk to your doctor if you are taking:
- bosentan (to treat high blood pressure in the blood vessels of the lungs)
- dexamethasone (cortisone medicine that is injected)
- rifapentine, rifabutin (to treat bacterial infections)
- oxcarbazepine (to prevent seizures)
The effects of other medicines may be affected if you take Symtuza
and your doctor may want to do some additional blood tests. Tell your doctor if you are taking:
- amlodipine, diltiazem, disopyramide, felodipine, flecainide, mexiletine, nicardipine, nifedipine, propafenone, lidocaine, verapamil (for heart disease), as the treatment effect or side effects of these medicines, may be increased.
- bosentan (to treat high blood pressure in the blood vessels of the lungs)
- apixaban, dabigatran etexilate, edoxaban, rivaroxaban, warfarin, and clopidogrel (to reduce blood clotting) as the treatment effect or side effects may change.
- clonazepam (to prevent seizures).
- estrogen-based hormonal contraceptives or hormone replacement therapy. Symtuza can reduce their effect. When used as a contraceptive, non-hormonal contraceptive methods are recommended.
- ethinylestradiol/drospirenone . Symtuza may increase the risk of elevated potassium levels caused by drospirenone.
- corticosteroids include betamethasone, budesonide, fluticasone, mometasone, prednisone, and triamcinolone. These medicines are used to treat allergies, asthma, inflammatory bowel diseases, inflammation of the skin, eyes, joints, and muscles as well as other inflammatory conditions. These drugs are usually taken by mouth, inhaled, injected, or applied to the skin. If alternative drugs cannot be used, these drugs should only be used after medical evaluation and under close supervision by your doctor about the side effects of corticosteroids.
- buprenorphine/naloxone, methadone (medicine to treat opioid addiction)
- salmeterol (medicine to treat asthma )
- artemether/lumefantrine (a combination drug against malaria )
- dasatinib, irinotecan, nilotinib, vinblastine, vincristine (medicines to treat cancer)
- sildenafil, tadalafil, and vardenafil (for erectile dysfunction or to treat a heart and lung disease called pulmonary arterial hypertension ).
- glecaprevir/pibrentasvir (to treat hepatitis C virus infection)
- fentanyl, oxycodone, tramadol (to treat pain)
- fesoterodine, solifenacin (to treat urinary tract problems).
Your doctor may want to do some additional blood tests and the dose of other medicines may need to be changed because their or Symtuza’s treatment effect or side effects may be affected when they are combined. Tell your doctor if you are taking:
- dabigatran etexilate, edoxaban, warfarin (to reduce blood clotting)
- alfentanil (strong and short-acting injectable painkiller used in surgery)
- carvedilol, metoprolol, timolol (for heart disease)
- digoxin (to treat certain heart conditions)
- clarithromycin ( antibiotic )
- clotrimazole, fluconazole , isavuconazole, itraconazole, posaconazole (for treating fungal infections). Voriconazole should only be taken after a medical assessment.
- atorvastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin (to lower cholesterol levels). The risk of muscle damage may increase. The doctor will evaluate which cholesterol-lowering treatment best suits your specific situation.
- rifabutin (for bacterial infections)
- tadalafil, sildenafil, vardenafil (for erectile dysfunction or high blood pressure in the blood vessels in the lungs)
- amitriptyline, desipramine, imipramine, nortriptyline, paroxetine, sertraline, trazodone (to treat depression and anxiety)
- perphenazine, risperidone, thioridazine (psychiatric drugs)
- ciclosporin, everolimus, tacrolimus, and sirolimus (to suppress the immune system) as the treatment effect or side effects of these medicines may increase.
- colchicine (medicine for gout ). 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 by injection (medicines to treat sleep problems or anxiety)
- metformin (to treat type 2 diabetes )
This is not a complete list of medicines. Inform the healthcare professional about all medicines you are taking.
Pregnancy and breastfeeding
Tell your doctor immediately if you are pregnant, planning to become pregnant, or breastfeeding. Pregnant or nursing mothers should not take Symtuza.
It is recommended that women with HIV do not breastfeed their babies because there is a risk that the baby will become infected with HIV through breast milk and that the medicine may affect the baby.
Driving ability and use of machinery
Symtuza can cause dizziness. Do not drive or use machines if you feel dizzy after taking Symtuza.
Symtuza contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is almost ‘sodium-free’.
How to take Symtuza
Always take this medicine as directed by your doctor or pharmacist. Ask your doctor or pharmacist if you are unsure.
The recommended dosage for adults and adolescents aged 12 years or older and weighing at least 40 kg is 1 tablet once daily with food.
You must take Symtuza every day and always with food. You must eat a meal or a snack for at least 30 minutes before taking 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, e.g. water or milk, or other nutritional drink. Take Symtuza at about the same time each day.
Open the childproof cover
| The plastic jar has a child-proof lid and must be opened as follows: Press down on the plastic cap while turning it counterclockwise. Remove the cover. |
If you have taken too much Symtuza
Immediately contact a doctor or the nearest emergency department for advice. Bring the tablet container with you, so you can show what you have taken.
If you forget to take Symtuza
You mustn’t miss a dose of Symtuza.
If you miss a dose:
- If you notice this within 12 hours of the time you usually take Symtuza, take the tablet immediately, with food. Take the next dose at the same time as usual.
- If you notice this at 12 hours or later after the time you usually take Symtuza, skip the missed dose, and take the next dose with food at the same time as usual. Do not take a double dose to make up for a missed dose.
If you vomit within 1 hour of taking the medicine, 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 a doctor if you are unsure what to do if you miss a dose or vomit.
Do not stop taking Symtuza without first talking to your doctor
Anti – HIV medicines can make you feel better. Even if you feel better, do not stop taking Symtuza. Talk to your doctor first.
If you run out of Symtuza tablets, get more from your doctor or pharmacist. This is very important because the viral load can start to increase if you stop taking the drug, even if only for a short time. It can then become more difficult to treat the disease.
If you have both HIV infection and hepatitis B, it is very important not to stop taking Symtuza without first talking to your doctor. You may need blood tests for several months after treatment with Symtuza has ended. In some patients with advanced liver disease or cirrhosis, discontinuation of treatment may lead to worsening of hepatitis A, and this may be life-threatening.
Tell your doctor immediately if any new and unexpected symptoms appear after stopping treatment, especially symptoms that you usually associate with hepatitis B infection.
If you have any further questions about this medicine, ask your doctor, pharmacist, or nurse.
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, which in some cases can be serious, have been reported. Your doctor should take a blood test before starting treatment with Symtuza. If you have chronic hepatitis B or C infection, your doctor should take blood tests more often because you have an increased risk of developing liver problems. Talk to your doctor about the signs and symptoms of liver problems. These may be yellowing of the skin or the whites of the eyes, dark (tea-colored) urine, pale stools (bowel movements), nausea, vomiting, loss of appetite, or pain, ache or pain, and discomfort on the right side under the ribs.
Skin rash affects more than 1 in 10 patients receiving Symtuza. Although most rashes are mild and disappear over time as treatment continues, sometimes the rashes can be severe or potentially life-threatening. It is therefore important that you consult your doctor if you develop a rash. Your doctor will advise you on how to manage the symptoms or if treatment with Symtuza needs to be stopped.
Other serious side effects, occurring in up to 1 in 10 patients, were diabetes, elevated blood lipids, 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 users)
- headache
- diarrhea
- rash
Common side effects (may affect up to 1 in 10 users)
- low red blood cell count ( anemia )
- allergic reactions such as hives ( urticaria ), itching
- decreased appetite ( anorexia )
- abnormal dreams
- vomiting, abdominal pain or swelling, indigestion, flatulence
- abnormal blood test results, such as certain tests of the kidneys. The doctor will explain these to you.
- dizziness
- joint pain
- muscle pain, muscle cramps, or muscle weakness
- weakness
- fatigue
- nausea
Uncommon side effects (may affect up to 1 in 100 users)
- severe swelling of the skin or other tissues (usually lips or eyes)
- symptoms of infection or autoimmune disorders (immune reactivation syndrome)
- breast augmentation
- osteonecrosis (bone tissue damage as a result of reduced blood supply to the bone tissue)
- abnormal blood test results such as certain pancreatic tests. The doctor will explain these to you.
Rare side effects (may affect up to 1 in 1,000 users)
- a reaction called DRESS [severe rash that may be followed by fever, fatigue, swelling of the face or lymph nodes, increased number of eosinophils (a type of white blood cell ), effect on the liver, kidneys, or lungs].
- severe rash with blisters and scaly skin, especially around the mouth, nose, eyes, and genitals (Stevens-Johnson syndrome).
Side effects that have been reported: a rash may be severe or possibly life-threatening:
- rash with blisters and scaly skin over most of the body
- the red rash covered with small wart-filled bumps that may spread over the body, sometimes with a fever.
Some side effects are typical of anti – HIV drugs similar to Symtuza. These are:
- elevated blood sugar and worsening diabetes
- aches, pains, or weakness in muscles. In rare cases, these muscle problems have been severe.
- immune reactivation syndrome. In some patients with advanced HIV infection ( AIDS ) and a history of opportunistic infection ( uncommon infection due to a weakened immune system), signs and symptoms of inflammation from the previous infection may appear shortly after starting HIV treatment, also for Symtuza. In addition to opportunistic infections, autoimmune disorders (conditions where the immune system attacks healthy body tissue) can also occur after you start taking medicines to treat your HIV infection. Autoimmune disorders may appear many months after treatment has begun.
Tell your doctor if you get any of these symptoms.
During HIV treatment, you may gain weight, have higher blood sugar levels, and increase in blood fats. This is partly due to improved health and lifestyle, and in the case of blood, lipids sometimes to the HIV drugs themselves. Your doctor will do tests to check for these changes.
How to store Symtuza
Keep this medicine out of the sight and reach of children.
Use before the expiry date stated on the carton and the can after “EXP”. The expiration date is the last day of the specified month.
Do not use this medicine for more than 6 weeks after first opening the can.
Store in the original packaging to protect against moisture. The jar must be kept tightly closed. Tablets can be stored outside the original packaging for up to 7 days and should then be discarded if not used. Tablets stored outside the original packaging must not be put back in the packaging.
Medicines must not be thrown into the drain or among the household waste. Ask the pharmacist how to dispose of medicines that are no longer used. These measures will help to protect the environment.
Contents of the packaging and other information
Contents declaration
The active substances are darunavir, cobicistat, emtricitabine and tenofovir alafenamide. 1 film-coated tablet (tablet) contains 800 mg darunavir (as ethanolate), 150 mg cobicistat, 200 mg emtricitabine and 10 mg tenofovir alafenamide (as fumarate).
Other ingredients are
Tablet core:
The tablet core contains croscarmellose sodium, magnesium stearate, microcrystalline cellulose, and colloidal silicon dioxide (see section 2 “Symtuza contains sodium”).
Film coating:
The film coating contains polyethylene glycol (macrogol), polyvinyl alcohol (partially hydrolyzed), talc, titanium dioxide (E171), and yellow iron oxide (E172).
Appearance and package sizes of the medicine
Yellow to yellowish brown capsule-shaped film-coated tablet, debossed with “8121” on one side and “JG” on the other side.
Symtuza is supplied in tins of 30 tablets (with a desiccant, in the form of silica gel, which must be kept in the tin to protect the tablets). The desiccant is in a separate sachet or container and should not be swallowed.
Symtuza tablets are available in packs containing one can or three cans 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