Label: information for the user

Eviplera 200mg/25mg/245mg film-coated tablets

emtricitabina/rilpivirina/tenofovir disoproxilofumarato

Read this label carefully before starting to take this medicine, because it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any doubts, consult your doctor or pharmacist.
• This medicine has been prescribedonlyto you, and you should not give it to other people even if they have the same symptoms as you, as it may harm them.
• Ifyou experienceadverse effects, consult your doctor or pharmacist, evenifthey do not appearin this label.See section4.

1.What Eviplera is and for what it is used

2.What you need to knowbeforestarting to take Eviplera

3.How to take Eviplera

4.Possible adverse effects

5.Storage of Eviplera

6.Contents of the package and additional information

Eviplera contains three active ingredientsthat are used to treat Human Immunodeficiency Virus (HIV) infection:

• Emtricitabine, a nucleoside reverse transcriptase inhibitor (NRTI) analogue.
• Rilpivirine, a non-nucleoside reverse transcriptase inhibitor (NNRTI).
• Tenofovir disoproxil, a nucleotide reverse transcriptase inhibitor (NtRTI) analogue.

Each of these active ingredients, also known as antiretroviral medications, acts by interfering with an enzyme (a protein called “reverse transcriptase”) essential for viral multiplication.

Eviplerareduces the amount of HIV present in the body. This improves the immune system and decreases the risk of developing diseases associated with HIV infection.

Eviplera is a medication used to treat Human Immunodeficiency Virus (HIV) infectionin adults aged 18years or older.

Do not take Eviplera

• If you are allergicto emtricitabine, rilpivirina, tenofovir disoproxil, or any of the other components ofthis medication (listed in section6 of this leaflet).

→If this happens, inform your doctor immediately.

→If you are currently taking any of the following medications

• carbamazepine, oxcarbazepine, phenobarbital, and phenytoin(medications for treating epilepsy and preventing seizures)
• rifampicin and rifapentine(used to treat certain bacterial infections such as tuberculosis)
• omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole(proton pump inhibitors, used to prevent and treat stomach ulcers, heartburn, and acid reflux disease)
• dexamethasone(a corticosteroid used to treat inflammation and suppress the immune system) when taken orally or injected (except in single-dose treatment)
• products containing St. John's Wort(Hypericum perforatum) (a medicinal plant used to treat depression and anxiety)

Advertencias and precautions

You must remain under the supervision of your doctor while taking Eviplera.

• While taking this medicationyou may still transmit HIV to others, although effective antiviral treatment reduces the risk.Consult your doctor about the necessary precautions to avoid infecting others.This medication is not a cure for HIV infection. While you are taking Eviplera, you may still experience infections or other diseases associated with HIV infection.

• If you have had kidney disease,or if blood tests have shown kidney problems, inform yourdoctor.Eviplera may affect your kidneys. Before and during treatment, your doctor may request that you undergo blood tests to measure kidney function. Eviplera is not recommended for patients with moderate or severe kidney disease.

Eviplera is usually not taken with other medications that may damage your kidneys (seeOther medications and Eviplera). If this is unavoidable, your doctor will monitor your kidney function once a week.

• Consult your doctor if you have a history of liver disease, including hepatitis.Patients with HIV and liver disease (including chronic hepatitisB orC) treated with antiretrovirals have a higher risk of developing severe and potentially fatal liver complications. If you have hepatitisB, your doctor will carefully consider the best treatment regimen for you. Two of the active ingredients in Eviplera (tenofovir disoproxil and emtricitabine) show some activity against hepatitisB virus. If you have a history of liver disease, or chronic hepatitisB, your doctor may perform blood tests to monitor liver function.

If you have hepatitisB, liver problems may worsen after stopping Eviplera administration. It is essential that you do not stop taking Eviplera without first consulting your doctor: see section3, Do not interrupt Eviplera treatment.

• Inform your doctor immediately and stop taking Eviplera if you develop a skin rash accompanied by the following symptoms: fever, blisters, eye redness, and facial, mouth, or body swelling.This may be severe or potentially fatal.

• Consult your doctor if you are over 65years old.Not enough patients over 65years old have been studied. If you are over 65years old and are prescribed Eviplera, your doctor will closely monitor you.

While taking Eviplera

Once you start taking Eviplera, be aware of:

• any signs of inflammation or infectionn
• bone problems

→If you notice any of these symptoms, inform your doctor immediately.

Children and adolescents

Do not administer this medication to childrenand adolescents under 18years old.

Othermedications and Eviplera

Inform your doctor or pharmacist if you are taking, have taken recently, or may need to take any other medication.This includes medications and herbal remedies obtained without a prescription.

Inform your doctorif you are takingany of the following medications:

• Any other medication that contains:

• emtricitabine
• rilpivirina
• tenofovir disoproxil
• tenofovir alafenamida
• any other antiviral medication containing lamivudine or adefovir dipivoxil

Evipleramay interact with other medications. As a result, the blood levels ofEvipleraor other medications may be affected. This may prevent your medications from working correctly or worsen their potential side effects. In some cases, your doctor may need to adjust the dose or check your blood concentrations.

• Medications that may damage the kidneys,such as:
• aminoglycosides (such as streptomycin, neomycin, and gentamicin), vancomycin (for bacterial infections)
• foscarnet, ganciclovir, cidofovir (for viral infections)
• amphotericinB, pentamidine (for fungal infections)
• interleukin‑2, also known as aldesleukin (for cancer treatment)
• nonsteroidal anti-inflammatory drugs (NSAIDs, for relieving bone or muscle pain)

• Medications containing didanosine (for HIV infection):Taking Eviplera with other antiviral medications containing didanosine may increase didanosine levels in your blood and reduce CD4 cell counts. When taken together, medications containing tenofovir disoproxil and didanosine have been associated with rare cases of pancreatitis and lactic acidosis (excess lactic acid in the blood) in some cases, fatal. Your doctor will carefully considerwhether to treat you withother medications used to treat HIV infection (seeOther medications used to treat HIV infection).

• Othermedications used to treat HIV infection:Inhibitors of reverse transcriptase non-nucleoside analogs (ITINN). Eviplera contains an ITINN (rilpivirina), so Eviplera should not be combined with other medications of this type. Your doctor will prescribe a different medication, if necessary.

• Rifabutin,a medicationused to treat certain bacterial infections. This medication may reduce rilpivirina levels (a component of Eviplera) in the blood. Your doctor may need to administer an additional dose of rilpivirina to treat your HIV infection(seesection3,Taking Eviplera).

• Antibioticsused to treat bacterial infections,including tuberculosis, that contain:

• clarithromycin
• erythromycin

These medications may increase rilpivirina levels (a component of Eviplera) in the blood. Your doctor may need to change the antibiotic dose or prescribe a different one.

• Medications forstomach ulcers, heartburn, or acid reflux,such as:
• antacids (aluminum/magnesium hydroxide or calcium carbonate)
• H2antagonists (famotidine, cimetidine, nizatidine, or ranitidine)

These medications may reduce rilpivirina levels (a component of Eviplera) in the blood. If you are taking one of these medications, your doctor will prescribe a different one for stomach ulcers, heartburn, or acid reflux, or advise you on how and when to take it.

• If you are taking anantacid(such as medications containing magnesium or potassium), take it at least 2hours before or at least 4hours after Eviplera (see section3,Taking Eviplera).

• If you are taking anH2antagonist (also used to treat stomach acid or gastroesophageal reflux disease), take it at least 12hours before or at least 4hours after Eviplera. H2antagonists can only be taken once a day if you are taking Eviplera. H2antagonists should not be taken in a twice-daily regimen. Consult your doctor to indicate an alternative regimen(seesection3,Taking Eviplera).

• Methadone,a medicationused to treat opioid addiction, as your doctor may need to change your dose.

• Dabigatran etexilate,a medication used to treat cardiovascular diseases, as your doctor may need to monitor the levels of this medication in your blood.

→Inform your doctor if you are taking any of these medications. Do not interrupt your treatment without consulting your doctor.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

• Use an effective method of contraceptionwhile taking Eviplera.
• Inform your doctor immediately if you become pregnant or intend to become pregnant.Pregnant women should discuss the use of Eviplera with their doctor. Your doctor will explain the potential risks and benefits of taking Eviplera for you and your child.
• If you have taken Evipleraduring pregnancy, your doctor may request periodic blood tests and other diagnostic tests to monitor your child's development. In children whose mothers took ITIN during pregnancy, the benefit of HIV protection was greater than the risk of adverse effects.

Do not breastfeed your child during Eviplera treatment:

• This is because the active ingredients in this medication pass into breast milk.
• If you are an HIV-positive woman, it is recommended that you do not breastfeed to avoid passing the virus to the child through breast milk.

Driving and operating machinery

Do not drive or operate machinery if you feel tired, drowsy, or experience dizziness after taking this medication.

Eviplera contains lactose, aluminum lake yellow-orange S (E110), and sodium

• If your doctor has told you that you have a certain sugar intolerance, consult them before taking this medication.
• Inform your doctor if you have an allergy to aluminum lake yellow-orange S (E110).Eviplera contains aluminum lake yellow-orange S, also known as “E110”, which may cause allergic reactions.
• 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. In case of doubt, consult your doctor or pharmacist again.

The usual dose is a tablet taken every day by mouth. The tablet must be taken with food.This is important to achieve the appropriate levels of active principle in the body. A nutritional beverage alone does not replace food.

Swallow the tablet whole with water.

Do not chew, crush, or break it,as it could affect the way the medication is released in the body.

If your doctor decides to suspend one of the components of Eviplera or change the dose of Eviplera, they may give you emtricitabine, rilpivirine, and/or tenofovir disoproxil separately or with other medications for the treatment of HIV infection.

If you are taking an antacidsuch as medications containing magnesium or potassium.Take it at least 2hours before or at least 4hours after Eviplera.

If you are taking an H2antagonist such as famotidine, cimetidine, nizatidine, or ranitidine. Take it at least 12hours before or at least 4hours after Eviplera. H2antagonists can only be taken once a day if you are taking Eviplera. H2antagonists should not be taken twice a day. Consult your doctor to indicate an alternative schedule.

If you are taking rifabutin.Your doctor may need to administer an additional dose ofrilpivirine. Take the rilpivirine tablet at the same time as you take Eviplera. In case of doubt, consult your doctor or pharmacist again.

If you take more Eviplera than you should

If you accidentally took more than the recommended dose of Eviplera, you may be at greater risk of experiencing possible adverse effects with this medication (see section4,Adverse effects).

Consult your doctor or go to the nearest emergency service immediately. Bring the tablet container with you so that you can easily describe what you have taken.

If you forgot to take Eviplera

It is essential not to forget a dose of Eviplera.

If you forget a dose:

• If you realize within 12hoursafter the time you normally takeEviplera, you must take the tablet as soon as possible. Take the tablet always with food. Then take the next dose as usual.
• If you realize 12hoursor moreafter the time you normally takeEviplera, do not takethe missed dose. Wait and take the next dose, with food, at the usual time.

If you vomit before 4hours after taking Eviplera,take another tablet with food. If you vomit more than 4hours after taking Eviplera,you do not need to take another tablet until the next scheduled dose as usual.

Do not interrupt the treatment withEviplera

Do not interrupt the treatment with Eviplera without first talking to your doctor.Interrupting Eviplera can severely affect your response to future treatments. If Eviplera is interrupted for any reason, consult your doctor before restarting treatment with Eviplera. Your doctor may consider giving you the components of Eviplera separately if you are experiencing any problems or need a dose adjustment.

When you see that you have little Eviplera left,go to your doctor or pharmacist to get more. This is very important, as the amount of virus may start to increase if the medication is interrupted, even for a short period of time. It is possible that the virus will then become more difficult to treat.

If you have HIV and hepatitisB,it is especially important not to suspend your treatment with Eviplera without first consulting your doctor. Some patients have presented blood tests or symptoms indicating that their hepatitis had worsened after suspending emtricitabine or tenofovir disoproxil (two of the three active principles of Eviplera). If Eviplera is interrupted, your doctor may recommend restarting treatment for hepatitisB. You may need to undergo blood tests to check liver function for 4months after suspending treatment. In some patients with advanced liver disease or cirrhosis, it is not recommended to suspend treatment as this can lead to worsening of their hepatitis, which can be life-threatening.

→Consult your doctor immediatelyabout new or unusual symptoms after suspending treatment, particularly symptoms associated with hepatitisB virus infection.

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

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

Possible side effects: report to a doctor immediately

• Lactic acidosis (excess of lactic acid in the blood) is a rare but potentially life-threatening side effect of some HIV medicines. Lactic acidosis occurs more frequently in women, especially if they are overweight, and in people with liver disease. The following may be signs of lactic acidosis:
• Deep and rapid breathing
• Fatigue or drowsiness
• Nausea and vomiting
• Abdominal pain

→If you think you may have lactic acidosis, report to your doctor immediately.

Any sign of inflammation or infection.In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (infections that occur in people with a weakened immune system), signs and symptoms of inflammation from previous infections may occur shortly after starting HIV treatment. It is believed that these symptoms are due to an improvement in the body's immune response, which allows it to fight off infections that may have been present without obvious symptoms.

In addition to opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also appear after you have started taking medicines for HIV treatment. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness starting in the hands and feet and rising to the trunk of the body, palpitations, tremors, or hyperactivity, report to your doctor immediately to receive the necessary treatment.

→If you notice any symptoms of inflammation or infection, report to your doctor immediately.

Frequent side effects

(may affect more than 1 in 10 people)

• Diarrhea, vomiting, nausea
• Difficulty sleeping (insomnia)
• Dizziness, headache
• Rash
• Feeling weak

Tests may also show:

• Decreased levels of phosphate in the blood
• Increased levels of creatine kinase in the blood that may cause muscle pain and weakness
• Increased levels of cholesterol and/or pancreatic amylase in the blood
• Increased levels of liver enzymes in the blood

→If any of the side effects worsen, report to your doctor..

Frequent side effects

(may affect up to 1 in 10 people)

• Loss of appetite
• Depression and depressed mood
• Tiredness, drowsiness
• Sopor
• Pain, abdominal pain or discomfort, feeling bloated, dry mouth
• Abnormal dreams, sleep disorders
• Digestive problems with discomfort after meals, gas (flatulence)
• Rashes (including red patches or spots sometimes with blisters and swelling of the skin), which may be allergic reactions, itching, changes in skin color such as darkening of the skin in patches
• Other allergic reactions, such as difficulty breathing, swelling, or feeling slightly dizzy

Tests may also show:

• Low white blood cell count(a reduced white blood cell count may make you more prone to infections)

• Low platelet count (a type of blood cell involved in blood clotting)

• Decreased hemoglobin levels in the blood (low red blood cell count)
• Increased triglycerides, bilirubin, or sugar in the blood
• Pancreatic problems

→If any of the side effects worsen, report to your doctor.

Rare side effects

(may affect up to 1 in 1,000 people)

• Lactic acidosis (see Possible side effects: report to a doctor immediately)
• Back pain due to kidney problems, including kidney failure. Your doctor may perform blood tests to see if your kidneys are functioning properly
• Fatty liver
• Yellow skin or eyes, itching, or abdominal pain caused by liver inflammation
• Renal inflammation, increased urine volume, and feeling thirsty
• Weakening of the bones (with bone pain and sometimes resulting in fractures)

You may experience muscle rupture, weakening of the bones (with bone pain and sometimes resulting in fractures), muscle pain, muscle weakness, and decreased levels of potassium or phosphate in the blood due to damage to the renal tubular cells.

→If any of the side effects worsen, report to your doctor.

Other effects that may be observed during HIV treatment

The frequency of the following side effects is unknown (the frequency cannot be estimated from the available data).

• Bone problems.Some patients treated with combined antiretroviral medications such as Eviplera may develop a bone disease called osteonecrosis (death of bone tissue due to a loss of blood supply to the bone). Taking this type of medication for a prolonged period, taking corticosteroids, drinking alcohol, having a very weakened immune system, and being overweight may be some of the many risk factors for developing this disease. The signs of osteonecrosis are:
• Joint stiffness
• Pain and joint pain (especially in the hip, knee, and shoulder)
• Difficulty moving

→If you notice any of these symptoms, report to your doctor.

During HIV treatment, there may be an increase in weight and blood glucose and lipid levels. This may be partly related to recovery of health and lifestyle, and in the case of blood lipids, sometimes to HIV medicines themselves. Your doctor will monitor these changes.

Reporting side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this prospectus.You can also report them directly through the national notification system included in theAppendix V. By reporting side effects, you can contribute to providing more information on 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 bottle and the box after{CAD}. The expiration date is the last day of the month indicated.

Store in the original packaging to protect it from moisture. Keep the bottle perfectly closed.

Medicines 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 Eviplera

• The active ingredients areemtricitabina, rilpivirinaandtenofovir disoproxilo. Each Eviplera film-coated tablet contains 200mg of emtricitabina, 25mg of rilpivirina (as hydrochloride) and 245mg of tenofovir disoproxilo (as fumarate).

• The other components are

Tablet core:

Microcrystalline cellulose, lactose monohydrate, povidone, pregelatinized maize starch, polisorbate20, croscarmellose sodium and magnesium stearate.

Film coating:

Hydroxypropyl methylcellulose, indigo carmine lake, lactose monohydrate, polyethylene glycol, iron oxide red, yellow-orange aluminium lake (E110), titanium dioxide and triacetin.

Appearance of the product and contents of the pack

Eviplera is a pink-violet film-coated tablet in capsule shape, engraved with “GSI” on one face and smooth on the other. Eviplera is available in bottles of 30tablets and in packs consisting of 3bottles of 30tablets each. Each bottle contains a silica gel desiccant that must be kept inside the bottle to protect the tablets. Thesilica gel desiccant is contained in a separate sachet or container and must not be taken.

Only some pack sizes may be marketed.

Marketing authorisation holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Responsible person for manufacturing

Gilead Sciences Ireland UC

IDA Business & Technology Park

Carrigtohill

County Cork

Ireland

For further information about this medicinal product, please consult the representative of the marketing authorisation holder:

Last update of the summary of product characteristics:

The detailed information on this medicinal product is available on the website of the European Medicines Agency http://www.ema.europa.eu