EVIPLERA 200 mg/25 mg/245 mg FILM-COATED TABLETS

2. What you need to know before you take Eviplera

Do not take Eviplera

• If you are allergicto emtricitabine, rilpivirine, tenofovir disoproxil or any of the other ingredients of this medicine (listed in section 6 of this leaflet).

→If this happens, tell your doctor immediately.

→If you are currently taking any of the following medicines

• carbamazepine, oxcarbazepine, phenobarbital and phenytoin(medicines used to treat epilepsy and prevent convulsions)
• rifampicin and rifapentine(used to treat some bacterial infections such as tuberculosis)
• omeprazole, lansoprazole, rabeprazole, pantoprazole and esomeprazole(proton pump inhibitors, which are medicines 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 herbal medicine used for depression and anxiety)

Warnings and precautions

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

• While taking this medicine, you can still transmit HIV to others, although effective antiviral treatment reduces the risk. Ask your doctor about the precautions needed to avoid infecting others. This medicine 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 tests have shown kidney problems, tell your doctor. Eviplera can affect your kidneys. Before and during treatment, your doctor may ask you to have blood tests to measure your kidney function. Eviplera is not recommended if you have moderate or severe kidney disease.

Eviplera is not normally taken with other medicines that can harm your kidneys (see Other medicines and Eviplera). If this is unavoidable, your doctor will monitor your kidney function once a week.

• Tell your doctor if you have a history of liver disease, including hepatitis.Patients with HIV and liver disease (including chronic hepatitis B or C) treated with antiretrovirals have a greater risk of developing severe and potentially life-threatening liver complications. If you have hepatitis B, your doctor will carefully consider the best treatment regimen for you. Two of the active substances in Eviplera (tenofovir disoproxil and emtricitabine) have some activity against hepatitis B virus. If you have a history of liver disease or chronic hepatitis B infection, your doctor may perform blood tests to monitor liver function.

If you have a hepatitis B infection, liver problems may worsen after stopping Eviplera. It is important that you do not stop taking Eviplera without first talking to your doctor: see section 3, Do not stop taking Eviplera.

• Tell your doctor immediately and stop taking Eviplera if you develop a skin rash accompanied by the following symptoms: fever, blisters, redness of the eyes and swelling of the face, mouth or body.This can become severe or potentially life-threatening.

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

While taking Eviplera

Once you start taking Eviplera, be aware of:

• any signs of inflammation or infection
• bone problems

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

Children and adolescents

Do not give this medicine to childrenand adolescents under 18 years of age.

Othermedicines and Eviplera

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.This includes medicines and herbal medicines bought without a prescription.

Tell your doctorif you are taking any of the following medicines:

• Any other medicine that contains:

• emtricitabine
• rilpivirine
• tenofovir disoproxil
• tenofovir alafenamide
• any other antiviral medicine that contains lamivudine or adefovir dipivoxil

Eviplera may interact with other medicines. As a result, the levels of Eviplera or other medicines in your blood may be affected. This may prevent your medicines from working properly or may increase the risk of side effects. In some cases, your doctor may need to adjust the dose or monitor the levels of the medicines in your blood.

• Medicines that can harm your kidneys, such as:
• aminoglycosides (such as streptomycin, neomycin and gentamicin), vancomycin (for bacterial infections)
• foscarnet, ganciclovir, cidofovir (for viral infections)
• amphotericin B, pentamidine (for fungal infections)
• interleukin-2, also known as aldesleukin (for cancer treatment)
• non-steroidal anti-inflammatory drugs (NSAIDs, for relieving bone or muscle pain)

• Medicines that contain didanosine (for HIV infection):Taking Eviplera with other antiviral medicines that contain didanosine may increase the levels of didanosine in your blood and may reduce the CD4+ cell count. When medicines containing tenofovir disoproxil and didanosine are taken together, rare cases of pancreatitis and lactic acidosis (excess lactic acid in the blood) have been reported, sometimes resulting in death. Your doctor will carefully consider whether to treat you with other medicines used to treat HIV infection (see Other medicines used to treat HIV infection).

• Othermedicines used to treat HIV infection:Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Eviplera contains an NNRTI (rilpivirine), so Eviplera must not be combined with other medicines of this type. Your doctor will consider an alternative medicine if necessary.

• Rifabutin, a medicine used to treat some bacterial infections. This medicine may reduce the levels of rilpivirine (a component of Eviplera) in the blood. Your doctor may need to give you an additional dose of rilpivirine to treat your HIV infection (seesection 3, How to take Eviplera).

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

• clarithromycin
• erythromycin

These medicines may increase the levels of rilpivirine (a component of Eviplera) in the blood. Your doctor may need to change the dose of the antibiotic or give you a different one.

• Medicines forstomach ulcers, heartburn or acid reflux, such as:
• antacids (aluminium/magnesium hydroxide or calcium carbonate)
• H2 antagonists (famotidine, cimetidine, nizatidine or ranitidine)

These medicines may reduce the levels of rilpivirine (a component of Eviplera) in the blood. If you are taking one of these medicines, your doctor will give you a different one for stomach ulcers, heartburn or acid reflux or recommend how and when to take that medicine.

• If you are taking anantacid(such as medicines containing magnesium or potassium), take it at least 2 hours before or at least 4 hours after Eviplera (see section 3, How to take Eviplera).

• If you are taking anH2 antagonist(also used to treat stomach acid or gastroesophageal reflux disease), take it at least 12 hours before or at least 4 hours after Eviplera. H2 antagonists should only be taken once a day if you are taking Eviplera. H2 antagonists should not be taken in a twice-daily regimen. Consult your doctor for an alternative regimen (see section 3, How to take Eviplera).

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

• Dabigatran etexilate, a medicine used to treat heart conditions, as your doctor may need to monitor the levels of this medicine in your blood.

→Tell your doctor if you are taking any of these medicines. Do not stop your treatment without consulting your doctor.

Pregnancy and breastfeeding

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, consult your doctor or pharmacist before taking this medicine.

• Use effective contraceptionwhile taking Eviplera.
• Tell your doctor immediately if you become pregnant or plan to become pregnant.Pregnant women should discuss the use of Eviplera with their doctor. Your doctor will explain the risks and benefits of taking Eviplera for you and your baby.
• If you have taken Evipleraduring your pregnancy, your doctor may ask you to have regular blood tests and other diagnostic tests to monitor the development of your baby. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV was greater than the risk of side effects.

Do not breastfeed your child while taking Eviplera:

• This is because the active substances of this medicine pass into breast milk.
• If you are a woman with HIV infection, it is recommended that you do not breastfeed your baby to prevent passing the virus to your baby through breast milk.

Driving and using machines

Do not drive or operate machines if you feel tired, sleepy or dizzy after taking this medicine.

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

• If your doctor has told you that you have an intolerance to some sugars, consult your doctor before taking this medicine.
• Tell your doctor if you are allergic to yellow-orange aluminium lake (E110).Eviplera contains yellow-orange aluminium lake (E110), which may cause allergic reactions.
• This medicine contains less than 1 mmol of sodium (23 mg) per tablet; this is essentially “sodium-free”.

3. How to take Eviplera

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

The normal dose is one tablet that is taken every day by mouth. The tablet must be taken with food.This is important to achieve the adequate levels of active ingredient in the body. A single nutritional drink 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 that contain magnesium or potassium. Take it at least 2 hours before or at least 4 hours after Eviplera.

If you are taking an H2 antagonistsuch as famotidine, cimetidine, nizatidine, or ranitidine. Take it at least 12 hours before or at least 4 hours after Eviplera. H2 antagonists can only be taken once a day if you are taking Eviplera. H2 antagonists should not be taken twice a day. Consult your doctor for an alternative schedule.

If you are taking rifabutin. Your doctor may need to administer an additional dose of rilpivirine. Take the rilpivirine tablet at the same time 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 a higher risk of experiencing possible side effects with this medication (see section 4, Possible side effects).

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

If you forgot to take Eviplera

It is important that you do not forget a dose of Eviplera.

If you forget a dose:

• If you realize within 12 hoursafter the time you normally take Eviplera, 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 12 hours or moreafter the time you normally take Eviplera, do not take the missed dose. Wait and take the next dose, with food, at the usual time.

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

Do not interrupt treatment with Eviplera

Do not interrupt treatment with Eviplera without speaking to your doctor first.Interrupting Eviplera can seriously 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 so that they can provide you with more. This is very important, as the amount of virus can start to increase if the medication is interrupted even for a short period of time. It is possible that the virus may then become more difficult to treat.

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

→ Consult your doctor immediatelyabout new or unusual symptoms after stopping your treatment, particularly symptoms that you associate with hepatitis B infection.

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

4. Possible side effects

Like all medications, this medication can cause side effects, although not all people experience them.

Possible side effects: inform a doctor immediately

• The lactic acidosis(excess of lactic acid in the blood) is a rare but potentially life-threatening side effect of some HIV medications. 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:
• Rapid and deep breathing
• Fatigue or drowsiness
• Nausea and vomiting
• Stomach pain

→ If you think you may have lactic acidosis, inform 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 weak immune system), signs and symptoms of inflammation due to 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 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 start taking medications for the treatment of your HIV infection. Autoimmune disorders can appear many months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness that starts in the hands and feet and moves up to the body, palpitations, tremors, or hyperactivity, inform your doctor immediately to receive the necessary treatment.

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

Very common side effects

(may affect more than 1 in 10 people)

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

Tests may also show:

• Decrease in phosphate levels in the blood
• Increase in creatine kinase levels in the blood that can cause muscle pain and weakness
• Increase in cholesterol and/or amylase levels in the blood
• Increase in liver enzyme levels in the blood

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

Common side effects

(may affect up to 1 in 10 people)

• Decreased appetite
• Depression and depressed mood
• Fatigue, drowsiness
• Drowsiness
• Pain, stomach pain or discomfort, feeling bloated, dry mouth
• Abnormal dreams, sleep disorders
• Digestive problems with discomfort after meals, gas (flatulence)
• Rashes (including red spots or pimples sometimes with blisters and swelling of the skin), which can 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 lightheaded

Tests may also show:

• Low white blood cell count (a reduced number of white blood cells can make you more prone to infections)

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

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

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

Uncommon side effects

(may affect up to 1 in 100 people)

• Anemia (low red blood cell count)
• Abdominal pain (belly) caused by pancreatitis
• Muscle rupture, muscle pain, muscle weakness
• Swelling of the face, lips, tongue, or throat
• Signs or symptoms of inflammation or infection
• Severe skin reactions including rashes accompanied by fever, swelling, and liver problems
• Kidney tubular damage

Tests may also show:

• Decrease in potassium levels in the blood
• Increase in creatinine levels in the blood
• Changes in your urine

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

Rare side effects

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

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

Muscle rupture, weakening of the bones (with bone pain and which sometimes ends in fractures), muscle pain, muscle weakness, and decrease in potassium or phosphate levels in the blood due to kidney tubular damage may occur.

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

Other effects that can 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 combination antiretroviral medications like Eviplera may develop a bone disease called osteonecrosis (death of bone tissue due to loss of blood supply to the bone). Taking this type of medication for a long time, taking corticosteroids, drinking alcohol, having a very weak immune system, and being overweight can 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, inform your doctor.

During HIV treatment, there may be an increase in weight and glucose and lipid levels in the blood. This may be partly related to the recovery of health and lifestyle, and in the case of blood lipids, sometimes to the HIV medications 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 is not listed in this leaflet.You can also report them directly through the national reporting system included in Appendix V. By reporting side effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Eviplera

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 tightly closed.

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

6. Package Contents and Additional Information

Eviplera Composition

• The active ingredients areemtricitabine, rilpivirineand tenofovir disoproxil. Each Eviplera film-coated tablet contains 200 mg of emtricitabine, 25 mg of rilpivirine (as hydrochloride) and 245 mg of tenofovir disoproxil (as fumarate).

• The other ingredients are

Core of the tablet:

Microcrystalline cellulose, lactose monohydrate, povidone, pregelatinized corn starch, polysorbate 20, sodium croscarmellose and magnesium stearate.

Film coating:

Hypromellose, aluminum indigo carmine lake, lactose monohydrate, polyethylene glycol, iron oxide red, aluminum yellow orange lake (E110), titanium dioxide and triacetin.

Appearance and Packaging of the Product

Eviplera is a pink-purple film-coated tablet, capsule-shaped, engraved with “GSI” on one side and smooth on the other. Eviplera comes in bottles of 30 tablets and in packs consisting of 3 bottles of 30 tablets each. Each bottle contains a silica gel desiccant that should be kept inside the bottle to protect the tablets. The silica gel desiccant is contained in a separate sachet or container and should not be swallowed.

Only certain pack sizes may be marketed.

Marketing Authorization Holder

Gilead Sciences Ireland UC

Carrigtohill

County Cork, T45 DP77

Ireland

Manufacturer

Gilead Sciences Ireland UC

IDA Business & Technology Park

Carrigtohill

County Cork

Ireland

For further information about this medicinal product, please contact the local representative of the marketing authorization holder:

Date of Last Revision of this Leaflet:

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