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

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

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

emtricitabine/rilpivirine/tenofovir disoproxil fumarate

Read the entire leaflet carefully before you start 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 or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
• If you experience side effects, talk to your doctor or pharmacist, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet:

1. What Eviplera is and what it is used for
2. What you need to know before taking Eviplera
3. How to take Eviplera
4. Possible side effects
5. How to store Eviplera
6. Contents of the pack and other information

1. What Eviplera is and what it is used for

Eviplera contains three active substances used to treat infection with the Human Immunodeficiency Virus (HIV):

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

Each of these active substances, also known as antiretroviral drugs, works by interfering with an enzyme (a protein called "reverse transcriptase") that is essential for the virus to multiply.

Eviplera reduces the amount of HIV in the body. This improves the immune system and reduces the risk of developing illnesses associated with HIV infection.

Eviplera is a medicine used to treat infection with the Human Immunodeficiency Virus (HIV) in adults aged 18 years and older.

2. What you need to know before taking Eviplera

Do not take Eviplera

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

→If this applies to you, inform 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 seizures)
• rifampicin and rifapentine (used to treat certain bacterial infections such as tuberculosis)
• omeprazole, lansoprazole, rabeprazole, pantoprazole, and esomeprazole (proton pump inhibitors, 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 by injection (except for single-dose treatment)
• products containing St. John’s wort (Hypericum perforatum) (a herbal remedy used for depression and anxiety)

Warnings and precautions

You must remain under your doctor’s supervision while taking Eviplera.

• While taking this medicine, you may still transmit HIV to others, even though effective antiviral treatment reduces the risk. Consult your doctor about which precautions are necessary to avoid infecting others. This medicine is not a cure for HIV infection. While you are taking Eviplera, you may continue to develop infections or other illnesses associated with HIV infection.

• If you have had kidney disease, or if blood tests have shown kidney problems, tell your doctor. Eviplera may affect your kidneys. Before and during treatment, your doctor may request blood tests to monitor kidney function. Eviplera is not recommended if you have moderate or severe kidney disease.

Eviplera is generally not taken with other drugs that may harm your kidneys (see Other medicines 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 hepatitis B or C) treated with antiretrovirals are at higher risk of developing serious, 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 ingredients in Eviplera (tenofovir disoproxil and emtricitabine) have some activity against the 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 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 interrupt treatment with Eviplera.*

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

• Consult your doctor if you are over 65 years of age. A sufficient number of patients over 65 years of age has not been studied. If you are over 65 and prescribed Eviplera, your doctor will closely monitor you.

While taking Eviplera

Once you start taking Eviplera, be alert for:

• any signs of inflammation or infection
• bone problems

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

Children and adolescents

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

Other medicines and Eviplera

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines. This includes medicines and herbal remedies purchased without a prescription.

Inform your doctor if you are taking any of the following medicines:

• Any other medicine containing:

• emtricitabine

• rilpivirine

• tenofovir disoproxil

• tenofovir alafenamide

• any other antiviral medicine containing lamivudine or adefovir dipivoxil

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

• Medicines that may harm the 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 containing didanosine (for HIV infection): Taking Eviplera with other antiviral medicines containing didanosine may increase levels of didanosine in your blood and may reduce CD4+ cell counts. 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, some of which were fatal. Your doctor will carefully consider whether to treat you with other medicines used for HIV infection (see Other medicines used for HIV infection).

• Other medicines used for HIV infection: Non-nucleoside reverse transcriptase inhibitors (NNRTIs). Eviplera contains an NNRTI (rilpivirine), so Eviplera should not be combined with other medicines of this type. Your doctor will consider a different medicine if necessary.

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

• Antibiotics used to treat bacterial infections, including tuberculosis, containing:

• clarithromycin

• erythromycin

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

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

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

• If you are taking an antacid (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 an H2 antagonist (also used to treat stomach acidity or gastroesophageal reflux disease), take it at least 12 hours before or at least 4 hours after Eviplera. H2 antagonists can only be taken once daily if you are taking Eviplera. H2 antagonists should not be taken on a twice-daily schedule. 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 adjust your dose.

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

→Inform 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 plan to become pregnant, consult your doctor or pharmacist before using this medicine.

• Use an effective method of contraception while taking Eviplera.
• Inform 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 potential risks and benefits of taking Eviplera for you and your child.
• If you have taken Eviplera during pregnancy, your doctor may request periodic blood tests and other diagnostic tests to monitor your child’s development. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV was greater than the risk of adverse effects.

Do not breastfeed while being treated with Eviplera:

• This is because the active ingredients of this medicine pass into breast milk.
• If you are a woman with HIV infection, you are advised not to breastfeed, to avoid transmitting the virus to your child through breast milk.

Driving and using machines

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

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

• If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.
• Inform your doctor if you are allergic to orange-yellow aluminum lake S (E110). Eviplera contains orange-yellow aluminum lake S, also known as “E110”, which may cause allergic reactions.
• This medicine contains less than 1 mmol of sodium (23 mg) per tablet; that is, essentially “sodium-free”.

3. How to take Eviplera

Follow exactly the instructions for using this medicine as given by your doctor. If you are unsure, consult your doctor or pharmacist again.

The usual dose is one tablet taken by mouth once daily. The tablet must be taken with food. This is important to achieve adequate levels of active substance in the body. A nutritional drink alone does not replace food.

Swallow the tablet whole with water.

Do not chew, crush, or split the tablet, as this could affect how the medicine is released in the body.

If your doctor decides to discontinue one of the components of Eviplera or to change the dose of Eviplera, you may be given emtricitabine, rilpivirine, and/or tenofovir disoproxil separately or with other medicines for the treatment of HIV infection.

If you are taking an antacid such as medicines containing magnesium or potassium, take it at least 2 hours before or at least 4 hours after taking Eviplera.

If you are taking an H2 antagonist such as famotidine, cimetidine, nizatidine, or ranitidine, take it at least 12 hours before or at least 4 hours after Eviplera. H2 antagonists may only be taken once daily while you are taking Eviplera. H2 antagonists should not be taken twice daily. Consult your doctor for an alternative dosing schedule.

If you are taking rifabutin, your doctor may need to give you an additional dose of rilpivirine. Take the rilpivirine tablet at the same time as you take Eviplera. If in doubt, consult your doctor or pharmacist.

If you take more Eviplera than you should

If you accidentally take more than the recommended dose of Eviplera, you may be at increased risk of experiencing possible side effects with this medicine (see section 4, Possible side effects).

Contact your doctor or go to the nearest emergency room immediately. Bring the medicine bottle with you so you can clearly describe what you have taken.

If you forget to take Eviplera

It is important not to miss a dose of Eviplera.

If you forget a dose:

• If you remember within 12 hours after the time you usually take Eviplera, take the tablet as soon as possible. Always take the tablet with food. Then take your next dose at the usual time.
• If you remember 12 hours or more after the time you usually take Eviplera, do not take the missed dose. Wait and take your next dose at the usual time with food.

If you vomit within 4 hours 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 your next scheduled dose.

Do not stop treatment with Eviplera

Do not stop treatment with Eviplera without first talking to your doctor. Stopping Eviplera may seriously affect your response to future treatments. If Eviplera is stopped 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 require a dose adjustment.

When you notice that you are running low on Eviplera, contact your doctor or pharmacist to get more. This is very important, as the amount of virus may start to increase if the medicine is interrupted even for a short period of time. The virus may then become more difficult to treat.

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

→Contact your doctor immediately about any new or unusual symptoms after stopping your treatment, particularly symptoms you associate with hepatitis B virus infection.

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

4. Possible adverse effects

Like all medicines, this medicine can cause adverse effects, although not everyone experiences them.

Possible adverse effects: tell a doctor immediately

• Lactic acidosis (excess 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:
• Rapid and deep breathing
• Tiredness or drowsiness
• Feeling sick (nausea) and vomiting
• Stomach pain

→If you think you may have lactic acidosis, tell 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 anti-HIV treatment. These symptoms are believed to result from an improved immune response, enabling the body to fight infections that may have been present without obvious symptoms.

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

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

Very common adverse effects

(may affect more than 1 in 10 people)

• Diarrhoea, vomiting, feeling sick (nausea)
• Difficulty sleeping (insomnia)
• Dizziness, headache
• Rash
• Feeling weak

Blood tests may also show:

• Decreased levels of phosphate in the blood
• Increased levels of creatine kinase in the blood, which 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 these adverse effects worsen, tell your doctor.

Common adverse effects

(may affect up to 1 in 10 people)

• Loss of appetite
• Depression and low mood
• Tiredness, feeling sleepy (somnolence)
• Drowsiness
• Pain, stomach ache or discomfort, feeling bloated, dry mouth
• Abnormal dreams, sleep disturbances
• Digestive problems with discomfort after meals, gas (flatulence)
• Rashes (including red spots or pimples, sometimes with blisters and skin swelling), which may be allergic reactions, itching, changes in skin colour such as darkening of the skin in patches
• Other allergic reactions, such as difficulty breathing, swelling, or feeling slightly dizzy

Blood tests may also show:

• Low white blood cell count (a reduced number of white blood cells may make you more prone to infections)
• Low platelet count (a type of blood cell involved in blood clotting)
• Decreased levels of haemoglobin in the blood (low number of red blood cells)
• Increased levels of fatty acids (triglycerides), bilirubin, or blood sugar
• Pancreatic problems

→If any of these adverse effects worsen, tell your doctor.

Uncommon adverse effects

(may affect up to 1 in 100 people)

• Anaemia (low number of red blood cells)
• Abdominal (stomach) pain caused by inflammation of the pancreas
• 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
• Damage to renal tubule cells

Blood tests may also show:

• Decreased levels of potassium in the blood
• Increased creatinine in the blood
• Changes in your urine

→If any of these adverse effects worsen, tell your doctor.

Rare adverse effects

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

• Lactic acidosis (see Possible adverse effects: tell a doctor immediately)
• Back pain due to kidney problems, including kidney failure. Your doctor may carry out blood tests to check whether your kidneys are functioning properly
• Fatty liver
• Yellowing of the skin or eyes, itching, or abdominal (stomach) pain caused by liver inflammation
• Inflammation of the kidney, increased urine volume, and feeling thirsty
• Weakening of the bones (with bone pain and sometimes leading to fractures)

Muscle rupture, weakening of the bones (with bone pain and sometimes leading to fractures), muscle pain, muscle weakness, and decreased levels of potassium or phosphate in the blood may occur due to damage to renal tubule cells.

→If any of these adverse effects worsen, tell your doctor.

Other effects that may occur during HIV treatment

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

• Bone problems. Some patients treated with combined antiretroviral medicines such as 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 medicine for a long time, taking corticosteroids, drinking alcohol, having a very weak immune system, and being overweight may be some of the many risk factors for developing this disease. Signs of osteonecrosis include:
• Joint stiffness
• Pain and joint pain (especially in the hip, knee, and shoulder)
• Difficulty moving

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

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

Reporting of adverse effects

If you experience any adverse effect, talk to your doctor or pharmacist, even if it is a possible adverse effect not listed in this leaflet. You may also report them directly through the national reporting system detailed in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Eviplera

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date stated on the bottle and carton after {EXP}. The expiry date is the last day of the month indicated.

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

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of any unused medicines and their packaging. This will help protect the environment.

6. Contents of the container and other information

Composition of Eviplera

• The active substances are emtricitabine, rilpivirine, and 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 components are

Tablet core:

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

Film coating:

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

Appearance of the product and contents of the container

Eviplera is a film-coated tablet, purple-pink in colour, capsule-shaped, engraved on one side with “GSI” and smooth on the other. Eviplera is available in bottles of 30 tablets and in packaging consisting of 3 bottles containing 30 tablets each. Each bottle contains a silica gel desiccant, which must remain inside the bottle to protect the tablets. The silica gel desiccant is contained in a separate sachet or container and must 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 more information about this medicine, contact the local representative of the Marketing Authorization Holder:

Date of the most recent revision of this leaflet:

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