Eviplera
emtricitabine, rilpivirine, tenofovir disoproxil
emtricitabine/rilpivirine/tenofovir disoproxil
Keep this leaflet. You may need to read it again.
If you have any further 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 signs of illness are the same as yours.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side
effects not listed in this leaflet. See section 4.
What Eviplera is and what it is used for
What you need to know before you take Eviplera
How to take Eviplera
Possible side effects
How to store Eviplera
Contents of the pack and other information
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 medicines, 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 your body. This, will improve your immune system and reduces the risk of developing illnesses linked to HIV infection.
If this applies to you, tell your doctor immediately.
products that contain St. John’s wort (Hypericum perforatum) (a herbal remedy used for depression and anxiety)
You must remain under the care of your doctor while taking Eviplera.
Eviplera is not usually taken with other medicines that can damage your kidneys (see Other medicines and Eviplera). If this is unavoidable, your doctor will monitor your kidney function once a week.
If you have hepatitis B infection, liver problems may become worse after you stop taking Eviplera. It is important not to stop taking Eviplera without talking to your doctor: see section 3, Do not stop taking Eviplera.
Once you start taking Eviplera, look out for:
any signs of inflammation or infection
bone problems (manifesting as persistent or worsening bone pain and sometimes resulting in fractures) may also occur due to damage to kidney tubule cells (see section 4, Possible side effects). Tell your doctor if you have bone pain or fractures.
Tenofovir disoproxil (a component of Eviplera) may also cause loss of bone mass. Overall, the effects of tenofovir disoproxil on long-term bone health and future fracture risk in adult patients are uncertain. Tell your doctor if you know you suffer from osteoporosis. Patients with osteoporosis are at a higher risk for fractures.
If you notice any of these symptoms, tell your doctor immediately. Children and adolescents
emtricitabine
rilpivirine
tenofovir disoproxil
tenofovir alafenamide
any other antiviral medicines that contain lamivudine or adefovir dipivoxil
Eviplera may interact with other medicines. As a result, the amounts of Eviplera or other medicines in your blood may be affected. This may stop your medicines from working properly, or may make any side effects worse. In some cases, your doctor may need to adjust your dose or check your blood levels.
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 called aldesleukin (to treat cancer)
non-steroidal anti-inflammatory drugs (NSAIDs, to relieve bone or muscle pains)
Medicines containing didanosine (for HIV infection): Taking Eviplera with other antiviral medicines that contain didanosine can raise the levels of didanosine in your blood and may reduce CD4+ cell counts. Inflammation of the pancreas and lactic acidosis (excess lactic acid in the blood), which sometimes caused death, have been reported rarely when medicines containing tenofovir disoproxil and didanosine were taken together. Your doctor will carefully consider whether to treat you with other medicines used for treating HIV infection (see Other medicines used for HIV infection).
Rifabutin, a medicine to treat some bacterial infections. This medicine can decrease the amount of rilpivirine (a component of Eviplera) in your blood. Your doctor may need to give you an additional dose of rilpivirine to treat your HIV infection (see section 3, How to take Eviplera).
clarithromycin
erythromycin
These medicines can increase the amount of rilpivirine (a component of Eviplera) in your blood. Your doctor may need to change the dose of the antibiotic or give you a different antibiotic.
antacids (aluminium/magnesium hydroxide or calcium carbonate)
H2-antagonists (famotidine, cimetidine, nizatidine or ranitidine)
These medicines can decrease the amount of rilpivirine (a component of Eviplera) in your blood. If you are taking one of these medicines your doctor will either give you a different medicine for stomach ulcers, heartburn or acid reflux, or recommend how and when you take
that medicine.
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 acid or acid reflux disease), 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 take Eviplera. H2-antagonists should not be taken in a twice a day regimen. Talk to your doctor about an alternative regimen (see section 3, How to take Eviplera).
Tell your doctor if you are taking any of these medicines. Do not stop your treatment without contacting your doctor.
If you are pregnant or breast‑feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.
Pregnant women should discuss the use of Eviplera with their doctor. Your doctor will discuss the potential benefits and risks of taking Eviplera to you and your child.
This is because the active substances in this medicine pass into human breast milk.
If you are a woman with HIV it is recommended that you do not breast-feed, to avoid passing the virus to the baby in breast milk.
Do not drive or operate machines if you feel tired, sleepy or dizzy after taking your medicine.
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.
Always take this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure.
Swallow the tablet whole with water.
If your doctor decides to stop one of the components of Eviplera or 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 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 can only be taken once a day if you take Eviplera. H2-antagonists should not be taken twice a day. Talk to your doctor about an alternative regimen.
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 nearest emergency department immediately for advice. Keep the tablet bottle with you so that you can easily describe what you have taken.
It is important not to miss a dose of Eviplera. If you do miss a dose:
4 months after stopping treatment. In some patients with advanced liver disease or cirrhosis, stopping treatment is not recommended as this may lead to worsening of your 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 or pharmacist.
Like all medicines, this medicine can cause side effects, although not everybody gets them.
Deep, rapid breathing
Tiredness or drowsiness
Feeling sick (nausea), being sick (vomiting)
Stomach pain
If you think you may have lactic acidosis, tell your doctor immediately.
In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection. 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 beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.
If you notice any symptoms of inflammation or infection, tell your doctor immediately.
(may affect more than 1 in 10 people)
Diarrhoea, being sick (vomiting), feeling sick (nausea)
Difficulty sleeping (insomnia)
Dizziness, headache
Rash
Feeling weak
Tests may also show:
Decreases in phosphate levels in the blood
Increased levels of creatine kinase in the blood that may result in 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 get serious tell your doctor.
(may affect up to 1 in 10 people)
Decreased appetite
Depression and depressed mood
Tiredness, feeling sleepy (somnolence)
Drowsiness
Pain, stomach pain or discomfort, feeling bloated, dry mouth
Abnormal dreams, sleep disorders
Problems with digestion resulting in discomfort after meals, wind (flatulence)
Rashes (including red spots or blotches sometimes with blistering and swelling of the skin), which may be allergic reactions, itching, changes in skin colour including darkening of the skin in patches
Other allergic reactions, such as wheezing, swelling or feeling light-headed
Tests may also show:
Low white blood cell count (a reduced white blood cell count can make you more prone to infection)
Low platelet count (a type of blood cell involved in clotting blood)
Decrease in haemoglobin in your blood (low red blood cell count)
Increased fatty acids (triglycerides), bilirubin or sugar in the blood
Pancreas problems
If any of the side effects get serious tell your doctor.
(may affect up to 1 in 100 people)
Anaemia (low red blood cell count)
Pain in the abdomen (tummy) caused by inflammation of the pancreas
Breakdown of muscle, muscle pain or weakness
Swelling of the face, lips, tongue or throat
Signs or symptoms of inflammation or infection
Severe skin reactions including rash accompanied by fever, swelling and liver problems
Damage to kidney tubule cells
Tests may also show:
Decreases in potassium in the blood
Increases in creatinine in your blood
Changes to your urine
If any of the side effects get serious tell your doctor.
(may affect up to 1 in 1,000 people)
Lactic acidosis (see Possible side effects: tell a doctor immediately)
Back pain caused by kidney problems, including kidney failure. Your doctor may do blood tests to see if your kidneys are working properly
Fatty liver
Yellow skin or eyes, itching or pain in the abdomen (tummy) caused by inflammation of the liver
Inflammation of the kidney, passing a lot of urine and feeling thirsty
Softening of the bones (with bone pain and sometimes resulting in fractures)
The breakdown of muscle, softening of the bones (with bone pain and sometimes resulting in fractures), muscle pain, muscle weakness and decreases in potassium or phosphate in the blood may occur due to damage to kidney tubule cells.
If any of the side effects get serious tell your doctor. Other effects that may be seen during HIV treatment
The frequency of the following side effects is not known (frequency cannot be estimated from the available data).
Bone problems. Some patients taking combination antiretroviral medicines such as Eviplera may develop a bone disease called osteonecrosis (death of bone tissue caused by 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 are:
Joint stiffness
Joint aches and pains (especially of the hip, knee and shoulder)
Difficulty with movement
If you notice any of these symptoms tell your doctor.
During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting
system listed in Appendix V. By reporting side effects you can help provide more information on the safety of this medicine.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date which is stated on the bottle and carton after {EXP}. The expiry date refers to the last day of that month.
Store in the original package in order to protect from moisture. Keep the bottle tightly closed.
Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.
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).
Tablet core:
Microcrystalline cellulose, lactose monohydrate, povidone, pregelatinised maize starch, polysorbate 20, croscarmellose sodium, and magnesium stearate.
Film-coating:
Hypromellose, indigo carmine aluminium lake, lactose monohydrate, polyethylene glycol, red iron oxide, sunset yellow aluminium lake (E110), titanium dioxide, and triacetin.
Eviplera is a purplish-pink, capsule-shaped, film-coated tablet debossed on one side with “GSI” and plain on the other side. Eviplera comes in bottles of 30 tablets and in packs made up of 3 bottles, each containing 30 tablets. Each bottle contains 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.
Not all pack sizes may be marketed.
County Cork, T45 DP77 Ireland
Gilead Sciences Ireland UC
IDA Business & Technology Park Carrigtohill
County Cork Ireland
For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Gilead Sciences Belgium SRL-BV Tél/Tel: + 32 (0) 24 01 35 50
Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702
Gilead Sciences Ireland UC
Тел.: + 353 (0) 1 686 1888
Gilead Sciences Belgium SRL-BV Tél/Tel: + 32 (0) 24 01 35 50
Gilead Sciences Ireland UC Tel.: + 353 (0) 1 686 1888
Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1849
Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888
Gilead Sciences GmbH Tel: + 49 (0) 89 899890-0
Gilead Sciences Netherlands B.V. Tel: + 31 (0) 20 718 36 98
Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702
Gilead Sciences Sweden AB Tlf: + 46 (0) 8 5057 1849
Gilead Sciences Ελλάς Μ.ΕΠΕ. Τηλ: + 30 210 8930 100
Gilead Sciences GesmbH Tel: + 43 1 260 830
Gilead Sciences, S.L. Tel: + 34 91 378 98 30
Gilead Sciences Poland Sp. z o.o. Tel.: + 48 22 262 8702
Gilead Sciences
Tél: + 33 (0) 1 46 09 41 00
Gilead Sciences, Lda. Tel: + 351 21 7928790
Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888
Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888
Gilead Sciences Ireland UC Tel: + 353 (0) 214 825 999
Gilead Sciences Ireland UC Tel: + 353 (0) 1 686 1888
Gilead Sciences Sweden AB Sími: + 46 (0) 8 5057 1849
Gilead Sciences Slovakia s.r.o. Tel: + 421 232 121 210
Gilead Sciences S.r.l. Tel: + 39 02 439201
Gilead Sciences Sweden AB Puh/Tel: + 46 (0) 8 5057 1849
Gilead Sciences Ελλάς Μ.ΕΠΕ. Τηλ: + 30 210 8930 100
Gilead Sciences Sweden AB Tel: + 46 (0) 8 5057 1849
Gilead Sciences Poland Sp. z o.o. Tel: + 48 22 262 8702
Gilead Sciences Ireland UC Tel: + 44 (0) 8000 113 700
Taking into account the PRAC Assessment Report on the PSUR(s) for emtricitabine / rilpivirine / tenofovir disoproxil, the scientific conclusions of CHMP are as follows:
Having reviewed the cumulative safety review on osteopenia/osteoporosis, the PRAC considers that section 4.4 of the emtricitabine / rilpivirine / tenofovir disoproxil SmPC needs changing to enhance
the information on bone effects. The Package leaflet is to be updated accordingly.
The CHMP agrees with the scientific conclusions made by the PRAC.
On the basis of the scientific conclusions for emtricitabine / rilpivirine / tenofovir disoproxil the CHMP is of the opinion that the benefit-risk balance of the medicinal product(s) containing emtricitabine / rilpivirine / tenofovir disoproxil is unchanged subject to the proposed changes to the product information
The CHMP recommends that the terms of the MARKETING AUTHORISATION(S) should be varied.