EMTRICITABINE/TENOFOVIR DISOPROXIL KRKA 200 MG/245 MG FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Emtricitabine/Tenofovir Disoproxil Krka 200 mg/245 mg Film-Coated Tablets EFG

emtricitabine/tenofovir disoproxil

Read all of this 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 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.

Contents of the pack and other information

1. What is Emtricitabine/Tenofovir Disoproxil Krka and what is it used for
2. What you need to know before you take Emtricitabine/Tenofovir Disoproxil Krka
3. How to take Emtricitabine/Tenofovir Disoproxil Krka
4. Possible side effects
5. Storage of Emtricitabine/Tenofovir Disoproxil Krka
6. Contents of the pack and further information

1. What is Emtricitabine/Tenofovir Disoproxil Krka and what is it used for

Emtricitabine/Tenofovir Disoproxil Krka contains two active substances, emtricitabineand tenofovirdisoproxil. Both active substances are antiretroviralmedicines used to treat HIV infection. Emtricitabine is a nucleoside analogue reverse transcriptase inhibitorand tenofoviris a nucleotide analogue reverse transcriptase inhibitor. They are generally known by the name NRTI and work by interfering with the normal working of an enzyme (reverse transcriptase) that is essential for the virus to reproduce.

• Emtricitabine/Tenofovir Disoproxil Krka is used to treat HIV-1 infectionin adults
• It is also used to treat HIV in adolescents from 12 to less than 18 years of age with a body weight of at least 35 kgand who have already been treated with other HIV medicines that are no longer effective or have caused side effects.
• Emtricitabine/Tenofovir Disoproxil Krka must always be used in combination with other medicines to treat HIV infection.
• Emtricitabine/Tenofovir Disoproxil Krka can be taken instead of emtricitabine and tenofovir disoproxil taken separately at the same doses.

People with HIV infection should be aware thatHIV infection can be passed on to others through sexual contact, sharing needles, or from mother to child during pregnancy or childbirth.

Consult your doctor about the precautions you can take to avoid infecting others.

This medicine is not a cure for HIV infection. While taking Emtricitabine/Tenofovir Disoproxil Krka, you may still develop infections or other illnesses associated with HIV.

• Emtricitabine/Tenofovir Disoproxil Krka is also used to reduce the risk of getting HIV-1 infectionin adults and adolescents from 12 to less than 18 years of age with a body weight of at least 35 kg when taken daily, in combination with safer sex practices:

See section 2 for a list of precautions to take against HIV infection.

2. What you need to know before you take Emtricitabine/Tenofovir Disoproxil Krka

Do not take Emtricitabine/Tenofovir Disoproxil Krka to treat HIV or reduce the risk of getting HIV: if you are allergic to emtricitabine, tenofovir, tenofovir disoproxil, or any of the other ingredients of this medicine (listed in section 6).

If this applies to you, tell your doctor immediately.

Before taking Emtricitabine/Tenofovir Disoproxil Krka to reduce the risk of getting HIV:

Emtricitabine/Tenofovir Disoproxil Krka can only help reduce the risk of getting HIV

beforeyou are infected.

• You must not be infected with HIV before starting Emtricitabine/Tenofovir Disoproxil Krka to reduce the risk of getting HIV. You will need to have an HIV test to make sure you are not already infected with HIV. Do not take Emtricitabine/Tenofovir Disoproxil Krka to reduce the risk of getting HIV unless you have been confirmed to be HIV-negative. People with HIV should take Emtricitabine/Tenofovir Disoproxil Krka in combination with other medicines.

• Many HIV tests can miss a recent infection. If you get a flu-like illness, it could mean that you have recently been infected with HIV.

These can be signs of HIV infection:

• fatigue
• fever
• joint or muscle pain
• headache
• vomiting or diarrhea
• rash
• night sweats
• enlarged lymph nodes in the neck or groin

Tell your doctor about any flu-like illness, either in the month before starting Emtricitabine/Tenofovir Disoproxil Krka or at any time while taking Emtricitabine/Tenofovir Disoproxil Krka.

Warnings and precautions

When taking Emtricitabine/Tenofovir Disoproxil Krka to reduce the risk of getting HIV:

• Take Emtricitabine/Tenofovir Disoproxil Krka every day to reduce your risk, not just when you think you have been at risk of getting HIV. Do not miss any doses of Emtricitabine/Tenofovir Disoproxil Krka or stop taking it. Missed doses can increase the risk of getting HIV.

• You should have regular HIV tests.

• If you think you have been infected with HIV, tell your doctor immediately. They may want to do more tests to make sure you are still not infected with HIV.

• Using Emtricitabine/Tenofovir Disoproxil Krka on its own may not prevent you from getting HIV.
• Always practice safer sex. Use condoms to reduce contact with semen, vaginal fluids, or blood.
• Do not share personal items that may contain blood or bodily fluids, such as toothbrushes or razor blades.
• Do not share or reuse needles or other injections or medications.
• You should have tests for other sexually transmitted infections like syphilis or gonorrhea. These infections make it easier for you to get HIV.

Talk to your doctor if you have any questions about how to prevent getting HIV or passing it on to others.

When taking Emtricitabine/Tenofovir Disoproxil Krka to treat HIV or reduce the risk of getting HIV:

• Emtricitabine/Tenofovir Disoproxil Krka can affect your kidneys. Before and during treatment, your doctor may do blood tests to check your kidney function. If you have had kidney disease or if the tests show kidney problems, tell your doctor. Emtricitabine/Tenofovir Disoproxil Krka should not be given to adolescents with existing kidney problems. If you have kidney problems, your doctor may advise you to stop taking Emtricitabine/Tenofovir Disoproxil Krka or, if you already have HIV, take Emtricitabine/Tenofovir Disoproxil Krka less often. Emtricitabine/Tenofovir Disoproxil Krka is not recommended if you have severe kidney disease or are on dialysis.

• Bone problems can also occur(which show up as persistent or worsening bone pain and sometimes result in fractures) due to damage to the kidney tubule cells (see section 4, Possible side effects). Tell your doctor if you have bone pain or fractures.

• Tenofovir disoproxil can also cause bone loss. The most pronounced bone loss was seen in clinical studies when patients received HIV treatment with tenofovir disoproxil in combination with a boosted protease inhibitor.

In general, the effects of tenofovir disoproxil on long-term bone health and the risk of future fractures in adult and pediatric patients are not known.

Tell your doctor if you know that you have osteoporosis. Patients with osteoporosis are at a greater risk of fractures.

• Tell your doctor if you have a history of liver disease, including hepatitis. Patients with HIV who also have liver disease (including chronic hepatitis B or C), who are treated with antiretrovirals, have a greater risk of serious and potentially life-threatening liver problems. If you have hepatitis B or C, your doctor will carefully consider the best treatment regimen for you.

• Know your hepatitis B virus (HBV) status before starting Emtricitabine/Tenofovir Disoproxil Krka. If you have HBV, there is a serious risk of liver problems when you stop taking Emtricitabine/Tenofovir Disoproxil Krka, whether you also have HIV or not. It is important not to stop taking Emtricitabine/Tenofovir Disoproxil Krka without talking to your doctor: see section 3, Do not stop taking Emtricitabine/Tenofovir Disoproxil Krka.

• If you are over 65, talk to your doctor. Emtricitabine/Tenofovir Disoproxil Krka has not been studied in patients over 65 years of age.

• Talk to your doctor if you are lactose intolerant(see Emtricitabine/Tenofovir Disoproxil Krka contains lactose below).

Children and adolescents

Emtricitabine/Tenofovir Disoproxil Krka should not be given to children under 12 years of age.

Other medicines and Emtricitabine/Tenofovir Disoproxil Krka

Do not take Emtricitabine/Tenofovir Disoproxil Krkaif you are already taking other medicines that contain the ingredients of Emtricitabine/Tenofovir Disoproxil Krka (emtricitabine and tenofovir disoproxil) or any other antiviral medicine that contains tenofovir alafenamide, lamivudine, or adefovir dipivoxil.

Taking Emtricitabine/Tenofovir Disoproxil Krka with other medicines that can harm your kidneys: it is especially important that you tell your doctor if you are taking any of these medicines. These include:

• aminoglycosides (for bacterial infection)
• amphotericin B (for fungal infection)
• foscarnet (for viral infection)
• ganciclovir (for viral infection)
• pentamidine (for infections)
• vancomycin (for bacterial infection)
• interleukin-2 (for cancer treatment)
• cidofovir (for viral infection)
• non-steroidal anti-inflammatory drugs (NSAIDs, for pain relief or to reduce inflammation)

If you are taking another antiviral medicine called a protease inhibitor to treat HIV, your doctor may do blood tests to closely monitor your kidney function.

It is also important that you tell your doctorif you are taking ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir to treat hepatitis C infection.

Taking Emtricitabine/Tenofovir Disoproxil Krka with other medicines that contain didanosine (for HIV treatment):Taking Emtricitabine/Tenofovir Disoproxil Krka with other antiviral medicines that contain didanosine can increase the levels of didanosine in the 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 causing death. Your doctor will carefully consider whether to treat you with combinations of tenofovir and didanosine.

Tell your doctorif you are taking any of these medicines. Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Taking Emtricitabine/Tenofovir Disoproxil Krka with food and drink

• Whenever possible, Emtricitabine/Tenofovir Disoproxil Krka should be taken with food.

Pregnancy and breastfeeding

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

If you have been taking Emtricitabine/Tenofovir Disoproxil Krka during your pregnancy, your doctor may do regular blood tests and other diagnostic tests to monitor the development of your child. 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 Emtricitabine/Tenofovir Disoproxil Krka. This is because the active substances of this medicine pass into breast milk.

• If you are a woman with HIV, you are advised not to breastfeed your child to avoid passing the virus to your child through your breast milk.

Driving and using machines

Emtricitabine/Tenofovir Disoproxil Krka can cause dizziness. If you feel dizzy while taking Emtricitabine/Tenofovir Disoproxil Krka, do not drive or use machines.

Emtricitabine/Tenofovir Disoproxil Krka contains lactose

If your doctor has told you that you have an intolerance to some sugars, talk to them before taking this medicine.

Emtricitabine/Tenofovir Disoproxil Krka contains sodium

This medicine contains less than 23 mg of sodium (1 mmol) per tablet, which is essentially "sodium-free".

3. How to take Emtricitabine/Tenofovir disoproxil Krka

• Follow your doctor's instructions for taking this medicine exactly. If you are unsure, consult your doctor or pharmacist again.

The recommended dose of Emtricitabine/Tenofovir disoproxil Krka for treating HIV is:

• Adults: one tablet a day, whenever possible, with food.
• Adolescents from 12 to less than 18 years of age with a weight of at least 35 kg: one tablet a day, whenever possible, with food.

The recommended dose of Emtricitabine/Tenofovir disoproxil Krka for reducing the risk of getting HIV is:

• Adults: one tablet a day, whenever possible, with food.
• Adolescents from 12 to less than 18 years of age with a weight of at least 35 kg: one tablet a day, whenever possible, with food.

If you have difficulty swallowing, you can use the tip of a spoon to crush the tablet. Then, mix the powder with approximately 100 ml of water (half a glass), orange juice, or grape juice, and drink it immediately.

• Always take the dose recommended by your doctor. This is to ensure that your medicine is completely effective and to reduce the risk of developing resistance to treatment. Do not change the dose unless your doctor tells you to do so.

• If you are receiving treatment for HIV infection, your doctor will prescribe Emtricitabine/Tenofovir disoproxil Krka with other antiretroviral medicines. Consult the leaflets of the other antiretrovirals to know how to take these medicines.

• If you are taking Emtricitabine/Tenofovir disoproxil Krka to reduce the risk of getting HIV, take Emtricitabine/Tenofovir disoproxil Krka every day, not just when you think you have been at risk of getting HIV infection.

Consult your doctor if you have any questions about how to prevent HIV transmission or prevent its transmission to others.

If you take more Emtricitabine/Tenofovir disoproxil Krka than you should

If you accidentally took more than the recommended dose of Emtricitabine/Tenofovir disoproxil Krka, consult your doctor or go to the nearest emergency room. Bring the tablet bottle with you so that you can easily describe what you have taken.

If you forget a dose

It is important that you do not miss any dose of Emtricitabine/Tenofovir disoproxil Krka.

• If you realize it in less than 12 hoursafter the time you usually take Emtricitabine/Tenofovir disoproxil Krka, take the tablet as soon as possible, preferably with food, and then take the next dose at your usual time.
• If 12 hours or more have passedsince the time you usually take Emtricitabine/Tenofovir disoproxil Krka, do not take the missed dose. Wait and take the next dose, preferably with food, at your usual time.

If you vomit before 1 hour has passed after taking Emtricitabine/Tenofovir disoproxil Krka, take another tablet. You do not need to take another tablet if you vomited more than an hour after taking Emtricitabine/Tenofovir disoproxil Krka.

Do not stop treatment with Emtricitabine/Tenofovir disoproxil Krka

• If you are taking Emtricitabine/Tenofovir disoproxil Krka for the treatment of HIV infection, stopping treatment may reduce the effectiveness of the recommended HIV therapy by your doctor.

• If you are taking Emtricitabine/Tenofovir disoproxil Krka to reduce the risk of getting HIV, do not stop taking Emtricitabine/Tenofovir disoproxil Krka or miss any doses. Stopping treatment with Emtricitabine/Tenofovir disoproxil Krka, or missing doses, may increase the risk of getting HIV infection.

Do not stop treatment with Emtricitabine/Tenofovir disoproxil Krka without consulting your doctor.

• If you have hepatitis B, it is especially important not to stop your treatment with Emtricitabine/Tenofovir disoproxil Krka without first talking to your doctor. You may need to have blood tests for several months after stopping treatment. In some patients with advanced liver disease or cirrhosis, it is not recommended to stop treatment as this may cause worsening of hepatitis, which can be potentially fatal.

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

If you have any other questions about using this medicine, ask your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Severe side effects:

• Lactic acidosis (excess of lactic acid in the blood)is a rare but potentially fatal side effect. Lactic acidosis is more common 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
• drowsiness
• nausea, vomiting
• stomach pain

If you think you may have lactic acidosis, seek medical attention 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 of previous infections 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 allows the body to fight infections that may be present without any apparent symptoms.

• Autoimmune disorders may also appear when the immune system attacks healthy body tissue after starting to take medicines for HIV treatment. Autoimmune disorders can occur many months after starting treatment. Pay attention to 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

If you notice these or any symptoms of inflammation or infection, seek medical attention immediately.

Side effects:

Very common side effects

(may affect more than 1 in 10 people)

• diarrhea, vomiting, feeling sick (nausea)
• dizziness, headache
• rash
• feeling weak

Tests may also show:

• decrease in phosphate levels in the blood
• increase in creatine kinase

Common side effects

(may affect up to 1 in 10 people)

• pain, stomach pain
• difficulty sleeping, abnormal dreams
• digestive problems with discomfort after meals, feeling bloated (gas), flatulence
• rash (including red spots or patches, 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 slightly dizzy

Tests may also show:

• low white blood cell count (a reduced number of white blood cells can make you more prone to infections)
• increase in triglycerides (fatty acids), bile, or sugar in the blood
• liver and pancreas problems

Uncommon side effects

(may affect up to 1 in 100 people)

• stomach pain caused by pancreas inflammation
• swelling of the face, lips, tongue, or throat
• anemia (low red blood cell count)
• muscle breakdown, muscle pain, or muscle weakness that can occur in case of damage to the renal tubule cells

Tests may also show:

• decrease in potassium levels in the blood
• increase in creatinine in the blood
• changes in your urine

Rare side effects

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

• lactic acidosis (see Severe side effects)
• fatty liver
• yellow skin or eyes, itching, or stomach pain caused by liver inflammation
• kidney inflammation, increased urine volume, and feeling of thirst, kidney failure, damage to the renal tubule cells
• weakening of the bones (with bone pain and which sometimes ends in fractures)
• back pain due to kidney problems

Damage to the renal tubule cells can be associated with muscle breakdown, weakening of the bones (with bone pain and which sometimes ends in fractures), muscle pain, muscle weakness, and decreased levels of potassium or phosphate in the blood.

If you notice any of the above side effects or if any of the side effects get worse, talk to your doctor or pharmacist.

The frequency of the following side effects is not known.

• Bone problems.Some patients taking antiretroviral combination therapies like Emtricitabine/Tenofovir disoproxil Krka 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, consuming alcohol, having a very weakened immune system, and being overweight may be some of the many risk factors for developing this disease. Signs of osteonecrosis are:

• joint stiffness
• joint pain or discomfort (especially in the hip, knee, and shoulder)
• difficulty moving

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

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

Other side effects in children

• Children who receive emtricitabine often suffer from frequent changes in skin color, including
• dark spots on the skin
• Children often have a low number of red blood cells (anemia)
• this can cause fatigue or shortness of breath

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

Reporting side effects

If you experience any side effects, 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 help provide more information on the safety of this medicine.

5. Storage of Emtricitabine/Tenofovir disoproxil Krka

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

Do not use this medicine after the expiration date that appears on the packaging after EXP. The expiration date is the last day of the month indicated.

Blister packs

Do not store above 30°C.

Store in the original blister pack to protect from moisture and light.

Bottle

Do not store above 30°C.

Keep the bottle tightly closed to protect from moisture and light.

Validity period after opening the bottle: 2 months.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package contents and additional information

Composition of Emtricitabine/Tenofovir disoproxil Krka

• The active ingredients are emtricitabine and tenofovir disoproxil.

Each film-coated tablet of Emtricitabine/Tenofovir disoproxil Krka contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300.7 mg of tenofovir disoproxil succinate or 136 mg of tenofovir).

• The other ingredients are:

Core:pregelatinized starch, sodium croscarmellose, lactose monohydrate, microcrystalline cellulose, sodium stearyl fumarate, stearic acid.

Film coating:hypromellose 5 cP, titanium dioxide (E171), macrogol, aluminum lake indigo carmine (E132). See section 2 "Emtricitabine/Tenofovir disoproxil Krka contains lactose", "Emtricitabine/Tenofovir disoproxil Krka contains sodium".

Appearance and packaging of the product

Emtricitabine/Tenofovir disoproxil Krka film-coated tablets (tablets) are blue, oval, biconvex, 20 mm x 10 mm in size.

Emtricitabine/Tenofovir disoproxil Krka is available in boxes of 28, 84 film-coated tablets in blister packs and 28 x 1 film-coated tablet.

Emtricitabine/Tenofovir disoproxil Krka is also available in child-resistant bottles of 30 tablets, with an integrated silica gel desiccant that helps protect the tablets.

The following pack sizes are available: pack of 1 bottle of 30 tablets and 90 (3 bottles of 30) tablets.

Not all pack sizes may be marketed.

Marketing authorization holder:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturer:

KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

You can request more information about this medicine by contacting the local representative of the marketing authorization holder:

Date of the last revision of this leaflet:

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