Emtricitabine/tenofovir disoproxil Zentiva: detailed information

Package leaflet: Information for the user

Emtricitabine/Tenofovir disoproxil Zentiva 200 mg/245 mg film-coated tablets

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 questions, ask your doctor or pharmacist.
This medicine has been prescribed for you only. Do not give it to other people, even if they have the same symptoms as yours, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of this leaflet:

What Emtricitabine/Tenofovir disoproxil Zentiva is and what it is used for
What you need to know before taking Emtricitabine/Tenofovir disoproxil Zentiva
How to take Emtricitabine/Tenofovir disoproxil Zentiva
Possible side effects
How to store Emtricitabine/Tenofovir disoproxil Zentiva
Contents of the pack and other information

1. What Emtricitabine/Tenofovir disoproxil Zentiva is and what it is used for

Emtricitabine/Tenofovir disoproxil Zentiva contains two active substances, emtricitabine and tenofovir disoproxil. Both of these active substances are antiretroviral medicines used to treat HIV infection. Emtricitabine is a nucleoside reverse transcriptase inhibitor and tenofovir is a nucleotide reverse transcriptase inhibitor. However, both are generally known as NRTIs and work by interfering with the normal activity of an enzyme (reverse transcriptase) that is essential for the virus to replicate.

Emtricitabine/Tenofovir disoproxil Zentiva is used to treat human immunodeficiency virus type 1 (HIV-1) infection in adults.
It is also used to treat HIV in adolescents aged between 12 and 18 years with a body weight of at least 35 kg, who have previously been treated with other HIV medicines that are no longer effective or have caused undesirable effects.
Emtricitabine/Tenofovir disoproxil Zentiva must always be used in combination with other medicines for the treatment of HIV infection.
Emtricitabine/Tenofovir disoproxil Zentiva may be administered as a substitute for separate emtricitabine and tenofovir disoproxil taken at the same doses.

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

Emtricitabine/Tenofovir disoproxil Zentiva is also used to reduce the risk of acquiring HIV-1 infection in adults and adolescents aged between 12 and less than 18 years with a body weight of at least 35 kg, when taken daily in combination with safe sexual practices: See section 2 for a list of precautions to prevent HIV infection.

2. What you should know before taking Emtricitabine/Tenofovir disoproxil Zentiva

Do not take Emtricitabine/Tenofovir disoproxil Zentiva to treat HIV or to reduce the risk of acquiring HIV
if you are allergic to emtricitabine, tenofovir, tenofovir disoproxil, or to any of the other
components of this medicine (listed in section 6).
→ If this applies to you, inform your doctor immediately.
Before taking Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk of acquiring HIV:

Emtricitabine/Tenofovir disoproxil Zentiva can only help reduce the risk of acquiring HIV before you become infected.

To start taking Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk of acquiring HIV, you must be HIV-negative. You must undergo an HIV test to ensure you do not already have an HIV infection. Do not take Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk unless it has been confirmed that you are HIV-negative. People who have HIV must take Emtricitabine/Tenofovir disoproxil Zentiva in combination with other medicines.
Many HIV tests may not detect a recent infection. If you develop flu-like illness, it could mean you have recently been infected with HIV. Symptoms of HIV infection may include:
- fatigue
- fever
- joint or muscle pain
- headache
- vomiting or diarrhoea
- rash
- night sweats
- swelling of lymph nodes in the neck or groin
  Tell your doctor if you develop flu-like illness – either within the month before starting Emtricitabine/Tenofovir disoproxil Zentiva or at any time while taking Emtricitabine/Tenofovir disoproxil Zentiva.

Warnings and precautions
While taking Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk of acquiring HIV:

Take Emtricitabine/Tenofovir disoproxil Zentiva every day to reduce the risk, not only when you think you may have been exposed to HIV infection. Do not miss any doses of Emtricitabine/Tenofovir disoproxil Zentiva and do not stop taking it. Skipping doses may increase the risk of acquiring HIV infection.
Have regular HIV tests.
If you think you may have been infected with HIV, inform your doctor immediately. Your doctor may perform additional tests to confirm that you are still HIV-negative.

Simply taking Emtricitabine/Tenofovir disoproxil Zentiva may not prevent you from acquiring HIV.

Always practice safe sex. Use condoms to reduce contact with semen, vaginal fluid, or blood.
Do not share personal items that may have blood or body fluids on them, such as toothbrushes or razor blades.
Do not share or reuse needles or other injection or medication administration equipment.
Get tested for other sexually transmitted infections such as syphilis and gonorrhoea. These infections can make it easier to acquire HIV.

Talk to your doctor if you have further questions about how to avoid acquiring HIV or how to avoid spreading HIV to others.
While taking Emtricitabine/Tenofovir disoproxil Zentiva to treat HIV or to reduce the risk of acquiring HIV:

Emtricitabine/Tenofovir disoproxil Zentiva may affect the kidneys. Before and during treatment, your doctor may order blood tests to assess proper kidney function. Inform your doctor if you have had kidney disease or if blood tests have shown kidney problems. Emtricitabine/Tenofovir disoproxil Zentiva must not be administered to adolescents with kidney problems. If you have kidney problems, your doctor may advise you to stop taking Emtricitabine/Tenofovir disoproxil Zentiva or, if you already have HIV, to take Emtricitabine/Tenofovir disoproxil Zentiva less frequently. Emtricitabine/Tenofovir disoproxil Zentiva is not recommended if you have severe kidney disease or are on dialysis.
Inform your doctor if you have osteoporosis. Patients with osteoporosis are at higher risk of fractures.

Bone problems (manifesting as persistent or worsening bone pain and sometimes resulting in fractures) may occur due to damage to the renal tubular cells (see section 4, Possible side effects). Inform your doctor if you experience bone pain or fractures.
Tenofovir disoproxil can also cause loss of bone mineral density. The greatest loss of bone mineral density has been observed in clinical studies where patients were treated for HIV with tenofovir disoproxil in combination with a boosted protease inhibitor.
In general, the long-term effects of tenofovir disoproxil on bone health and the future risk of fractures in adult and paediatric patients are uncertain.

Inform your doctor if you have previously had liver problems, including hepatitis. HIV-infected patients with concurrent liver disease (including chronic hepatitis B or C) treated with antiretrovirals have a higher risk of serious, potentially fatal liver complications. If you have hepatitis B or C, your doctor will carefully evaluate the best treatment regimen for you.
Get tested for hepatitis B virus (HBV) infection before starting Emtricitabine/Tenofovir disoproxil Zentiva. If you have HBV infection, there is a serious risk of liver problems if you stop taking Emtricitabine/Tenofovir disoproxil Zentiva, whether or not you have HIV. It is important that you do not stop taking Emtricitabine/Tenofovir disoproxil Zentiva without speaking to your doctor: see section 3, Do not stop treatment with Emtricitabine/Tenofovir disoproxil Zentiva.
Inform your doctor if you are over 65 years old. The combination of emtricitabine and tenofovir disoproxil has not been studied in patients over 65 years of age.

Children and adolescents
Emtricitabine/Tenofovir disoproxil Zentiva is not indicated in children under 12 years of age.

Other medicines and Emtricitabine/Tenofovir disoproxil Zentiva
Do not take Emtricitabine/Tenofovir disoproxil Zentiva if you are already taking other medicines containing the components of Emtricitabine/Tenofovir disoproxil Zentiva (emtricitabine and tenofovir disoproxil) or any other antiviral medicine containing tenofovir alafenamide, lamivudine, or adefovir dipivoxil.
Taking Emtricitabine/Tenofovir disoproxil Zentiva with other medicines that may damage the kidneys: It is particularly important to inform your doctor if you are taking any of the following medicines, including:

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, used to relieve bone or muscle pain).

If you are taking another antiviral medicine called a protease inhibitor to treat HIV, your doctor may prescribe blood tests to monitor your kidney function more closely.
It is also important to inform your doctor if you are taking ledipasvir/sofosbuvir, sofosbuvir/velpatasvir, or sofosbuvir/velpatasvir/voxilaprevir to treat hepatitis C infection.
Taking Emtricitabine/Tenofovir disoproxil Zentiva with other medicines containing didanosine (for the treatment of HIV infection): Taking Emtricitabine/Tenofovir disoproxil Zentiva with other antiviral medicines containing didanosine may increase levels of didanosine in the blood and may reduce CD4 cell count. When medicines containing tenofovir disoproxil and didanosine have been taken together, rare cases of pancreatitis and lactic acidosis (excess lactic acid in the blood) have been reported, which sometimes led to death. Your doctor will need to carefully consider whether to treat you with tenofovir and didanosine in combination.
Inform your doctor if you are taking any of these medicines. Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.

Emtricitabine/Tenofovir disoproxil Zentiva with food and drink
Emtricitabine/Tenofovir disoproxil Zentiva should be taken with food whenever possible.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant, are planning to become pregnant, or are breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
If you have taken Emtricitabine/Tenofovir disoproxil Zentiva during pregnancy, your doctor may regularly request blood tests and other diagnostic examinations to monitor the baby's development. In babies whose mothers took NRTIs during pregnancy, the benefit of protection against HIV has outweighed the risk of side effects.

Do not breastfeed while being treated with Emtricitabine/Tenofovir disoproxil Zentiva. This is because the active substances of this medicine are excreted in breast milk.
Breastfeeding is not recommended for HIV-positive women because HIV infection can be transmitted to the baby through breast milk.
If you are breastfeeding or considering breastfeeding, you must discuss this with your doctor as soon as possible.

Driving and using machines
Emtricitabine/Tenofovir disoproxil Zentiva may cause dizziness. If dizziness occurs while taking Emtricitabine/Tenofovir disoproxil Zentiva, do not drive and do not operate tools or machinery.

Emtricitabine/Tenofovir disoproxil Zentiva contains sodium
This medicine contains less than 1 mmol of sodium (23 mg) per tablet, i.e., essentially “sodium-free”.

3. How to take Emtricitabine/Tenofovir disoproxil Zentiva

Always take this medicine exactly as your doctor has told you. If you are unsure, consult your doctor or pharmacist.

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

Adults: one tablet daily. Emtricitabine/Tenofovir disoproxil Zentiva should be taken with food, whenever possible.
Adolescents aged 12 to 18 years weighing at least 35 kg: one tablet daily. The tablet should be taken with food, whenever possible.

The recommended dose of Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk of acquiring HIV is:

Adults: one tablet daily, preferably taken with food.
Adolescents aged 12 to less than 18 years weighing at least 35 kg: one tablet daily, preferably taken with food.

If you have difficulty swallowing, you may use the back of a spoon to crush the tablet. Then mix the powder in about 100 ml (half a glass) of water, orange juice, or grape juice and drink immediately.

Always take the dose prescribed by your doctor. This is important to ensure that your medicine remains fully effective and to reduce the risk of developing treatment resistance. Do not change the dose unless your doctor tells you to do so.
If you are being treated for HIV infection, your doctor will prescribe Emtricitabine/Tenofovir disoproxil Zentiva together with other antiretroviral medicines. Refer to the patient leaflets of the other antiretrovirals for guidance on how to take them.
If you are taking Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk of acquiring HIV, take Emtricitabine/Tenofovir disoproxil Zentiva every day, not only when you think you may have been exposed to HIV.

Talk to your doctor if you have any questions about how to avoid getting HIV or prevent spreading HIV to others.

If you take more Emtricitabine/Tenofovir disoproxil Zentiva than you should
If you accidentally take more Emtricitabine/Tenofovir disoproxil Zentiva than recommended, contact your doctor or the nearest emergency department immediately. Take the medicine container with you so you can clearly describe what you have taken.

If you forget to take Emtricitabine/Tenofovir disoproxil Zentiva
It is important not to miss a dose of Emtricitabine/Tenofovir disoproxil Zentiva.

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

If you vomit within 1 hour of taking Emtricitabine/Tenofovir disoproxil Zentiva, take another tablet. Do not take another tablet if you vomit more than 1 hour after taking Emtricitabine/Tenofovir disoproxil Zentiva.

Do not stop taking Emtricitabine/Tenofovir disoproxil Zentiva

If you are taking Emtricitabine/Tenofovir disoproxil Zentiva for the treatment of HIV infection, stopping the tablets may reduce the effectiveness of the anti-HIV therapy prescribed by your doctor.
If you are taking Emtricitabine/Tenofovir disoproxil Zentiva to reduce the risk of acquiring HIV, do not stop taking Emtricitabine/Tenofovir disoproxil Zentiva and do not skip doses. If you stop taking Emtricitabine/Tenofovir disoproxil Zentiva or miss doses, your risk of acquiring HIV infection may increase. Do not stop taking Emtricitabine/Tenofovir disoproxil Zentiva without first talking to your doctor.
If you have hepatitis B, it is especially important not to stop treatment with Emtricitabine/Tenofovir disoproxil Zentiva without first consulting your doctor. Blood tests may need to be repeated for several months after stopping treatment. In some patients with advanced liver disease or cirrhosis, stopping treatment is not recommended, as it may lead to worsening of hepatitis, which could potentially be fatal.

Inform your doctor immediately about any new or unusual symptoms occurring after stopping treatment, particularly symptoms associated with hepatitis B infection.

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

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

Possible serious side effects:

Lactic acidosis (excess lactic acid in the blood) is a rare but potentially fatal side effect. Lactic acidosis occurs more frequently in women, especially if overweight, and in people with liver disease. The following may be signs of lactic acidosis:
- shortness of breath,
- drowsiness,
- nausea, vomiting,
- stomach pain. If you think you have lactic acidosis, contact a doctor immediately.
Any signs 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 due to previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from an improved immune response, allowing the body to fight infections that may have been present without noticeable symptoms.
Autoimmune disorders, in which the immune system attacks healthy body tissue, may also occur after starting medicines to treat HIV infection. Autoimmune disorders may occur many months after starting treatment. Look out for symptoms of infection or other symptoms such as:
- muscle weakness,
- weakness starting in the hands and feet and moving up towards the trunk,
- palpitations, tremor, or hyperactivity. If you notice these or other symptoms of inflammation or infection, contact a doctor immediately.

Possible side effects:
Very common side effects (may affect more than 1 in 10 people):

diarrhoea, vomiting, nausea,
dizziness, headache,
rash,
feeling weak.

Blood tests may also show:

reduced phosphate levels in the blood,
elevated creatine kinase.

Common side effects (may affect up to 1 in 10 people):

pain, stomach ache,
difficulty sleeping, nightmares,
digestive problems resulting in discomfort after meals, feeling of fullness, intestinal gas,
skin rashes (including red spots or pustules, sometimes with blisters and skin swelling), which may be allergic reactions, burning, changes in skin colour with appearance of dark patches,
other allergic reactions such as shortness of breath, swelling, or light-headedness,
loss of bone mass.

Blood tests may also show:

decreased white blood cell count (this may make you more susceptible to infection),
increased triglycerides (fatty acids), bile, or blood sugar,
problems with liver and pancreas.

Uncommon side effects (may affect up to 1 in 100 people):

abdominal pain caused by inflammation of the pancreas,
swelling of the face, lips, tongue, or throat,
anaemia (low red blood cell count),
muscle breakdown, muscle pain, or muscle weakness, which may occur due to damage to renal tubular cells.

Blood tests may also show:

reduced potassium levels in the blood,
increased creatinine in the blood,
changes in urine.

Rare side effects (may affect up to 1 in 1,000 people):

lactic acidosis (see "Possible serious side effects"),
fatty liver,
yellowing of the skin and eyes, itching, or abdominal pain caused by liver inflammation,
kidney inflammation, excessive urination and thirst, kidney failure, damage to renal tubular cells,
softening of the bones (with bone pain and sometimes fractures),
back pain caused by kidney problems.

Damage to renal tubular cells may be associated with muscle breakdown, softening of the bones (with bone pain and sometimes fractures), muscle pain, muscle weakness, and decreased potassium or phosphate levels in the blood.
If you notice any of the side effects listed above, or if any of them become severe, contact your doctor or pharmacist.
The frequency of the following side effects is not known.

Bone problems. Some patients taking combination antiretroviral medicines such as Emtricitabine/Tenofovir disoproxil Zentiva may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). Long-term use of this type of medicine, use of corticosteroids, alcohol consumption, a very weak immune system, and being overweight may be among the many risk factors for developing this condition. Signs of osteonecrosis include:
- joint stiffness,
- discomfort and pain in the joints (especially hip, knee, and shoulder),
- difficulty moving. If you notice any of these symptoms, contact your doctor.

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

Other effects in children

Children who have been given emtricitabine have very commonly developed changes in skin pigmentation including the appearance of dark patches on the skin.
Children have commonly developed a low red blood cell count (anaemia), which may cause tiredness or shortness of breath in the child. If you notice any of these symptoms, contact your doctor.

Reporting of side effects
If you get any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Emtricitabine/Tenofovir disoproxil Zentiva

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.
This medicine does not require any special storage temperature. Store in the
original packaging to protect the medicine from moisture.
Do not store above 30°C after first opening.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how
to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Emtricitabine/Tenofovir disoproxil Zentiva contains

Active substances: emtricitabine and tenofovir disoproxil fumarate. Each film-coated tablet contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 291.5 mg of tenofovir disoproxil fumarate or 136 mg of tenofovir).
Other components:
Tablet core: microcrystalline cellulose, croscarmellose sodium, talc, hydrophobic colloidal silica, magnesium stearate.
Film coating: polyvinyl alcohol, titanium dioxide, macrogol, talc, indigo carmine aluminum lake (E 132).

Description of the appearance of Emtricitabine/Tenofovir disoproxil Zentiva and contents of the pack
Emtricitabine/Tenofovir disoproxil Zentiva 200 mg/245 mg film-coated tablets are blue, oval, biconvex, film-coated tablets without a break line, with approximate dimensions of 19.35 mm x 9.75 mm.
Pack contents:
Outer packaging containing 1 bottle with 30 film-coated tablets and outer packaging containing 3 bottles with 30 film-coated tablets each.
Not all pack sizes may be marketed.
Open the bottles by pressing down the child-resistant cap and turning it counterclockwise.
Each bottle contains silica gel as a desiccant, which must remain in the bottle to protect the tablets. The silica gel is contained in a separate container and must not be ingested.

Marketing Authorization Holder
Zentiva, k.s.
U Kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturer
S.C. Zentiva S.A.
50 Theodor Pallady Blvd.
Bucharest 032266
Romania

For further information on this medicinal product, please contact the local representative of the Marketing Authorization Holder:

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