Emtricitabine/tenofovir disoproxil Krka: detailed information

Patient Information Leaflet

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

emtricitabine/tenofovir disoproxil
Read this entire leaflet carefully before 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 their symptoms are the same as yours, as 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 Krka is and what it is used for
What you need to know before taking Emtricitabine/Tenofovir Disoproxil Krka
How to take Emtricitabine/Tenofovir Disoproxil Krka
Possible side effects
How to store Emtricitabine/Tenofovir Disoproxil Krka
Package contents and other information

1. What Emtricitabine/tenofovir disoproxil Krka is and what it is used for

Emtricitabine/tenofovir disoproxil Krka contains two active substances, emtricitabine and tenofovir disoproxil. Both active substances are antiretroviral medicines used for the treatment of HIV infection. Emtricitabine is a nucleoside reverse transcriptase inhibitor and tenofovir is a nucleotide reverse transcriptase inhibitor. However, they 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 Krka 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 who weigh at least 35 kg and who have previously been treated with other HIV medicines that are no longer effective or have caused undesirable effects.
Emtricitabine/tenofovir disoproxil Krka must always be used in combination with other medicines for the treatment of HIV infection.
Emtricitabine/tenofovir disoproxil Krka may be administered as a replacement for separate emtricitabine and tenofovir disoproxil taken at the same doses.

People who are HIV-positive can still transmit HIV even while taking this medicine, although the risk is reduced by effective antiviral therapy. Discuss with your doctor the precautions necessary to avoid transmitting the infection to 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 infection.

Emtricitabine/tenofovir disoproxil Krka is also used to reduce the risk of acquiring HIV-1 infection in adults and adolescents aged 12 years and above but less than 18 years of age who weigh 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 need to know before taking Emtricitabine/tenofovir disoproxil Krka

Do not take Emtricitabine/tenofovir disoproxil Krka to treat HIV or to reduce the risk
of acquiring HIV if you are allergic to emtricitabine, tenofovir, tenofovir disoproxil, or 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 Krka to reduce the risk of acquiring
HIV:

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

To start taking Emtricitabine/tenofovir disoproxil Krka 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 Krka to reduce the risk unless it has been confirmed that you are HIV-negative. People who have HIV must take Emtricitabine/tenofovir disoproxil Krka in combination with other medicines.
Many HIV tests may not detect a recent infection. If you develop an illness resembling the flu, it could mean you have recently been infected with HIV. Signs of HIV infection may include:
fatigue
fever
joint or muscle pain
headache
vomiting or diarrhoea
rash
night sweats
swollen lymph nodes in the neck or groin
Inform your doctor if you experience flu-like symptoms within the month before starting Emtricitabine/tenofovir disoproxil Krka or at any time during treatment with Emtricitabine/tenofovir disoproxil Krka.

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

Take Emtricitabine/tenofovir disoproxil Krka every day to reduce the risk, not only when you think you may have been exposed to HIV infection. Do not skip any doses of Emtricitabine/tenofovir disoproxil Krka and do not stop taking it. Skipping doses may increase the risk of acquiring HIV infection.
Get tested for HIV regularly.
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.
Taking Emtricitabine/tenofovir disoproxil Krka alone 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 delivery 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 or spreading HIV to others.
While taking Emtricitabine/tenofovir disoproxil Krka to treat HIV or to reduce the risk of acquiring HIV:

Emtricitabine/tenofovir disoproxil Krka may affect the kidneys. Before and during treatment, your doctor may order blood tests to monitor proper kidney function. Inform your doctor if you have had kidney disease or if your blood tests have shown kidney problems. Emtricitabine/tenofovir disoproxil Krka 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 Krka or, if you already have HIV, to take Emtricitabine/tenofovir disoproxil Krka less frequently. Emtricitabine/tenofovir disoproxil Krka is not recommended if you have severe kidney disease or are on dialysis.
Bone problems (manifesting as persistent or worsening bone pain, and sometimes leading to fractures) may occur due to damage to renal tubular cells (see section 4, Possible side effects). Inform your doctor if you experience bone pain or fractures.

Tenofovir disoproxil may also cause loss of bone mass. More pronounced bone mass loss has been observed in clinical studies in patients 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 osteoporosis. Patients with osteoporosis are at higher risk of fractures.

Inform your doctor if you have previously had liver problems, including hepatitis. HIV-infected patients with liver problems (including chronic hepatitis B or C) treated with antiretrovirals have a higher risk of severe liver complications, which may be fatal. 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 Krka. If you have HBV infection, there is a serious risk of liver problems if you stop taking Emtricitabine/tenofovir disoproxil Krka, whether or not you have HIV. It is important not to stop taking Emtricitabine/tenofovir disoproxil Krka without speaking to your doctor: see section 3, Do not stop treatment with Emtricitabine/tenofovir disoproxil Krka.
Inform your doctor if you are over 65 years of age. Emtricitabine/tenofovir disoproxil Krka has not been studied in patients over 65 years of age.
Inform your doctor if you are lactose intolerant (see Emtricitabine/tenofovir disoproxil Krka contains lactose below in this section).

Children and adolescents
Emtricitabine/tenofovir disoproxil Krka is not indicated for children under 12 years of age.
Other medicines and Emtricitabine/tenofovir disoproxil Krka
Do not take Emtricitabine/tenofovir disoproxil Krka if you are already taking other medicines containing the components of Emtricitabine/tenofovir disoproxil Krka (emtricitabine and tenofovir disoproxil) or any other antiviral medicine containing tenofovir alafenamide, lamivudine, or adefovir dipivoxil.
Taking Emtricitabine/tenofovir disoproxil Krka 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 for the treatment of HIV, your doctor may order 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 for the treatment of hepatitis C infection.
Taking Emtricitabine/tenofovir disoproxil Krka with other medicines containing didanosine (for the treatment of HIV infection): Taking Emtricitabine/tenofovir disoproxil Krka with other antiviral medicines containing didanosine may increase the level 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 must 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 medicine.

Emtricitabine/tenofovir disoproxil Krka with food and drink

Emtricitabine/tenofovir disoproxil Krka 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 Krka during pregnancy, your doctor may request regular blood tests and other diagnostic examinations to monitor the child's development. In children whose mothers took NRTIs during pregnancy, the benefit of protection against HIV has outweighed the risk of side effects.

Do not breastfeed during treatment with Emtricitabine/tenofovir disoproxil Krka. This is because the active substance of this medicine is excreted in breast milk.
If you are a woman infected with HIV, you are advised not to breastfeed in order to avoid transmitting the HIV virus to the newborn through breast milk.

Driving and using machines
Emtricitabine/tenofovir disoproxil Krka may cause dizziness. If dizziness occurs while taking Emtricitabine/tenofovir disoproxil Krka, do not drive and do not operate tools or machinery.
Emtricitabine/tenofovir disoproxil Krka contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking this medicine.
Emtricitabine/tenofovir disoproxil Krka contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. essentially sodium-free.

3. How to take Emtricitabine/tenofovir disoproxil Krka

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 Krka for treating HIV is:

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

The recommended dose of Emtricitabine/tenofovir disoproxil Krka to reduce the risk of acquiring HIV is:

Adults: one tablet daily, taken with food whenever possible.

If you have difficulty swallowing, you may use the edge of a spoon to crush the tablet. Then mix the powder in approximately 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 is fully 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 being treated for HIV infection, your doctor will prescribe Emtricitabine/tenofovir disoproxil Krka together with other antiretrovirals. Refer to the package leaflet of the other antiretrovirals for guidance on how to take them.
If you are taking Emtricitabine/tenofovir disoproxil Krka to reduce the risk of acquiring HIV, take Emtricitabine/tenofovir disoproxil Krka every day, not only when you think you may have been exposed to HIV.

Talk to your doctor if you have questions about how to avoid contracting HIV or prevent its transmission to others.

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

If you miss a dose
It is important not to miss doses of Emtricitabine/tenofovir disoproxil Krka.

If you remember within 12 hours of your usual time of taking Emtricitabine/tenofovir disoproxil Krka, 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 time of taking Emtricitabine/tenofovir disoproxil Krka, 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 after taking Emtricitabine/tenofovir disoproxil Krka, take another tablet. You do not need to take another tablet if you vomit more than 1 hour after taking Emtricitabine/tenofovir disoproxil Krka.

Do not stop taking Emtricitabine/tenofovir disoproxil Krka

If you are taking Emtricitabine/tenofovir disoproxil Krka to treat 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 Krka to reduce the risk of acquiring HIV, do not stop taking Emtricitabine/tenofovir disoproxil Krka and do not miss doses. If you stop taking Emtricitabine/tenofovir disoproxil Krka or miss doses, your risk of acquiring HIV infection may increase.

→ Do not stop treatment with Emtricitabine/tenofovir disoproxil Krka without first talking to your doctor.

If you have hepatitis B, it is especially important not to stop treatment with Emtricitabine/tenofovir disoproxil Krka 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 be potentially fatal.

Contact your doctor immediately if you experience any new or unusual symptoms after stopping treatment, particularly symptoms typically 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
feeling sick, vomiting
stomach ache

If you think you have lactic acidosis, seek immediate medical advice.

Any sign of inflammation or infection. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections (infections occurring in people with weakened immune systems), 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, enabling the body to fight infections that may have been present without obvious 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 beginning in the hands and feet and moving up towards the trunk
palpitations, tremor, or hyperactivity

If you notice any of these or other symptoms of inflammation or infection, seek immediate medical advice.
Possible side effects:
Very common side effects
(may occur in more than 1 in 10 patients)

diarrhoea, vomiting, nausea
dizziness, headache
rash
feeling weak, muscle weakness

Blood tests may also show:

reduced phosphate levels in the blood
elevated creatine kinase

Common side effects
(may occur in up to 1 in 10 patients)

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 an allergic reaction, burning sensation, skin colour changes with appearance of dark patches
other allergic reactions such as shortness of breath, swelling, or light-headed feeling

Blood tests may also show:

decreased white blood cell count (this may make you more susceptible to infection)
increased triglycerides (fatty acids), bile, or glucose in the blood
problems affecting liver and pancreas

Uncommon side effects
(may occur in up to 1 in 100 patients)

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 occur in up to 1 in 1,000 patients)

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, consult your doctor or pharmacist.
The frequency of the following side effects is unknown.

Bone problems. Some patients taking combination antiretroviral medicines such as emtricitabine/tenofovir disoproxil 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 severely weakened immune system, and being overweight may be among the many risk factors for developing this condition. Signs of osteonecrosis include:
joint stiffness
joint pain (especially of the hip, knee, and shoulder)
difficulty moving
If you notice any of these symptoms, consult your doctor.

During HIV treatment, 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 HIV medicines themselves. Your doctor will monitor these changes.
Other effects in children

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

Reporting of side effects
If you get any side effects, including ones not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system 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 Krka

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "Exp.". The expiry date refers to the last day of that month.
Blister
Do not store above 30°C. Keep the medicine in the original blister to protect it from moisture and light.
Container
Do not store above 30°C. Keep the container tightly closed to protect the medicine from moisture and light.
Period of validity after first opening of the container: 2 months.
Do not dispose of any medicine 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 Krka contains

The active substances are emtricitabine and tenofovir disoproxil. Each tablet contains 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (equivalent to 300.7 mg of tenofovir disoproxil fumarate or 136 mg of tenofovir).
The other excipients are: Tablet core: pregelatinized starch, croscarmellose sodium, monohydrate lactose, microcrystalline cellulose, sodium stearate fumarate, stearic acid. Film coating: hypromellose 5 cP, titanium dioxide (E171), macrogol, aluminium lacquer indigo carmine (E132). See section 2 "Emtricitabine/Tenofovir Disoproxil Krka contains lactose", see section 2 "Emtricitabine/Tenofovir Disoproxil Krka contains sodium".

Description of the appearance of Emtricitabine/Tenofovir Disoproxil Krka and contents of the package
Emtricitabine/Tenofovir Disoproxil Krka film-coated tablets (tablets) are blue, oval, biconvex tablets, 20 mm x 10 mm in size.
Emtricitabine/Tenofovir Disoproxil Krka is available in boxes containing 28 and 84 film-coated tablets in blister packs.
Emtricitabine/Tenofovir Disoproxil Krka is also available in bottles of 30 tablets, with child-resistant tamper-evident closure made of polypropylene and containing silica gel as desiccant to protect the tablets. The following pack sizes are available: box containing 1 bottle of 30 film-coated tablets and 90 tablets (3 bottles of 30) in film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia

Manufacturers:
KRKA, d.d., Novo mesto, Šmarješka cesta 6, 8501 Novo mesto, Slovenia
TAD Pharma GmbH, Heinz-Lohmann-Straße 5, 27472 Cuxhaven, Germany

For further information about this medicine, contact the local representative of the Marketing Authorization Holder:

België/Belgique/Belgien Lietuva
KRKA Belgium, SA. UAB KRKA Lietuva
Tél/Tel: +32 (0) 487 50 73 62 Tel: + 370 5 236 27 40

България Luxembourg/Luxemburg
КРКА България ЕООД KRKA Belgium, SA.
Teл.: + 359 (02) 962 34 50 Tél/Tel: +32 (0) 487 50 73 62 (BE)

Česká republika Magyarország
KRKA ČR, s.r.o. KRKA Magyarország Kereskedelmi Kft.
Tel: + 420 (0) 221 115 150 Tel.: + 36 (1) 355 8490

Danmark Malta
KRKA Sverige AB E. J. Busuttil Ltd.
Tlf: + 46 (0)8 643 67 66 (SE) Tel: + 356 21 445 885

Deutschland Nederland
TAD Pharma GmbH KRKA Belgium, SA.
Tel: + 49 (0) 4721 606-0 Tel: +32 (0) 487 50 73 62 (BE)

Eesti Norge
KRKA, d.d., Novo mesto Eesti filiaal KRKA Sverige AB
Tel: + 372 (0) 6 671 658 Tlf: + 46 (0)8 643 67 66 (SE)

Ελλάδα Österreich
KRKA ΕΛΛΑΣ ΕΠΕ KRKA Pharma GmbH, Wien
Τηλ: + 30 2100101613 Tel: + 43 (0)1 66 24 300

España Polska
KRKA Farmacéutica, S.L. KRKA-POLSKA Sp. z o.o.
Tel: + 34 911 61 03 80 Tel.: + 48 (0)22 573 7500

France Portugal
KRKA France Eurl KRKA Farmacêutica, Sociedade Unipessoal Lda.
Tél: + 33 (0)1 57 40 82 25 Tel: + 351 (0)21 46 43 650

Hrvatska România
KRKA - FARMA d.o.o. KRKA Romania S.R.L., Bucharest
Tel: + 385 1 6312 100 Tel: + 4 021 310 66 05

Ireland Slovenija
KRKA Pharma Dublin, Ltd. KRKA, d.d., Novo mesto
Tel: + 353 1 413 3710 Tel: + 386 (0) 1 47 51 100

Ísland Slovenská republika
LYFIS ehf. KRKA Slovensko, s.r.o.
Sími: + 354 534 3500 Tel: + 421 (0) 2 571 04 501

Italia Suomi/Finland
KRKA Farmaceutici Milano S.r.l. KRKA Finland Oy
Tel: + 39 02 3300 8841 Puh/Tel: +358 20 754 5330

Κύπρος Sverige
KI.PA. (PHARMACAL) LIMITED KRKA Sverige AB
Τηλ: + 357 24 651 882 Tel: + 46 (0)8 643 67 66 (SE)

Latvija United Kingdom (Northern Ireland)
KRKA Latvija SIA KRKA Pharma Dublin, Ltd.
Tel: + 371 6 733 86 10 Tel: + 353 1 413 3710

This summary of product characteristics was last revised on:
More detailed information on this medicine is available on the European Medicines Agency website: http://www.ema.europa.eu