Emtricitabine/tenofovir disoproxil Krka d.d.: detailed information

B. PACKAGE LEAFLET

Package leaflet: information for the patient

Emtricitabine/tenofovir disoproxil Krka d.d. 200 mg/245 mg film-coated tablets

emtricitabine/tenofovir disoproxil
Please read this 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 effect, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.
Contents of this leaflet:

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

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

Emtricitabina/tenofovir disoproxil Krka d.d. contains two active substances, emtricitabine and
tenofovir disoproxil. Both 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, 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.

Emtricitabina/tenofovir disoproxil Krka d.d. is used to treat human immunodeficiency virus 1 (HIV-1) infection in adults
It is also used to treat HIV in adolescents aged between 12 and 18 years weighing at least 35 kg
who have previously been treated with other HIV medicines that are no longer effective or have caused undesirable effects.
Emtricitabina/tenofovir disoproxil Krka d.d. must always be used in combination with other medicines for the treatment of HIV infection.
Emtricitabina/tenofovir disoproxil Krka d.d. may be administered as a substitute for emtricitabine and tenofovir disoproxil taken separately at the same doses. This medicine is not a cure for HIV infection. While taking Emtricitabina/tenofovir disoproxil Krka d.d., you may still develop infections or other illnesses associated with HIV infection.

2. What you need to know before taking Emtricitabine/tenofovir disoproxil Krka d.d.

Do not take Emtricitabine/tenofovir disoproxil Krka d.d. 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, inform your doctor immediately.
Warnings and precautions
While taking Emtricitabine/tenofovir disoproxil Krka d.d. for HIV treatment

Emtricitabine/tenofovir disoproxil Krka d.d. may affect the kidneys. Before and during treatment, your doctor may prescribe blood tests to monitor proper kidney function. Inform your doctor if you have had kidney disease or if blood tests have shown kidney problems. Emtricitabine/tenofovir disoproxil Krka d.d. 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 d.d. or, if you already have HIV, to take Emtricitabine/tenofovir disoproxil Krka d.d. less frequently. Emtricitabine/tenofovir disoproxil Krka d.d. is not recommended if you have severe kidney disease or are on dialysis.
Inform your doctor if you have osteoporosis, have had bone fractures in the past, or have bone problems.
Bone problems (manifesting as persistent or worsening bone pain and sometimes resulting in 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 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 pediatric patients are uncertain.
Inform your doctor if you have previously had liver problems, including hepatitis. HIV-infected patients who also have liver problems (including chronic hepatitis B or C), treated with antiretrovirals, have a higher risk of severe and potentially fatal liver complications. If you have hepatitis B or C, your doctor will carefully evaluate the most appropriate treatment regimen for you.
Discuss your hepatitis B virus (HBV) infection status before starting Emtricitabine/tenofovir disoproxil Krka d.d. If you have an HBV infection, there is a serious risk of liver problems if you stop taking Emtricitabine/tenofovir disoproxil Krka d.d., whether or not you have HIV. It is important that you do not stop taking Emtricitabine/tenofovir disoproxil Krka d.d. without consulting your doctor: see section 3, Do not stop treatment with Emtricitabine/tenofovir disoproxil Krka d.d.
Inform your doctor if you are over 65 years of age. Emtricitabine/tenofovir disoproxil Krka d.d. has not been studied in patients over 65 years of age.
Inform your doctor if you are lactose intolerant (see Emtricitabine/tenofovir disoproxil Krka d.d. contains lactose later in this section). Children and adolescents Emtricitabine/tenofovir disoproxil Krka d.d. is not indicated in children under 12 years of age. Other medicines and Emtricitabine/tenofovir disoproxil Krka d.d. Do not take Emtricitabine/tenofovir disoproxil Krka d.d. if you are already taking other medicines containing the components of Emtricitabine/tenofovir disoproxil Krka d.d. (emtricitabine and tenofovir disoproxil) or any other antiviral medicine containing tenofovir alafenamide, lamivudine, or adefovir dipivoxil.
Taking Emtricitabine/tenofovir disoproxil Krka d.d. with other medicines that may harm 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 HIV treatment, your doctor may prescribe blood tests to better monitor your kidney function. 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 d.d. with other medicines containing didanosine (for the treatment of HIV infection): Taking Emtricitabine/tenofovir disoproxil Krka d.d. 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 resulted in 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 medicines.

Emtricitabine/tenofovir disoproxil Krka d.d. with food and drinks

Emtricitabine/tenofovir disoproxil Krka d.d. should be taken with food whenever possible. Pregnancy and breastfeeding If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before taking this medicine. If you have taken Emtricitabine/tenofovir disoproxil Krka d.d. during pregnancy, your doctor may require 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 d.d. The reason is that 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 child 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 Krka d.d. may cause dizziness. If dizziness occurs while taking Emtricitabine/tenofovir disoproxil Krka d.d., do not drive and do not operate tools or machinery.

Emtricitabine/tenofovir disoproxil Krka d.d. contains lactose
If your doctor has diagnosed you with an intolerance to certain sugars, contact him before taking
this medicine.
Emtricitabine/tenofovir disoproxil Krka d.d. 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 d.d.

Always take this medicine exactly as your doctor has instructed you. If you have any doubts, consult your doctor or pharmacist.

The recommended dose of Emtricitabine/tenofovir disoproxil Krka d.d. is:

Adults: one tablet daily, preferably taken with food.
Adolescents aged 12 to 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 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 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.
Your doctor will prescribe Emtricitabine/tenofovir disoproxil Krka d.d. together with other antiretroviral medicines. Please refer to the package leaflets of the other antiretrovirals for instructions on how to take them.

Consult your doctor if you have any questions about how to avoid contracting HIV or preventing transmission of HIV to others.
If you take more Emtricitabine/tenofovir disoproxil Krka d.d. than you should
If you accidentally take more Emtricitabine/tenofovir disoproxil Krka d.d. than recommended, contact your doctor or the nearest emergency department immediately. Take the bottle of tablets with you so you can clearly describe what you have taken.
If you forget to take Emtricitabine/tenofovir disoproxil Krka d.d.
It is important not to miss doses of Emtricitabine/tenofovir disoproxil Krka d.d.

If you remember within 12 hours of your usual dosing time, take the tablet as soon as possible, preferably with food.

Then take the next dose at your usual scheduled 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, preferably with food, at your usual scheduled time.
If you vomit within 1 hour of taking Emtricitabine/tenofovir disoproxil Krka d.d., take another tablet. You should not take another tablet if you vomit more than one hour after taking Emtricitabine/tenofovir disoproxil Krka d.d.
If you stop taking Emtricitabine/tenofovir disoproxil Krka d.d.
Stopping treatment may reduce the effectiveness of your prescribed anti-HIV therapy. → Do not stop treatment with Emtricitabine/tenofovir disoproxil Krka d.d. without first consulting your doctor.
If you have hepatitis B, it is especially important not to stop treatment with Emtricitabine/tenofovir disoproxil Krka d.d. without first talking to 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. Contact your doctor immediately if you notice 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:
- rapid or deep breathing
- drowsiness
- feeling of nausea, vomiting
- stomach pain

If you think you have lactic acidosis, contact a doctor immediately.

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 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, 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 medications to treat HIV infection.
Autoimmune disorders may occur many months after the start of treatment. Be alert for the appearance of any 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, muscle weakness
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 from 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, change in skin colour with appearance of dark patches
other allergic reactions such as shortness of breath, swelling, or feeling of light-headedness
loss of bone mass
Blood tests may also show:
- decreased white blood cell count (this may make you more susceptible to infections)
- increased triglycerides (fatty acids), bile, or glucose in the blood
- 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 or 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 may develop a bone disease called osteonecrosis (death of bone tissue due to reduced 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
- joint pain (especially in the hip, knee, or shoulder)
- difficulty moving
  If you notice any of these symptoms, contact 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 changes in skin pigmentation including
- appearance of dark patches on the skin
Children have commonly experienced low red blood cell count (anaemia)
- this may cause tiredness or shortness of breath in the child
  If you notice any of these symptoms, contact a doctor.

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

5. How to store Emtricitabine/tenofovir disoproxil Krka d.d.

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack after "Exp". The expiry date refers to the last day of that month.
Blister
Do not store above 30°C. Store in the original blister to protect the medicine 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 no longer in use. This will help protect the environment.

6. Package contents and other information

What Emtricitabine/Tenofovir Disoproxil Krka d.d. 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 succinate or 136 mg of tenofovir).
The other excipients are: Tablet core: pregelatinized starch, croscarmellose sodium, monohydrate lactose, microcrystalline cellulose, sodium stearyl fumarate, stearic acid. Film coating: hypromellose 5 cP, titanium dioxide (E171), macrogol, indigo carmine aluminum lake (E132). See section 2 "Emtricitabine/Tenofovir Disoproxil Krka d.d. contains lactose", see section 2 "Emtricitabine/Tenofovir Disoproxil Krka d.d. contains sodium".

Description of the appearance of Emtricitabine/Tenofovir Disoproxil Krka d.d. and contents of the
package
Emtricitabine/Tenofovir Disoproxil Krka d.d. film-coated tablets (tablets) are blue, oval, biconvex tablets measuring 20 mm x 10 mm.
Emtricitabine/Tenofovir Disoproxil Krka d.d. is available in boxes containing 28 x 1 and 84 film-coated tablets in blisters.
Emtricitabine/Tenofovir Disoproxil Krka d.d. is also available in bottles of 30 tablets, with child-resistant tamper-proof closure made of polypropylene and containing silica gel as a desiccant to protect the tablets. The following pack sizes are available: box containing 1 bottle of 30 film-coated tablets and 90 film-coated tablets (3 bottles of 30).
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 medicinal product, please 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 101 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
KRKA Latvija SIA
Tel: + 371 6 733 86 10

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