Efavirenz/emtricitabine/tenofovir disoproxil Krka: detailed information

Patient Information Leaflet

Efavirenz/Emtricitabine/Tenofovir Disoproxil Krka 600 mg/200 mg/245 mg film-coated tablets

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

1. What Efavirenz/Emtricitabina/Tenofovir disoproxil Krka is and what it is used for

Efavirenz/Emtricitabina/Tenofovir disoproxil Krka contains three active substances used in
the treatment of human immunodeficiency virus (HIV) infection:

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI)
Emtricitabina is a nucleoside reverse transcriptase inhibitor (NRTI)
Tenofovir is a nucleotide reverse transcriptase inhibitor (NtRTI)

Each of these active substances, also known as antiretroviral medicines, works by interfering with the
normal activity of an enzyme (reverse transcriptase) that is essential for the virus to replicate.
Efavirenz/Emtricitabina/Tenofovir disoproxil Krka is a treatment for human immunodeficiency
virus (HIV) infection in adults aged 18 years and older who have previously been treated with other
antiretroviral medicines and whose HIV-1 infection has been under control for at least three
months. Patients must not have experienced failure of a prior anti-HIV therapy.

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

Do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka

if you are allergic to efavirenz, emtricitabine, tenofovir, tenofovir disoproxil, or any of the other ingredients of this medicine (listed in section 6).
if you have severe liver disease.
if you have a heart condition, such as an abnormal electrical signal called QT interval prolongation, which puts you at risk of serious heart rhythm problems (torsades de pointes).
if any member of your family (parents, grandparents, siblings) has died suddenly due to heart problems or was born with heart defects.
if your doctor has told you that you have low or high levels of electrolytes such as potassium or magnesium in your blood.
if you are currently taking any of the following medicines (see also “Other medicines and Efavirenz/Emtricitabine/Tenofovir disoproxil Krka”):
astemizole or terfenadine (used to treat hay fever or other allergies)
bepridil (used to treat heart diseases)
cisapride (used to treat heartburn)
elbasvir/grazoprevir (used to treat hepatitis C)
ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergonovine, and methylergonovine) (used to treat migraine and cluster headache)
midazolam or triazolam (used to help sleep)
pimozide, imipramine, amitriptyline or clomipramine (used to treat certain mental conditions)
St. John’s wort (Hypericum perforatum) (a herbal remedy for depression and anxiety)
voriconazole (used to treat fungal infections)
flecainide, metoprolol (used to treat irregular heartbeat)
some antibiotics (macrolides, fluoroquinolones, imidazoles)
triazole antifungals
some antimalarial agents
methadone (used to treat opioid dependence)

Tell your doctor immediately if you are taking any of these medicines. Taking
these medicines together with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may cause serious or potentially fatal side effects, or may prevent these medicines from working properly.

Warnings and precautions

Talk to your doctor or pharmacist before taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka.

This medicine is not a cure for HIV infection. While taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, you may still develop infections or other illnesses associated with HIV infection.
While taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, you must remain under medical supervision.
Tell your doctor:
if you are taking other medicines containing efavirenz, emtricitabine, tenofovir disoproxil, tenofovir alafenamide, lamivudine, or adefovir dipivoxil. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka must not be taken together with these medicines.
if you have or have had kidney disease, or if blood tests have shown kidney problems. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka is not recommended in cases of moderate to severe kidney disease. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may affect the kidneys. Before starting treatment, your doctor may order blood tests to assess kidney function. Your doctor may also order blood tests during treatment to monitor kidney function.
Generally, Efavirenz/Emtricitabine/Tenofovir disoproxil Krka should not be taken with other
medicines that may damage the kidneys (see Other medicines and
Efavirenz/Emtricitabine/Tenofovir disoproxil Krka). If this is unavoidable, your doctor
will monitor your kidney function weekly.
if you have a heart condition, such as an abnormal electrical signal called QT interval prolongation.
if you have previously had mental health disorders, including depression, or if you have abused certain substances or alcohol. Inform your doctor immediately if you feel depressed, have suicidal thoughts, or experience unusual thoughts (see section 4, Possible side effects).
if you have previously had seizures or are being treated with anticonvulsants such as carbamazepine, phenobarbital, or phenytoin. If you are taking any of these medicines, your doctor may need to monitor the level of the anticonvulsant in your blood to ensure there are no problems during treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka. Your doctor may also prescribe a different anticonvulsant.
if you have previously had liver problems, including active chronic hepatitis. Patients with liver problems, including chronic hepatitis B or C, treated with combination antiretroviral therapy, have a higher risk of serious and potentially fatal liver complications. Your doctor may request blood tests to closely monitor liver function or may prescribe an alternative medicine. If you have severe liver disease, do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka (see above, section 2, Do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka). If you have hepatitis B, your doctor will carefully evaluate the best treatment regimen for you. Tenofovir disoproxil and emtricitabine, two of the active substances in Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, have some activity against the hepatitis B virus, although emtricitabine is not authorized for the treatment of hepatitis B infection. Symptoms of hepatitis may worsen after stopping treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka. Your doctor may request regular blood tests to closely monitor liver function (see section 3, If you stop taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka).
Regardless of any previous liver problems, your doctor may request regular blood tests to monitor liver function.
if you are over 65 years old. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka has not been studied in a sufficient number of patients over 65 years of age. If you are over 65 and have been prescribed Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, your doctor will monitor you closely.
Once you start taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, be alert for:
signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating, or unusual dreams. These side effects may occur during the first 1-2 days of treatment and usually disappear after the first 2-4 weeks.
any sign of skin rash. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may cause skin rashes. If you notice signs of a severe rash, with blistering or fever, stop taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka and inform your doctor immediately. If you have experienced a rash during treatment with another NNRTI, you may have a higher risk of developing skin rashes with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka.
any sign of inflammation or infection. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infections, inflammatory signs and symptoms of previous infections may occur shortly after starting anti-HIV treatment. These symptoms are believed to result from improved immune response, allowing the body to fight infections that may have been present without clear symptoms. If you notice any symptoms of infection, inform your doctor immediately. In addition to opportunistic infections, autoimmune disorders (a condition where the immune system attacks healthy body tissue) may also occur after starting medicines for HIV infection. Autoimmune disorders may occur several months after starting treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, initial weakness in hands and feet progressing toward the trunk, palpitations, tremor, or hyperactivity, inform your doctor immediately to receive necessary treatment.
bone problems. Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood supply to the bone). Prolonged combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the numerous risk factors for developing this condition. Signs of osteonecrosis include joint stiffness, discomfort, and pain (especially in hips, knees, and shoulders) and difficulty moving. Consult your doctor if you notice any of these symptoms. Bone problems (manifesting as persistent or worsening bone pain and sometimes resulting in fractures) may also occur following damage to renal tubular cells (see section 4, Possible side effects). Inform your doctor if you have bone pain or fractures. Tenofovir disoproxil may also cause loss of bone mass. The most pronounced bone mass loss 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 future fracture risk in adult and pediatric patients are uncertain. Inform your doctor if you have osteoporosis. Patients with osteoporosis are at higher risk of fractures.

Children and adolescents

Do not administer Efavirenz/Emtricitabine/Tenofovir disoproxil Krka to children and adolescents under 18 years of age. The use of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka in children and adolescents has not been studied.

Other medicines and Efavirenz/Emtricitabine/Tenofovir disoproxil Krka
You must not take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka with certain medicines. These medicines are listed in Do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka,
at the beginning of section 2. They include some commonly used medicines and some herbal remedies (including St. John’s wort), which may cause serious interactions.
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Additionally, Efavirenz/Emtricitabine/Tenofovir disoproxil Krka must not be taken together with other
medicines containing efavirenz (unless advised by your doctor), emtricitabine, tenofovir disoproxil, tenofovir alafenamide, lamivudine, or adefovir dipivoxil.
Tell your doctor if you are taking other medicines that may damage the kidneys. These include, for example:

aminoglycosides, vancomycin (medicines for bacterial infections)
foscarnet, ganciclovir, cidofovir (medicines for viral infections)
amphotericin B, pentamidine (medicines for fungal infections)
interleukin-2 (for treating cancer)
non-steroidal anti-inflammatory drugs (NSAIDs, used to relieve bone or muscle pain)

Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may interact with other medicines, including herbal remedies such as Ginkgo biloba extracts. As a result, blood levels of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka or other medicines may be altered.
This may prevent the medicines from working properly or may worsen side effects. In some cases, your doctor may need to adjust the dose or monitor medicine levels in your blood. It is important that you inform your doctor or pharmacist if you are taking any of the following medicines:

Medicines containing didanosine (for HIV infection): taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka with other antiviral medicines containing didanosine may increase blood levels of didanosine and reduce CD4 cell count. Rare cases of pancreatitis and lactic acidosis (excess lactic acid in the blood) have been reported when medicines containing tenofovir disoproxil and didanosine were taken together, sometimes resulting in death. Your doctor must carefully consider whether to treat you with medicines containing tenofovir and didanosine.
Other medicines used for HIV infection: The following protease inhibitors: darunavir, indinavir, lopinavir/ritonavir, ritonavir or boosted ritonavir, atazanavir, or saquinavir. Your doctor may prescribe a different medicine or adjust the dose of the protease inhibitor. Also inform your doctor if you are taking maraviroc.
Medicines used to treat hepatitis C virus-related infections: elbasvir/grazoprevir, glecaprevir/pibrentasvir, sofosbuvir/velpatasvir, sofosbuvir/velpatasvir/voxilaprevir.
Lipid-lowering medicines (also known as statins): atorvastatin, pravastatin, or simvastatin. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may reduce blood levels of statins. Your doctor will monitor your cholesterol levels and, if necessary, adjust the statin dose.
Medicines used to treat seizures (anticonvulsants): carbamazepine, phenytoin, phenobarbital. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may reduce blood levels of anticonvulsants. Carbamazepine may reduce blood levels of efavirenz, one of the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka. Your doctor may prescribe a different anticonvulsant.
Medicines used to treat bacterial infections, including tuberculosis and Mycobacterium avium complex infection associated with AIDS: clarithromycin, rifabutin, rifampicin. Your doctor may decide to adjust the dose or prescribe an alternative antibiotic. Additionally, your doctor may prescribe a higher dose of efavirenz for HIV treatment.
Medicines used to treat fungal infections (antifungals): itraconazole or posaconazole. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may reduce blood levels of itraconazole or posaconazole. Your doctor may consider treating you with a different antifungal.
Medicines used to treat malaria: atovaquone/proguanil or artemether/lumefantrine. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may reduce blood levels of atovaquone/proguanil or artemether/lumefantrine.
Hormonal contraceptives, such as birth control pills, an injectable contraceptive (e.g., Depo-Provera), or a contraceptive implant (e.g., Implanon): you must also use a reliable barrier contraceptive method (see Pregnancy and breastfeeding). Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may reduce the effectiveness of hormonal contraceptives. Cases of pregnancy have occurred in women taking efavirenz, a component of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, while using a contraceptive implant, although it has not been established that efavirenz therapy causes contraceptive failure.
Praziquantel, a medicine used to treat parasitic worm infections.
Sertraline, a medicine used to treat depression, because your doctor may need to adjust the sertraline dose.
Metamizole, a medicine used to treat pain and fever.
Bupropion, a medicine used to treat depression or to quit smoking, because your doctor may need to adjust the bupropion dose.
Diltiazem or similar medicines (called calcium channel blockers): when you start taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, your doctor may need to adjust the dose of the calcium channel blocker.
Medicines used to prevent organ transplant rejection (also called immunosuppressants) such as cyclosporine, sirolimus, or tacrolimus. When you start or stop taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, your doctor must closely monitor your blood levels of the immunosuppressant and may adjust the dose.
Warfarin or acenocoumarol (medicines used to reduce blood clotting): your doctor may need to adjust the dose of warfarin or acenocoumarol.
Ginkgo biloba extracts (a herbal remedy).

Pregnancy and breastfeeding
If you are pregnant, think you might be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
Women must not become pregnant during treatment with
Efavirenz/Emtricitabine/Tenofovir disoproxil Krka and for 12 weeks after
treatment. Your doctor may perform a pregnancy test to confirm you are not pregnant before starting treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka.
If there is a possibility of becoming pregnant during treatment with
Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, you must use a reliable barrier contraceptive method (e.g., a condom) together with other contraceptive methods, including oral contraceptives (the pill) or other hormonal contraceptives (e.g., subcutaneous implant, injection). Efavirenz, one of the active substances in Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, may remain in the blood for some time after treatment ends. Therefore, you must continue using contraceptive methods, as described above, for 12 weeks after stopping treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka.
Inform your doctor immediately if you become pregnant or intend to become pregnant. If you are pregnant, you should take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka only if, with your doctor’s advice, it is decided that it is absolutely necessary.
Severe birth defects have been observed in unborn animals and infants of women treated with efavirenz during pregnancy.
Ask your doctor or pharmacist for advice before taking any medicine.
If you have already taken Efavirenz/Emtricitabine/Tenofovir disoproxil Krka during pregnancy, your doctor may request periodic blood tests and other diagnostic tests to monitor the baby’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 Efavirenz/Emtricitabine/Tenofovir disoproxil Krka. Both HIV and the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka can pass into breast milk and cause serious harm to the baby.
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, discuss this with your doctor as soon as possible.

Driving and using machines
Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may cause dizziness, reduced concentration, and drowsiness. If you are affected, do not drive and do not use tools or machinery.

Efavirenz/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 Efavirenz/Emtricitabine/Tenofovir disoproxil Krka

Take this medicine exactly as directed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

Recommended dose:
One tablet daily, taken by mouth. Efavirenz/Emtricitabine/Tenofovir disoproxil Krka should be taken on an empty stomach (commonly understood as 1 hour before or 2 hours after a meal), preferably before going to bed. This may reduce the bothersome nature of certain side effects (e.g. dizziness, drowsiness). Swallow the Efavirenz/Emtricitabine/Tenofovir disoproxil Krka tablet whole with water.

Efavirenz/Emtricitabine/Tenofovir disoproxil Krka must be taken every day.

If your doctor decides to discontinue one of the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, you may be given efavirenz, emtricitabine and/or tenofovir disoproxil separately, or in combination with other medicines for the treatment of HIV infection.

If you take more Efavirenz/Emtricitabine/Tenofovir disoproxil Krka than you should
If you accidentally take too many tablets of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka, the risk of experiencing possible side effects related to this medicine may increase (see section 4, Possible side effects). Contact your doctor or the nearest emergency department. Bring the bottle of tablets with you so that you can clearly describe what you have taken.

If you forget to take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka
It is important that you do not miss any dose of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka.

If you miss a dose of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka within 12 hours of your usual dosing time, take it as soon as possible, then take your next dose at the regular time.

If it is almost time for your next dose (less than 12 hours away), do not take the missed dose. Wait and take your next dose at the regular time. Do not take a double dose to make up for the forgotten tablet.

If you vomit the tablet (within 1 hour after taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka), take another tablet. Do not wait until the time of your next dose. You should not take another tablet if you vomited more than one hour after taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka.

If you stop taking Efavirenz/Emtricitabine/Tenofovir disoproxil Krka
Do not stop treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka without first contacting your doctor. Stopping Efavirenz/Emtricitabine/Tenofovir disoproxil Krka may seriously compromise the response to future treatment. If treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka is stopped, talk to your doctor before restarting the tablets. If problems occur, or if dose adjustment becomes necessary, your doctor may decide to prescribe the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka separately.

When your supply of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka starts to run low, obtain a new supply from your doctor or pharmacist. This is very important because if you stop taking the medicine, even for a short time, the virus may start to multiply again, making it more difficult to control.

If you have both HIV and hepatitis B infection, it is especially important not to stop treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka without first consulting your doctor. Some patients have experienced worsening of their hepatitis after stopping emtricitabine or tenofovir disoproxil (two of the three components of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka). If treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Krka is stopped, your doctor may recommend that you restart treatment for hepatitis B. Blood tests may be required for up to 4 months after stopping treatment to monitor liver function. In some patients with advanced liver disease or cirrhosis, stopping treatment is not recommended, as this may lead to a worsening of hepatitis that could be life-threatening.

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

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

4. Possible side effects

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

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

Serious possible side effects: inform your doctor immediately

Lactic acidosis (excess lactic acid in the blood) is a rare (may affect up to 1 in 1,000 people), but serious side effect, which can be fatal. The following side effects may be signs of lactic acidosis:
- rapid and deep breathing
- fatigue
- feeling sick, vomiting and stomach pain.

→ If you think you have lactic acidosis, contact your doctor immediately.

Other possible serious side effects

The following side effects are uncommon (may affect up to 1 in 100 people):

allergic reaction (hypersensitivity) which may cause severe skin reactions (Stevens-Johnson syndrome, erythema multiforme, see section 2)
swelling of the face, lips, tongue or throat
aggressive behaviour, suicidal thoughts, strange thoughts, paranoia, difficulty thinking clearly, mood disturbances, sensation of seeing or hearing non-existent things (hallucinations), suicide attempt, personality changes (psychosis), catatonia (a condition in which the patient remains motionless and mute for a period of time)
abdominal pain (in the stomach area) caused by inflammation of the pancreas
forgetfulness, confusion, seizures, incoherent speech, tremor (shaking)
yellowing of the skin and eyes, itching or abdominal pain (in the stomach area) caused by inflammation of the liver
damage to the kidney tubules

Undesirable psychiatric effects, in addition to those already mentioned, include delirium (false beliefs), neurosis. Some patients have died by suicide. These problems tend to occur more frequently in those who have had mental illnesses. In all cases, if you experience these symptoms, always inform your doctor.

Liver-related side effects: if you also have hepatitis B, your hepatitis may worsen after stopping treatment (see section 3).

The following side effects are rare (may affect up to 1 in 1,000 people):

liver failure, which in some cases has been fatal or required liver transplantation. Most cases occurred in patients already suffering from liver disease, but some cases have been reported in patients without pre-existing liver disease
kidney inflammation, excessive urination and feeling thirsty
back pain caused by kidney problems, including kidney failure. Your doctor may perform blood tests to monitor kidney function.
softening of the bones (with bone pain and sometimes fractures), which may be a consequence of damage to kidney tubule cells
fatty liver

→ If you think you have any of these serious side effects, inform your doctor.

More frequent side effects

The following side effects are very common (may affect more than 1 in 10 people):

dizziness, headache, diarrhoea, feeling unwell (nausea), feeling sick (vomiting)
skin rashes (including red spots or pustules, sometimes with blisters and swelling of the skin) which may be an allergic reaction
feeling weak

Blood tests may also show:

reduced levels of phosphate in the blood
increased levels of creatine kinase in the blood, leading to muscle pain and weakness

Other possible side effects

The following side effects are common (may affect up to 1 in 10 people):

allergic reactions
coordination problems and balance disorders
anxiety or depression
difficulty sleeping, unusual dreams, difficulty concentrating, drowsiness
pain, stomach ache
digestive problems with discomfort after meals, feeling of fullness, excess intestinal gas (flatulence)
loss of appetite
fatigue
itching
change in skin colour with appearance of dark patches, often starting on the hands and soles of the feet

Blood tests may also show:

decrease in white blood cell count (this may make you more susceptible to infection)
problems with liver and pancreas
increased levels of fatty acids (triglycerides), bilirubin or glucose in the blood

The following side effects are uncommon (may affect up to 1 in 100 people):

muscle breakdown, muscle pain or muscle weakness
anaemia (low red blood cell count)
sensation of dizziness, ringing, buzzing or other persistent noise in the ear
blurred vision
chills
increased breast size in men
decreased sex drive
flushing
dry mouth
increased appetite

Blood tests may also show:

reduced potassium levels in the blood
increased creatinine levels in the blood
protein in the urine
increased cholesterol levels in the blood

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 may occur due to damage to kidney tubule cells.

The following side effects are rare (may affect up to 1 in 1,000 people):

itchy skin rashes caused by sunlight

Reporting of side effects

If you experience any side effect, 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 Efavirenz/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.
Do not store above 30 °C.
Keep the bottle tightly closed to protect the medicine from moisture.
The shelf life after first opening is 2 months, if not stored above 25 °C.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Efavirenz/Emtricitabine/Tenofovir disoproxil Krka contains

The active substances are efavirenz, emtricitabine and tenofovir disoproxil. Each film-coated tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (as fumarate).
The other components are: Tablet core: microcrystalline cellulose, hydroxypropylcellulose, sodium lauryl sulfate, croscarmellose sodium, red iron oxide (E172), magnesium stearate, sodium fumarate. Film coating: poly(vinyl alcohol), macrogol 3350, titanium dioxide (E171), talc, red iron oxide (E172), yellow iron oxide (E172). See section 2 “Efavirenz/Emtricitabine/Tenofovir disoproxil Krka contains sodium”.

Description of the appearance of Efavirenz/Emtricitabine/Tenofovir disoproxil Krka and contents of the
package
Efavirenz/Emtricitabine/Tenofovir disoproxil Krka film-coated tablets (tablets) are light pink, oval, biconvex film-coated tablets with bevelled edges.
Tablet dimensions: 20 x 11 mm.
Efavirenz/Emtricitabine/Tenofovir disoproxil Krka is available in bottles containing 30 tablets, with a child-resistant closure made of polypropylene and a silica gel desiccant to help protect the tablets from moisture.
The following pack sizes are available: boxes containing one bottle of 30 film-coated tablets (1x30) or 90 film-coated tablets (3 bottles of 30).
Not all pack sizes may be marketed.

Marketing Authorisation 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 Authorisation 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

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