Efavirenz / emtricitabine / tenofovir disoproxil Zentiva: detailed information

Patient Information Leaflet

Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva
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 you, because it may be harmful.
If you experience any side effects, including those not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

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

Efavirenz is a non-nucleoside reverse transcriptase inhibitor (NNRTI)
Emtricitabine 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/Emtricitabine/Tenofovir disoproxil Zentiva 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 prior failure of an anti-HIV therapy.

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

Do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva

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 prolongation that 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 Zentiva”):
- 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)

Inform your doctor immediately if you are taking any of these medicines. Taking
these medicines together with Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva 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
Zentiva.

This medicine is not a cure for HIV infection. While taking Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, you may still develop infections or other illnesses associated with HIV infection.
While taking Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, you must remain under medical supervision.
Inform your doctor:
- if you are taking other medicines containing efavirenz, emtricitabine, tenofovir disoproxil, tenofovir alafenamide, lamivudine or adefovir dipivoxil. Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva 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 Zentiva is not recommended in cases of moderate to severe kidney disease.

Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva may affect the kidneys. Before starting treatment, your doctor may prescribe blood tests to assess kidney function. Your doctor may also order blood tests during treatment to monitor kidney function.
Generally, Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva should not be taken
with other medicines that may damage the kidneys (see Other medicines and
Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva). If this is unavoidable, your
doctor will monitor your kidney function once a week.

if you have a heart condition, such as an abnormal electrical signal called QT 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 unusual thoughts (see section 4, Possible side effects).
if you have previously had seizures or if you 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 Zentiva. 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 another medicine. If you have severe liver disease, do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva (see above, section 2, Do not take Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva).

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 Zentiva, have some activity against 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 Zentiva. Your doctor may request regular blood tests to closely monitor liver function (see section 3, If you stop taking Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva).

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 Zentiva 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 Zentiva, your doctor will monitor you closely.
- Once you start taking Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, 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 signs of rash. Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva may cause skin rash. If you notice signs of a severe rash, with blistering or fever, stop taking Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva and inform your doctor immediately. If you have experienced a rash during treatment with another NNRTI, you may have a higher risk of developing rashes with Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva.
any signs 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 appear shortly after starting anti-HIV treatment. These symptoms are believed to be due to improved immune response, allowing the body to fight infections that may have been present without clear symptoms. If you notice any signs of infection, inform your doctor immediately.

In addition to opportunistic infections, autoimmune disorders (a condition in which 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 signs 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. (manifesting as persistent or worsening bone pain and sometimes fractures) may occur following 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 most pronounced bone loss has been observed in clinical studies where patients were treated with tenofovir disoproxil in combination with a boosted protease inhibitor.
In general, the long-term effects of tenofovir disoproxil on bone health and the risk of future fractures in adult and pediatric patients are uncertain.
Some adult HIV patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue due to reduced blood flow to the bone). Duration of 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.
Inform your doctor if you have osteoporosis, a history of bone fractures or bone problems.

Children and adolescents

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

Other medicines and Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva
You must not take Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva with certain
medicines. These medicines are listed in Do not take Efavirenz/Emtricitabine/Tenofovir
disoproxil Zentiva, at the beginning of section 2. They include some commonly used medicines and
some herbal preparations (including St. John’s wort), which may cause serious interactions.
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicine.
Additionally, Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva must not be taken together with
other medicines containing efavirenz (unless advised by your doctor), emtricitabine, tenofovir disoproxil, tenofovir alafenamide, lamivudine or adefovir dipivoxil.
Inform 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 cancer treatment)
non-steroidal anti-inflammatory drugs (NSAIDs, used to relieve bone or muscle pain)

Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva may interact with other medicines, including herbal preparations such as Ginkgo biloba extracts. As a result, blood levels of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva or other medicines may be altered. This could prevent the medicines from working properly or could 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 Zentiva with other antiviral medicines containing didanosine may increase blood levels of didanosine and may 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 will need to 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 Zentiva may reduce statin levels in the blood. 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 Zentiva may reduce anticonvulsant levels in the blood.
Carbamazepine may reduce efavirenz levels, one of the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, in the blood. 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. In addition, your doctor may prescribe a higher dose of efavirenz for the treatment of HIV infection.
Medicines used to treat fungal infections (antifungals): itraconazole or posaconazole. Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva may reduce itraconazole or posaconazole levels in the blood. Your doctor may consider treating you with a different antifungal.
Medicines used to treat malaria: atovaquone/proguanil or artemether/lumefantrine. Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva may reduce atovaquone/proguanil or artemether/lumefantrine levels in the blood.
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 method of contraception (see Pregnancy and breastfeeding). Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva may reduce the effectiveness of hormonal contraceptives. Cases of pregnancy have occurred in women taking efavirenz, a component of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, while using a contraceptive implant, although it has not been established that efavirenz therapy causes contraceptive failure.
Sertraline, a medicine used to treat depression, because your doctor may need to adjust the sertraline dose.
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 starting Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, your doctor may need to adjust the calcium channel blocker dose.
Medicines used to prevent organ transplant rejection (also called immunosuppressants) such as cyclosporine, sirolimus or tacrolimus. When starting or stopping Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, your doctor will need to closely monitor your immunosuppressant blood levels and may adjust your 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 preparation).
Metamizole, a medicine used to treat pain and fever.
Praziquantel, a medicine used to treat certain parasitic infections.

Pregnancy and breastfeeding
If you are pregnant, think you may be pregnant or are planning to become pregnant, or if you are breastfeeding, consult your doctor or pharmacist before taking this medicine.
Women must not become pregnant during treatment with
Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva and for 12 weeks after
treatment ends. Your doctor may perform a pregnancy test to confirm you are not pregnant before starting treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva.
If there is a possibility of becoming pregnant during treatment with
Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, you must use a reliable barrier method of contraception (e.g., a condom) in combination with other contraceptive methods, including oral contraceptives (pill) or other hormonal contraceptives (e.g., subcutaneous implant, injection). Efavirenz, one of the active substances in Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, 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 Zentiva.
Inform your doctor immediately if you become pregnant or intend to become
pregnant. If you are pregnant, you should take Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva only if, after consulting your doctor, 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.
Consult your doctor or pharmacist before taking any medicine.
If you have already taken Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva during pregnancy, your doctor may request periodic blood tests and other diagnostic examinations 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
Zentiva. Both HIV and the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva 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, you must discuss this with your doctor as soon as possible.

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

Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva 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 Zentiva

Take this medicine exactly as prescribed by your doctor or pharmacist.
If you have any doubts, consult your doctor or pharmacist.
The recommended dose is:
One tablet daily, taken by mouth. Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva should be taken on an empty stomach (commonly defined as 1 hour before or 2 hours after a meal), preferably before going to bed. This may make some side effects (e.g. dizziness, drowsiness) less bothersome. Swallow the Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva tablet whole with water.
Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva must be taken every day.
If your doctor decides to discontinue one of the components of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, you may be given efavirenz, emtricitabine and/or tenofovir disoproxil separately or in combination with other medicines for the treatment of HIV infection.

Remove the child-resistant cap
Open the bottles by pressing down on the child-resistant cap and turning it counterclockwise.

If you take more Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva than you should
If you accidentally take too many tablets of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva, you may have an increased risk of experiencing possible side effects related to this medicine (see section 4, Possible side effects). Contact your doctor or the nearest emergency facility immediately. Take the bottle of tablets with you so you can easily describe what you have taken.

If you forget to take Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva
It is important that you do not miss any doses of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva.
If you miss a dose of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva within 12 hours of your usual dosing time, take it as soon as possible, then take the 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 the next dose at the regular time. Do not take a double dose to make up for a forgotten tablet.

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

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

When your supply of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva 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 begin to multiply, making it more difficult to control.

If you have both HIV and hepatitis B infection, it is particularly important not to stop treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva without first consulting your doctor. Some patients have experienced worsening of hepatitis after stopping emtricitabine or tenofovir disoproxil (two of the three components of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva), as shown by symptoms or blood tests. If treatment with Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva is stopped, your doctor may recommend restarting 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, discontinuation of treatment is not recommended, as it may lead to life-threatening worsening of hepatitis.

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 the use of 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.

Possible serious 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
- nausea, 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, unusual thoughts, paranoia, difficulty thinking clearly, mood disturbances, sensation of seeing or hearing things that are not there (hallucinations), suicide attempt, personality change (psychosis), catatonia (a condition in which patients remain 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
yellowing of the skin and eyes, itching or abdominal pain (in the stomach area) caused by liver inflammation
kidney tubule damage

Psychiatric side 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, inform your doctor immediately.

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 who already had 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 result from damage to kidney tubule cells, fatty liver

If you think you may be experiencing any of these serious side effects, inform your doctor.

More common 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 skin swelling) which may be an allergic reaction
feeling weak

Tests may also show:

reduced phosphate levels in the blood
increased creatine kinase levels 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, abnormal 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 dark patches, often starting on the hands and soles of the feet
loss of bone mass

Tests may also show:

decreased 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
breast enlargement in men
decreased sex drive
flushing
dry mouth
increased appetite

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 renal tubular cells.

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

itchy skin rash caused by sunlight

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. Reporting side effects can help provide more information on the safety of this medicine.

5. How to store Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and the outer carton after
“Exp.”. The expiry date refers to the last day of that month.
Use within 30 days of first opening. This medicine does not require any special storage
temperature. Store in the original packaging to protect the medicine from moisture. Keep the bottle tightly closed.
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 Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva contains

The active substances are efavirenz, emtricitabine and tenofovir disoproxil. Each film-coated tablet of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva contains 600 mg of efavirenz, 200 mg of emtricitabine and tenofovir disoproxil fumarate equivalent to 245 mg of tenofovir disoproxil.
The other ingredients in the tablet are microcrystalline cellulose, sodium croscarmellose, hydroxypropylcellulose, sodium lauryl sulfate, magnesium stearate, anhydrous colloidal silica, talc.
The other ingredients in the tablet coating are polyvinyl alcohol, titanium dioxide (E171), macrogol, talc, red iron oxide (E172), yellow iron oxide (E172), black iron oxide (E172).

Description of the appearance of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva and contents of the pack
The film-coated tablets of Efavirenz/Emtricitabine/Tenofovir disoproxil Zentiva are pink, oval-shaped, biconvex tablets, available in bottles of 30 tablets (with a sachet of silica gel desiccant which should remain in the bottle to protect the tablets). The silica gel desiccant is contained in a separate container and must not be swallowed.
The following pack sizes are available:
Outer packaging containing 1 bottle of 30 film-coated tablets and outer packaging containing 3 bottles of 30 film-coated tablets.
Not all pack sizes may be marketed.

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

Manufacturer
S.C. Zentiva S.A.
Bvd. Theodor Pallady, nr. 50
Sector 3
032266 Bucharest
Romania

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

België/Belgique/Belgien Lietuva
Zentiva, k.s. Zentiva, k.s.
Tél/Tel: +32 (78) 700 112 Tel: +370 52152025
[email protected] [email protected]

България Luxembourg/Luxemburg
Zentiva, k.s. Zentiva, k.s.
Тел: +359 2 441 7136 Tél/Tel: +352 208 82330
[email protected] [email protected]

Česká republika Magyarország
Zentiva, k.s. Zentiva Pharma Kft.
Tel: +420 267 241 111 Tel.: +36 1 299 1058
[email protected] [email protected]

Danmark Malta
Zentiva Denmark ApS Zentiva, k.s.
Tlf.: +45 787 68 400 Tel: +356 2034 1796
[email protected] [email protected]

Deutschland Nederland
Zentiva Pharma GmbH Zentiva, k.s.
Tel: +49 (0) 800 53 53 010 Tel: +31 202 253 638
[email protected] [email protected]

Eesti Norge
Zentiva, k.s. Zentiva Denmark ApS
Tel: +372 52 70308 Tlf: +45 787 68 400
[email protected] [email protected]

Ελλάδα Österreich
Zentiva, k.s. Zentiva, k.s.
Τηλ: +30 211 198 7510 Tel: +43 720 778 877
[email protected] [email protected]

España Polska
Zentiva Spain S.L.U. Zentiva Polska Sp. z o.o.
Tel: +34 671 365 828 Tel: +48 22 375 92 00
[email protected] [email protected]

France Portugal
Zentiva France Zentiva Portugal, Lda
Tél: +33 (0) 800 089 219 Tel: +351 210601360
[email protected] [email protected]

Hrvatska România
Zentiva d.o.o. ZENTIVA S.A.
Tel: +385 1 6641 830 Tel: +4 021.304.7597
[email protected] [email protected]

Ireland Slovenija
Zentiva, k.s. Zentiva, k.s.
Tel: +353 818 882 243 Tel: +386 360 00 408
[email protected] [email protected]

Ísland Slovenská republika
Zentiva Denmark ApS Zentiva, a.s.
Sími: +354 539 5025 Tel: +421 2 3918 3010
[email protected] [email protected]

Italia Suomi/Finland
Zentiva Italia S.r.l. Zentiva Denmark ApS
Tel: +39 800081631 Puh/Tel: +358 942 598 648
[email protected] [email protected]

Κύπρος Sverige
Zentiva, k.s. Zentiva Denmark ApS
Τηλ: +30 211 198 7510 Tel: +46 840 838 822
[email protected] [email protected]

Latvija
Zentiva, k.s.
Tel: +371 67893939
[email protected]

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