Efavirenz/Emtricitabine/Tenofovir disoproxil Krka - patient leaflet, side effects, dosage

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka 600 mg/200 mg/245 mg film-coated tablets efavirenz/emtri­citabine/teno­fovir disoproxil (efavirenzum/em­tricitabinum/te­nofovirum disoproxilum)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• – Keep this leaflet. You may need to read it again.

• – If you have any further questions, ask your doctor or pharmacist.

• – This medicine has been prescribed for you only. Do not pass it on to others. It may harm them,

even if their signs of illness are the same as yours.

• – If you get any side effects, talk to your doctor or pharmacist. This includes any possible side

effects not listed in this leaflet. See section 4.

What is in this leaflet

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

• 2. What you need to know before you take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka

• 3. How to take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka

• 4. Possible side effects

• 5. How to store Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka

• 6. Contents of the pack and other information

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

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka contains three active substances that are used to treat 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, work by interfering with an enzyme (reverse transcriptase) that is essential for the virus to multiply.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka is a treatment for Human

Immunodeficiency Virus (HIV) infection in adults aged 18 years and over who have previously been treated with other antiretroviral medicines and have their HIV-1 infection under control for at least three months. Patients must not have experienced failure of a previous HIV therapy.

2. What you need to know before you take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka

Do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka

• - if you are allergic to efavirenz, emtricitabine, 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 prolongation of

the QT interval that puts you at high risk for severe heart rhythm problems (Torsade de Pointes).

• – if any member of your family (parents, grandparents, brothers or sisters) has died suddenly due

to a heart problem or was born with heart problems.

• – if your doctor has told you that you have high or low 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 disease)

• - cisapride (used to treat heartburn)

• - elbasvir/grazo­previr (used to treat hepatitis C)

• - ergot alkaloids (for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine) (used to treat migraines and cluster headaches)

• - midazolam or triazolam (used to help you sleep)

• - pimozide, imipramine, amitriptyline or clomipramine (used to treat certain mental conditions)

• - St. John’s wort (Hypericum perforatum ) (a herbal preparation used for depression and anxiety)

• - voriconazole (used to treat fungal infections)

• - flecainide, metoprolol (used to treat irregular heart beat)

• - certain antibiotics (macrolides, fluoroquinolones, imidazole)

• - triazole antifungal agents

• - certain antimalarial agents

• - methadone (used to treat opiate addiction)

^ If you are taking any of these medicines, tell your doctor immediately. Taking these medicines with Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka could cause serious or life-threatening side effects or stop these medicines from working properly.

Warnings and precautions

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

• - You can still pass on HIV when taking this medicine, although the risk is lowered by effective

antiretroviral therapy. Discuss with your doctor the precautions needed to avoid infecting other people. 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.

• – You must remain under the care of your doctor while taking Efavirenz/Emtri­citabine/Teno­fovir

disoproxil Krka.

• - Tell your doctor :

• - if you are taking other medicines that contain efavirenz, emtricitabine, tenofovir disoproxil, tenofovir alafenamide, or lamivudine or adefovir dipivoxil. Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka should not be taken with any of these medicines.

• - if you have or have had kidney disease , or if tests have shown problems with your kidneys. Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka is not recommended if you have moderate to severe kidney disease.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka may affect your 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 your kidneys.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka is not usually taken with other medicines that can damage your kidneys (see Other medicines and Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka ). If this is unavoidable, your doctor will monitor your kidney function once a week.

• - if you have a heart disorder, such as abnormal electrical signal called prolongation of the QT interval.

• - if you have a history of mental illness , including depression, or of substance or alcohol abuse. Tell your doctor immediately if you feel depressed, have suicidal thoughts or have strange thoughts (see section 4, Possible side effects ).

• - if you have a history of convulsions (fits or seizures) or if you are being treated with anticonvulsant therapy such as carbamazepine, phenobarbital and phenytoin. If you are taking any of these medicines, your doctor may need to check the level of anticonvulsant medicine in your blood to ensure that it is not affected while taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka. Your doctor may give you a different anticonvulsant.

• - if you have a history of liver disease, including chronic active hepatitis. Patients with liver disease including chronic hepatitis B or C, who are treated with combination antiretrovirals, have a higher risk of severe and potentially life-threatening liver problems. Your doctor may conduct blood tests in order to check how well your liver is working or may switch you to another medicine. If you have severe liver disease, do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka (see earlier in section 2, Do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka ).

If you have hepatitis B infection, your doctor will carefully consider the best treatment regimen for you. Tenofovir disoproxil and emtricitabine, two of the active substances in Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka, show some activity against hepatitis B virus although emtricitabine is not approved for the treatment of hepatitis B infection. Symptoms of your hepatitis may become worse after discontinuation of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka. Your doctor may then conduct blood tests at regular intervals in order to check how well your liver is working (see section 3, If you stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka).

• – Independent of a history of liver disease, your doctor will consider regular blood tests to check how your liver is working.

• - if you are over 65. Insufficient numbers of patients over 65 years of age have been studied. If you are over 65 years of age and are prescribed Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka, your doctor will monitor you carefully.

Once you start taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka, look out for :

• - signs of dizziness, difficulty sleeping, drowsiness, difficulty concentrating or abnormal dreaming. These side effects may start in the first 1 or 2 days of treatment and usually go away after the first 2 to 4 weeks.

• - any signs of skin rash. Rashes may be caused by Efavirenz/Emtri­citabine/Teno­fovir

disoproxil Krka. If you see any signs of a severe rash with blistering or fever, stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka and tell your doctor at once. If you had a rash while taking another NNRTI, you may be at higher risk of getting a rash with Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka.

• - any signs of inflammation or infection. In some patients with advanced HIV infection (AIDS) and a history of opportunistic infection, signs and symptoms of inflammation from previous infections may occur soon after anti-HIV treatment is started. It is believed that these symptoms are due to improvement in the body’s immune response, enabling the body to fight infections that may have been present with no obvious symptoms. If you notice any symptoms of infection, please tell your doctor at once.

In addition to the opportunistic infections, autoimmune disorders (a condition that occurs when the immune system attacks healthy body tissue) may also occur after you start taking medicines for the treatment of your HIV infection. Autoimmune disorders may occur many months after the start of treatment. If you notice any symptoms of infection or other symptoms such as muscle weakness, weakness beginning in the hands and feet and moving up towards the trunk of the body, palpitations, tremor or hyperactivity, please inform your doctor immediately to seek necessary treatment.

• - bone problems. Some patients taking combination antiretroviral therapy may develop a bone disease called osteonecrosis (death of bone tissue caused by loss of blood supply to the bone). The length of combination antiretroviral therapy, corticosteroid use, alcohol consumption, severe immunosuppression, higher body mass index, among others, may be some of the many risk factors for developing this disease. Signs of osteonecrosis are joint stiffness, aches and pains (especially of the hip, knee and shoulder) and difficulty in movement. If you notice any of these symptoms please inform your doctor.

Bone problems (manifesting as persistent or worsening bone pain and sometimes resulting in fractures) may also occur due to damage to kidney tubule cells (see section 4, Possible side effects ). Tell your doctor if you have bone pain or fractures.

Tenofovir disoproxil may also cause loss of bone mass. The most pronounced bone loss was seen in clinical studies when patients were treated for HIV with tenofovir disoproxil in combination with a boosted protease inhibitor.

Overall, the effects of tenofovir disoproxil on long term bone health and future fracture risk in adult and paediatric patients are uncertain.

Tell your doctor if you know you suffer from osteoporosis. Patients with osteoporosis are at a higher risk of fractures.

Children and adolescents

• - Do not give 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 are listed under Do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka , at the start of section 2. They include some common medicines and some herbal preparations (including St. John’s wort) which can cause serious interactions.

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Also, Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka should not be taken with any other medicines that contain efavirenz (unless recommended by your doctor), emtricitabine, tenofovir disoproxil, tenofovir alafenamide, or lamivudine or adefovir dipivoxil.

Tell your doctor if you are taking other medicines which may damage your kidneys. Some examples include:

• – aminoglycosides, vancomycin (medicines for bacterial infections)

• – foscarnet, ganciclovir, cidofovir (medicines for viral infections)

• – amphotericin B, pentamidine (medicines for fungal infections)

• – interleukin-2 (to treat cancer)

• – non-steroidal anti-inflammatory drugs (NSAIDs, to relieve bone or muscle pains)

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka may interact with other medicines, including herbal preparations such as Ginkgo biloba extracts. As a result, the amounts of

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka or other medicines in your blood may be affected. This may stop your medicines from working properly, or may make any side effects worse. In some cases, your doctor may need to adjust your dose or check your blood levels. It is important to tell your doctor or pharmacist if you are taking any of the following :

• - Medicines containing didanosine (for HIV infection) : Taking

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka with other antiviral medicines that contain didanosine can raise the levels of didanosine in your blood and may reduce CD4 cell counts. Inflammation of the pancreas and lactic acidosis (excess lactic acid in the blood), which sometimes caused death, have been reported rarely when medicines containing tenofovir disoproxil and didanosine were taken together. Your doctor will 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 ritonavir boosted atazanavir or saquinavir. Your doctor may consider giving you an alternative medicine or changing the dose of the protease inhibitors. Also, tell your doctor if you are taking maraviroc.

• - Medicines used to treat infection with the hepatitis C virus : elbasvir/grazo­previr,

glecaprevir/pi­brentasvir, sofosbuvir/vel­patasvir, sofosbuvir/vel­patasvir/voxi­laprevir.

• - Medicines used to lower blood fats (also called statins) : Atorvastatin, pravastatin,

simvastatin. Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka can reduce the amount of statins in your blood. Your doctor will check your cholesterol levels and will consider changing the dose of your statin, if needed.

• - Medicines used to treat convulsions/se­izures (anticonvulsants) : Carbamazepine, phenytoin,

phenobarbital. Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka can reduce the amount of the anticonvulsant in your blood. Carbamazepine can reduce the amount of efavirenz, one of the components of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka, in your blood. Your doctor may need to consider giving you a different anticonvulsant.

• - Medicines used to treat bacterial infections , including tuberculosis and AIDS-related

mycobacterium avium complex: Clarithromycin, rifabutin, rifampicin. Your doctor may need to consider changing your dose or giving you an alternative antibiotic. In addition, your doctor may consider giving you an additional dose of efavirenz to treat your HIV infection.

• - Medicines used to treat fungal infections (antifungals) : Itraconazole or posaconazole.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka can reduce the amount of itraconazole or posaconazole in your blood. Your doctor may need to consider giving you a different antifungal.

• - Medicines used to treat malaria : Atovaquone/pro­guanil or artemether/lu­mefantrine.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka may reduce the amount of atovaquone/pro­guanil or artemether/lu­mefantrine in your blood.

• - Hormonal contraceptive, such as birth control pills, an injected contraceptive (for

example, Depo-Provera), or a contraceptive implant (for example, Implanon) : You must also use a reliable barrier method of contraception (see Pregnancy and breast-feeding ). Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka may make hormonal contraceptives less likely to work. Pregnancies 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 the efavirenz therapy caused the contraceptive to fail.

• - Sertraline , a medicine used to treat depression, as your doctor may need to change your dose of

sertraline.

• - Bupropion , a medicine used to treat depression or to help you stop smoking, as your doctor

may need to change your dose of bupropion.

• - Diltiazem or similar medicines (called calcium channel blockers) : When you start taking

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka, your doctor may need to adjust your 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 will closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.

• - Warfarin or acenocoumarol (medicines used to reduce clotting of the blood): Your doctor

may need to adjust your dose of warfarin or acenocoumarol.

• - Ginkgo biloba extracts (herbal preparation).

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Women should not get pregnant during treatment with Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka and for 12 weeks thereafter. Your doctor may require you to take a pregnancy test to ensure you are not pregnant before starting treatment with Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka.

If you could get pregnant while receiving Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka , you need to use a reliable form of barrier contraception (for example, a condom) with other methods of contraception including oral (pill) or other hormonal contraceptives (for example, implants, injection). Efavirenz, one of the active components of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka, may remain in your blood for a time after therapy is stopped. Therefore, you should continue to use contraceptive measures, as above, for 12 weeks after you stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are pregnant, you should take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka only if you and your doctor decide it is clearly needed.

Serious birth defects have been seen in unborn animals and in the babies of women treated with efavirenz during pregnancy.

Ask your doctor or pharmacist for advice before taking any medicine.

If you have taken Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka during your pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of your child. In children whose mothers took NRTIs during pregnancy, the benefit from the protection against HIV outweighed the risk of side effects.

Do not breast-feed during treatment with Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka. Both HIV and the ingredients of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka may pass through breast milk and cause serious harm to your baby.

Driving and using machines

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

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka contains sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

3. How to take Efavirenz/Emtricitabine/Tenofovir disoproxil Krka

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

The recommended dose is:

One tablet taken each day by mouth. Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka should be taken on an empty stomach (commonly defined as 1 hour before or 2 hours after a meal) preferably at bedtime. This may make some side effects (for example, dizziness, drowsiness) less troublesome. Swallow Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka whole with water.

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

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

If you take more Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka than you should

If you accidentally take too many Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka tablets you may be at increased risk of experiencing possible side effects with this medicine (see section 4, Possible side effects ). Contact your doctor or nearest emergency department for advice. Keep the tablet bottle with you so that you can easily describe what you have taken.

If you forget to take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka

It is important not to miss a dose of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka.

If you do miss a dose of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka within 12 hours of when it is usually taken , take it as soon as you can, and then take your next dose at its regular time.

If it is almost time (less than 12 hours) for your next dose anyway, 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 throw up the tablet (within 1 hour after taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka) , you should take another tablet. Do not wait until your next dose is due. You do not need to take another tablet if you were sick more than 1 hour after taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka.

If you stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka

Don’t stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka without talking to your doctor. Stopping Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka can seriously affect your response to future treatment. If Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka is stopped, speak to your doctor before you restart taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka tablets. Your doctor may consider giving you the components of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka separately if you are having problems or need your dose adjusted.

When your supply of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka starts to run low , get more from your doctor or pharmacist. This is very important because the amount of virus may start to increase if the medicine is stopped for even a short time. The virus may then become harder to treat.

If you have both HIV infection and hepatitis B , it is especially important not to stop your Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka treatment without talking to your doctor first.

Some patients have had blood tests or symptoms indicating that their hepatitis has got worse after stopping emtricitabine or tenofovir disoproxil (two of the three components of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka). If Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka is stopped your doctor may recommend that you resume hepatitis B treatment. You may require blood tests to check how your liver is working for 4 months after stopping treatment. In some patients with advanced liver disease or cirrhosis, stopping treatment is not recommended as this may lead to worsening of your hepatitis, which may be life-threatening.

^ Tell your doctor immediately about new or unusual symptoms after you stop treatment, particularly symptoms you associate with hepatitis B infection.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible side effects

During HIV therapy there may be an increase in weight and in levels of blood lipids and glucose. This is partly linked to restored health and life style, and in the case of blood lipids sometimes to the HIV medicines themselves. Your doctor will test for these changes.

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

Possible serious side effects: tell your doctor immediately

– Lactic acidosis (excess lactic acid in the blood) is a rare (may affect up to 1 in every 1,000

patients) but serious side effect that can be fatal. The following side effects may be signs of lactic acidosis:

• – deep rapid breathing

• – drowsiness

• – feeling sick (nausea), being sick (vomiting) and stomach pain.

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

Other possible serious side effects

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

• – allergic reaction (hypersensitivity) that may cause severe skin reactions (Stevens-Johnson

syndrome, erythema multiforme, see section 2)

• – swelling of the face, lips, tongue or throat

• – angry behaviour, suicidal thoughts, strange thoughts, paranoia, unable to think clearly, mood

being affected, seeing or hearing things that are not really there (hallucinations), suicide attempts, personality change (psychosis), catatonia (a condition in which the patient is rendered motionless and speechless for a period)

• – pain in the abdomen (stomach), caused by inflammation of the pancreas

• – forgetfulness, confusion, fitting (seizures), incoherent speech, tremor (shaking)

• – yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the

liver

• – damage to kidney tubules

Psychiatric side effects in addition to those listed above include delusions (false beliefs), neurosis. Some patients have committed suicide. These problems tend to occur more often in those who have a history of mental illness. Always notify your doctor immediately if you have these symptoms.

Side effects to the liver: If you are also infected with hepatitis B virus, you may experience a worsening of hepatitis after discontinuation of treatment (see section 3).

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

• – liver failure, in some cases leading to death or liver transplant. Most cases occurred in patients

who already had liver disease, but there have been a few reports in patients without any existing liver disease

• – inflammation of the kidney, passing a lot of urine and feeling thirsty

• – back pain caused by kidney problems, including kidney failure. Your doctor may do blood tests

to see if your kidneys are working properly

• – softening of the bones (with bone pain and sometimes resulting in fractures) which may occur

due to damage to the kidney tubule cells

• – fatty liver

^ If you think that you may have any of these serious side effects, talk to your doctor.

Most frequent side effects

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

• – dizziness, headache, diarrhoea, feeling sick (nausea), being sick (vomiting)

• – rashes (including red spots or blotches sometimes with blistering and swelling of the skin), which may be allergic reactions

• – feeling weak

Tests may also show:

• – decreases in phosphate levels in the blood

• – increased levels of creatine kinase in the blood that may result in muscle pain and weakness

Other possible side effects

The following side effects are common (these may affect up to 1 in 10 patients)

• – allergic reactions

• – disturbances of coordination and balance

• – feeling worried or depressed

• – difficulty sleeping, abnormal dreams, difficulty concentrating, drowsiness

• – pain, stomach pain

• – problems with digestion resulting in discomfort after meals, feeling bloated, wind (flatulence)

• – loss of appetite

• – tiredness

• – itching

• – changes in skin colour including darkening of the skin in patches often starting on hands and

soles of feet

Tests may also show:

• – low white blood cell count (a reduced white blood cell count can make you more prone to

infection)

• – liver and pancreas problems

• – increased fatty acids (triglycerides), bilirubin or sugar levels in the blood

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

• – breakdown of muscle, muscle pain or weakness

• – anaemia (low red blood cell count)

• – a feeling of spinning or tilting (vertigo), whistling, ringing or other persistent noise in the ears

• – blurred vision

• – chills

• – breast enlargement in males

• – decreased sexual drive

• – flushing

• – dry mouth

• – increased appetite

Tests may also show:

• – decreases in potassium in the blood

• – increases in creatinine in the blood

• – proteins in urine

• – increased cholesterol in the blood

The breakdown of muscle, softening of the bones (with bone pain and sometimes resulting in fractures), muscle pain, muscle weakness and decreases in potassium or phosphate in the blood may occur due to damage to kidney tubule cells.

The following side effects are rare (these may affect up to 1 in every 1,000 patients)

• – itchy rash to the skin caused by a reaction to sunlight

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system listed in Appendix 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 which is 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 in order to protect from moisture.

Shelf life after first opening is 2 months, if not stored above 25°C.

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. Contents of the pack 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 succinate).

• – The other ingredients are:

What Efavirenz/Emtricitabine/Tenofovir disoproxil Krka looks like and contents of the pack

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka film-coated tablets (tablets) are light orange pink, oval, biconvex, film-coated tablets with bevelled edges. Tablet dimension: 20 × 11 mm.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Krka is available in bottles of 30 tablets, with a childresistant tamper evident closer with integrated a desiccant, which helps to protect your tablets from moisture.

The following pack sizes are available: cartons containing 1 bottle of 30 film-coated tablets or 90 (3 bottles of 30) film-coated tablets.

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 any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

KRKA France Eurl Tel: + 33 (0)1 57 40 82 25	KRKA Farmacéutica, Sociedade Unipessoal Lda. Tel: + 351 (0)21 46 43 650
Hrvatska KRKA – FARMA d.o.o. Tel: + 385 1 6312 100	Romania KRKA Romania S.R.L., Bucharest Tel: + 4 021 310 66 05
Ireland KRKA Pharma Dublin, Ltd. Tel: + 353 1 413 3710	Slovenija KRKA, d.d., Novo mesto Tel: + 386 (0) 1 47 51 100
Ísland LYFIS ehf. Simi: + 354 534 3500	Slovenská republika KRKA Slovensko, s.r.o. Tel: + 421 (0) 2 571 04 501
Italia KRKA Farmaceutici Milano S.r.l. Tel: + 39 02 3300 8841	Suomi/Finland KRKA Finland Oy Puh/Tel: + 358 20 754 5330
Kitnpoc KI.PA. (PHARMACAL) LIMITED TnX: + 357 24 651 882	Sverige KRKA Sverige AB Tel: + 46 (0)8 643 67 66 (SE)
Latvija KRKA Latvija SIA Tel: + 371 6 733 86 10	United Kingdom (Northern Ireland) Consilient Health Limited Tel: + 353 (0)1 205 7760

This leaflet was last revised in

Detailed information on this medicine is available on the European Medicines Agency web site:

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