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

B. PACKAGE LEAFLET

Package leaflet: Information for the patient

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 600 mg/200 mg/245 mg film-coated tablets efavirenz/emtri­citabine/teno­fovir disoproxil

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 Mylan is and what it is used for

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

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

• 4. Possible side effects

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

• 6. Contents of the pack and other information

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

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 disoproxil 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 Mylan 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 Mylan

Do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan:

• - 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 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 Mylan”):

• - 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 Mylan 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 Mylan.

• - 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 Mylan 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 Mylan.

• - Tell your doctor:

• - if you are taking other medicines that contain efavirenz, emtricitabine, tenofovir disoproxil, tenofovir alafenamide, lamivudine or adefovir dipivoxil.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan is not recommended if you have moderate to severe kidney disease.

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan is not usually taken with other medicines that can damage your kidneys (see Other medicines and Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan ). 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 Mylan. 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 lifethreatening 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 Mylan (see earlier in section 2, Do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan).

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 Mylan, 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 Mylan. 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 Mylan).

• – 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 Mylan, your doctor will monitor you carefully.

– Once you start taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan, 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 Mylan. If you see any signs of a severe rash with blistering or fever, stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan.

• - 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 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 for fractures.

Children and adolescents

• - Do not give Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan to children and adolescents under 18 years of age. The use of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan in children and adolescents has not been studied.

Other medicines and Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan

You must not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan with certain medicines. These are listed under Do not take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan, 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 Mylan should not be taken with any other medicines that contain efavirenz (unless recommended by your doctor), emtricitabine, tenofovir disoproxil, tenofovir alafenamide, 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 Mylan may interact with other medicines, including herbal preparations such as Ginkgo biloba extracts. As a result, the amounts of

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan 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 Mylan 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 Mylan 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 Mylan, 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 Mylan 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 Mylan 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 Mylan may make hormonal contraceptives less likely to work. Pregnancies have occurred in women taking efavirenz, a component of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan, 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.

• - Metamizole, a medicine used to treat pain and fever.

• - 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 Mylan, 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 Mylan 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 Mylan 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 Mylan.

If you could get pregnant while receiving Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan , 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 Mylan, 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 Mylan.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are pregnant, you should take Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan 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 Mylan. Both HIV and the ingredients of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan may pass through breast milk and cause serious harm to your baby.

Driving and using machines

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan contains sodium and lactose

This medicine contains 7.5 mg of sodium metabisulfite per tablet, which may rarely cause severe hypersensitivity reactions and bronchospasm. It contains less than 1 mmol sodium (23 mg) per dose, that is to say essentially ‘sodium-free’. Each tablet also contains 105.5 mg of lactose per tablet. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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

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 Mylan 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 Mylan whole with water.

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

If your doctor decides to stop one of the components of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan, 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 Mylan than you should

If you accidentally take too many Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan

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

If you do miss a dose of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan) , 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 Mylan.

If you stop taking Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan

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

When your supply of Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan 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 Mylan). If Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan 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 Mylan

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 bottle and carton after ‘EXP’.

The expiry date refers to the last day of that month.

Bottle packs of 30 tablets: Write the date the bottle was opened on the label and/or carton in the space provided. Use within 60 days after first opening.

Do not store above 25°C. Store in the original package in order to protect from light.

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 Mylan contains

• – The active substances are efavirenz, emtricitabine and tenofovir disoproxil. Each Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan film-coated tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (as maleate).

• – The other ingredients in the tablet are croscarmellose sodium, hydroxypropyl­cellulose, low-substituted hydroxypropyl­cellulose, magnesium stearate, microcrystalline cellulose, silica colloidal anhydrous, sodium metabisulfite, lactose monohydrate and iron oxide red (E172).

• – This medicine contains sodium metabisulfite and lactose. See section 2.

• – The other ingredients in the tablet film coating are iron oxide yellow (E172), iron oxide red (E172), macrogol, poly(vinyl alcohol), talc, titanium dioxide (E171).

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

Efavirenz/Emtri­citabine/Teno­fovir disoproxil Mylan film-coated tablets are pink capsule-shaped tablets, engraved with ‘M’ on one side and ‘TME’ on the other side.

This medicine is available in plastic bottles containing a desiccant labelled ‘DO NOT EAT’ and 30 or 90 tablets and in multipacks of 90 tablets comprising 3 bottles, each containing 30 tablets.

Not all pack sizes may be marketed.

Marketing Authorisation Holder

Mylan Pharmaceuticals Limited

Damastown Industrial Park,

Mulhuddart, Dublin 15,

DUBLIN

Ireland

Manufacturer

Mylan Hungary Kft

Mylan utca 1, Komarom, 2900,

Hungary

McDermott Laboratories Limited t/a Gerard Laboratories t/a Mylan Dublin

35/36 Baldoyle Industrial Estate, Grange Road, Dublin 13

Ireland

Mylan Germany GmbH

Zweigniederlassung Bad Homburg v. d. Hoehe,

Benzstrasse 1, Bad Homburg v. d. Hoehe, Hessen, 61352, Germany

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

België/Belgiqu­e/Belgien Mylan bvba/sprl Tél/Tel: + 32 (0)2 658 61 00	Lietuva Mylan Healthcare UAB Tel: +370 5 205 1288
BtnrapuH MaönaH EOOfl, Ten: +359 2 44 55 400	Luxembourg/Lu­xemburg Mylan bvba/sprl Tel: + 32 (0)2 658 61 00 (Belgique/Belgien)
Česká republika Mylan Healthcare CZ Tel: +420 222 004 400	Magyarorszag Mylan EPD Kft Tel: + 36 1 465 2100
Danmark Viatris ApS Tlf: +45 28 11 69 32	Malta V.J. Salomone Pharma Ltd Tel: + 356 21 22 01 74
Deutschland Mylan Healthcare GmbH Tel: +49 800 0700 800	Nederland Mylan BV Tel: +31 (0)20 426 3300
Eesti BGP Products Switzerland GmbH Eesti filiaal	Norge Mylan Healthcare Norge AS Tel: + 47 66 75 33 00

Tel: +372 6363 052

EXXáSa Generics Pharma Hellas EnE Tn^: +30 210 993 6410	Österreich Arcana Arzneimittel GmbH Tel: +43 1 416 2418
España Mylan Pharmaceuticals, S.L Tel: + 34 900 102 712	Polska Mylan Healthcare Sp. z o.o. Tel: + 48 22 546 64 00
France Mylan S.A.S Tel: +33 4 37 25 75 00	Portugal Mylan, Lda. Tel: + 351 21 412 72 56
Hrvatska Mylan Hrvatska d.o.o. Tel: +385 1 23 50 599	Romania BGP Products SRL Tel: + 40 372 579 000

Ireland Mylan Ireland Limited Tel: +353 1 8711600	Slovenija Mylan Healthcare d.o.o. Tel: + 386 1 23 63 180
Ísland Icepharma hf Símí: +354 540 8000	Slovenská republika Mylan s.r.o. Tel: +421 2 32 199 100
Italia Mylan Italia S.r.l. Tel: + 39 02 612 46921	Suomi/Finland Mylan Finland OY Puh/Tel: +358 20 720 9555
Kúnpo^ Varnavas Hadjipanayis Ltd Tn^: +357 2220 7700	Sverige Mylan AB Tel: + 46 855 522 750
Latvija Mylan Healthcare SIA Tel: +371 676 055 80	United Kingdom (Northern Ireland) Mylan IRE Healthcare Limited Tel: +353 18711600

This leaflet was last revised in {MM/YYYY }.

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

77