Atripla 600 mg/200 mg/245 mg film-coated tablets

Atripla 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.

Atripla is a treatment for Human Immunodeficiency Virus (HIV) infection in adults aged 18 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.

Do not take Atripla

• if you are allergic (hypersensitive) to efavirenz, emtricitabine, tenofovir, tenofovir disoproxil fumarate, or any of the other ingredients of Atripla listed at the end of this leaflet.
• if you have severe liver disease.
• if you are currently taking any of the following medicines:
• astemizole or terfenadine (used to treat hay fever or other allergies)
• bepridil (used to treat heart disease)
• cisapride (used to treat heartburn)
• 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 (used to treat certain mental conditions)
• St. John?s wort ( Hypericum perforatum) (a herbal remedy used for depression and anxiety)
• voriconazole (used to treat fungal infections)

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines with Atripla could cause serious or life-threatening side effects or stop these medicines from working properly.

Take special care with Atripla

• Do not give Atripla to children and adolescents under 18 years of age. The use of Atripla in children and adolescents has not yet been studied.
• You can still pass on HIV when taking this medicine, so it is important to take precautions to avoid infecting other people through sexual contact or blood transfer. This medicine is not a cure for HIV infection. While taking Atripla you may still develop infections or other illnesses associated with HIV infection.
• You must remain under the care of your doctor while taking Atripla.
• Tell your doctor:
• if you are taking other medicines that contain efavirenz, emtricitabine, tenofovir disoproxil, or lamivudine or adefovir dipivoxil. Atripla 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. Atripla is not recommended if you have moderate to severe kidney disease.

Atripla 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.

Atripla is not usually taken with other medicines that can damage your kidneys (see Taking other medicines). If this is unavoidable, your doctor will monitor your kidney function once a week.

• 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 Atripla. 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 Atripla (see earlier in Section 2, Do not take Atripla).

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 Atripla, 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 Atripla. 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 Atripla).

• Independent of a history of liver disease, your doctor will consider regular blood tests to check how your liver is working.
• if you are diabetic, overweight or have high cholesterol. Combination antiretroviral therapies (including Atripla) may raise blood sugar levels, increase blood fats (hyperlipaemia), cause changes to body fat, and resistance to insulin (see Section 4, Possible side effects).
• 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 Atripla, your doctor will monitor you carefully.
• Once you start taking Atripla, look out for:
• possible signs of lactic acidosis. Some HIV medicines, including Atripla, that contain nucleoside analogues can cause lactic acidosis (excess of lactic acid in your blood), together with an enlarged liver. Deep, rapid breathing, drowsiness, and symptoms such as feeling sick (nausea), vomiting and stomach pain, might indicate the development of lactic acidosis. This rare but serious side effect has occasionally been fatal. Lactic acidosis occurs more often in women, particularly if they are very overweight, and people with liver disease. While you are being treated with Atripla, your doctor will monitor you closely for any signs that you may be developing lactic acidosis. If you notice any symptoms of lactic acidosis, please tell your doctor immediately.
• 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 Atripla. If you see any signs of a severe rash with blistering or fever, stop taking Atripla 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 Atripla.
• 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.
• 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 (sometimes resulting in fractures) may also occur in patients who develop damage to kidney tubule cells (see Section 4, Possible side effects).

Taking other medicines

You must not take Atripla with certain medicines. These are listed under Do not take Atripla, at the start of Section 2. They include some common medicines and some herbal remedies (including St. John?s wort) which can cause serious interactions.

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes non-prescription medicines and herbal remedies.

Also, Atripla should not be taken with any other medicines that contain efavirenz, emtricitabine, tenofovir disoproxil, or lamivudine or adefovir dipivoxil.

Tell your doctor if youare 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)

Atripla may interact with other medicines. As a result, the amounts of Atripla 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 if you are taking any of the following:

• Medicines containing didanosine (for HIV infection): taking Atripla 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 fumarate 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 lower blood fats (also called statins): atorvastatin, pravastatin, simvastatin. Atripla 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. Atripla can reduce the amount of the anticonvulsant in your blood. Carbamazepine can reduce the amount of efavirenz, one of the components of Atripla, 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. Atripla can reduce the amount of itraconazole or posaconazole in your blood. Your doctor may need to consider giving you a different antifungal.
• 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). Atripla may make hormonal contraceptives less likely to work. Pregnancies have occurred in women taking efavirenz, a component of Atripla, while using a contraceptive implant, although it has not been established that the efavirenz therapy caused the contraceptive to fail.
• Methadone, a medicine used to treat opiate addiction, as your doctor may need to change your methadone dose.
• Sertraline, a medicine used to treat depression, as your doctor may need to change your dose of sertraline.
• Diltiazem or similar medicines (called calcium channel blockers): when you start taking Atripla, 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 Atripla your doctor will closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.
• Warfarin (amedicine used to reduce clotting of the blood): your doctor may need to adjust your dose of warfarin.

Pregnancy and breast-feeding

Women should not get pregnantduring treatment with Atripla 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 Atripla.

If you could get pregnant while receiving Atripla, 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 Atripla, 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 Atripla.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are pregnant, you should take Atripla 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. If you have taken Atripla during your pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of your child.

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

Do not breast-feed during treatment with Atripla. Both HIV and the ingredients of Atripla may pass through breast milk and cause serious harm to your baby.

Driving and using machines

Atripla may cause dizziness, impaired concentration and drowsiness. If you are affected, do not drive and do not use any tools or machines.

Important information about some of the ingredients of Atripla

This medicine contains 1 mmol (23.6 mg) of sodium per tablet which should be taken into consideration if you are on a controlled sodium diet.

Always take Atripla exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

The usual dose for adults is one tablet taken each day by mouth. Atripla should be taken on an empty stomach (commonly defined as 1 hour before or 2 hours after a meal). Swallow Atripla whole with water.

Atripla must be taken every day.

It can help to take Atripla at bedtime. This may make some side effects (for example, dizziness, drowsiness) less troublesome.

If your doctor decides to stop one of the components of Atripla, 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 Atripla than you should

If you accidentally take too many Atripla tablets, 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 Atripla

It is important not to miss a dose of Atripla.

If you do miss a dose of Atripla, 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 (just after taking Atripla), you should take another tablet. Do not wait until your next dose is due.

If you stop taking Atripla

Don?t stop taking Atripla without talking to your doctor. Stopping Atripla can seriously affect your response to future treatment. If Atripla is stopped, speak to your doctor before you restart taking Atripla tablets. Your doctor may consider giving you the components of Atripla separately if you are having problems or need your dose adjusted.

Whenyour supply of Atripla 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.

Ifyou have both HIV infection and hepatitis B, it is especially important not to stop your Atripla 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 fumarate (two of the three components of Atripla). If Atripla 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 product, ask your doctor or pharmacist.

Like all medicines, Atripla can cause side effects, although not everybody gets them. When treating HIV infection, it is not always possible to tell whether some of the unwanted effects are caused by

Atripla or by other medicines that you are taking at the same time, or by the HIV disease itself. Tell your doctor if you notice any of the following side effects:

Very common side effects

(These can affect more than 1 user in 10)

• dizziness, headache, diarrhoea, feeling sick (nausea), 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

Common side effects

(These can affect 1 to 10 users in 100)

• changes in skin colour including darkening of the skin in patches often starting on hands and soles of feet
• pain, stomach pain
• difficulty sleeping, abnormal dreams, difficulty concentrating, drowsiness
• feeling worried or depressed
• problems with digestion resulting in discomfort after meals, feeling bloated, wind (flatulence)
• loss of appetite
• tiredness
• itching
• disturbances of coordination and balance
• allergic reactions

Tests may also show:

• low white blood cell count (a reduced white blood cell count can make you more prone to infection)
• increased fatty acids (triglycerides), bilirubin or sugar levels in the blood
• liver and pancreas problems

Uncommon side effects

(These can affect 1 to 10 users in 1,000)

• 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)
• forgetfulness, confusion, fitting (seizures), incoherent speech, tremor (shaking)
• blurred vision
• a feeling of spinning or tilting (vertigo), whistling, ringing or other persistent noise in the ears
• dry mouth
• allergic reaction (hypersensitivity) that may cause severe skin reactions (Stevens-Johnson syndrome, erythema multiforme, see section 2)
• flushing
• yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the liver
• pain in the abdomen (stomach), caused by inflammation of the pancreas
• increased appetite
• breast enlargement in males
• anaemia (low red blood cell count)
• decreased sexual drive
• chills
• breakdown of muscle, muscle pain or weakness
• swelling of the face, lips, tongue or throat

Tests may also show:

• decreases in potassium in the blood
• increases in creatinine in the blood
• proteins in urine

Rare side effects

(These can affect 1 to 10 users in 10,000)

• Lactic acidosis (excess lactic acid in the blood) is a serious side effect that can be life-threatening. The following side effects may be signs of lactic acidosis:
• deep rapid breathing
• tiredness
• feeling sick (nausea), vomiting and stomach pain. If you think you may have lactic acidosis, contact your doctor immediately.
• back pain caused by kidney problems, including kidney failure. Your doctor may do blood tests to see if your kidneys are working properly.
• fatty liver
• 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.
• itchy rash to the skin caused by a reaction to sunlight
• inflammation of the kidney, passing a lot of urine and feeling thirsty
• softening of the bones (with bone pain and sometimes resulting in fractures)

Tests may also show:

• damage to kidney tubule cells

Psychiatric side effectsin addition to those listed aboveinclude 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.

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.

Other possible effects

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).

Combination antiretroviral therapy (such as Atripla) may change your body shape, by changing the way body fat is distributed. You may lose fat from your legs, arms and face; gain fat around the abdomen (tummy) and internal organs; get larger breasts or fatty lumps on the back of the neck (?buffalo hump?). The cause and the long-term effects of these changes are not yet known.

Combination antiretroviral therapy may also cause increased fat levels in the blood (hyperlipaemia) and resistance to insulin. Your doctor will test for these changes.

If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

Keep out of the reach and sight of children.

Do not use Atripla after the expiry date which is stated on the bottle label and carton after {EXP}. The expiry date refers to the last day of that month.

Store in the original package in order to protect from moisture. Keep the bottle tightly closed.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

What Atripla contains

• The active substances are efavirenz, emtricitabine and tenofovir disoproxil. Each Atripla film-coated tablet contains 600 mg of efavirenz, 200 mg of emtricitabine and 245 mg of tenofovir disoproxil (as fumarate).
• The other ingredients in the tablet are croscarmellose sodium, hydroxypropylcellulose, magnesium stearate, microcrystalline cellulose, sodium laurilsulfate.
• The other ingredients in the tablet film coating are iron oxide black, iron oxide red, macrogol 3350, poly(vinyl alcohol), talc, titanium dioxide.

What Atripla looks like and contents of the pack

Atripla film-coated tablets are pink, capsule shaped tablets, engraved on one side with the number ?123? and plain on the other side. Atripla comes in bottles of 30 tablets (with a silica gel sachet that must be kept in the bottle to help protect your tablets). The silica gel desiccant is contained in a separate sachet and should not be swallowed.

The following pack sizes are available: outer cartons containing 1 x 30 film-coated tablet and 3 x 30 film-coated tablet bottles. Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder:
Bristol-Myers Squibb and Gilead Sciences Limited
IDA Business & Technology Park
Carrigtohill
Co. Cork
Ireland

Manufacturer:
Gilead Sciences Limited
Unit 13, Stillorgan Industrial Park
Blackrock
Co. Dublin
Ireland

or

Gilead Sciences Limited
IDA Business & Technology Park
Carrigtohill
Co. Cork
Ireland

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

BelgiëBelgiqueBelgien Gilead Sciences Belgium BVBA TélTel 32 0 24 01 35 79 LuxembourgLuxemburg Gilead Sciences Belgium BVBA TélTel 32 0 24 01 35 79

Bristol-Myers Squibb Gyógyszerkereskedelmi Kft. . 359 800 12 400 Magyarország Bristol-Myers Squibb Gyógyszerkereskedelmi Kft. Tel. 36 1 301 9700

eská republika Bristol-Myers Squibb spol. s r.o. Tel 420 221 016 111 Malta Gilead Sciences International Ltd Tel 44 0 20 7136 8820

Danmark Gilead Sciences Sweden AB Tlf 46 0 8 5057 1849 Nederland Gilead Sciences Netherlands B.V. Tel 31 0 20 718 3698

Deutschland Gilead Sciences GmbH Tel 49 0 89 899890-0 Norge Gilead Sciences Sweden AB Tlf 46 0 8 5057 1849

Österreich Gilead Sciences GesmbH Tel 43 1 260 830 Eesti Bristol-Myers Squibb Gyógyszerkereskedelmi Kft. Tel 372 640 1301

Gilead Sciences .. 30 210 8930 100 Polska Bristol-Myers Squibb Polska Sp. z o.o. Tel. 48 22 5796666

España Gilead Sciences, S.L. Tel 34 91 378 98 30 Portugal Gilead Sciences, Lda. Tel 351 21 7928790

France Gilead Sciences Tél 33 0 1 42 73 70 70 România Bristol-Myers Squibb Gyógyszerkereskedelmi Kft. Tel 40 0 21 272 16 00

Ireland Gilead Sciences Ltd Tel 44 0 1223 897555 Slovenija Bristol-Myers Squibb spol. s r.o. Tel 386 1 236 47 00

Ísland Gilead Sciences Sweden AB Sími 46 0 8 5057 1849 Slovenská republika Bristol-Myers Squibb spol. s r.o. Tel 421 2 59298411

Italia Gilead Sciences S.r.l. Tel 39 02 439201 SuomiFinland Gilead Sciences Sweden AB PuhTel 46 0 8 5057 1849

Gilead Sciences .. 30 210 8930 100 Sverige Gilead Sciences Sweden AB Tel 46 0 8 5057 1849

United Kingdom Gilead Sciences Ltd Tel 44 0 1223 897555 Latvija Bristol-Myers Squibb Gyógyszerkereskedelmi Kft. Tel 371 67 50 21 85

Lietuva
Bristol-Myers Squibb Gyógyszerkereskedelmi
Kft.
Tel: + 370 5 2790 762

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