SUSTIVA 50 mg hard capsules

SUSTIVA belongs to a class of antiretroviral medicines called non-nucleoside reverse transcriptase inhibitors (NNRTIs). It is an antiretroviral medicine that fights human immunodeficiency virus (HIV) infection by reducing the amount of the virus in blood.

Your doctor has prescribed SUSTIVA for you because you have HIV infection. SUSTIVA taken in combination with other antiretroviral medicines reduces the amount of the virus in the blood.

Do not take SUSTIVA

-- if you are allergic (hypersensitive) to efavirenz or any of the other ingredients of SUSTIVA listed at the end of this leaflet. Contact your doctor or pharmacist for advice.

--- if you have severe liver disease.

if you are currently taking any of the following medicines astemizole or terfenadine used to treat allergy symptoms bepridil used to treat heart disease cisapride used to treat heartburn ergot alkaloids for example, ergotamine, dihydroergotamine, ergonovine, and methylergonovine used to treat migraine and cluster headaches midazolam or triazolam used to help you sleep pimozide used to treat certain mental conditions St. Johns wort Hypericum perforatum a herbal remedy used for depression and anxiety

If you are taking any of these medicines, tell your doctor immediately. Taking these medicines with SUSTIVA could create the potential for serious and/or life-threatening side-effects or stop SUSTIVA from working properly.

Take special care with SUSTIVA

SUSTIVA must be taken with other medicines that act against the HIV virus. If SUSTIVA is started because your current treatment has not prevented the virus from multiplying, another medicine you have not taken before must be started at the same time.

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 and you may continue to develop infections or other illnesses associated with HIV disease.

You must remain under the care of your doctor while taking SUSTIVA. Tell your doctor

• 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 SUSTIVA. Your doctor may give you a different anticonvulsant.
• if you have a history of liver disease, including active chronic hepatitis. Patients with chronic hepatitis B or C and treated with combination antiretroviral agents have a higher risk for 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 SUSTIVA (see section 2, Do not take SUSTIVA).

Once you start taking SUSTIVA, 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. If you see any signs of a severe rash with blistering or fever, stop taking SUSTIVA and tell your doctor at once. If you had a rash while taking another NNRTI, you may be at a higher risk of getting a rash with SUSTIVA.
• 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 an 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 immediately.
• changes in body fat. Redistribution, accumulation or loss of body fat may occur in patients receiving combination antiretroviral therapy. Tell your doctor if you notice changes in your body fat.
• 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.

Use in children
SUSTIVA 50 mg hard capsules can be taken by children and adolescents 3 years of age and older and weighing at least 13 kg who are able to swallow the capsules. Opening the capsule and taking the contents with a small amount of food may be considered for children who cannot swallow the hard capsule and cannot tolerate the oral solution (see How to take SUSTIVA).

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

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription and herbal remedies.

SUSTIVA may interact with other medicines. As a result, the amounts of SUSTIVA or other medicines in your blood may be affected. This may stop the 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:

Other medicines used for HIV infection protease inhibitors darunavir, indinavir, lopinavirritonavir, ritonavir, ritonavir boosted atazanavir, saquinavir or fosamprenavirsaquinavir. Your doctor may consider giving you an alternative medicine or changing the dose of the protease inhibitors. maraviroc a combination medicine containing efavirenz, emtricitabine and tenofovir, which is currently known as ATRIPLA. SUSTIVA should not be taken with ATRIPLA since it contains efavirenz, the active ingredient of SUSTIVA.

Medicines used to treat bacterial infections, including tuberculosis and AIDS-related mycobacterium avium complex clarithromycin, rifabutin, rifampicin. Your doctor may consider changing your dose or giving you an alternative antibiotic. In addition, your doctor may prescribe a higher dose of SUSTIVA.

Medicines used to treat fungal infections antifungals voriconazole. SUSTIVA may reduce the amount of voriconazole in your blood and voriconazole may increase the amount of SUSTIVA in your blood. If you take these two medicines together, the dose of voriconazole must be increased and the dose of efavirenz must be reduced. You must check with your doctor first. itraconazole. SUSTIVA may reduce the amount of itraconazole in your blood. posaconazole. SUSTIVA may reduce the amount of posaconazole in your blood.

Medicines used to treat convulsionsseizures anticonvulsants carbamazepine, phenytoin, phenobarbital. SUSTIVA can reduce or increase the amount of anticonvulsant in your blood. Carbamazepine may make SUSTIVA less likely to work. Your doctor may need to consider giving you a different anticonvulsant.

Medicines used to lower blood fats also called statins atorvastatin, pravastatin, simvastatin. SUSTIVA 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.

--- Methadone (a medicine used to treat opiate addiction): your doctor may need to change your dose of methadone.

Sertraline a medicine used to treat depression your doctor may need to change your dose of sertraline.

--- Diltiazem or similar medicines (called calcium channel blockers): when you start taking SUSTIVA, your doctor may need to adjust your dose of the calcium channel blocker.

Immunosuppressants such as cyclosporine, sirolimus, or tacrolimus medicines used to prevent organ transplant rejection when you start or stop taking SUSTIVA, your doctor will closely monitor your plasma levels of the immunosuppressant and may need to adjust its dose.

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. SUSTIVA may make hormonal contraceptives less likely to work. Pregnancies have occurred in women taking SUSTIVA while using a contraceptive implant, although it has not been established that the SUSTIVA therapy caused the contraceptive to fail.

Warfarin a medicine used to reduce clotting of the blood your doctor may need to adjust your dose of warfarin.

Taking SUSTIVA with food and drink

Taking SUSTIVA on an empty stomach may reduce the undesirable effects.

Pregnancy and breast-feeding
Women should not get pregnant during treatment with SUSTIVA, 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 SUSTIVA.

If you could get pregnant while receiving SUSTIVA, 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 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 SUSTIVA.

Tell your doctor immediately if you are pregnant or intend to become pregnant. If you are pregnant, you should take SUSTIVA only if you and your doctor decide it is clearly needed. Ask your doctor or pharmacist for advice before taking any medicine.

Serious birth defects have been seen in unborn animals and in the babies of women treated with efavirenz during pregnancy. If you have taken SUSTIVA during your pregnancy, your doctor may request regular blood tests and other diagnostic tests to monitor the development of your child.

You should not breast feed your baby if you are taking SUSTIVA.

Driving and using machines
SUSTIVA 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 SUSTIVA

This medicinal product contains 342 mg of lactose in each 600-mg daily dose.

If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product. Individuals with these conditions may take SUSTIVA oral solution, which is free from lactose.

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

SUSTIVA is for oral use. SUSTIVA is recommended to be taken on an empty stomach preferably at bedtime. This may make some side effects for example, dizziness, drowsiness less troublesome. An empty stomach is commonly defined as 1 hour before or 2 hours after a meal. The dose for adults is 600 mg once daily. The dose for SUSTIVA may need to be increased or decreased if you are also taking certain medicines see Taking other medicines.

Your doctor will give you instructions for proper dosing.

SUSTIVA must be taken every day. SUSTIVA should never be used alone to treat HIV. SUSTIVA must always be taken in combination with other anti-HIV medicines.

Use in children

--The dose for children weighing 40 kg or more is 600 mg once daily.
--The dose for children weighing less than 40 kg is calculated by body weight and is taken once daily as shown below:

Body Weight kg 13 to 15 SUSTIVA Dose mg 200 15 to 20 250 20 to 25 300 25 to 32.5 350 32.5 to 40 400

SUSTIVA oral solution is preferred for children who are not able to swallow the capsules. However, if a child does not tolerate the oral solution, the doctor may recommend opening the hard capsule and mixing the contents with a small amount (1-2 teaspoons) of food (e.g., applesauce, grape jelly, yogurt or infant formula). In a taste preference study, efavirenz mixed with grape jelly received the highest rating. The capsules must be opened carefully so that the contents do not spill or escape into the air. Hold the capsule vertically with the cap facing up and pull the cap away from the body of the capsule. Use a small container for mixing. Give the mixture to the child as soon as possible, but no more than 30 minutes after mixing. Make sure the child eats the full amount of the mixture of food and capsule contents. Add another small amount (approximately 2 teaspoons) of the food to the empty mixing container, stirring to make sure there is no drug residue remaining in the container, and have the child eat the full amount again. The child should not be given any additional food for 2 hours. The doctor may also recommend this method of taking SUSTIVA for adults who cannot swallow capsules and do not tolerate the oral solution.

If you take more SUSTIVA than you should

If you take too much SUSTIVA contact your doctor or nearest emergency department for advice. Keep the medicine container with you so that you can easily describe what you have taken.

If you forget to take SUSTIVA

Try not to miss a dose. If you do miss a dose, take the next dose as soon as possible, but do not take a double dose to make up for a forgotten dose. If you need help in planning the best times to take your medicine, ask your doctor or pharmacist.

If you stop taking SUSTIVA
When your SUSTIVA supply 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 any further questions on the use of this product, ask your doctor or pharmacist.

Like all medicines, SUSTIVA 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 SUSTIVA or by other medicines that you are taking at the same time, or by the HIV disease itself.

The most notable unwanted effects reported with SUSTIVA in combination with other anti-HIV medicines are skin rash and nervous system symptoms.

You should consult your doctor if you have a rash, since some rashes may be serious; however, most cases of rash disappear without any change to your treatment with SUSTIVA. Rash was more common in children than in adults treated with SUSTIVA.

The nervous system symptoms tend to occur when treatment is first started, but generally decrease in the first few weeks. In one study, nervous system symptoms often occurred during the first 1-3 hours after taking a dose. If you are affected your doctor may suggest that you take SUSTIVA at bedtime and on an empty stomach. Some patients have more serious symptoms that may affect mood or the ability to think clearly. Some patients have actually 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 or any side effects while taking SUSTIVA.

The frequency of the side effects listed below is defined using the following conventions:

affects more than 1 user in 10 affects 1 to 10 users in 100 Very common Common Uncommon Rare affects 1 to 10 users in 1,000 affects 1 to 10 users in 10,000

Tell your doctor if you notice any of the following side effects:

Very common side effects

• skin rash

Common side effects

• abnormal dreams, difficulty concentrating, dizziness, headache, difficulty sleeping, drowsiness, problems with coordination or balance
• stomach pain, diarrhoea, feeling sick (nausea), vomiting
• itching
• tiredness
• feeling worried, feeling depressed

Uncommon side effects

• nervousness, forgetfulness confusion, fitting (seizures), abnormal thoughts
• blurred vision
• a feeling of spinning or tilting (vertigo)
• pain in the abdomen (stomach) caused by inflammation of the pancreas
• allergic reaction (hypersensitivity) that may cause severe skin reactions (erythema multiforme, Stevens-Johnson syndrome)
• yellow skin or eyes, itching, or pain in the abdomen (stomach) caused by inflammation of the liver
• breast enlargement in males
• angry behaviour, mood being affected, seeing or hearing things that are not really there (hallucinations), mania (mental condition characterised by episodes of overactivity, elation or irritability), paranoia, suicidal thoughts
• whistling, ringing or other persistent noise in the ears
• tremor (shaking)
• flushing

Rare

• itchy rash caused by a reaction to sunlight
• Liver failure, in some cases leading to death or liver transplant, has occurred with efavirenz. Most cases occurred in patients who already had liver disease, but there have been a few reports in patients without any existing liver disease.

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

Combination antiretroviral therapy may also cause raised lactic acid and sugar in the blood, 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 SUSTIVA after the expiry date which is stated on the bottle and on the carton after EXP. The expiry date refers to the last day of that month.

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 SUSTIVA contains

Each SUSTIVA hard capsule contains 50 mg of the active substance efavirenz. The other ingredients of the powder contained in the hard capsule are sodium laurilsulfate, lactose monohydrate, magnesium stearate and sodium starch glycolate. The capsule shell contains gelatine, sodium laurilsulfate, yellow iron oxide E172, titanium dioxide E171 and silicon dioxide. The capsules are printed with inks containing cochineal carminic acid E120, indigo carmine E132, and titanium dioxide E171.

What SUSTIVA looks like and contents of the pack

SUSTIVA 50 mg hard capsules are supplied in bottles of 30 capsules.

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder
Bristol-Myers Squibb Pharma EEIG
Uxbridge Business Park, Sanderson Road
Uxbridge UB8 1DH
United Kingdom

Manufacturer
Bristol-Myers Squibb
Champ "Lachaud", La Goualle
F- 19250 Meymac
France

Bristol-Myers Squibb S.r.l.
Contrada Fontana del Ceraso
03012 Anagni (FR)
Italy

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

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