Arava 20 mg film-coated tablets

Arava belongs to a group of medicines called anti-rheumatic medicines.

Arava is used to treat adult patients with active rheumatoid arthritis or with active psoriatic arthritis.

Symptoms of rheumatoid arthritis include inflammation of joints, swelling, difficulty moving and pain. Other symptoms that affect the entire body include loss of appetite, fever, loss of energy and anaemia (lack of red blood cells).

Symptoms of active psoriatic arthritis include inflammation of joints, swelling, difficulty moving, pain and patches of red, scaly skin (skin lesions).

Do not take Arava

• if you have ever had an allergic reaction to leflunomide (especially a serious skin reaction, often accompanied by fever, joint pain, red skin stains, or blisters e.g. Stevens-Johnson syndrome) or to any of the other ingredients of Arava,
• if you have any liver problems,
• if you have moderate to severe kidney problems,
• if you have severely low numbers of proteins in your blood (hypoproteinaemia),
• if you suffer from any problem which affects your immune system (e.g. AIDS),
• if you have any problem with your bone marrow, or if you have low numbers of red or white cells in your blood or a reduced number of blood platelets,
• if you are suffering from a serious infection,
• if you are pregnant, think you may be pregnant, or are breast-feeding.

Take special care with Arava

• if you have ever suffered from tuberculosis or interstitial lung disease (lung disease),
• if you are male and wish to father a child. As it can not be excluded that Arava passes into semen, reliable contraception should be used during treatment with Arava. Men wishing to father a child should contact their doctor who may advise them to stop taking Arava and take certain medicines to remove Arava rapidly and sufficiently from their body. You will then need a blood test to make sure that Arava has been sufficiently removed from your body, and you should then wait for at least another 3 months before attempting to father a child.

Arava can occasionally cause some problems with your blood, liver or lungs. It may also cause some serious allergic reactions, or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

Your doctor will carry out blood tests at regular intervals, before and during treatment with Arava, to monitor your blood cells and liver. Your doctor will also check your blood pressure regularly as Arava can cause an increase in blood pressure.

Arava is not recommended for use in children and adolescents below 18 years of age.

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

This is especially important if you are taking:
? other medicines for rheumatoid arthritis such as antimalarials (e.g. chloroquine and hydroxychloroquine), intramuscular or oral gold, D-penicillamine, azathioprine and other immunosuppressive drugs (e.g. methotrexate) as these combinations are not advisable,

a medicine called colestyramine used to reduce high cholesterol or activated charcoal as these medicines can reduce the amount of Arava which is absorbed by the body,

phenytoin used to treat epilepsy, warfarin or phenprocoumon used to thin the blood or tolbutamide used to treat type 2 diabetes as these medicines may increase the risk of side effects.

If you are already taking a nonsteroidal anti-inflammatory drug (NSAID) and/or corticosteroids, you may continue to take them after starting Arava.

Vaccinations
If you have to be vaccinated, ask your doctor for advice. Certain vaccinations should not be given while taking Arava, and for a certain amount of time after stopping treatment.

Taking Arava with food and drink

Arava may be taken with or without food.
It is not recommended to drink alcohol during treatment with Arava. Drinking alcohol while taking Arava may increase the chance of liver damage.

Pregnancy and breast -feedingDo not take Arava if you are, or think you may be pregnant. If you are pregnant or become pregnant while taking Arava, the risk of having a baby with serious birth defects is increased. Women of childbearing potential must not take Arava without using reliable contraceptive measures.

Tell your doctor if you plan to become pregnant after stopping treatment with Arava, as you need to ensure that all traces of Arava have left your body before trying to become pregnant. This may take up to 2 years. This may be reduced to a few weeks by taking certain medicines which speed up removal of Arava from your body.
In either case it should be confirmed by a blood test that Arava has been sufficiently removed from your body and you should then wait for at least another month before you become pregnant.

For further information on the laboratory testing please contact your doctor.

If you suspect that you are pregnant while taking Arava or in the two years after you have stopped treatment, you must contact your doctor immediately for a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest treatment with certain medicines to remove Arava rapidly and sufficiently from your body, as this may decrease the risk to your baby.

Do not take Arava when you are breast feeding, as leflunomide passes into the breast milk.

Driving and using machines
Arava can make you feel dizzy which may impair your ability to concentrate and react. If you are affected, do not drive, or use machines.

Important information about some of the ingredients of Arava

Arava contains lactose. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

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

The usual starting dosage of Arava is one 100 mg tablet once daily for the first three days. After this, most patients need a dose of:
- For rheumatoid arthritis: 10 or 20 mg Arava once daily, depending on the severity of the disease.
- For psoriatic arthritis: 20 mg Arava once daily.

Swallow the tablet whole and with plenty of water.

It may take about 4 weeks or longer until you start to feel an improvement in your condition. Some patients may even still feel further improvements after 4 to 6 months of therapy.
You will normally take Arava over long periods of time.

If you take more Arava than you should
If you take more Arava than you should, contact your doctor or get other medical advice. If possible, take your tablets or the box with you to show the doctor.

If you forget to take Arava
If you forget to take a dose, take it as soon as you remember, unless it is nearly time for your next dose. Do not take a double dose to make up for a forgotten dose.

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

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

Tell your doctor immediately and stop taking Arava:

• if you experience weakness, feel light-headed or dizzy or have difficulty breathing, as these may be signs of a serious allergic reaction,
• if you develop a skin rash or ulcers in your mouth, as these may indicate severe, sometimes life-threatening reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Tell your doctor immediately if you experience:

• pale skin, tiredness, or bruising, as these may indicate blood disorders caused by an imbalance in the different types of blood cells which make up blood,
• tiredness, abdominal pain, or jaundice (yellow discolouration of the eyes or skin), as these may indicate serious conditions such as liver failure, which may be fatal,
• any symptoms of an infection such as fever, sore throat or cough, as Arava may increase the chance of a severe infection which may be life-threatening,
• a cough or breathing problems as these may indicate inflammation of the lung (interstitial lung disease).

Common side effects (affects 1 to 10 users in 100)

• a slight decrease in the number of white blood cells (leucopenia),
• mild allergic reactions,
• loss of appetite, weight loss (usually insignificant),
• tiredness (asthenia),
• headache, dizziness,
• abnormal skin sensations like tingling (paraesthesia),
• mild increase in blood pressure,
• diarrhoea,
• nausea, vomiting,
• inflammation of the mouth or mouth ulcers,
• abdominal pain,
• an increase in some liver test results,
• increased hair loss,
• eczema, dry skin, rash, itching,
• tendonitis (pain caused by inflammation in the membrane surrounding the tendons usually in the feet or hands),
• an increase of certain enzymes in the blood (creatine phosphokinase).

Uncommon side effects (affects 1 to 10 users in 1,000)

• a decrease in the number of red blood cells (anaemia) and a decrease in the number of blood platelets (thrombocytopenia),
• a decrease in the levels of potassium in the blood,
• anxiety,
• taste disturbances,
• urticaria (nettle rash),
• tendon rupture,
• an increase in the levels of fat in the blood (cholesterol and triglycerides),
• a decrease in the levels of phosphate in the blood.

Rare side effects (affects 1 to 10 users in 10,000)

• an increase in the numbers of blood cells called eosinophiles (eosinophilia); mild decrease in the number of white blood cells (leucopenia); decrease in the number of all blood cells (pancytopenia),
• severe increase in blood pressure,
• inflammation of the lung (interstitial lung disease),
• an increase in some liver results which may develop into serious conditions such as hepatitis and jaundice,
• severe infections called sepsis which may be fatal,
• an increase of certain enzymes in the blood (lactate dehydrogenase).

Very rare side effects (affects less than 1 user in 10,000)

• a marked decrease of some white blood cells (agranulocytosis),
• severe and potentially severe allergic reactions,
• inflammation of the small vessels (vasculitis, including cutaneous necrotizing vasculitis),
• problems in the nerves of the arms or legs (peripheral neuropathy),
• inflammation of the pancreas (pancreatitis),
• sever liver injury such as liver failure or necrosis which may be fatal,
• severe sometimes life-threatening reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other side effects such as kidney failure, a decrease in the levels of uric acid in your blood, and male infertility (which is reversible once treatment with Arava is stopped) may also occur with an unknown frequency.

If any of the side effects gets 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 Arava after the expiry date which is stated on the packaging.
The expiry date refers to the last day of that month.

Blister Store in the original package.

Bottle Keep the container 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 Arava contains

• The active substance is leflunomide. One film-coated tablet contains 20 mg of leflunomide
• The other ingredients are: maize starch, povidone (E1201), crospovidone (E1202), silica colloidal anhydrous, magnesium stearate (E470b), and lactose monohydrate in the tablet core, as well as talc (E553b), hypromellose (E464), titanium dioxide (E171), macrogol 8000 and yellow ferric oxide (E172) in the film-coating.

What Arava looks like and contents of the pack

Arava 20 mg film-coated tablets are yellowish to ochre and triangular.
Imprint on one side: ZBO.

The tablets are packed in blisters or bottles.
Packs of 30, 50 and 100 tablets are available.

Not all pack size may be marketed.

Marketing Authorisation Holder

Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany

Manufacturer Sanofi Winthrop Industrie
56, Route de Choisy au Bac
F-60205 Compiegne Cedex
France

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

BelgiëBelgiqueBelgien sanofi-aventis Belgium TélTel 32 02 710 54 00 LuxembourgLuxemburg sanofi-aventis Belgium TélTel 32 02 710 54 00 BelgiqueBelgien

sanofi-aventis Bulgaria EOOD . 359 02 970 53 00 Magyarország sanofi-aventis zrt., Magyarország Tel. 36 1 505 0050

eská republika sanofi-aventis, s.r.o. Tel 420 233 086 111 Malta sanofi-aventis Malta Ltd. Tel 356 21493022

Danmark sanofi-aventis Denmark AS Tlf 45 45 16 70 00 Nederland sanofi-aventis Netherlands B.V. Tel 31 0182 557 755

Deutschland Sanofi-Aventis Deutschland GmbH Tel 49 0180 2 222010 Norge sanofi-aventis Norge AS Tlf 47 67 10 71 00

Eesti sanofi-aventis Estonia OÜ Tel 372 627 34 88 Österreich sanofi-aventis GmbH Tel 43 1 80 185 0

sanofi-aventis AEBE 30 210 900 16 00 Polska sanofi-aventis Sp. z o.o. Tel. 48 22 280 00 00

España sanofi-aventis, S.A. Tel 34 93 485 94 00 Portugal sanofi-aventis - Produtos Farmacêuticos, Lda Tel 351 21 35 89 400

România sanofi-aventis România S.R.L. Tel 40 0 21 317 31 36 France sanofi-aventis france Tél 0 800 222 555 Appel depuis létranger 33 1 57 63 23 23

Ireland sanofi-aventis Ireland Ltd. Tel 353 0 1 403 56 00 Slovenija sanofi-aventis d.o.o. Tel 386 1 560 48 00

Ísland Vistor hf. Sími 354 535 7000 Slovenská republika sanofi-aventis Pharma Slovakia s.r.o. Tel 421 2 33 100 100

Italia sanofi-aventis S.p.A. Tel 39 02 393 91 SuomiFinland sanofi-aventis Oy PuhTel 358 0 201 200 300

sanofi-aventis Cyprus Ltd. 357 22 871600 Sverige sanofi-aventis AB Tel 46 08 634 50 00

Latvija sanofi-aventis Latvia SIA Tel 371 67 33 24 51 United Kingdom sanofi-aventis Tel 44 0 1483 505 515

Lietuva

UAB sanofi-aventis Lietuva
Tel: +370 5 2755224

This leaflet was last approved in