leflunomide: package leaflet

Arava belongs to a group of medicines called anti-rheumatic medicines. It contains the active substance leflunomide.

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 this medicine (listed in section 6), or if you are allergic to teriflunomide (used to treat multiple sclerosis),
- 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.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Arava

• if you have ever suffered from inflammation of the lung (interstitial lung disease).
• if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
• 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.
• if you are due to have a specific blood test (calcium level). Falsely low levels of calcium can be detected.
• if you will have or have had recent major surgery, or if you still have an unhealed wound following surgery. ARAVA may impair wound healing.

Musculoskeletal disorders
There have been reports of inflammatory muscle disease and muscle breakdown (myositis and rhabdomyolysis), in patients taking Arava.

• Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking Arava: unexplained muscle pain, tenderness (soreness when the muscle is pressed) or muscle weakness.

Arava can occasionally cause some problems with your blood, liver, lungs, or nerves in your arms or legs. It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Haemophagocytic lymphohistiocytosis (HLH)
There have been reports of a rare but very serious immune system reaction, in patients taking ARAVA.
- Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking ARAVA: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

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.

Tell your doctor if you have unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.

Tell your doctor if you develop skin ulcer during treatment with Arava (see also section 4).

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

Other medicines and Arava
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes 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 medicines (e.g. methotrexate) as these combinations are not advisable,
• warfarin and other oral medicines used to thin the blood, as monitoring is necessary to reduce the risk of side effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence or in kidney disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, water pill)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• 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.

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.

Arava with food, drink and alcohol
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-feeding
Do 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.

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

The usual starting dose of Arava is 100 mg leflunomide 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, pharmacist or nurse.

Like all medicines, this medicine 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, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section 2.

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 this medicine may increase the chance of a severe infection which may be life-threatening,

• cough or breathing problems as these may indicate problems of the lung (interstitial lung disease or pulmonary hypertension or pulmonary nodule),
• unusual tingling, weakness or pain in your hands or feet as these may indicate problems with your nerves (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)
- 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,
- colitis,
- 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),
- problems in the nerves of the arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)
- 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 (may affect up to 1 in 1,000 people)
- 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 (may affect up to 1 in 10,000 people)
- a marked decrease of some white blood cells (agranulocytosis),
- severe and potentially severe allergic reactions,
- inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
- inflammation of the pancreas (pancreatitis),
- severe 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, pulmonary hypertension, male infertility (which is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light), psoriasis (new or worsening), DRESS and Skin ulcer (Round, open sore in the skin through which the underlying tissues can be seen), may also occur with an unknown frequency.

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.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging. The expiry date refers to the last day of that month.

Blister:
Store in the original package.

Bottle:
Keep the bottle tightly closed.

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.

What Arava contains
- The active substance is leflunomide. One film-coated tablet contains 10 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), and macrogol 8000 in the film- coating.

What Arava looks like and contents of the pack
Arava 10 mg film-coated tablets are white to almost white and round.
Imprint on one side: ZBN.

The tablets are packed in blisters or bottles.
Packs of 30 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
Opella Healthcare International SAS
56, Route de Choisy

60200 Compiègne
France

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

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
Sanofi s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
Sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel.: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 16 00

Österreich sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
Sanofi Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor ehf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 536389

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last revised in {MM/YYYY}

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.

Arava belongs to a group of medicines called anti-rheumatic medicines. It contains the active substance leflunomide.

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 this medicine (listed in section 6), or if you are allergic to teriflunomide (used to treat multiple sclerosis),
- 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.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Arava

• if you have ever suffered from inflammation of the lung (interstitial lung disease).
• if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
• 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.
• if you are due to have a specific blood test (calcium level). Falsely low levels of calcium can be detected.
• if you will have or have had recent major surgery, or if you still have an unhealed wound following surgery. ARAVA may impair wound healing.

Musculoskeletal disorders
There have been reports of inflammatory muscle disease and muscle breakdown (myositis and rhabdomyolysis), in patients taking Arava.

• Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking Arava: unexplained muscle pain, tenderness (soreness when the muscle is pressed) or muscle weakness.

Arava can occasionally cause some problems with your blood, liver, lungs, or nerves in your arms or legs. It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Haemophagocytic lymphohistiocytosis (HLH)
There have been reports of a rare but very serious immune system reaction, in patients taking ARAVA.
- Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking ARAVA: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

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.

Tell your doctor if you have unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.

Tell your doctor if you develop skin ulcer during treatment with Arava (see also section 4).

Children and adolescents

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

Other medicines and Arava
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes 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 medicines (e.g. methotrexate) as these combinations are not advisable,
• warfarin and other oral medicines used to thin the blood, as monitoring is necessary to reduce the risk of side effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence or in kidney disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, water pill)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• 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.

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.

Arava with food, drink and alcohol
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-feeding
Do 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.

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

The usual starting dose of Arava is 100 mg leflunomide 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, pharmacist or nurse.

Like all medicines, this medicine 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, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section 2.

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 this medicine may increase the chance of a severe infection which may be life-threatening,
• cough or breathing problems as these may indicate problems of the lung (interstitial lung disease or pulmonary hypertension or pulmonary nodule),
• unusual tingling, weakness or pain in your hands or feet as these may indicate problems with your nerves (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)
- 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,
- colitis,
- 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),
- problems in the nerves of the arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)
- 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 (may affect up to 1 in 1,000 people)
- 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 (may affect up to 1 in 10,000 people)

• a marked decrease of some white blood cells (agranulocytosis),
• severe and potentially severe allergic reactions,
• inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
• inflammation of the pancreas (pancreatitis),
• severe 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, pulmonary hypertension, male infertility (which is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light), psoriasis (new or worsening), DRESS and Skin ulcer (Round, open sore in the skin through which the underlying tissues can be seen), may also occur with an unknown frequency.

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.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the last day of that month.

Blister:
Store in the original package.

Bottle:
Keep the bottle tightly closed.

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.

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
Opella Healthcare International SAS
56, Route de Choisy
60200 Compiègne
France

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

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
Sanofi s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
Sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel.: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 16 00

Österreich sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
Sanofi Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500

România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor ehf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 536389

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last revised in {MM/YYYY}

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.

Arava belongs to a group of medicines called anti-rheumatic medicines. It contains the active substance leflunomide.

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 this medicine (listed in section 6), or if you are allergic to teriflunomide (used to treat multiple sclerosis),
- 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.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Arava

• if you have ever suffered from inflammation of the lung (interstitial lung disease).
• if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
• 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.
• if you are due to have a specific blood test (calcium level). Falsely low levels of calcium can be detected.
• if you will have or have had recent major surgery, or if you still have an unhealed wound following surgery. ARAVA may impair wound healing.

Musculoskeletal disorders
There have been reports of inflammatory muscle disease and muscle breakdown (myositis and rhabdomyolysis), in patients taking Arava.

• Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking Arava: unexplained muscle pain, tenderness (soreness when the muscle is pressed) or muscle weakness.

Arava can occasionally cause some problems with your blood, liver, lungs, or nerves in your arms or legs. It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Haemophagocytic lymphohistiocytosis (HLH)
There have been reports of a rare but very serious immune system reaction, in patients taking ARAVA.
- Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking ARAVA: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

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.

Tell your doctor if you have unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.

Tell your doctor if you develop skin ulcer during treatment with Arava (see also section 4).

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

Other medicines and Arava
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes 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 medicines (e.g. methotrexate) as these combinations are not advisable,
• warfarin and other oral medicines used to thin the blood, as monitoring is necessary to reduce the risk of side effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence or in kidney disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, water pill)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• 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.

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.

Arava with food, drink and alcohol
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-feeding
Do 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.

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

The usual starting dose of Arava is 100 mg leflunomide 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, pharmacist or nurse.

Like all medicines, this medicine 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, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section 2.

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 this medicine may increase the chance of a severe infection which may be life-threatening,

• cough or breathing problems as these may indicate problems of the lung (interstitial lung disease or pulmonary hypertension or pulmonary nodule),
• unusual tingling, weakness or pain in your hands or feet as these may indicate problems with your nerves (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)
- 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,
- colitis,
- 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),
- problems in the nerves of the arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)
- 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 (may affect up to 1 in 1,000 people)
- 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 (may affect up to 1 in 10,000 people)
- a marked decrease of some white blood cells (agranulocytosis),
- severe and potentially severe allergic reactions,
- inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
- inflammation of the pancreas (pancreatitis),
- severe 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, pulmonary hypertension, male infertility (which is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light), psoriasis (new or worsening), DRESS and Skin ulcer (Round, open sore in the skin through which the underlying tissues can be seen), may also occur with an unknown frequency.

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.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the last day of that month.

Store in the original package

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.

What Arava contains
- The active substance is leflunomide. One film-coated tablet contains 100 mg of leflunomide.
- The other ingredients are: maize starch, povidone (E1201), crospovidone (E1202), talc (E553b), silica colloidal anhydrous, magnesium stearate (E470b), and lactose monohydrate in the tablet core, as well as talc (E553b), hypromellose (E464), titanium dioxide (E171), and macrogol 8000 in the film-coating.

What Arava looks like and contents of the pack
Arava 100 mg film-coated tablets are white to almost white and round.
Imprint on one side: ZBP

The tablets are packed in blisters.
A pack of 3 tablets is available

Marketing Authorisation Holder
Sanofi-Aventis Deutschland GmbH
D-65926 Frankfurt am Main
Germany

Manufacturer
Opella Healthcare International SAS
56, Route de Choisy
60200 Compiègne
France

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

België/Belgique/Belgien
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00

Lietuva
Swixx Biopharma UAB
Tel: +370 5 236 91 40

България
Swixx Biopharma EOOD
Тел.: +359 (0)2 4942 480

Luxembourg/Luxemburg
Sanofi Belgium
Tél/Tel: +32 (0)2 710 54 00 (Belgique/Belgien)

Česká republika
Sanofi s.r.o.
Tel: +420 233 086 111

Magyarország
SANOFI-AVENTIS Zrt.
Tel.: +36 1 505 0050

Danmark
Sanofi A/S
Tlf: +45 45 16 70 00

Malta
Sanofi S.r.l.
Tel: +39 02 39394275

Deutschland
Sanofi-Aventis Deutschland GmbH
Tel.: 0800 52 52 010
Tel. aus dem Ausland: +49 69 305 21 131

Nederland
Sanofi B.V.
Tel: +31 20 245 4000

Eesti
Swixx Biopharma OÜ
Tel: +372 640 10 30

Norge sanofi-aventis Norge AS
Tlf: +47 67 10 71 00

Ελλάδα
Sanofi-Aventis Μονοπρόσωπη AEBE
Τηλ: +30 210 900 16 00

Österreich sanofi-aventis GmbH
Tel: +43 1 80 185 – 0

España sanofi-aventis, S.A.
Tel: +34 93 485 94 00

Polska
Sanofi Sp. z o.o.
Tel.: +48 22 280 00 00

France
Sanofi Winthrop Industrie
Tél: 0 800 222 555
Appel depuis l’étranger : +33 1 57 63 23 23

Portugal
Sanofi - Produtos Farmacêuticos, Lda
Tel: +351 21 35 89 400

Hrvatska
Swixx Biopharma d.o.o.
Tel: +385 1 2078 500
România
Sanofi Romania SRL
Tel: +40 (0) 21 317 31 36

Ireland sanofi-aventis Ireland Ltd. T/A SANOFI
Tel: +353 (0) 1 403 56 00

Slovenija
Swixx Biopharma d.o.o.
Tel: +386 1 235 51 00

Ísland
Vistor ehf.
Sími: +354 535 7000

Slovenská republika
Swixx Biopharma s.r.o.
Tel: +421 2 208 33 600

Italia
Sanofi S.r.l.
Tel: 800 536389

Suomi/Finland
Sanofi Oy
Puh/Tel: +358 (0) 201 200 300

Κύπρος
C.A. Papaellinas Ltd.
Τηλ: +357 22 741741

Sverige
Sanofi AB
Tel: +46 (0)8 634 50 00

Latvija
Swixx Biopharma SIA
Tel: +371 6 616 47 50

This leaflet was last revised in {MM/YYYY}

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
http://www.ema.europa.eu/.

Leflunomide Zentiva belongs to a group of medicines called anti-rheumatic medicines. It contains the active substance leflunomide.

Leflunomide Zentiva 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 Leflunomide Zentiva
- 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 this medicine (listed in section 6), or if you are allergic to teriflunomide (used to treat multiple sclerosis),
- 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.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Leflunomide Zentiva
- if you have ever suffered from inflammation of the lung (interstitial lung disease).
- if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
- if you are male and wish to father a child. As it can not be excluded that Leflunomide Zentiva passes into semen, reliable contraception should be used during treatment with Leflunomide Zentiva. Men wishing to father a child should contact their doctor who may advise them to stop taking Leflunomide Zentiva and take certain medicines to remove Leflunomide Zentiva rapidly and sufficiently from their body. You will then need a blood test to make sure that Leflunomide Zentiva has been sufficiently removed from your body, and you should then wait for at least another 3 months before attempting to father a child.
- if you are due to have a specific blood test (calcium level). Falsely low levels of calcium can be detected.
- if you will have or have had recent major surgery, or if you still have an unhealed wound following surgery. Leflunomide Zentiva may impair wound healing.

Leflunomide Zentiva can occasionally cause some problems with your blood, liver, lungs, or nerves in your arms or legs. It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Haemophagocytic lymphohistiocytosis (HLH)
There have been reports of a rare but very serious immune system reaction, in patients taking Leflunomide Zentiva.
- Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking Leflunomide Zentiva: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

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

Tell your doctor if you have unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.

Tell your doctor if you develop skin ulcer during treatment with Leflunomide Zentiva (see also section 4).

Children and adolescents
Leflunomide Zentiva is not recommended for use in children and adolescents below 18 years of age.

Other medicines and Leflunomide Zentiva
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes 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 medicines (e.g. methotrexate) as these combinations are not advisable,

• warfarin and other oral medicines used to thin the blood, as monitoring is necessary to reduce the risk of side effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence or in kidney disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, water pill)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• a medicine called colestyramine (used to reduce high cholesterol) or activated charcoal as these medicines can reduce the amount of Leflunomide Zentiva which is absorbed by the body.

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

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

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

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

Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomide Zentiva, as you need to ensure that all traces of Leflunomide Zentiva 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 Leflunomide Zentiva from your body.
In either case it should be confirmed by a blood test that Leflunomide Zentiva 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 Leflunomide Zentiva 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 Leflunomide Zentiva rapidly and sufficiently from your body, as this may decrease the risk to your baby.

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

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

Leflunomide Zentiva contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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 usual starting dose of Leflunomide Zentiva is 100 mg leflunomide once daily for the first three days. After this, most patients need a dose of:
- For rheumatoid arthritis: 10 or 20 mg Leflunomide Zentiva once daily, depending on the severity of the disease.
- For psoriatic arthritis: 20 mg Leflunomide Zentiva 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 Leflunomide Zentiva over long periods of time.

If you take more Leflunomide Zentiva than you should
If you take more Leflunomide Zentiva 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 Leflunomide Zentiva
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, pharmacist or nurse.

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

Tell your doctor immediately and stop taking Leflunomide Zentiva:
- 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, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section 2.

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 this medicine may increase the chance of a severe infection which may be life-threatening,

• cough or breathing problems as these may indicate problems of the lung (interstitial lung disease or pulmonary hypertension or pulmonary nodule),
• unusual tingling, weakness or pain in your hands or feet as these may indicate problems with your nerves (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)
- 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,
- colitis,
- 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),
- problems in the nerves of the arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)
- 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 (may affect up to 1 in 1,000 people)
- 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 (may affect up to 1 in 10,000 people)
- a marked decrease of some white blood cells (agranulocytosis),
- severe and potentially severe allergic reactions,
- inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
- inflammation of the pancreas (pancreatitis),
- severe 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, pulmonary hypertension, male infertility (which is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light), psoriasis (new or worsening), DRESS and skin ulcer (round, open sore in the skin through which the underlying tissues can be seen), may also occur with an unknown frequency.

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.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging. The expiry date refers to the last day of that month.

Blister:
Store in the original package.

Bottle:
Keep the bottle tightly closed.

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.

What Leflunomide Zentiva contains
- The active substance is leflunomide. One film-coated tablet contains 10 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), and macrogol 8000 in the film-coating.

What Leflunomide Zentiva looks like and contents of the pack
Leflunomide Zentiva 10 mg film-coated tablets are white to almost white and round.
Imprint on one side: ZBN.

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

Not all pack size may be marketed.

Marketing Authorisation Holder
Zentiva k.s.
U kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturer
LABORMED- PHARMA S.A.
B-dul. Theodor Pallady no. 44B, sector 3 code 032266, Bucharest,
Romania

ZENTIVA S.A.
B-dul Theodor Pallady no. 50, sector 3 code 032266, Bucharest,
Romania

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

België/Belgique/Belgien
Zentiva, k.s.
Tél/Tel: +32 (78) 700 112
PV-Belgium@zentiva.com

Lietuva
Zentiva, k.s.
Tel: +370 52152025
PV-Lithuania@zentiva.com
България
Zentiva, k.s.
Тел: +35924417136
PV-Bulgaria@zentiva.com

Luxembourg/Luxemburg
Zentiva, k.s.
Tél/Tel: +352 208 82330
PV-Luxembourg@zentiva.com
Česká republika
Zentiva, k.s.
Tel: +420 267 241 111
PV-Czech-Republic@zentiva.com

Magyarország
Zentiva Pharma Kft.
Tel.: +36 1 299 1058
PV-Hungary@zentiva.com
Danmark
Zentiva Denmark ApS
Tlf.: +45 787 68 400
PV-Denmark@zentiva.com

Malta
Zentiva, k.s.
Tel: +356 2034 1796
PV-Malta@zentiva.com
Deutschland
Zentiva Pharma GmbH
Tel: +49 (0) 800 53 53 010
PV-Germany@zentiva.com

Nederland
Zentiva, k.s.
Tel: +31 202 253 638
PV-Netherlands@zentiva.com
Eesti
Zentiva, k.s.
Tel: +372 530 107 59
PV-Estonia@zentiva.com

Norge
Zentiva Denmark ApS
Tlf: +45 787 68 400
PV-Norway@zentiva.com
Ελλάδα
Zentiva, k.s.
Τηλ: +30 211 198 7510
PV-Greece@zentiva.com

Österreich
Zentiva, k.s.
Tel: +43 720 778 877
PV-Austria@zentiva.com
España
Zentiva Spain S.L.U.
Tel: +34 671 365 828
PV-Spain@zentiva.com

Polska
Zentiva Polska Sp. z o.o.
Tel: + 48 22 375 92 00
PV-Poland@zentiva.com

France
Zentiva France
Tél: +33 (0) 800 089 219
PV-France@zentiva.com

Portugal
Zentiva Portugal, Lda
Tel: +351210601360
PV-Portugal@zentiva.com
Hrvatska
Zentiva d.o.o.
Tel: +385 1 6641 830
PV-Croatia@zentiva.com

Ireland
Zentiva, k.s.
Tel: +353 818 882 243
PV-Ireland@zentiva.com

România
ZENTIVA S.A.
Tel: +4 021.304.7597
PV-Romania@zentiva.com

Slovenija
Zentiva, k.s.
Tel: +386 360 00 408
PV-Slovenia@zentiva.com
Ísland
Zentiva Denmark ApS
Sími: +354 539 5025
PV-Iceland@zentiva.com

Slovenská republika
Zentiva, a.s.
Tel: +421 2 3918 3010
PV-Slovakia@zentiva.com
Italia
Zentiva Italia S.r.l.
Tel: +39 800081631
PV-Italy@zentiva.com
Suomi/Finland
Zentiva Denmark ApS
Puh/Tel: +358 942 598 648
PV-Finland@zentiva.com

Κύπρος
Zentiva, k.s.
Τηλ: +30 211 198 7510
PV-Cyprus@zentiva.com

Sverige
Zentiva Denmark ApS
Tel: +46 840 838 822
PV-Sweden@zentiva.com
Latvija
Zentiva, k.s.
Tel: +371 67893939
PV-Latvia@zentiva.com

This leaflet was last revised in {MM/YYYY}

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu/.

Leflunomide Zentiva belongs to a group of medicines called anti-rheumatic medicines. It contains the active substance leflunomide.

Leflunomide Zentiva 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 Leflunomide Zentiva
- 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 this medicine (listed in section 6), or if you are allergic to teriflunomide (used to treat multiple sclerosis),
- 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.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Leflunomide Zentiva
- if you have ever suffered from inflammation of the lung (interstitial lung disease).
- if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
- if you are male and wish to father a child. As it can not be excluded that Leflunomide Zentiva passes into semen, reliable contraception should be used during treatment with Leflunomide Zentiva. Men wishing to father a child should contact their doctor who may advise them to stop taking Leflunomide Zentiva and take certain medicines to remove Leflunomide Zentiva rapidly and sufficiently from their body. You will then need a blood test to make sure that Leflunomide Zentiva has been sufficiently removed from your body, and you should then wait for at least another 3 months before attempting to father a child.
- if you are due to have a specific blood test (calcium level). Falsely low levels of calcium can be detected.
- if you will have or have had recent major surgery, or if you still have an unhealed wound following surgery. Leflunomide Zentiva may impair wound healing.

Leflunomide Zentiva can occasionally cause some problems with your blood, liver, lungs, or nerves in your arms or legs. It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Haemophagocytic lymphohistiocytosis (HLH)
There have been reports of a rare but very serious immune system reaction, in patients taking Leflunomide Zentiva.
- Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking Leflunomide Zentiva: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

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

Tell your doctor if you have unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.

Tell your doctor if you develop skin ulcer during treatment with Leflunomide Zentiva (see also section 4).

Children and adolescents
Leflunomide Zentiva is not recommended for use in children and adolescents below 18 years of age.

Other medicines and Leflunomide Zentiva
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes 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 medicines (e.g. methotrexate) as these combinations are not advisable,

• warfarin and other oral medicines used to thin the blood, as monitoring is necessary to reduce the risk of side effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence or in kidney disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, water pill)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• a medicine called colestyramine (used to reduce high cholesterol) or activated charcoal as these medicines can reduce the amount of Leflunomide Zentiva which is absorbed by the body.

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

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

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

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

Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomide Zentiva, as you need to ensure that all traces of Leflunomide Zentiva 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 Leflunomide Zentiva from your body.
In either case it should be confirmed by a blood test that Leflunomide Zentiva 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 Leflunomide Zentiva 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 Leflunomide Zentiva rapidly and sufficiently from your body, as this may decrease the risk to your baby.

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

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

Leflunomide Zentiva contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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 usual starting dose of Leflunomide Zentiva is 100 mg leflunomide once daily for the first three days. After this, most patients need a dose of:
- For rheumatoid arthritis: 10 or 20 mg Leflunomide Zentiva once daily, depending on the severity of the disease.
- For psoriatic arthritis: 20 mg Leflunomide Zentiva 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 Leflunomide Zentiva over long periods of time.

If you take more Leflunomide Zentiva than you should
If you take more Leflunomide Zentiva 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 Leflunomide Zentiva
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, pharmacist or nurse.

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

Tell your doctor immediately and stop taking Leflunomide Zentiva:
- 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, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section 2.

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 this medicine may increase the chance of a severe infection which may be life-threatening,

• cough or breathing problems as these may indicate problems of the lung (interstitial lung disease or pulmonary hypertension or pulmonary nodule),
• unusual tingling, weakness or pain in your hands or feet as these may indicate problems with your nerves (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)
- 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,
- colitis,
- 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),
- problems in the nerves of the arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)
- 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 (may affect up to 1 in 1,000 people)
- 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 (may affect up to 1 in 10,000 people)
- a marked decrease of some white blood cells (agranulocytosis),
- severe and potentially severe allergic reactions,
- inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
- inflammation of the pancreas (pancreatitis),
- severe 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, pulmonary hypertension, male infertility (which is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light), psoriasis (new or worsening), DRESS and skin ulcer (round, open sore in the skin through which the underlying tissues can be seen), may also occur with an unknown frequency.

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.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the last day of that month.

Blister:
Store in the original package.

Bottle:
Keep the bottle tightly closed.

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.

What Leflunomide Zentiva 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 Leflunomide Zentiva looks like and contents of the pack
Leflunomide Zentiva 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
Zentiva k.s.
U kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturer
LABORMED- PHARMA S.A.
B-dul. Theodor Pallady no. 44B, sector 3 code 032266, Bucharest,
Romania

ZENTIVA S.A.
B-dul. Theodor Pallady no. 50, sector 3 code 032266, Bucharest,
Romania

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

België/Belgique/Belgien
Zentiva, k.s.
Tél/Tel: +32 (78) 700 112
PV-Belgium@zentiva.com

Lietuva
Zentiva, k.s.
Tel: +370 52152025
PV-Lithuania@zentiva.com
България
Zentiva, k.s.
Тел: +35924417136
PV-Bulgaria@zentiva.com

Luxembourg/Luxemburg
Zentiva, k.s.
Tél/Tel: +352 208 82330
PV-Luxembourg@zentiva.com
Česká republika
Zentiva, k.s.
Tel: +420 267 241 111
PV-Czech-Republic@zentiva.com

Magyarország
Zentiva Pharma Kft.
Tel.: +36 1 299 1058
PV-Hungary@zentiva.com
Danmark
Zentiva Denmark ApS
Tlf.: +45 787 68 400
PV-Denmark@zentiva.com

Malta
Zentiva, k.s.
Tel: +356 2034 1796
PV-Malta@zentiva.com
Deutschland
Zentiva Pharma GmbH
Tel: +49 (0) 800 53 53 010
PV-Germany@zentiva.com

Nederland
Zentiva, k.s.
Tel: +31 202 253 638
PV-Netherlands@zentiva.com
Eesti
Zentiva, k.s.
Tel: +372 530 107 59
PV-Estonia@zentiva.com

Norge
Zentiva Denmark ApS
Tlf: +45 787 68 400
PV-Norway@zentiva.com
Ελλάδα
Zentiva, k.s.
Τηλ: +30 211 198 7510
PV-Greece@zentiva.com

Österreich
Zentiva, k.s.
Tel: +43 720 778 877
PV-Austria@zentiva.com
España
Zentiva Spain S.L.U.
Tel: +34 671 365 828
PV-Spain@zentiva.com

Polska
Zentiva Polska Sp. z o.o.
Tel: + 48 22 375 92 00
PV-Poland@zentiva.com

France
Zentiva France
Tél: +33 (0) 800 089 219
PV-France@zentiva.com

Portugal
Zentiva Portugal, Lda
Tel: +351210601360
PV-Portugal@zentiva.com
Hrvatska
Zentiva d.o.o.
Tel: +385 1 6641 830
PV-Croatia@zentiva.com

Ireland
Zentiva, k.s.
Tel: +353 818 882 243
PV-Ireland@zentiva.com

România
ZENTIVA S.A.
Tel: +4 021.304.7597
PV-Romania@zentiva.com

Slovenija
Zentiva, k.s.
Tel: +386 360 00 408
PV-Slovenia@zentiva.com
Ísland
Zentiva Denmark ApS
Sími: +354 539 5025
PV-Iceland@zentiva.com

Slovenská republika
Zentiva, a.s.
Tel: +421 2 3918 3010
PV-Slovakia@zentiva.com
Italia
Zentiva Italia S.r.l.
Tel: +39 800081631
PV-Italy@zentiva.com
Suomi/Finland
Zentiva Denmark ApS
Puh/Tel: +358 942 598 648
PV-Finland@zentiva.com

Κύπρος
Zentiva, k.s.
Τηλ: +30 211 198 7510
PV-Cyprus@zentiva.com

Sverige
Zentiva Denmark ApS
Tel: +46 840 838 822
PV-Sweden@zentiva.com
Latvija
Zentiva, k.s.
Tel: +371 67893939
PV-Latvia@zentiva.com

This leaflet was last revised in {MM/YYYY}

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu/.

Leflunomide Zentiva belongs to a group of medicines called anti-rheumatic medicines. It contains the active substance leflunomide.

Leflunomide Zentiva 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 Leflunomide Zentiva
- 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 this medicine (listed in section 6), or if you are allergic to teriflunomide (used to treat multiple sclerosis),
- 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.

Warnings and precautions
Talk to your doctor, pharmacist or nurse before taking Leflunomide Zentiva
- if you have ever suffered from inflammation of the lung (interstitial lung disease).
- if you have ever had tuberculosis or if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
- if you are male and wish to father a child. As it can not be excluded that Leflunomide Zentiva passes into semen, reliable contraception should be used during treatment with Leflunomide Zentiva. Men wishing to father a child should contact their doctor who may advise them to stop taking Leflunomide Zentiva and take certain medicines to remove Leflunomide Zentiva rapidly and sufficiently from their body. You will then need a blood test to make sure that Leflunomide Zentiva has been sufficiently removed from your body, and you should then wait for at least another 3 months before attempting to father a child.
- if you are due to have a specific blood test (calcium level). Falsely low levels of calcium can be detected.
- if you will have or have had recent major surgery, or if you still have an unhealed wound following surgery. Leflunomide Zentiva may impair wound healing.

Leflunomide Zentiva can occasionally cause some problems with your blood, liver, lungs or nerves in your arms or legs. It may also cause some serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the chance of a severe infection. For more information on these, please read section 4 (Possible side effects).

DRESS appears initially as flu-like symptoms and a rash on the face then an extended rash with a high temperature, increased levels of liver enzymes seen in blood tests and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Haemophagocytic lymphohistiocytosis (HLH)
There have been reports of a rare but very serious immune system reaction, in patients taking Leflunomide Zentiva.
- Contact your doctor or pharmacist immediately if you experience any of the following symptoms while taking Leflunomide Zentiva: fever, rash, neurological symptoms (e.g. shaking or tremor, confusional state, disturbances of brain function).

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

Tell your doctor if you have unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.

Tell your doctor if you develop skin ulcer during treatment with Leflunomide Zentiva (see also section 4).

Children and adolescents
Leflunomide Zentiva is not recommended for use in children and adolescents below 18 years of age.

Other medicines and Leflunomide Zentiva
Please tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines. This includes 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 medicines (e.g. methotrexate) as these combinations are not advisable,

• warfarin and other oral medicines used to thin the blood, as monitoring is necessary to reduce the risk of side effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence or in kidney disease in diabetics
• alosetron for the management of severe diarrhoea
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indomethacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, water pill)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
• a medicine called colestyramine (used to reduce high cholesterol) or activated charcoal as these medicines can reduce the amount of Leflunomide Zentiva which is absorbed by the body.

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

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

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

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

Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomide Zentiva, as you need to ensure that all traces of Leflunomide Zentiva 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 Leflunomide Zentiva from your body.
In either case it should be confirmed by a blood test that Leflunomide Zentiva 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 Leflunomide Zentiva 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 Leflunomide Zentiva rapidly and sufficiently from your body, as this may decrease the risk to your baby.

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

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

Leflunomide Zentiva contains lactose
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product.

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 usual starting dose of Leflunomide Zentiva is 100 mg leflunomide once daily for the first three days. After this, most patients need a dose of:
- For rheumatoid arthritis: 10 or 20 mg Leflunomide Zentiva once daily, depending on the severity of the disease.
- For psoriatic arthritis: 20 mg Leflunomide Zentiva 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 Leflunomide Zentiva over long periods of time.

If you take more Leflunomide Zentiva than you should
If you take more Leflunomide Zentiva 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 Leflunomide Zentiva
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, pharmacist or nurse.

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

Tell your doctor immediately and stop taking Leflunomide Zentiva:
- 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, Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), see section 2.

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 this medicine may increase the chance of a severe infection which may be life-threatening,

• cough or breathing problems as these may indicate problems of the lung (interstitial lung disease or pulmonary hypertension or pulmonary nodule),
• unusual tingling, weakness or pain in your hands or feet as these may indicate problems with your nerves (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)
- 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,
- colitis,
- 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),
- problems in the nerves of the arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)
- 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 (may affect up to 1 in 1,000 people)
- 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 (may affect up to 1 in 10,000 people)
- a marked decrease of some white blood cells (agranulocytosis),
- severe and potentially severe allergic reactions,
- inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
- inflammation of the pancreas (pancreatitis),
- severe 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, pulmonary hypertension, male infertility (which is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema on skin areas that are exposed to light), psoriasis (new or worsening), DRESS and skin ulcer (round, open sore in the skin through which the underlying tissues can be seen), may also occur with an unknown frequency.

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.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the packaging.
The expiry date refers to the last day of that month.

Store in the original package.

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.

What Leflunomide Zentiva contains
- The active substance is leflunomide. One film-coated tablet contains 100 mg of leflunomide.
- The other ingredients are: maize starch, povidone (E1201), crospovidone (E1202), talc (E553b), silica colloidal anhydrous, magnesium stearate (E470b), and lactose monohydrate in the tablet core, as well as talc (E553b), hypromellose (E464), titanium dioxide (E171), and macrogol 8000 in the film-coating.

What Leflunomide Zentiva looks like and contents of the pack
Leflunomide Zentiva 100 mg film-coated tablets are white to almost white and round.
Imprint on one side: ZBP

The tablets are packed in blisters.
A pack of 3 tablets is available

Marketing Authorisation Holder
Zentiva k.s.
U kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturer
Opella Healthcare International SAS
56, Route de Choisy
60200 Compiègne
France

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

België/Belgique/Belgien
Zentiva, k.s.
Tél/Tel: +32 (78) 700 112
PV-Belgium@zentiva.com

Lietuva
Zentiva, k.s.
Tel: +370 52152025
PV-Lithuania@zentiva.com
България
Zentiva, k.s.
Тел: +35924417136
PV-Bulgaria@zentiva.com

Luxembourg/Luxemburg
Zentiva, k.s.
Tél/Tel: +352 208 82330
PV-Luxembourg@zentiva.com
Česká republika
Zentiva, k.s.
Tel: +420 267 241 111
PV-Czech-Republic@zentiva.com

Magyarország
Zentiva Pharma Kft.
Tel.: +36 1 299 1058
PV-Hungary@zentiva.com
Danmark
Zentiva Denmark ApS
Tlf.: +45 787 68 400
PV-Denmark@zentiva.com

Malta
Zentiva, k.s.
Tel: +356 2034 1796
PV-Malta@zentiva.com
Deutschland
Zentiva Pharma GmbH
Tel: +49 (0) 800 53 53 010
PV-Germany@zentiva.com

Nederland
Zentiva, k.s.
Tel: +31 202 253 638
PV-Netherlands@zentiva.com
Eesti
Zentiva, k.s.
Tel: +372 530 107 59
PV-Estonia@zentiva.com

Norge
Zentiva Denmark ApS
Tlf: +45 787 68 400
PV-Norway@zentiva.com
Ελλάδα
Zentiva, k.s.
Τηλ: +30 211 198 7510
PV-Greece@zentiva.com

Österreich
Zentiva, k.s.
Tel: +43 720 778 877
PV-Austria@zentiva.com
España
Zentiva Spain S.L.U.
Tel: +34 671 365 828
PV-Spain@zentiva.com

Polska
Zentiva Polska Sp. z o.o.
Tel: + 48 22 375 92 00
PV-Poland@zentiva.com
France
Zentiva France
Tél: +33 (0) 800 089 219
PV-France@zentiva.com

Portugal
Zentiva Portugal, Lda
Tel: +351210601360
PV-Portugal@zentiva.com

Hrvatska
Zentiva d.o.o.
Tel: +385 1 6641 830
PV-Croatia@zentiva.com

Ireland
Zentiva, k.s.
Tel: +353 818 882 243
PV-Ireland@zentiva.com

România
ZENTIVA S.A.
Tel: +4 021.304.7597
PV-Romania@zentiva.com

Slovenija
Zentiva, k.s.
Tel: +386 360 00 408
PV-Slovenia@zentiva.com
Ísland
Zentiva Denmark ApS
Sími: +354 539 5025
PV-Iceland@zentiva.com

Slovenská republika
Zentiva, a.s.
Tel: +421 2 3918 3010
PV-Slovakia@zentiva.com
Italia
Zentiva Italia S.r.l.
Tel: +39 800081631
PV-Italy@zentiva.com
Suomi/Finland
Zentiva Denmark ApS
Puh/Tel: +358 942 598 648
PV-Finland@zentiva.com

Κύπρος
Zentiva, k.s.
Τηλ: +30 211 198 7510
PV-Cyprus@zentiva.com

Sverige
Zentiva Denmark ApS
Tel: +46 840 838 822
PV-Sweden@zentiva.com
Latvija
Zentiva, k.s.
Tel: +371 67893939
PV-Latvia@zentiva.com

This leaflet was last revised in {MM/YYYY}

Other sources of information
Detailed information on this medicine is available on the European Medicines Agency web site:
https://www.ema.europa.eu/.