ARAVA 100 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Arava 100 mg film-coated tablets

leflunomide

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.
• If you have any further questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack:

1. What is Arava and what is it used for
2. What you need to know before you take Arava
3. How to take Arava
4. Possible side effects
5. Storing Arava
6. Contents of the pack and other information

1. What is Arava and what is it used for

Arava belongs to a group of medicines called antirheumatic medicines. It contains leflunomide as the active substance.

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

The symptoms of rheumatoid arthritis include joint inflammation, swelling, difficulty moving, and pain. Other symptoms that affect the whole body include loss of appetite, fever, lack of energy, and anemia (reduction in the number of red blood cells in the blood).

The symptoms of active psoriatic arthritis include joint inflammation, swelling, difficulty moving, pain, red-colored plaques, and scaly skin (skin lesions).

2. What you need to know before you take Arava

Do not take Arava

if you have ever had an allergic reactionto leflunomide (especially a severe skin reaction, often accompanied by fever, joint pain, red spots on the skin, 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 kidney problemsof moderate to severe degree,
• if you have a severe decrease in the concentration of proteins in the blood(hypoproteinemia),
• if you have any problem that affects the immune system, (e.g., AIDS),
• if you have any problem with the bone marrowor if you have a reduced number of red or white blood cells or platelets in the blood,
• if you have a severe infection,
• if you are pregnant, think you may be pregnant, or are breast-feeding.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Arava,

• if you have ever had lung inflammation(interstitial lung disease)
• if you have ever had tuberculosisor 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 maleand wish to have children. As it cannot be excluded that Arava passes into semen, reliable contraceptive methods should be used during treatment with Arava.

Men who wish to have children should contact their doctor, who may advise them to stop treatment with Arava and take certain medications to quickly and sufficiently eliminate Arava from their body. In this case, a blood test will be necessary to ensure that Arava has been sufficiently eliminated from their body, and then they should wait at least 3 months before trying to have children.

• if you are scheduled to have a specific blood test (calcium level). A false decrease in calcium levels may be detected.

Occasionally, Arava may cause some blood, liver, lung, or nerve problems in the arms or legs. It may also cause some severe allergic reactions (including drug rash with eosinophilia and systemic symptoms [DRESS]), or increase the risk of serious infections. For more information on these side effects, see section 4 (Possible side effects).

DRESS initially appears with symptoms similar to those of the flu and a skin rash on the face, followed by a widespread skin rash with fever, elevated liver enzyme levels in the blood, and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Your doctor will perform blood testsat regular intervals, before and during treatment with Arava, to monitor blood cells and liver function. Your doctor should also check your blood pressure regularly, as Arava may cause an increase in blood pressure.

Consult your doctor if you experience chronic diarrhea of unknown origin. You may undergo additional tests to establish a differential diagnosis.

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

Children and adolescents

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

Using Arava with other medicines

Tell your doctor or pharmacist if you are using, have recently used, or might use any other medicines. This includes medicines obtained without a prescription.

This is especially important if you are taking:

• other medicines for rheumatoid arthritissuch as antimalarials (e.g., chloroquine and hydroxychloroquine), gold salts by intramuscular or oral route, D-penicillamine, azathioprine, and other immunosuppressive medicines (e.g., methotrexate), as the use of these combinations is not recommended.

warfarin (used as a blood anticoagulant), as monitoring is necessary to reduce the risk of adverse 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 kidney insufficiency in diabetics
• alosetron for severe diarrhea
• 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 pills)
• zidovudine for HIV infection

• rosuvastatin, simvastatin, atorvastatin, pravastatin for high cholesterol

• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis

• a medicine called cholestyramine (used to reduce high cholesterol) or activated charcoal, as these medicines may reduce the amount of Arava absorbed by the body.

If you are taking a non-steroidal anti-inflammatory medicine(NSAIDs) and/or corticosteroids, you may continue taking them after starting treatment with Arava.

Vaccinations

Consult your doctor if you need to be vaccinated. Some vaccines may not be given while you are being treated with Arava or for a certain period after stopping treatment.

Taking Arava with food, drink, and alcohol

Arava can be taken with or without food.

It is not recommended to drink alcohol during treatment with Arava. Drinking alcohol during treatment with Arava may increase the risk of liver damage.

Pregnancy and breast-feeding

Do nottake Arava if you are or think you may be pregnant. If you are pregnant or become pregnant while taking Arava, there is an increased risk of having a child with serious birth defects. Women of childbearing age must not take Arava without using reliable contraceptive methods.

Tell your doctor if you plan to become pregnant after stopping treatment with Arava, as it is necessary to ensure that there are no remaining amounts of Arava in your body before becoming pregnant. The elimination of the medicine from the body may take up to 2 years. This time period can be reduced to a few weeks by taking certain medicines that accelerate the elimination of Arava from the body. In any case, before becoming pregnant, a blood test must be performed to confirm that Arava has been sufficiently eliminated from your body, and once this test is done, you should wait at least 1 month before becoming pregnant.

For more information on laboratory tests, contact your doctor.

If you suspect that you may be pregnant during treatment with Arava or in the 2 years after treatment, you must contact your doctor immediatelyfor a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest that you start treatment with certain medicines to quickly and sufficiently eliminate Arava from your body, thereby reducing the risk to your child.

Do nottake Arava while breast-feeding, as leflunomide passes into breast milk.

Driving and using machines

Arava may make you feel dizzy, which can affect your ability to concentrate and react. If this happens, do not drive or use machines.

Arava contains lactose

If your doctor has told you that you have an intolerance to some sugars, consult them before taking this medicine.

3. How to take Arava

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 initial dose of Arava is 100 mg of leflunomide once a day for the first three days. After this, most people need a dose of:

• For rheumatoid arthritis: 10 mg or 20 mg of Arava once a day, depending on the severity of the disease.
• For psoriatic arthritis: 20 mg of Arava once a day.

Swallowthe tablet wholeand with plenty of water.

It may take about 4 weeks or even longer before you start to feel better. Some patients may even notice a new improvement after 4 or 6 months of treatment. In general, Arava should be taken for prolonged periods of time.

If you take more Arava than you should

If you take more Arava than you should, consult your doctor or any other healthcare service. If possible, take the 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 almost 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.

4. Possible side effects

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

Tell your doctor immediatelyand stop taking Arava:

• if you feel weak, dizzy, or lightheaded, or have difficulty breathing, as these may be symptoms of a severe allergic reaction,
• if you get skin rashesor mouth ulcers, as these may indicate severe reactions that can sometimes be life-threatening (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic symptoms [DRESS]), see section 2.

Tell your doctor immediatelyif you experience:

• pale skin, tiredness, or bruising, as these may indicate blood problems caused by an imbalance in the different types of cells that make up the blood,
• tiredness, abdominal pain, or jaundice(yellowing of the eyes or skin), as these may indicate serious problems such as liver failure, which can be life-threatening,
• any symptoms of infectionsuch as fever, sore throat, or cough, as this medicine may increase the risk of serious infections that can be life-threatening,
• coughor respiratory problems, as these may indicate lung problems (interstitial lung disease or pulmonary hypertension),
• numbness, weakness, or pain in the hands or feet, as these may indicate nerve problems (peripheral neuropathy).

Common side effects(may affect up to 1 in 10 people)

• mild decrease in the number of white blood cells in the blood (leucopenia),
• mild allergic reactions,
• loss of appetite, weight loss (usually insignificant),
• fatigue (asthenia),
• headache, dizziness,
• abnormal sensations in the skin such as tingling (paresthesia),
• mild increase in blood pressure,
• colitis
• diarrhea,
• nausea, vomiting,
• mouth inflammation, mouth ulcers,
• abdominal pain,
• increase in liver test results,
• increase in hair loss,
• eczema, dry skin, skin rash, and itching (pruritus),
• tendinitis (pain caused by inflammation of the membrane surrounding the tendons, usually in the feet or hands),
• increase in certain enzyme levels in the blood (creatine phosphokinase),
• nerve problems in the arms or legs (peripheral neuropathy).

Uncommon side effects(may affect up to 1 in 100 people)

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

Rare side effects(may affect up to 1 in 1,000 people)

• increase in the number of blood cells called eosinophils (eosinophilia), mild decrease in the number of white blood cells in the blood (leucopenia), and decrease in the number of all blood cells (pancytopenia),
• severe increase in blood pressure,
• lung inflammation (interstitial lung disease),
• increase in liver test values that can lead to serious conditions such as hepatitis and jaundice,
• serious infections known as sepsis, which can be life-threatening,
• increase in certain enzyme levels in the blood (lactate dehydrogenase).

Very rare side effects(may affect up to 1 in 10,000 people)

• significant decrease in the number of certain white blood cells in the blood (agranulocytosis),
• severe allergic reactions and potentially severe allergic reactions,
• inflammation of blood vessels (vasculitis, including necrotizing cutaneous vasculitis),
• inflammation of the pancreas (pancreatitis),
• severe liver damage such as liver failure or necrosis, which can be life-threatening,
• severe reactions that can sometimes be life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other side effects may also occur, with a frequency that is not known, such as kidney failure, decrease in uric acid levels in the blood, pulmonary hypertension, male infertility (this effect is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by skin rash/erythema in sun-exposed areas), psoriasis (new or worsening), DRESS, and skin ulcers (open sores in the skin that can show the underlying tissues), which may occur with an unknown frequency.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is possible that they are not listed in this leaflet. You can also report side effects directly through the national reporting system listed in Appendix V. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storing Arava

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 carton. The expiry date refers to the last day of the month shown.

Store in the original package.

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

6. Packaging Contents and Additional Information

Composition of Arava 100 mg

• The active ingredient is leflunomide. Each film-coated tablet contains 100 mg of leflunomide.
• The other components are: corn starch, povidone (E1201), crospovidone (E1202), talc (E553b), colloidal anhydrous silica, 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 coating.

Appearance of the Product and Packaging Contents

Arava 100 mg film-coated tablets are white to off-white and round.

The tablets are marked with ZBP on one side.

The tablets are packaged in blisters.

Packaging of 3 tablets is available.

Marketing Authorization Holder

Sanofi-Aventis Deutschland GmbH

D-65926 Frankfurt am Main

Germany

Manufacturer

Opella Healthcare International SAS

56, Route de Choisy

60200 Compiègne

France

You can request more information about this medication by contacting the local representative of the marketing authorization holder.

Date of the Last Revision of this Leaflet:

Other Sources of Information

Detailed information about this medication is available on the European Medicines Agency website http://www.ema.europa.eu/.