Arava 10 mg film-coated tablets

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Arava 10 mg film-coated tablets

Leflunomide

Read the entire leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only, and you should not give it to others, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor, pharmacist or nurse, even if they are adverse effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

1. What Arava is and what it is used for

Arava belongs to a group of medicines called disease-modifying antirheumatic drugs (DMARDs). It contains leflunomide as the active substance.

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

Symptoms of rheumatoid arthritis include joint inflammation, swelling, difficulty moving, and pain. Other systemic symptoms include loss of appetite, fever, fatigue, and anemia (reduced number of red blood cells in the blood).

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

2. What you need to know before taking Arava

Do not take Arava

• if you have ever had an allergic reaction to leflunomide (especially a severe skin reaction, often accompanied by fever, joint pain, red skin rashes, 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 in the treatment of multiple sclerosis),
• if you have any liver problems,
• if you have moderate to severe kidney problems,
• if you have a severe decrease in blood protein levels (hypoproteinemia),
• if you have a condition affecting the immune system (e.g., AIDS),
• if you have a bone marrow disorder or have low levels of red or white blood cells or low platelet counts,
• if you have a serious infection,
• if you are pregnant, think you might be pregnant, or are breastfeeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before starting Arava

• if you have ever had lung inflammation (interstitial lung disease),
• if you have ever had tuberculosis or have been in close contact with someone who has or has had tuberculosis. Your doctor may carry out tests to check whether you have tuberculosis,
• if you are a man and wish to father a child. Since it cannot be ruled out that Arava passes into semen, reliable contraceptive methods must be used during treatment with Arava.
• Men who wish to father a child should consult their doctor, who may advise stopping Arava treatment and taking certain medications to rapidly and sufficiently eliminate Arava from the body. In this case, a blood test will be needed to confirm that Arava has been sufficiently eliminated from your body, and you should then wait at least another 3 months before attempting to father a child.
• if you are scheduled for or have recently undergone a specific blood test (calcium level). A falsely low calcium level may be detected.
• if you are scheduled for or have recently undergone major surgery, or if you still have an unhealed surgical wound. ARAVA may impair wound healing.

Occasionally, Arava may cause certain problems with the blood, liver, lungs, or nerves in the arms or legs. It may also cause serious allergic reactions (including drug rash with eosinophilia and systemic symptoms [DRESS syndrome]), or increase the risk of developing a serious infection. For more information about these adverse effects, see section 4 (Possible side effects).

DRESS syndrome initially presents with flu-like symptoms and a skin rash on the face, followed by a widespread rash, fever, elevated liver enzymes in the blood, an increase in a type of white blood cell (eosinophilia), and enlarged lymph nodes.

Your doctor will perform regular blood tests before and during treatment with Arava to monitor blood cells and liver function. Your doctor should also monitor 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 need 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.

Taking Arava with other medicines

Tell your doctor or pharmacist if you are taking, have recently taken, or might need to 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 salts, D-penicillamine, azathioprine, or other immunosuppressive medicines (e.g., methotrexate), as these combinations are not recommended,
• warfarin (used as a blood anticoagulant), as monitoring is needed 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 diabetic kidney disease,
• alosetron for control of 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 hypercholesterolemia (high cholesterol),
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis,
• a medicine called colestyramine (used to lower 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 drug (NSAID) and/or corticosteroids, you may continue taking them after starting Arava treatment.

Vaccinations

Talk to your doctor if you need to be vaccinated. Some vaccines cannot be administered while you are being treated with Arava, nor for a certain period after treatment has ended.

Taking Arava with food, drink, and alcohol

Arava may be taken with or without food.

Alcohol consumption is not recommended during treatment with Arava. Drinking alcohol while taking Arava may increase the risk of liver damage.

Pregnancy and breastfeeding

Do not take Arava if you are or think you might be pregnant. If you are pregnant or become pregnant while taking Arava, there is an increased risk of having a baby with serious birth defects. Women of childbearing potential must not take Arava unless using reliable contraception.

Inform your doctor if you plan to become pregnant after stopping Arava treatment, as it is necessary to ensure that no traces of Arava remain in your body before conception. Elimination of the drug from the body may take up to 2 years. This time period can be reduced to a few weeks by taking certain medications that accelerate the elimination of Arava from the body.

In any case, before becoming pregnant, you must have a blood test to confirm that Arava has been sufficiently eliminated from your body, and after this test, you must wait at least 1 month before attempting to become pregnant.

For more information about laboratory tests, contact your doctor.

If you suspect you might be pregnant during treatment with Arava or within two years after treatment, you must contact your doctor immediately for a pregnancy test. If the test confirms pregnancy, your doctor may recommend starting treatment with certain medications to rapidly and sufficiently eliminate Arava from your body, thereby reducing the risk to your baby.

Do not take Arava while breastfeeding, as leflunomide passes into breast milk.

Driving and using machines

Arava may cause dizziness, which could affect your ability to concentrate and react. If this occurs, do not drive or operate machinery.

Arava contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, consult with 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 have any doubts.

The usual starting dose of Arava is 100 mg of leflunomide once daily for the first three days. After this, most people require a maintenance dose of:

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

Swallow the tablet whole with plenty of water.

It may take about 4 weeks, or even longer, before you start to notice an improvement in your condition. Some patients may experience further improvement after 4 to 6 months of treatment.

Generally, Arava should be taken for long 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 provider immediately. If possible, take the tablets or the pack 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 the forgotten dose.

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

4. Possible adverse effects

Like all medicines, Arava can cause adverse effects, although not everyone experiences them.

Tell your doctor immediately and stop taking Arava:

• if you feel weak, dizzy, or short of breath, as these may be symptoms of a severe allergic reaction,
• if you develop skin rashes or mouth ulcers, as these may indicate serious reactions that can sometimes be fatal (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic symptoms [DRESS syndrome]), see section 2.

Tell your doctor immediately if you experience:

• pallor, fatigue, or bruising, as these may indicate blood problems caused by an imbalance in the different types of blood cells,
• fatigue, abdominal pain, or jaundice (yellowing of the eyes or skin), as these may indicate serious liver problems, which could be fatal,
• any signs of infection such as fever, sore throat, or cough, as this medicine may increase the risk of developing serious infections, which could be fatal,
• cough or breathing difficulties, as these may indicate lung problems (interstitial lung disease, pulmonary hypertension, or pulmonary nodule),
• unusual tingling, weakness, or pain in the hands or feet, as this may indicate nerve problems (peripheral neuropathy).

Frequent adverse reactions (may affect up to 1 in 10 patients)

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

Uncommon adverse reactions (may affect up to 1 in 100 patients)

• decrease in red blood cell count (anaemia) and platelets (thrombocytopenia),
• low blood potassium levels,
• anxiety,
• taste disturbances,
• skin rash (urticaria),
• tendon rupture,
• increased levels of fat in the blood (cholesterol and triglycerides),
• low blood phosphate levels.

Rare adverse reactions (may affect up to 1 in 1,000 patients)

• increase in a type of white blood cell called eosinophils (eosinophilia), mild decrease in white blood cell count (leucopenia), and decrease in all blood cells (pancytopenia),
• severe increase in blood pressure,
• lung inflammation (interstitial lung disease),
• increased values in certain liver function tests that may lead to serious conditions such as hepatitis and jaundice,
• severe infections known as sepsis, which may be fatal,
• increased levels of certain blood enzymes (lactate dehydrogenase).

Very rare adverse reactions (may affect up to 1 in 10,000 patients)

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

Other adverse effects may also occur, with unknown frequency, such as kidney failure, decreased levels of uric acid 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 skin areas exposed to light), psoriasis (new onset or worsening), DRESS syndrome, and skin ulcer (a round, open sore in the skin through which underlying tissues can be seen), which may occur with unknown frequency.

Reporting of adverse effects

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

5. Storage of Arava

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

Do not use this medicine after the expiry date stated on the packaging. The expiry date is the last day of the month indicated.

Blister: Store in the original packaging.

Bottle: Keep the bottle tightly closed.

Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines and packaging that you no longer need. This will help protect the environment.

6. Contents of the pack and other information

Composition of Arava 10 mg

• The active substance is leflunomide. Each film-coated tablet contains 10 mg of leflunomide.
• The other components are: maize starch, povidone (E1201), crospovidone (E1202), anhydrous colloidal silica, magnesium stearate (E470b), and monohydrate lactose 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 contents of the pack

Arava 10 mg film-coated tablets are white to off-white, round tablets.

The tablets are marked with the code ZBN on one side.

The tablets are packed in blisters or bottles.

Pack sizes of 30 and 100 tablets are available.

Only certain pack sizes may be marketed.

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

Further information on this medicinal product is available upon request by contacting the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet:

Other sources of information

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