Label: information for the user

Arava 20 mg film-coated tablets

leflunomide

Read this label carefully before starting to take this medicine, as it contains important information for you.

• Keep this label, as you may need to read it again.
• If you have any questions, consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed only for you, and you should not give it to other people, even if they have the same symptoms of disease as you, as it may harm them.

If you experience any adverse effects, consult your doctor, pharmacist, or nurse, even if they are not listed in this label. See section 4.

1. What Arava is and for what it is used

2. What you need to know before starting to take Arava

3. How to take Arava

4. Possible adverse effects

5. Storage of Arava

6. Contents of the pack and additional information

Arava belongs to a group of medications known as anti-rheumatic medications. It contains leflunomide as the active ingredient.

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 affecting the entire body include loss of appetite, fever, fatigue, and anemia (reduction in the number of red blood cells).

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

Do not take Arava

• If you have ever had an allergic reaction to leflunomida (especially a severe skin reaction, often accompanied by fever, joint pain, red skin patches, or blisters, such as Stevens-Johnson syndrome) or to any of the other components of this medication (listed in section 6), or if you are allergic to teriflunomida (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 the concentration of proteins in your blood (hypoproteinemia),
• If you have any condition that affects your immune system (for example, HIV/AIDS),
• If you have any problems with your bone marrow or if you have a reduced number of red or white blood cells in your blood or a reduced number of platelets,
• If you have a severe infection,
• If you are pregnant, think you may be pregnant, or are breastfeeding.

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 tuberculosis or 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 a male and wish to have children. As Arava cannot be ruled out from passing into semen, reliable contraceptive methods should be used during treatment with Arava.

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

• If a specific blood test (calcium level) is planned. A false decrease in calcium levels may be detected
• If you are scheduled to undergo or have recently undergone a major surgical procedure, or if you still have an open wound after a surgical procedure. Arava may interfere with wound healing.

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

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

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

Consult your doctor if you experience chronic diarrhea of unknown origin. Additional tests may be performed 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 old.

Use of Arava with other medications

Inform your doctor or pharmacist if you are using, have used recently, or may need to use any other medication. This includes medications purchased without a prescription.

This is especially important if you are taking:

• Other medications for rheumatoid arthritis, such as antimalarials (e.g., chloroquine and hydroxychloroquine), gold salts administered intramuscularly or orally, D-penicillamine, azathioprine, and other immunosuppressive medications (e.g., methotrexate), as the use of these combinations is not recommended.
• Warfarin (used as an anticoagulant), as a control is necessary to reduce the risk of adverse effects of this medication
• Teriflunomida for multiple sclerosis
• Repaglinida, pioglitazona, nateglinida, or rosiglitazona for diabetes
• Daunorubicina, doxorubicina, paclitaxel, or topotecán for cancer
• Duloxetina for depression, urinary incontinence, or renal insufficiency in diabetics
• Alosetron for severe diarrhea control
• Theophylline for asthma
• Tizanidina, a muscle relaxant
• Oral contraceptives (containing ethinylestradiol and levonorgestrel)
• Cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• Indometacina, ketoprofeno for pain or inflammation
• Furosemida for heart disease (diuretic, diuretic pills)
• Zidovudina for HIV infection
• Rosuvastatina, simvastatina, atorvastatina, pravastatina for hypercholesterolemia (high cholesterol)
• Sulfasalazina for inflammatory bowel disease or rheumatoid arthritis
• A medication called colestiramina (used to reduce high cholesterol) or activated charcoal, as these medications may reduce the amount of Arava absorbed by the body.

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

Vaccinations

Consult your doctor if you need to be vaccinated. Some vaccines cannot be administered while you are taking 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 consume alcohol during treatment with Arava. Drinking alcohol during treatment with Arava may increase the risk of liver damage.

Pregnancy and breastfeeding

Do not take Arava if you are or think you may bepregnant. If you are pregnant or become pregnant while taking Arava, the risk of having a child with severe birth defects increases. Women of childbearing age should not take Arava without using reliable contraceptive methods.

Inform your doctor if you plan to become pregnant after stopping treatment with Arava, as it is necessary to ensure that Arava has been eliminated sufficiently from your body before becoming pregnant. The elimination of the medication from the body may take up to 2 years. This time period may be reduced to a few weeks by taking certain medications that accelerate the elimination of Arava from the body.

Regardless, before becoming pregnant, a blood test should be performed to confirm that Arava has been eliminated sufficiently from your body, and once this test has been performed, 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 should contact your doctor immediately for a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest that you start taking certain medications to quickly and sufficiently eliminate Arava from your body, and thus reduce the risk to your child.

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

Driving and operating machines

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

Arava contains lactose

If your doctor has told you that you have an intolerance to certain sugars, consult with them before taking this medication.

Take this medication exactly as your doctor or pharmacist has told you. Consult with your doctor or pharmacist if you have any doubts.

The usual initial dose of Arava is 100 mg of leflunomida 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 tabletwholeand with plenty ofwater.

You may notice an improvement in your condition within 4 weeks or even longer. Some patients may even notice a new improvement after 4 or 6 months of treatment.

Arava is usually taken for prolonged periods of time.

If you take more Arava than you should

If you take more Arava than you should, consult with your doctor or any other healthcare service. If possible, bring the tablets or the box to show the doctor.

If you forgot to take Arava

If you forgot to take a dose, take it as soon as you remember, unless it is almost time to take the next one. Do not take a double dose to make up for the missed dose.

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

Like all medicines, Arava can cause side effects, although not everyone will experience them.

Inform your doctorimmediatelyand stop taking Arava:

• if you feelweak, dizzy or lightheaded, or havedifficulty breathing, as these may be symptoms of a severe allergic reaction,
• if you developskin rashesormouth ulcers, as this may indicate severe reactions that can be life-threatening (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms [DRESS syndrome]), see section 2.

Inform your doctorimmediatelyif you experience:

• pale skin, fatigueorbruising, as this may indicate blood problems caused by an imbalance of different types of blood cells,
• fatigue, abdominal painorjaundice(yellowing of the eyes or skin), as this may indicate serious problems such as liver failure, which could be life-threatening,
• any symptoms ofinfectionsuch asfever, sore throatorcough, as this medication may increase the risk of severe infections, which could be life-threatening,
• coughorrespiratory problems, as these may indicate lung problems (interstitial lung disease or pulmonary hypertension),
• unusual tingling, weakness or pain in the hands or feet, as this may indicate nerve problems (peripheral neuropathy).

Frequent side effects (may affect up to 1 in 10 patients)

• 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 skin sensations such as tingling (paresthesia),
• mild increase in blood pressure,
• colitis,
• diarrhea,
• nausea, vomiting,
• inflammation of the mouth, mouth ulcers,
• abdominal pain,
• increase in liver test results that may lead to serious conditions such as hepatitis and jaundice,
• 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 blood enzyme levels (creatinine phosphokinase),
• nerve problems in the arms or legs (peripheral neuropathy).

Rare side effects (may affect up to 1 in 100 patients)

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

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

• increase in the number of eosinophils in the blood (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,
• inflammation of the lung (interstitial lung disease),
• increase in liver test results that may lead to serious conditions such as hepatitis and jaundice,
• severe infections known as sepsis, which can be life-threatening,
• increase in certain blood enzyme levels (lactate dehydrogenase).

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

• 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, including unknown frequency, such as kidney failure, decrease in uric acid levels in the blood, pulmonary hypertension, male infertility (this effect is reversible once treatment with this medication is discontinued), cutaneous lupus (characterized by skin rash/erythema in exposed skin areas), psoriasis (new or worsening), DRESS syndrome, and skin ulcers (round, open sores in the skin through which underlying tissues can be seen), may occur with an unknown frequency.

Reporting of side effects

If you experience any type of side effect, consult your doctor or pharmacist, even if it is a possible side effect that does not appear in this leaflet. You can also report them directly through the national notification system included in theAppendixV. By reporting side effects, you can contribute to providing more information on the safety of this medication.

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

Do not use this medication after the expiration date that appears on the packaging. The expiration date is the last day of the month indicated.

Blister:Store in the original packaging.

Bottle:Keep the bottle perfectly closed.

Medicines should not be disposed of through drains or in the trash. Ask your pharmacist how to dispose of the packaging and medications that you no longer need. In this way, you will help protect the environment.

Composition of Arava 20 mg

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

Appearance of the product and contents of the package

Arava 20 mg film-coated tablets are yellowish to ochre-colored triangular tablets.

The tablets bear the inscription ZBO on one face.

The tablets are packaged in blisters or bottles.

They are available in pack sizes of 30, 50, and 100 tablets.

Only some pack sizes may be marketed.

Marketing Authorization Holder

Sanofi-Aventis Deutschland GmbHFrankfurt am MainGermany

Responsible for manufacturing

Opella Healthcare International SASCompiègneFrance

For more information about this medicinal product, please contact the local representative of the marketing authorization holder.

Last revision date of this leaflet:

Other sources of information

The detailed information on this medicinal product is available on the website of the European Medicines Agencyhttp://www.ema.europa.eu/.