LEFLUNOMIDE RATIOPHARM 20 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Leflunomide ratiopharm 20mg film-coated tabletsEFG

Leflunomide

Read all of this 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 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 Leflunomide ratiopharm and what is it used for
2. What you need to know before you take Leflunomide ratiopharm
3. How to take Leflunomide ratiopharm
4. Possible side effects
5. Storage of Leflunomide ratiopharm
6. Contents of the pack and further information

1. What is Leflunomide ratiopharm and what is it used for

Leflunomide ratiopharm contains the active substance leflunomide, which belongs to a group of medicines called antirheumatic medicines.

Leflunomide ratiopharm 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 Leflunomide ratiopharm

Do not takeLeflunomide ratiopharm

• 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), peanuts, or soy, or 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 blood protein levels(hypoproteinemia),
• if you have any immune system problems(e.g., AIDS),
• if you have any bone marrow problemsor if you have a low number of red or white blood cells or platelets in your blood,
• 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 Leflunomide ratiopharm

• 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 a male and wish to have children. Since it cannot be excluded that Leflunomide ratiopharm passes into semen, reliable contraceptive methods should be used during treatment with Leflunomide ratiopharm.

Males who wish to have children should contact their doctor, who may advise them to stop treatment with Leflunomide ratiopharm, take certain medications to quickly and sufficiently eliminate Leflunomide ratiopharm from their body. In this case, a blood test will be necessary to ensure that Leflunomide ratiopharm has been sufficiently eliminated from their body, and then they should wait at least another 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, Leflunomide ratiopharm may cause some problems in the blood, liver, lungs, or nerves of the arms or legs. It may also cause some severe allergic reactions (including drug rash with eosinophilia and systemic symptoms [DRESS syndrome]) or increase the risk of serious infections. For more information on these side effects, see section 4 (Possible side effects).

DRESS syndrome 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 Leflunomide ratiopharm, to monitor blood cells and liver function. Your doctor should also regularly check your blood pressure, as Leflunomide ratiopharm may cause an increase in blood pressure.

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

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

Children and adolescents

The use of Leflunomide ratiopharm is not recommended in children and adolescents under 18 years of age.

Other medicines and Leflunomide ratiopharm

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 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 these combinations are not recommended.
• warfarin and other oral medicines used as blood anticoagulants, as monitoring is required 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 renal 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.
• osuvastatin, 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 may reduce the amount of Leflunomide ratiopharm absorbed by the body.

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

Vaccinations

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

Taking Leflunomide ratiopharm with food, drinks, and alcohol

Leflunomide ratiopharm can be taken with or without food.

Do notdrink alcohol during treatment with Leflunomide ratiopharm. Drinking alcohol during treatment with Leflunomide ratiopharm may increase the risk of liver damage.

Pregnancy and breastfeeding

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

Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomide ratiopharm, as it is necessary to ensure that there are no remaining amounts of Leflunomide ratiopharm 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 Leflunomide ratiopharm from the body.

In any case, before becoming pregnant, a blood test will be necessary to confirm that Leflunomide ratiopharm has been sufficiently eliminated from your body, and after this test, 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 Leflunomide ratiopharm 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 Leflunomide ratiopharm from your body, thereby reducing the risk to your child.

Do nottake Leflunomide ratiopharm while breastfeeding, as leflunomide passes into breast milk.

Driving and using machines

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

Leflunomide ratiopharm contains lactose

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

Leflunomide ratiopharm contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet; this is essentially "sodium-free".

Leflunomide ratiopharm contains soy lecithin

Do not use this medicine if you are allergic to peanuts or soy.

3. How to take Leflunomide ratiopharm

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

The usual initial dose of Leflunomide ratiopharm is 100 mg once daily for the first three days. After this, most people need a dose of:

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

Takethe tablet with plenty of water.

It may take about 4 weeks or even longer before you start to feel better. Some patients may even notice further improvement after 4 or 6 months of treatment.

Leflunomide ratiopharm is usually taken for long periods of time.

If you take moreLeflunomide ratiopharmthan you should

If you take more Leflunomide ratiopharm 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 takeLeflunomide ratiopharm

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 Adverse Effects

Like all medicines, Leflunomida ratiopharm can cause adverse effects, although not all people suffer from them.

Inform your doctor immediately and stop taking Leflunomida ratiopharm:

weak, dizzy or lightheaded, or have difficulty breathing, because these may be symptoms of a severe allergic reaction,skin rashesor mouth ulcers, because they 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).

Inform your doctor immediatelyif you experience:

• pale skin, fatigueor bruises, because they may indicate blood problems caused by an imbalance in the different types of cells that make up the blood,
• fatigue, abdominal painor jaundice(yellowing of the eyes or skin), because they may indicate serious problems such as liver failure, which could be life-threatening,
• any symptoms of infectionsuch as fever, sore throator cough, because this medication may increase the chances of developing serious infections, which could be life-threatening,
• coughor respiratory problems, as they may indicate lung problems (interstitial lung disease or pulmonary hypertension),
• unusual tingling, weakness or pain in the hands or feet, because it may indicate nerve problems (peripheral neuropathy).

Frequent Adverse Reactions (may affect up to one in 10 patients)

• mild decrease in the number of white blood cells (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 (creatinine phosphokinase),
• nerve problems in the arms or legs (peripheral neuropathy)

Uncommon Adverse Reactions (may affect up to one in 100 patients)

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

Rare Adverse Reactions (may affect up to one in 1,000 patients)

• increase in the number of blood cells called eosinophils (eosinophilia), mild decrease in the number of white blood cells (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 situations 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 Adverse Reactions (may affect up to one in 10,000 patients)

• significant decrease in the number of certain white blood cells (agranulocytosis),
• severe allergic reactions and potentially severe allergic reactions,
• inflammation of blood vessels (vasculitis, including necrotizing cutaneous vasculitis),
• 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 adverse reactions 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 stopped), cutaneous lupus (characterized by skin rash/erythema in sun-exposed 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 Adverse Effects

If you experience any adverse effects, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You can also report them directly through the national reporting system included in Appendix V. By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Leflunomida ratiopharm

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the outer carton and on the bottle after EXP. The expiration date is the last day of the month indicated.

Keep the bottle tightly closed to protect it from moisture.

Medicines should not be disposed of through wastewater or household waste. Ask your pharmacist how to dispose of the packaging and any unused medication. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Leflunomida ratiopharm

• The active ingredient is leflunomide.

Each film-coated tablet contains 20 mg of leflunomide.

• The other ingredients are lactose monohydrate, low-substituted hydroxypropylcellulose, tartaric acid, sodium lauryl sulfate, and magnesium stearate (E470b) in the tablet core, and lecithin (soybeans), poly(vinyl) alcohol, talc, titanium dioxide (E171), and xanthan gum in the coating.

Appearance of the Product and Package Contents

Leflunomida ratiopharm 20 mg film-coated tablets EFG are white to off-white, round tablets with a diameter of approximately 8 mm and a break line on one side. The tablet can be divided into two equal halves.

The tablets are packaged in bottles.

They are available in package sizes of 30 or 100 film-coated tablets per bottle.

Not all package sizes may be marketed.

Marketing Authorization Holder

ratiopharm GmbH

Graf-Arco-Straße 3,

89079 Ulm

Germany

Manufacturer

Haupt Pharma Münster GmbH

Schleebrüggenkamp 15

48159 Münster

Germany

Merckle GmbH

Ludwig-Merckle-Straße 3

89143 Blaubeuren

Germany

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

Date of Last Revision of this Leaflet:{MM/AAAA}.

Other Sources of Information

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