Package Leaflet: Information for the User

Leflunomida ratiopharm 10mg Film-Coated Tablets EFG

leflunomida

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

1.What isLeflunomida ratiopharmand what it is used for

2.What you need to know beforestarting to takeLeflunomida ratiopharm

3.How to takeLeflunomida ratiopharm

4.Possible side effects

5.Storage ofLeflunomida ratiopharm

6.Contents of the pack and additional information

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

Leflunomida 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 affecting the whole body include loss of appetite, fever, lack of energy, and anemia (reduction in the number of red blood cells).

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

Do not takeLeflunomida ratiopharm

• if you have ever had a severe allergic reaction to leflunomide (especially a reaction in the skin, often accompanied by fever, joint pain, red skin patches, or blisters, for example, Stevens-Johnson syndrome), to peanuts or to soy or to any of the other components of this medication (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 the concentration of proteins in the blood (hypoproteinemia),
• if you have any condition that affects the immune system (for example, HIV/AIDS),
• if you have any problem with the bone marrow or if you have a reduced number of red or white blood cells in the 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 Leflunomida ratiopharm.

• 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 it cannot be ruled out that Leflunomida ratiopharm may pass into the semen, reliable contraceptive methods should be used during treatment with Leflunomida ratiopharm.

Males who wish to have children should contact their doctor, who may advise them to interrupt treatment with Leflunomida ratiopharm and take certain medications to quickly and sufficiently remove Leflunomida ratiopharm from their body. In this case, a blood test will be necessary to ensure that Leflunomida ratiopharm has been removed sufficiently from their body, and they should then wait at least 3 months before attempting to have children.

• if a specific blood test (calcium level) is planned. A false decrease in calcium levels may be detected.

Occasionally, Leflunomida ratiopharm 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 rash 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 initially appears 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 enlarged lymph nodes.

Your doctor will perform regular blood tests, before and during treatment with Leflunomida ratiopharm, to monitor blood cells and the liver. Your doctor should also regularly check your blood pressure, as Leflunomida ratiopharm 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 Leflunomida ratiopharm (see section 4).

Children and adolescents

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

Other medications and Leflunomida ratiopharm

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

• other medications for rheumatoid arthritis, such as antimalarials (for example: chloroquine and hydroxychloroquine), gold salts administered intramuscularly or orally, D-penicillamine, azathioprine, and other immunosuppressive medications (for example: methotrexate), as the use of these combinations is not recommended.
• warfarin and other oral medications used as blood anticoagulants, as a control is necessary to reduce the risk of adverse effects of this medication.
• 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 control.
• 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, diuretic pills).
• zidovudine for HIV infection.
• rosuvastatin, simvastatin, atorvastatin, pravastatin for high cholesterol (high cholesterol).
• sulfasalazine for inflammatory bowel disease or for rheumatoid arthritis.
• a medication called cholestyramine (used to reduce high cholesterol)oractivated charcoalas these medications may reduce the amount of Leflunomida ratiopharm 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 Leflunomida ratiopharm.

Vaccinations

Consult your doctor if you need to be vaccinated. Some vaccines cannot be administered while you are being treated with Leflunomida ratiopharm, or not for a certain period of time after treatment is completed.

Taking Leflunomida ratiopharm with food, drinks, and alcohol

Leflunomida ratiopharm can be taken with or without food.

Do notconsume alcohol during treatment with Leflunomida ratiopharm. Alcohol consumption during treatment with Leflunomida ratiopharm may increase the risk of liver damage.

Pregnancy and lactation

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

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

In any case, a blood test should be performed before becoming pregnant to confirm that Leflunomida ratiopharm has been removed 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 Leflunomida ratiopharm 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 treatment with certain medications to quickly and sufficiently remove Leflunomida ratiopharm from your body, and thus reduce the risk to your child.

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

Driving and operating machines

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

Leflunomida ratiopharm contains lactose

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

Leflunomida ratiopharm contains sodium

This medication contains less than 1 mmol of sodium (23 mg) per coated tablet; that is, it is essentially “sodium-free”.

Leflunomida ratiopharm contains soy lecithin

Do not use the medication if you are allergic to peanuts or soy.

Follow exactly the administration instructions for this medication as indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The usual initial dose of Leflunomida ratiopharm is 100 mg 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 Leflunomida ratiopharm once a day, depending on the severity of the disease.
• For psoriatic arthritis: 20 mg of Leflunomida ratiopharm once a day.

Swallowthe tabletwholeand with plenty ofwater.

You may take up to 4 weeks or even more time to notice an improvement in your condition. Some patients may even notice a new improvement after 4 or 6 months of treatment.

Leflunomida ratiopharm is usually taken for prolonged periods of time.

If you take moreLeflunomida ratiopharmthan you should

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

If you forgot to takeLeflunomida ratiopharm

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, Leflunomida ratiopharmcan cause side effects, although not everyone will experience them.

Inform your doctor immediately and stop taking Leflunomida ratiopharm:

• 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 in some cases can be fatal (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug eruption with eosinophilia and systemic symptoms [DRESS syndrome]), see section2).

Inform your doctorimmediatelyif you experience:

• pale skin,fatigueorbruising,as this may indicate blood problems caused by an imbalance of the different types of cells that make up the blood,
• fatigue,abdominal painorjaundice(yellowing of the eyes or skin), as this may indicate serious problems such as liver failure, which could be fatal,
• any symptoms ofinfectionsuch asfever,sore throatorcough,as this medication may increase the risk of severe infections, which could be fatal,
• 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).

Common 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 sensations in the skin 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,
• increase in hair loss,
• eczema, dry skin, skin rash and itching (pruritus),
• tendinitis (pain caused by inflammation of the membrane surrounding the tendons of, usually, the feet or hands),
• increase in certain enzyme levels in the blood (creatinine phosphokinase),
• nerve problems in the arms or legs (peripheral neuropathy).

Uncommon 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 levels of fat in the blood (cholesterol and triglycerides),
• decrease in levels of phosphate in the blood.

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 fatal,
• increase in levels of certain enzymes in the blood (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 that can be fatal,
• severe reactions that can sometimes be potentially fatal (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

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

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if it is a possible adverse effect that does not appear in this leaflet. You can also report them directly through thenational notification system included in theAppendixV. By reporting adverse 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 usethis medicationafter the expiration date that appears on the outer box and on the bottle after EXP. The expiration date is the last day of the month indicated.

Keep the bottle perfectly closed to protect it from moisture.

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

Composition of Leflunomide ratiopharm

• The active ingredient is leflunomide.

Each film-coated tablet contains 10mg of leflunomide.

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

Appearance of the product and contents of the package

Leflunomide ratiopharm 10mg film-coated tablets EFG are white to off-white, round tablets with a diameter of approximately 6mm.

The tablets are packaged in bottles.

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

Only some bottle sizes may be marketed.

Marketing Authorization Holder

ratiopharm GmbH

Graf-Arco-Straße 3,

89079 Ulm

Germany

Responsible Person

Haupt Pharma Münster GmbH

Schleebrüggenkamp 15

48159 Münster

Germany

Merckle GmbH

Ludwig-Merckle-Straße 3

89143 Blaubeuren

Germany

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

Last date of revision of this leaflet:{MM/YYYY}.

Other sources of information

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