Leflunomide Ratiopharm 10 mg film-coated tablets EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Leflunomida ratiopharm 10 mg film-coated tablets EFG

leflunomide

Read the entire 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 questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only and must not be given to other people, even if they have the same symptoms as you. It may harm them.
• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if they are side effects not listed in this leaflet. See section 4.

Contents of the leaflet

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

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

Leflunomida ratiopharm contains the active substance leflunomide, which belongs to a group of medicines known as antirheumatic drugs.

Leflunomida ratiopharm 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, lack of energy, and anemia (reduction in the number of red blood cells in the blood).

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 taking Leflunomide ratiopharm

Do not take Leflunomide ratiopharm

• if you have ever had an allergic reaction to leflunomide (especially a serious skin reaction, often accompanied by fever, joint pain, red skin rashes, or blisters, e.g., Stevens-Johnson syndrome), to peanuts or soy, or to any of the other components 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 platelets in your blood,
• if you have a serious infection,
• if you are pregnant, think you may be pregnant, or are breastfeeding.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting Leflunomide 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 check whether you have tuberculosis.
• if you are a man and wish to father a child. Since it cannot be ruled out that Leflunomide ratiopharm passes into semen, reliable contraceptive methods must be used during treatment with Leflunomide ratiopharm.

Men who wish to father a child should contact their doctor, who may advise stopping treatment with Leflunomide ratiopharm and taking certain medications to rapidly and sufficiently eliminate Leflunomide ratiopharm from the body. In this case, a blood test will be required to confirm that Leflunomide ratiopharm has been sufficiently eliminated from your body, after which you should wait at least another 3 months before attempting to father a child.

• if you are scheduled to have a specific blood test (calcium level). A falsely low calcium level may be detected.

Occasionally, Leflunomide ratiopharm may cause problems in the blood, liver, lungs, or nerves of 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 blood tests at regular intervals before and during treatment with Leflunomide ratiopharm to monitor blood cells and liver function. Your doctor should also monitor your blood pressure regularly, as Leflunomide ratiopharm may cause an increase in blood pressure.

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

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

Children and adolescents

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

Other medicines and Leflunomide ratiopharm

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines, including those 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, and other immunosuppressants (e.g., methotrexate), as these combinations are not recommended.
• warfarin and other oral anticoagulant medicines, 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 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 cholestyramine (used to lower 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 drug (NSAID) and/or corticosteroids, you may continue taking them after starting treatment with Leflunomide ratiopharm.

Vaccinations

Consult your doctor if you need to be vaccinated. Some vaccines should not be administered while you are being treated with Leflunomide ratiopharm, nor for a certain period after stopping treatment.

Taking Leflunomide ratiopharm with food, drinks, and alcohol

Leflunomide ratiopharm may be taken with or without food.

Do not consume alcohol during treatment with Leflunomide ratiopharm. Drinking alcohol during treatment with Leflunomide ratiopharm may increase the risk of liver damage.

Pregnancy and breastfeeding

Do not take 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 potential must not take Leflunomide ratiopharm without using reliable contraceptive measures.

Inform your doctor if you plan to become pregnant after stopping treatment with Leflunomide ratiopharm, as it is necessary to ensure that no traces of Leflunomide ratiopharm remain in your body before becoming pregnant. 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 medications that accelerate the elimination of Leflunomide ratiopharm from the body.

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

For more information about laboratory tests, contact your doctor.

If you suspect you may be pregnant during treatment with Leflunomide ratiopharm 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 Leflunomide ratiopharm from your body, thereby reducing the risk to your child.

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

Driving and using machines

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

Leflunomide ratiopharm contains lactose

If your doctor has informed you that you have an intolerance to certain sugars, consult with him before taking this medicine.

Leflunomide ratiopharm contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per film-coated tablet; hence, it 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 Leflunomida ratiopharm

Follow exactly the instructions for use of this medicine as given by your doctor or pharmacist. If in doubt, consult your doctor or pharmacist again.

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

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

Swallow the tablet whole and with plenty of water.

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

Generally, Leflunomida ratiopharm should be taken for long periods of time.

If you take more Leflunomida ratiopharm than you should

If you take more Leflunomida ratiopharm than you should, consult your doctor or any other healthcare provider. If possible, take the tablets or the package with you to show the doctor.

If you forget to take Leflunomida 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 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, Leflunomide ratiopharm can produce adverse effects, although not everyone experiences them.

Contact your doctor immediately and stop taking Leflunomide ratiopharm if:

• you feel weak, dizzy, or lightheaded, or have difficulty breathing, as these may be symptoms of a severe allergic reaction,
• you develop skin rashes or mouth ulcers, as these may indicate serious reactions, which in some cases can be fatal (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms [DRESS syndrome]), see section 2).

Contact 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 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 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 certain liver function tests,
• increased hair loss,
• eczema, dry skin, skin rash, and itching (pruritus),
• tendinitis (pain due to 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),
• decreased blood potassium levels,
• anxiety,
• taste disturbances,
• skin rash (urticaria),
• tendon rupture,
• increased levels of fat in the blood (cholesterol and triglycerides),
• decreased 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),
• marked increase in blood pressure,
• lung inflammation (interstitial lung disease),
• increased liver test values 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)

• severe 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 may sometimes be potentially fatal (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other adverse reactions such as renal failure, decreased blood uric acid levels, pulmonary hypertension, male infertility (this effect is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by skin rash/erythema in areas of skin 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) may occur with an 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 included in Appendix V. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Leflunomide ratiopharm

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

Do not use this medicine after the expiry date stated on the outer carton and on the bottle after EXP. The expiry date refers to the last day of the month indicated.

Keep the bottle tightly closed to protect it from moisture.

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

6. Contents of the pack and other information

Composition of Leflunomide ratiopharm

• The active substance is leflunomide.

Each film-coated tablet contains 10 mg of leflunomide.

• The other components 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 contents of the pack

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

The tablets are packed in bottles.

Pack sizes of 30 or 100 film-coated tablets per bottle are available.

Only some pack 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

For further information about this medicinal product, please contact the local representative of the Marketing Authorization Holder.

Date of the most recent review of this leaflet: {MM/YYYY}.

Other sources of information

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