LEFLUNOMIDE EGIS

Patient Information Leaflet

Leflunomid Egis, 15 mg, film-coated tablets
Leflunomidum
Please read the entire leaflet carefully before using the medicine, as it contains
important information for the patient.

• Keep this leaflet, so that you can read it again if necessary.
• If you have any questions, please consult your doctor, pharmacist, or nurse.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of Contents

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

1. What Leflunomid Egis is and what it is used for

Leflunomid Egis belongs to a group of medicines known as disease-modifying antirheumatic drugs (DMARDs).
It contains the active substance leflunomide.
Leflunomid Egis is used in adult patients for the treatment of active rheumatoid arthritis or active psoriatic arthritis.
Symptoms of rheumatoid arthritis include joint inflammation, swelling, difficulty in movement, and pain. Other systemic symptoms include loss of appetite, fever, fatigue, and anaemia (lack of red blood cells).
Symptoms of psoriatic arthritis include joint inflammation, swelling, difficulty in movement, pain, as well as redness and scaling of the skin (skin lesions).

2. Important information before using Leflunomid Egis

When not to use Leflunomid Egis

• if the patient has ever had an allergic reaction to leflunomide (especially severe skin reactions, often accompanied by fever, joint pain, red skin patches or blisters (e.g. Stevens-Johnson syndrome)), or to any of the other ingredients of this medicine (listed in section 6), or if allergic to teriflunomide (used in the treatment of multiple sclerosis),
• if the patient has liver function disorders,
• if the patient has moderate to severe kidney function disorders,
• if the patient has been diagnosed with significant reduction in blood protein levels (hypoproteinaemia),
• if the patient has any concurrent diseases affecting the immune system (e.g. AIDS),
• if the patient has bone marrow dysfunction or reduced numbers of red blood cells, white blood cells or platelets,
• if the patient has a serious infection,
• if the patient is pregnant or suspects she may be pregnant, or is breastfeeding.

Warnings and precautions
Before starting treatment with Leflunomid Egis, consult a doctor, pharmacist,
or nurse:

• if the patient has ever suffered from pneumonia (interstitial lung disease).
• if the patient has ever had tuberculosis or has had close contact with someone who has or has previously had tuberculosis. The doctor may recommend tests to determine whether the patient has tuberculosis.
• if the patient is a man planning to father a child. It cannot be ruled out that leflunomide passes into semen; therefore, patients taking Leflunomid Egis should use effective contraception. A man planning to father a child should consult a doctor, who may advise discontinuation of Leflunomid Egis and recommend appropriate medication to rapidly and effectively eliminate the drug from the body. Effective elimination of leflunomide must be confirmed by appropriate blood tests, and a decision about fathering a child should not be made earlier than 3 months after this confirmation.
• if the patient is to undergo or has undergone a specific blood test (calcium level measurement). Test results for calcium levels may be falsely low.
• if the patient is scheduled for or has recently undergone major surgery, or still has an unhealed postoperative wound. Leflunomid Egis may impair wound healing.

Leflunomid Egis may cause blood disorders, liver function abnormalities, lung problems, or nerve disorders in the hands or feet. It may also cause severe allergic reactions (including drug rash with eosinophilia and systemic symptoms – DRESS) or increase the risk of serious infections. For more information, see section 4 („Possible side effects”).
DRESS syndrome initially presents with flu-like symptoms and a facial rash, followed by spreading of the rash to other body areas, high fever, increased liver enzyme activity detectable in blood tests, increased numbers of certain white blood cells (eosinophilia), and enlarged lymph nodes.
Before starting treatment with Leflunomid Egis and during its use, the doctor will recommend regular blood tests to monitor blood cell counts and liver function. Blood pressure should also be monitored regularly, as leflunomide may increase it.
Inform the doctor if chronic diarrhoea of unknown cause occurs. The doctor may order additional tests to establish a diagnosis.
Inform the doctor if skin ulceration occurs during treatment with Leflunomid Egis (see also section 4).

Children and adolescents
Leflunomid Egis is not recommended for use in children and adolescents under 18 years of age.

Leflunomid Egis and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take. This includes medicines available without a prescription.
This is particularly important if the patient is taking:

• other medicines used for rheumatoid arthritis, such as antimalarial drugs (e.g. chloroquine and hydroxychloroquine), intramuscular or oral gold preparations, D-penicillamine, azathioprine, and other immunosuppressive drugs (e.g. methotrexate), as such combinations are not recommended,
• warfarin and other oral anticoagulants, as patient monitoring is required to reduce the risk of adverse effects of this medicine,
• teriflunomide (a medicine used in the treatment of multiple sclerosis),
• repaglinide, pioglitazone, nateglinide, or rosiglitazone (medicines used to treat diabetes),
• daunorubicin, doxorubicin, paclitaxel, or topotecan (anticancer medicines),
• duloxetine (a medicine used to treat depression, urinary incontinence, or kidney disease in people with diabetes),
• alosetron (a medicine used to treat severe diarrhoea),
• theophylline (a medicine used to treat asthma),
• tizanidine (a muscle relaxant),
• oral contraceptives (containing ethinylestradiol and levonorgestrel),
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin (medicines used to treat infections),
• indometacin, ketoprofen (medicines used to treat pain or inflammation),
• furosemide (a diuretic used to treat heart conditions),
• zidovudine (a medicine used to treat HIV infection),
• rosuvastatin, simvastatin, atorvastatin, pravastatin (medicines used to treat hypercholesterolemia – high cholesterol levels),
• sulfasalazine (a medicine used to treat inflammatory bowel disease or rheumatoid arthritis),
• colestyramine (used to treat high cholesterol levels) or activated charcoal, as they may reduce the absorption of leflunomide.

If the patient is taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, these may continue to be used after starting Leflunomid Egis.

Vaccinations
If the patient plans to be vaccinated, consult a doctor. Certain vaccines should not be administered during or for some time after treatment with Leflunomid Egis.

Leflunomid Egis with food, drink and alcohol
Leflunomid Egis may be taken with food or independently of meals.
During treatment with leflunomide, consumption of alcoholic beverages is not recommended. Drinking alcohol while taking Leflunomid Egis may increase the risk of liver damage.

Pregnancy and breastfeeding
Do not use Leflunomid Egis if the woman is pregnant or suspects she may be pregnant.
If a woman is pregnant or becomes pregnant while taking leflunomide, there is an increased risk of severe congenital malformations in the child. Women of childbearing potential must not use Leflunomid Egis unless they are using effective contraception.
If a woman plans to become pregnant after completing treatment with Leflunomid Egis, she should inform her doctor in advance, as it is necessary to ensure that leflunomide has been completely eliminated from the body before attempting pregnancy. After stopping treatment with Leflunomid Egis, a waiting period of 2 years is recommended; however, this period can be shortened to several weeks by taking medicines that accelerate the elimination of leflunomide from the body.
In all cases, appropriate blood tests must be performed to confirm that leflunomide has been effectively eliminated from the body. After obtaining a normal blood test result, at least one month should be waited before attempting pregnancy.
For further information about the laboratory test, consult a doctor.
If a patient suspects she became pregnant while taking leflunomide or within two years after stopping treatment, she must immediately inform her doctor and perform a pregnancy test.
If the test confirms pregnancy, the doctor may recommend treatment with specific medicines to rapidly and effectively eliminate leflunomide from the body, which may reduce the risk to the unborn child.
Do not take Leflunomid Egis during breastfeeding, as leflunomide passes into human milk.

Driving and operating machinery
Leflunomid Egis may cause dizziness, which may impair the ability to concentrate and reaction speed. Patients should not drive or operate machinery if these symptoms occur.

Leflunomid Egis contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.

3. How to use Leflunomid Egis

This medicine should always be taken exactly as your doctor or pharmacist has advised. If in doubt,
you should consult your doctor or pharmacist.
The usual starting dose of Leflunomid Egis is 100 mg once daily for the first three days. After this period, the following doses are used in most patients:

• for the treatment of rheumatoid arthritis: 10 or 20 mg of Leflunomid Egis once daily, depending on the severity of the disease.
• for the treatment of psoriatic arthritis: 20 mg of Leflunomid Egis once daily.

The tablet should be swallowed whole with a large amount of water.
Noticeable improvement in health may occur after about 4 weeks of treatment or later.
Some patients experience further improvement after 4 to 6 months of treatment.
Leflunomid Egis is usually taken for a long period of time.
Taking more than the recommended dose of Leflunomid Egis
If you take more than the recommended dose of Leflunomid Egis, contact your doctor or seek medical advice immediately. If possible, bring the tablets or the medicine packaging with you to show the doctor.
Missing a dose of Leflunomid Egis
If a patient forgets to take a dose, they should take it as soon as they remember, unless it is almost time for the next dose. Do not take a double dose to make up for a missed dose.
If you have any further doubts about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
You should inform your doctor immediately and stop taking Leflunomid Egis if:

• the patient experiences weakness, dizziness or vertigo, or has difficulty breathing, as these may be symptoms of a severe allergic reaction,
• the patient develops skin rash or oral mucosal ulceration, as these may indicate severe, sometimes life-threatening reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic symptoms – DRESS), see section 2.

You should inform your doctor immediately if the patient experiences:

• pallor of the skin, feeling of fatigue, tendency to develop bruising, as these may be symptoms of blood disorders,
• feeling of fatigue, abdominal pain, or jaundice (yellowing of eyes or skin), as these may indicate serious disorders such as liver failure, sometimes leading to death,
• signs of infection such as fever, sore throat, or cough, because this medicine may increase the risk of severe, potentially life-threatening infections,
• cough or difficulty breathing which may indicate lung disease (interstitial lung disease or pulmonary hypertension),
• unusual tingling, weakness, or pain in hands or feet, as these symptoms may indicate nerve disorders (peripheral neuropathy).

Common adverse reactions (may occur in up to 1 in 10 people)

• mild decrease in white blood cell count (leukopenia),
• mild allergic reactions,
• loss of appetite, weight loss (usually mild),
• weakness (asthenia),
• headache, dizziness,
• unusual sensory sensations such as tingling (paresthesia),
• mild increase in blood pressure,
• colitis,
• diarrhea,
• nausea, vomiting,
• inflammation or ulceration of the oral mucosa,
• abdominal pain,
• increased values of certain liver function tests,
• excessive hair loss,
• rash, dry skin, skin eruptions, itching,
• tendonitis (pain due to inflammation of the membrane surrounding tendons, usually in the area of feet or hands),
• increased activity of certain blood enzymes (creatine kinase),
• nerve disorders in hands or feet (peripheral neuropathy).

Uncommon adverse reactions (may occur in up to 1 in 100 people)

• decrease in red blood cell count (anemia) and decrease in platelet count (thrombocytopenia),
• decreased potassium levels in blood,
• anxiety,
• taste disturbances,
• urticaria (hives),
• tendon rupture,
• increased blood lipid levels (cholesterol and triglycerides),
• decreased phosphate levels in blood.

Rare adverse reactions (may occur in up to 1 in 1000 people)

• increase in white blood cells called eosinophils (eosinophilia), mild decrease in white blood cell count (leukopenia), and decrease in all types of blood cells (pancytopenia),
• significant increase in blood pressure,
• lung inflammation (interstitial lung disease),
• increased values of certain liver function tests, which may indicate development of serious disorders such as hepatitis and jaundice,
• severe infections called sepsis, which may result in death,
• increased activity of certain blood enzymes (lactate dehydrogenase).

Very rare adverse reactions (may occur in up to 1 in 10,000 people)

• marked decrease in certain white blood cells (agranulocytosis),
• severe and potentially life-threatening allergic reactions,
• inflammation of small blood vessels (including cutaneous necrotizing vasculitis),
• pancreatitis,
• severe liver damage, such as liver failure or necrosis, which may result in death,
• severe, sometimes life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other adverse reactions such as renal failure, decreased uric acid levels in blood, pulmonary hypertension, male infertility (reversible after discontinuation of this medicine), cutaneous lupus erythematosus (characterized by rash/erythema on skin areas exposed to light), psoriasis (new onset or worsening of existing disease), DRESS, and skin ulceration (a round, open wound in the skin through which subcutaneous tissues are visible) may also occur with unknown frequency.

Reporting of adverse reactions
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 02-222 Warsaw
Tel.: +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Leflunomid Egis

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister pack and carton after "EXP".
The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the pack and other information

What Leflunomid Egis contains

• The active substance is leflunomide. One coated tablet contains 15 mg of leflunomide.
• The other ingredients are:

Tablet core
Microcrystalline cellulose (type 102), pregelatinized corn starch, povidone K 30, crospovidone,
colloidal anhydrous silica, magnesium stearate, lactose monohydrate.
Coating
Opadry II White OY-LS-28908 with the following composition: titanium dioxide (E171), lactose monohydrate,
hypromellose 15cP, hypromellose 3cP, hypromellose 50cP, macrogol 4000.

What Leflunomid Egis looks like and contents of the pack
Leflunomid Egis 15 mg are white, round, biconvex coated tablets, printed with the mark "15" on one side, approximately 7.2 mm in diameter.
The medicine is packed in cardboard boxes containing blisters made of OPA/Aluminium/PVC/Aluminium foil.
Pack sizes: 14, 28, 30, 56, 60, 90 coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Egis Pharmaceuticals PLC
Keresztúri út 30-38
1106 Budapest
Hungary

Manufacturer
PHARMATHEN S.A.
Dervenakion 6
Pallini 15351
Attiki, Greece
Pharmathen International S.A
Industrial Park Sapes,
Rodopi Prefecture, Block No 5,
Rodopi 69300,
Ellas, Greece

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
EGIS Polska Sp. z o.o.
ul. Komitetu Obrony Robotników 45D
02-146 Warsaw
Tel.: +48 22 417 92 00