Leflunomide egis

Patient Information Leaflet

Leflunomid Egis, 10 mg, film-coated tablets
Leflunomidum
Please read this leaflet carefully before taking this medicine, because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please 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 symptoms are the same as yours.
• If you experience any side effects, including any not listed in this leaflet, tell 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 called 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 moving, and pain. Other systemic symptoms include loss of appetite, fever, fatigue, and anaemia (a deficiency in red blood cells).
Symptoms of psoriatic arthritis include joint inflammation, swelling, difficulty in moving, 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 a significant decrease in blood protein levels (hypoproteinaemia),
• if the patient has any concomitant diseases affecting the immune system function (e.g. AIDS),
• if the patient has bone marrow disorders 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 been in close contact with someone who has or has 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 excluded that leflunomide passes into semen; therefore, male patients taking Leflunomid Egis should use effective contraception. A man planning fatherhood should contact his 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 the decision to father a child should not be made earlier than 3 months after this confirmation.
• if the patient is due to undergo a specific blood test (calcium level measurement). Results of calcium level tests may be falsely lowered.
• if the patient is scheduled for or has recently undergone major surgery, or still has an unhealed surgical 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 further information, see section 4 („Possible side effects”).
The DRESS syndrome initially presents with flu-like symptoms and a facial rash, followed by spreading of the rash to other parts of the body, high fever, increased liver enzyme activity evident 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 currently used, recently used, or planned to be used, including those 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, or 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,
• 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 drugs), or 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 hypercholesterolaemia (high cholesterol levels)),
• sulfasalazine (a medicine used to treat inflammatory bowel disease or rheumatoid arthritis),
• cholestyramine (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, they may continue to use them after starting Leflunomid Egis.

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

Leflunomid Egis with food, drink and alcohol
Leflunomid Egis may be taken with or without food.
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 during treatment with 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, although this can be shortened to several weeks by taking medications 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, wait at least one month before attempting pregnancy.
For further information about the laboratory test, consult your 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 undergo a pregnancy test.
If the test confirms pregnancy, the doctor may recommend treatment with specific medications to rapidly and effectively eliminate leflunomide from the body, which may reduce the risk to the child.

Do not take Leflunomid Egis during breastfeeding, as leflunomide passes into human milk.

Driving and using machines
Leflunomid Egis may cause dizziness, which may impair concentration and reaction speed. Patients should not drive or operate machinery if they experience such symptoms.

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

3. How to use Leflunomid Egis

This medicine should always be used as directed by a doctor or pharmacist. If in doubt,
consult a 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 about 4 weeks after starting 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 more than the recommended dose of Leflunomid Egis has been taken, contact a doctor or seek medical advice immediately. If possible, bring the tablets or the medicine packaging along 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 there are any further doubts regarding the use of this medicine, consult a doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.

Immediately inform your doctor and discontinue treatment with 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 a skin rash or oral ulceration, as these may indicate serious, sometimes life-threatening reactions (e.g. Stevens-Johnson syndrome,
  toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms - DRESS), see section 2.

Immediately inform your doctor if the patient experiences:

• pale skin, feeling tired, tendency to develop bruising, as these may be symptoms of blood disorders,
• feeling tired, abdominal pain or jaundice (yellowing of the 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 serious, 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 the hands or feet, as these symptoms may indicate nerve disorders (peripheral neuropathy).

Frequently occurring 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 slight),
• weakness (asthenia),
• headache, dizziness,
• unusual sensations such as tingling (paresthesia),
• mild increase in blood pressure,
• colitis,
• diarrhea,
• nausea, vomiting,
• inflammation or ulceration of the mucous membranes of the mouth,
• abdominal pain,
• increased values of certain liver function tests,
• increased hair loss,
• rash, dry skin, skin eruptions, itching,
• tendonitis (pain caused by inflammation of the membrane surrounding tendons, usually in the area of the feet or hands),
• increased activity of certain enzymes in the blood (creatine kinase),
• nerve disorders in the arms or legs (peripheral neuropathy).

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

• decreased number of red blood cells (anemia) and decreased number of platelets (thrombocytopenia),
• decreased potassium levels in the blood,
• anxiety,
• taste disturbances,
• urticaria (hives),
• tendon rupture,
• increased blood lipid levels (cholesterol and triglycerides),
• decreased phosphate levels in the blood.

Rare adverse reactions (may occur in up to 1 in 1,000 people)

• increased number of white blood cells called eosinophils (eosinophilia), mild decrease in white blood cell count (leukopenia), and decreased number of 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 enzymes in the blood (lactate dehydrogenase).

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

• significant decrease in certain white blood cells (agranulocytosis),
• severe and potentially life-threatening allergic reactions,
• inflammation of small blood vessels (including vasculitis with skin necrosis),
• 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 kidney failure, decreased uric acid levels in the blood, pulmonary hypertension, male infertility (reversible after discontinuation of treatment with 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 reactions occur, including any adverse reactions 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 of the 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.

By reporting adverse reactions, additional information on the safety of the medicine can be collected.

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 specified month.
No special storage instructions apply.
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 10 mg of leflunomide.
• Other ingredients are: Tablet core
  Microcrystalline cellulose (type 102), pregelatinized corn starch, povidone K 30, crospovidone,
  anhydrous colloidal silica, magnesium stearate, lactose monohydrate.
  Coating
  Opadry II White OY-LS-28908 with the following composition: titanium dioxide (E171), lactose monohydr combustible,
  hypromellose 15cP, hypromellose 3cP, hypromellose 50cP, macrogol 4000.

What Leflunomid Egis looks like and contents of the pack
Leflunomid Egis 10 mg are white, round, biconvex coated tablets with a diameter of approximately 6.1 mm.
The medicine is packed in a cardboard box containing blisters made of OPA/Aluminium/PVC/Aluminium foil.
Pack sizes: 30, 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