Leflunomide Zentiva: detailed information

Patient Information Leaflet: Information for the User

Leflunomide Zentiva 10 mg film-coated tablets

leflunomide
Please read all of this 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. Do not pass it on to other people, even if their symptoms are the same as yours, as it may be harmful.
If you experience any side effect, including any not listed in this leaflet, inform your doctor, pharmacist or nurse. See section 4.

Contents of this leaflet:

What Leflunomide Zentiva is and what it is used for
What you need to know before taking Leflunomide Zentiva
How to take Leflunomide Zentiva
Possible side effects
How to store Leflunomide Zentiva
Contents of the pack and other information

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

Leflunomide Zentiva belongs to a group of medicines called antirheumatic agents.
Leflunomide Zentiva is used to treat adult patients with active rheumatoid arthritis or active psoriatic arthritis.
Symptoms of rheumatoid arthritis include joint inflammation, swelling, difficulty in movement, and pain. Other symptoms that may affect the whole body include loss of appetite, fever, loss of strength, and anaemia (reduction in the number of red blood cells).
Symptoms of active psoriatic arthritis include joint inflammation, swelling, difficulty in movement, pain, and red, scaly skin patches (skin lesions).

2. What you need to know before taking Leflunomide Zentiva

Do not take Leflunomide Zentiva:

if you have previously had an allergic reaction to leflunomide (especially a severe skin reaction, often accompanied by fever, joint pain, red skin spots or blisters, for example Stevens-Johnson syndrome), or to 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 moderate or severe kidney problems,
if you have extremely low blood protein levels (hypoproteinemia),
if you suffer from any condition affecting your immune system (e.g. AIDS),
if you have any bone marrow disorder, or if your red blood cell or white blood cell count is low, or if your platelet count is reduced,
if you have a serious infection,
if you are pregnant, planning a pregnancy, or breastfeeding.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Leflunomide Zentiva

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 carry out tests to check whether you have tuberculosis.
if you are male and intend to father a child. Since it cannot be ruled out that Leflunomide Zentiva passes into semen, a reliable contraceptive method must be used during treatment with Leflunomide Zentiva. Men who intend to father a child should contact their doctor, who may advise stopping treatment with Leflunomide Zentiva and taking certain medicines to rapidly and adequately eliminate Leflunomide Zentiva from the body. After this, a blood test should be performed to ensure that Leflunomide Zentiva has been sufficiently removed from the body, and then you must wait at least another 3 months before trying to conceive.
if you are due to have a specific blood test (calcium level). Falsely low calcium levels may be observed.
if you are scheduled for or have recently undergone major surgery, or if you still have an unhealed wound following surgery. Leflunomide Zentiva may impair wound healing.

Rarely, Leflunomide Zentiva may cause problems affecting the blood, liver, lungs, or
nerves in the arms or legs. Leflunomide Zentiva may also cause severe allergic reactions (including
Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]), or increase the risk of serious
infections. For further information, see section 4 (Possible side effects).
DRESS syndrome initially presents with flu-like symptoms and facial rash, followed by widespread rash, fever, elevated liver enzymes, increased levels of a type of white blood cell (eosinophilia) in blood tests, and swollen lymph nodes.
Before starting Leflunomide Zentiva and during treatment, your doctor will prescribe regular blood tests to monitor blood cells and liver function. Your doctor will also check your blood pressure regularly, as Leflunomide Zentiva may cause an increase in blood pressure.
Inform your doctor if you develop unexplained chronic diarrhoea. Your doctor may perform additional tests for differential diagnosis.
Inform your doctor if a skin ulcer develops during treatment with Leflunomide Zentiva (see also section 4).

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

Other medicines and Leflunomide Zentiva
Inform your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines purchased without a prescription.
This information is particularly important if you are taking:

other medicines for the treatment of rheumatoid arthritis, such as antimalarials (e.g. chloroquine and hydroxychloroquine), gold salts administered intramuscularly or orally, D-penicillamine, azathioprine, and other immunosuppressive medicines (e.g. methotrexate), as these combinations are not recommended,
warfarin and other oral anticoagulants (blood thinners), as monitoring is required to reduce the risk of side effects,
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 managing severe diarrhoea,
theophylline for asthma,
tizanidine, to relax muscles,
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 pill"),
zidovudine for HIV infection,
rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol),
sulfasalazine for inflammatory bowel disease or rheumatoid arthritis,
a medicine called colestyramine (used to lower cholesterol) or activated charcoal, as these medicines may reduce the amount of Leflunomide Zentiva absorbed by the body.

If you are already taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, you may continue taking them after starting treatment with Leflunomide Zentiva.

Vaccinations
If you need to be vaccinated, consult your doctor. Certain vaccinations should not be given while you are taking Leflunomide Zentiva, and for a certain period after stopping treatment.

Leflunomide Zentiva with food, drinks and alcohol
Leflunomide Zentiva may be taken with or without food.
It is recommended not to drink alcohol during treatment with Leflunomide Zentiva. Drinking alcohol while taking Leflunomide Zentiva may increase the risk of liver damage.

Pregnancy and breastfeeding
Do not take Leflunomide Zentiva if you are pregnant or think you might be pregnant. If you become pregnant while taking Leflunomide Zentiva, the risk of having a baby with serious birth defects is increased. Women must use reliable contraceptive measures when taking Leflunomide Zentiva and while of childbearing age.
If you plan to start a pregnancy after stopping treatment with Leflunomide Zentiva, it is important to inform your doctor in advance, as you must ensure that all traces of Leflunomide Zentiva have been eliminated from your body before trying to conceive.
Elimination of Leflunomide Zentiva may take up to two years. This period can be reduced to a few weeks by taking certain medicines that accelerate the removal of Leflunomide Zentiva from your body.
In either case, blood tests must confirm that Leflunomide Zentiva has been sufficiently eliminated from your body before you become pregnant, and after this, you must wait at least another month.
For further information on laboratory tests, contact your doctor.
If you suspect you are pregnant while taking Leflunomide Zentiva or within two years after stopping treatment, you must inform your doctor immediately. Your doctor will arrange for a pregnancy test. If this confirms that you are pregnant, your doctor will advise treatment with certain medicines to rapidly and adequately eliminate Leflunomide Zentiva from your body, thereby reducing the risk to your baby.
Do not take Leflunomide Zentiva during breastfeeding, as leflunomide passes into breast milk.

Driving and using machines
Leflunomide Zentiva may make you feel unsteady, and this sensation may affect your ability to concentrate and react. In this case, do not drive or operate machinery.

Leflunomide Zentiva contains lactose.
If your doctor has informed you that you have an intolerance to certain sugars, contact your doctor before taking this medicine.

3. How to take Leflunomide Zentiva

Always take this medicine exactly as instructed by your doctor or pharmacist. If
you have any doubts, consult your doctor or pharmacist.
The usual starting dose of Leflunomide Zentiva is 100 mg of leflunomide once daily for the
first three days. Afterwards, most patients require:

for rheumatoid arthritis: a daily dose of 10 or 20 mg of Leflunomide Zentiva, depending on the severity of the disease.
for psoriatic arthritis: a daily dose of 20 mg of Leflunomide Zentiva.

Take the tablet whole and with plenty of water.
It may take approximately 4 weeks or longer before you begin to notice an
improvement in your condition. Some patients may continue to experience further improvements even
after 4–6 months of treatment.
Generally, Leflunomide Zentiva is taken for long periods of time.
If you take more Leflunomide Zentiva than you should
If you take more Leflunomide Zentiva than recommended, contact your doctor or
seek medical advice immediately. If possible, bring the tablets or the pack with you to show your doctor.
If you forget to take Leflunomide Zentiva
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 doubts about how to use this medicine, consult your doctor, pharmacist, or
nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Stop treatment with Leflunomide Zentiva and contact your doctor immediately if you:

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

Contact your doctor immediately if you experience:

pallor, fatigue or bruising, as these may indicate blood disorders due to 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 such as liver failure, which can be fatal,
any signs of infection such as fever, sore throat or cough, as this medicine may increase the risk of serious, life-threatening infections,
cough or breathing difficulties, as these may indicate lung problems (interstitial lung disease or pulmonary hypertension),
tingling, weakness or unusual pain in the hands or feet, as these may indicate nerve problems (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)

mild decrease in white blood cell count (leucopenia),
mild allergic reactions,
loss of appetite, weight loss (usually not significant),
fatigue (asthenia),
headache, dizziness,
abnormal skin sensations such as tingling (paraesthesia),
moderate increase in blood pressure,
colitis,
diarrhoea,
nausea, vomiting,
mouth inflammation or mouth ulcers,
abdominal pain,
increased levels in certain liver function tests,
increased hair loss,
eczema, dry skin, redness, itching,
tendinitis (pain due to inflammation of the sheath covering tendons, usually in feet or hands),
increased levels of certain blood enzymes (creatine phosphokinase),
nerve problems in arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)

decrease in red blood cell count (anaemia) and decrease in platelet count (thrombocytopenia),
decreased potassium levels in the blood,
anxiety,
taste disturbances,
urticaria (red, itchy rash),
tendon rupture,
increased levels of fats in the blood (cholesterol and triglycerides),
decreased phosphate levels in the blood.

Rare side effects (may affect up to 1 in 1,000 people)

increase in a type of white blood cell called eosinophils (eosinophilia); mild decrease in white blood cell count (leucopenia); reduction in all blood cell counts (pancytopenia),
increased blood pressure,
lung inflammation (interstitial lung disease),
increased liver function test values, which may lead to serious clinical conditions such as hepatitis and jaundice,
severe infections known as sepsis, which may be fatal,
increased levels of certain enzymes in the blood (lactate dehydrogenase).

Very rare side effects (may affect up to 1 in 10,000 people)

marked decrease in certain white blood cells (agranulocytosis),
severe and potentially life-threatening 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, which may be fatal,
serious, sometimes fatal, skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

In addition, the following side effects may occur with unknown frequency: kidney failure, decreased levels of uric acid in the blood, pulmonary hypertension, male infertility (which is reversible when treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema in skin areas exposed to light), psoriasis (onset or worsening), DRESS, and skin ulcer (a round, open sore in the skin through which underlying tissue can be seen).

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system detailed in Annex V.
By reporting side effects, you help provide more information on the safety of this medicine.

5. How to store Leflunomide Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging.
The expiry date refers to the last day of the month.
Blister pack: store in the original packaging.
Bottle: keep the bottle tightly closed.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Pack contents and other information

What Leflunomide Zentiva contains

The active substance is leflunomide. Each film-coated tablet contains 10 mg of leflunomide.
The other components are: maize starch, povidone (E1201), crospovidone (E1202), anhydrous colloidal silica, magnesium stearate (E470b) and monohydrate lactose in the tablet core, and talc (E553b), hypromellose (E464), titanium dioxide (E171) and macrogol 8000 in the coating.

Description of the appearance of Leflunomide Zentiva and pack contents
Leflunomide Zentiva 10 mg film-coated tablets are white or almost white and round.
Marked on one side: ZBN.
The tablets are packed in blisters or bottles.
Pack sizes of 30 and 100 tablets are available.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Zentiva k.s.
U kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturer
LABORMED- PHARMA S.A.
B-dul. Theodor Pallady no. 44B, sector 3
code 032266, Bucharest,
Romania
ZENTIVA S.A.
B-dul. Theodor Pallady no. 50, sector 3
code 032266, Bucharest,
Romania

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

België/Belgique/Belgien Lietuva
Zentiva, k.s. Zentiva, k.s.
Tél/Tel: +32 (78) 700 112 Tel: +370 52152025
[email protected] [email protected]

България Luxembourg/Luxemburg
Zentiva, k.s. Zentiva, k.s.
Тел: +35924417136 Tél/Tel: +352 208 82330
[email protected] [email protected]

Česká republika Magyarország
Zentiva, k.s. Zentiva Pharma Kft.
Tel: +420 267 241 111 Tel.: +36 1 299 1058
[email protected] [email protected]

Danmark Malta
Zentiva Denmark ApS Zentiva, k.s.
Tlf.: +45 787 68 400 Tel: +356 2034 1796
[email protected] [email protected]

Deutschland Nederland
Zentiva Pharma GmbH Zentiva, k.s.
Tel: +49 (0) 800 53 53 010 Tel: +31 202 253 638
[email protected] [email protected]

Eesti Norge
Zentiva, k.s. Zentiva Denmark ApS
Tel: +372 52 70308 Tlf: +45 787 68 400
[email protected] [email protected]

Ελλάδα Österreich
Zentiva, k.s. Zentiva, k.s.
Τηλ: +30 211 198 7510 Tel: +43 720 778 877
[email protected] [email protected]

España Polska
Zentiva Spain S.L.U. Zentiva Polska Sp. z o.o.
Tel: +34 671 365 828 Tel: +48 22 375 92 00
[email protected] [email protected]

France Portugal
Zentiva France Zentiva Portugal, Lda
Tél: +33 (0) 800 089 219 Tel: +351 210601360
[email protected] [email protected]

Hrvatska România
Zentiva d.o.o. ZENTIVA S.A.
Tel: +385 1 6641 830 Tel: +4 021.304.7597
[email protected] [email protected]

Ireland Slovenija
Zentiva, k.s. Zentiva, k.s.
Tel: +353 818 882 243 Tel: +386 360 00 408
[email protected] [email protected]

Ísland Slovenská republika
Zentiva Denmark ApS Zentiva, a.s.
Sími: +354 539 5025 Tel: +421 2 3918 3010
[email protected] [email protected]

Italia Suomi/Finland
Zentiva Italia S.r.l. Zentiva Denmark ApS
Tel: +39 800081631 Puh/Tel: +358 942 598 648
[email protected] [email protected]

Κύπρος Sverige
Zentiva, k.s. Zentiva Denmark ApS
Τηλ: +30 211 198 7510 Tel: +46 840 838 822
[email protected] [email protected]

Latvija
Zentiva, k.s.
Tel: +371 67893939
[email protected]

This leaflet was last updated on:

Other sources of information
More detailed information on this medicinal product is available on the website of the European Medicines Agency: https://www.ema.europa.eu/ .

Package leaflet: Information for the user

Leflunomide Zentiva 20 mg film-coated tablets

leflunomide
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 questions, ask your doctor, pharmacist, or nurse.
This medicine has been prescribed for you only. Do not give it to other people, even if their symptoms are the same as yours, as it may be harmful. If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist, or nurse. See section 4.

Contents of this leaflet:

What Leflunomide Zentiva is and what it is used for
What you need to know before taking Leflunomide Zentiva
How to take Leflunomide Zentiva
Possible side effects
How to store Leflunomide Zentiva
Contents of the pack and other information

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

Leflunomide Zentiva belongs to a group of medicines called disease-modifying antirheumatic drugs (DMARDs).
Leflunomide Zentiva is used to treat adult patients with active rheumatoid arthritis or active psoriatic arthritis.
Symptoms of rheumatoid arthritis include joint inflammation, swelling, limited mobility, and pain. Other symptoms that may affect the whole body include loss of appetite, fever, weakness, and anaemia (reduction in the number of red blood cells).
Symptoms of active psoriatic arthritis include joint inflammation, swelling, limited mobility, pain, and red, scaly skin patches (skin lesions).

2. What you need to know before taking Leflunomide Zentiva

Do not take Leflunomide Zentiva

if you have previously had an allergic reaction to leflunomide (especially a severe skin reaction, often accompanied by fever, joint pain, red skin spots or blisters, for example Stevens-Johnson syndrome) or to 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 moderate or severe kidney problems,
if you have extremely low blood protein levels (hypoproteinemia),
if you suffer from any condition affecting your immune system (e.g. AIDS),
if you have any bone marrow disorder, or if your red or white blood cell count is low, or if your platelet count is reduced,
if you have a serious infection,
if you are pregnant, planning a pregnancy, or breastfeeding.

Warnings and precautions
Talk to your doctor, pharmacist, or nurse before taking Leflunomide Zentiva

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 for tuberculosis.
if you are male and intend to father a child. Since it cannot be ruled out that Leflunomide Zentiva passes into semen, a reliable contraceptive method must be used during treatment with Leflunomide Zentiva. Men who intend to father a child should contact their doctor, who may advise stopping treatment with Leflunomide Zentiva and taking certain medications to rapidly and sufficiently eliminate Leflunomide Zentiva from the body. After this, a blood test must be performed to confirm that Leflunomide Zentiva has been sufficiently removed from the body, and then you must wait at least another 3 months before attempting conception.
if you need to undergo a specific blood test (calcium level). Falsely low calcium levels may be observed.
if you are scheduled for or have recently undergone major surgery, or if you still have an unhealed surgical wound. Leflunomide Zentiva may impair wound healing.

Rarely, Leflunomide Zentiva may cause problems affecting the blood, liver, lungs, or nerves in the arms or legs. Leflunomide Zentiva may also cause serious allergic reactions (including drug reaction with eosinophilia and systemic symptoms [DRESS]), or increase the risk of serious infections. For further information, see section 4 (Possible side effects).
DRESS syndrome initially presents with flu-like symptoms and a rash on the face, followed by widespread rash, fever, elevated liver enzymes, increased levels of a type of white blood cell (eosinophilia) in blood tests, and swollen lymph nodes.
Before starting and during treatment with Leflunomide Zentiva, your doctor will prescribe regular blood tests to monitor blood cells and liver function. Your doctor will also regularly check your blood pressure, as Leflunomide Zentiva may cause an increase in blood pressure.
Inform your doctor if you develop unexplained chronic diarrhea. Your doctor may perform additional tests for differential diagnosis.
Inform your doctor if a skin ulcer develops during treatment with Leflunomide Zentiva (see also section 4).

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

Other medicines and Leflunomide Zentiva
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
This information is particularly important if you are taking:

other medicines for the treatment of rheumatoid arthritis, such as antimalarials (e.g. chloroquine and hydroxychloroquine), gold salts administered intramuscularly or orally, D-penicillamine, azathioprine, or other immunosuppressive medicines (e.g. methotrexate), as these combinations are not recommended,
warfarin or other oral anticoagulants (blood thinners), as monitoring is required to reduce the risk of side effects,
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 managing severe diarrhea,
theophylline for asthma,
tizanidine, to relax muscles,
oral contraceptives (containing ethinylestradiol and levonorgestrel),
cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections,
indometacin, ketoprofen for pain or inflammation,
furosemide for heart disease (diuretic, water pill),
zidovudine for HIV infection,
rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol),
sulfasalazine for inflammatory bowel disease or rheumatoid arthritis,
a medicine called colestyramine (used to lower cholesterol) or activated charcoal, as these medicines may reduce the amount of Leflunomide Zentiva absorbed by the body.

If you are already taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, you may continue taking them after starting treatment with Leflunomide Zentiva.

Vaccinations
If you need to be vaccinated, consult your doctor. Certain vaccinations should not be given while taking Leflunomide Zentiva, and for a certain period after stopping treatment.

Leflunomide Zentiva with food, drinks and alcohol
Leflunomide Zentiva can be taken with or without food.
It is recommended not to drink alcohol during treatment with Leflunomide Zentiva. Drinking alcohol while taking Leflunomide Zentiva may increase the risk of liver damage.

Pregnancy and breastfeeding
Do not take Leflunomide Zentiva if you are pregnant or think you might be pregnant. If you become pregnant while taking Leflunomide Zentiva, the risk of having a baby with serious birth defects is increased. Women of childbearing potential must not take Leflunomide Zentiva without using reliable contraception.
If you plan to become pregnant after stopping treatment with Leflunomide Zentiva, it is important to inform your doctor in advance, as you must ensure that all traces of Leflunomide Zentiva have been eliminated from your body before attempting to conceive.
Elimination of Leflunomide Zentiva may take up to two years. This period can be reduced to a few weeks by taking certain medications that accelerate the removal of Leflunomide Zentiva from the body. In both cases, blood tests must confirm that Leflunomide Zentiva has been sufficiently eliminated from the body before attempting pregnancy, and then you must wait at least another month.
For further information on laboratory tests, contact your doctor.
If you suspect you are pregnant during treatment with Leflunomide Zentiva or within two years after stopping treatment, you must inform your doctor immediately, who will arrange for a pregnancy test. If pregnancy is confirmed, your doctor will advise treatment with certain medications to rapidly and sufficiently eliminate Leflunomide Zentiva from your body, thereby reducing the risk to your baby.
Do not take Leflunomide Zentiva during breastfeeding, as leflunomide passes into breast milk.

Driving and using machines
Leflunomide Zentiva may make you feel dizzy, and this sensation may affect your ability to concentrate and react. In this case, do not drive or operate machinery.

Leflunomide Zentiva contains lactose.
If your doctor has informed you that you have an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Leflunomide Zentiva

Always take this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts, consult your doctor or pharmacist.

The initial dose of Leflunomide Zentiva is usually 100 mg of leflunomide once daily for the first three days. Afterwards, most patients require:

for rheumatoid arthritis: a daily dose of 10 or 20 mg of Leflunomide Zentiva, depending on the severity of the disease,
for psoriatic arthritis: a daily dose of 20 mg of Leflunomide Zentiva.

Swallow the tablet whole with plenty of water.

It may take approximately 4 weeks or longer before you begin to notice an improvement in your condition. Some patients may experience further improvements even after 4–6 months of treatment.

Generally, Leflunomide Zentiva is taken for long periods of time.

If you take more Leflunomide Zentiva than you should
If you take more Leflunomide Zentiva than prescribed, contact your doctor or seek medical advice immediately. If possible, bring the tablets or the pack with you to show the doctor.

If you forget to take Leflunomide Zentiva
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 missed dose.

If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Stop treatment with Leflunomide Zentiva and contact your doctor immediately if you:

feel weak, lightheaded, or dizzy, or if you have difficulty breathing, as these signs may indicate a severe allergic reaction,
develop skin redness or mouth ulcers, as these may indicate serious, sometimes fatal, allergic reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms [DRESS]), see section 2.

Contact your doctor immediately if you experience:

pallor, fatigue, or bruising, as these may indicate blood disorders 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 conditions such as liver failure, which can be fatal,
any signs of infection such as fever, sore throat, or cough, as this medicine may increase the risk of serious, potentially life-threatening infections,
cough or breathing difficulties, as these may indicate lung problems (interstitial lung disease or pulmonary hypertension),
tingling, weakness, or unusual pain in the hands or feet, as these may indicate nerve problems (peripheral neuropathy).

Common side effects (may affect up to 1 in 10 people)

mild decrease in white blood cell count (leucopenia),
mild allergic reactions,
loss of appetite, weight loss (usually not significant),
fatigue (asthenia),
headache, dizziness,
abnormal skin sensations such as tingling (paraesthesia),
moderate increase in blood pressure,
colitis,
diarrhoea,
nausea, vomiting,
inflammation of the mouth or mouth ulcers,
abdominal pain,
increased values in some liver function tests,
increased hair loss,
eczema, dry skin, redness, and itching,
tendinitis (pain due to inflammation of the sheath covering tendons, usually in the hands or feet),
increased levels of certain blood enzymes (creatine phosphokinase),
nerve problems in arms or legs (peripheral neuropathy).

Uncommon side effects (may affect up to 1 in 100 people)

decreased number of red blood cells (anaemia) and decreased number of platelets (thrombocytopenia),
decreased potassium levels in the blood,
anxiety,
taste disturbances,
urticaria (itchy red rash),
tendon rupture,
increased levels of fats in the blood (cholesterol and triglycerides),
decreased phosphate levels in the blood.

Rare side effects (may affect up to 1 in 1,000 people)

increased number of a type of white blood cell called eosinophils (eosinophilia); mild decrease in white blood cell count (leucopenia); reduced numbers of all blood cells (pancytopenia),
increased blood pressure,
lung inflammation (interstitial lung disease),
increased liver function test values that may lead to serious clinical conditions such as hepatitis and jaundice,
severe infections known as sepsis, which may be fatal,
increased levels of certain enzymes in the blood (lactate dehydrogenase).

Very rare side effects (may affect up to 1 in 10,000 people)

marked decrease in certain white blood cells (agranulocytosis),
severe and potentially life-threatening 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, which may be fatal,
serious, sometimes fatal, skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Additionally, the following side effects may occur with unknown frequency: kidney failure, decreased levels of uric acid in the blood, pulmonary hypertension, male infertility (which is reversible when treatment with this medicine is stopped), cutaneous lupus (characterized by rash/erythema in skin areas exposed to light), psoriasis (onset or worsening), DRESS, and skin ulcer (a round, open sore in the skin through which underlying tissues can be seen).

Reporting of side effects
If you experience any side effects, including those not listed in this leaflet, inform your doctor or pharmacist. You can also report side effects directly via the national reporting system listed in Annex V.
By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Leflunomide Zentiva

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the outer packaging.
The expiry date refers to the last day of the month.
Blister: store in the original packaging.
Bottle: keep the bottle tightly closed.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package Contents and Other Information

What Leflunomide Zentiva Contains

The active substance is leflunomide. Each film-coated tablet contains 20 mg of leflunomide.
The other components are: maize starch, povidone (E1201), crospovidone (E1202), anhydrous colloidal silica, magnesium stearate (E470b), and monohydrate lactose in the tablet core, as well as talc (E553b), hypromellose (E464), titanium dioxide (E171), macrogol 8000, and yellow iron oxide (E172) in the coating.

Description of the Appearance of Leflunomide Zentiva and Contents of the Pack
Leflunomide Zentiva 20 mg film-coated tablets are yellowish to ochre in colour and triangular in shape.
Marked on one side: ZBO.
The tablets are packed in blisters or bottles.
Pack sizes of 30, 50, and 100 tablets are available.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Zentiva k.s.
U kabelovny 130
102 37 Prague 10
Czech Republic

Manufacturers
LABORMED-PHARMA S.A.
B-dul. Theodor Pallady no. 44B, sector 3
code 032266, Bucharest,
Romania
ZENTIVA S.A.
B-dul. Theodor Pallady no. 50, sector 3
code 032266, Bucharest,
Romania

For further information about this medicinal product, please contact the local representative of the marketing authorization holder.