Patient Information Leaflet

Leflunomide Mylan 10 mg film-coated tablets, 20 mg film-coated tablets, 100 mg film-coated tablets

leflunomide
Generic Medicine
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 or pharmacist.
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 effects, including those not listed in this leaflet, inform your doctor or pharmacist. See section 4.

What is in this leaflet:

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

1. What Leflunomide Mylan is and what it is used for
Leflunomide belongs to a group of medicines known as "disease-modifying antirheumatic drugs" (DMARDs). Leflunomide 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 systemic symptoms include loss of appetite, fever, fatigue, and anaemia (reduction in 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 Mylan

Do not take Leflunomide Mylan:

if you are allergic to leflunomide (especially a severe skin reaction, often accompanied by fever, joint pain, red or blistering skin rash, e.g. Stevens-Johnson syndrome), to a medicine called teriflunomide (which is related to leflunomide), or to any of the other ingredients of this medicine (listed in section 6)
if you have liver problems
if you have moderate to severe kidney problems
if you have a very low level of proteins in the blood (hypoproteinemia)
if you have any disorder affecting the immune system (e.g. AIDS)
if you have any bone marrow disorder, or if you have a low number of red or white blood cells or a reduced number of platelets due to causes other than rheumatoid or psoriatic arthritis
if you have a serious infection
if you are pregnant, think you may be pregnant, or are breastfeeding
if you are a woman of childbearing potential and are not using effective contraceptive measures.

Warnings and precautions
Talk to your doctor or pharmacist before taking leflunomide:

if you have previously suffered from 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 a man and wish to father a child. Since it cannot be ruled out that leflunomide passes into semen, a reliable contraceptive method must be used during treatment with leflunomide. Men who wish to father a child should contact their doctor, who may advise stopping Leflunomide Mylan and taking certain medicines to rapidly and sufficiently eliminate leflunomide from the body. A blood test will then be required to confirm that leflunomide has been sufficiently removed from the body, and you must wait at least another 3 months before attempting to conceive a child. if you are due to have a specific blood test (calcium level). It is possible to observe falsely low calcium levels. Leflunomide Mylan may occasionally cause blood, liver, lung, or nerve problems (in arms and legs). It may also cause serious allergic reactions (including Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS]) or increase the risk of serious infections. For more information on this, please read section 4 “Possible side effects”.

Drug Reaction with Eosinophilia and Systemic Symptoms [DRESS] initially presents with flu-like symptoms and a skin rash on the face which then spreads, associated with high fever, increased liver enzyme levels detected in blood tests, increased levels of a type of white blood cell (eosinophilia), and swollen lymph nodes.
Your doctor may prescribe regular blood tests before and during treatment with Leflunomide Mylan to monitor blood cells and liver function. Additionally, your doctor will regularly check your blood pressure, as leflunomide may cause an increase in blood pressure.
Inform your doctor if you have persistent and unexplained diarrhoea. Your doctor may perform additional tests to determine the cause.

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

Other medicines and Leflunomide Mylan
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines.
This is particularly important if you are taking:

other medicines for rheumatoid arthritis, such as antimalarials (e.g. chloroquine and hydroxychloroquine), gold salts (by intramuscular injection or orally), d-penicillamine, azathioprine, tumour necrosis factor alpha inhibitors (e.g. adalimumab, infliximab), or other immunosuppressive medicines (e.g. methotrexate), as these combinations are not recommended
a medicine called cholestyramine (used to lower high cholesterol) or activated charcoal, as these medicines may reduce the amount of leflunomide absorbed by the body
a medicine called teriflunomide (used to treat multiple sclerosis)
warfarin and other oral anticoagulants (blood thinners), as monitoring is required to reduce the risk of side effects
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)
rifampicin (used to treat tuberculosis)
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 hypercholesterolaemia (high cholesterol)
sulfasalazine for inflammatory bowel disease or rheumatoid arthritis
cimetidine (to reduce stomach acid).

If you are already taking a non-steroidal anti-inflammatory drug (NSAID) and/or a corticosteroid, you may continue taking them after starting treatment with Leflunomide Mylan.

Vaccinations
If you need to be vaccinated, consult your doctor. Some vaccines should not be administered while taking leflunomide and for a certain period after stopping treatment.

Leflunomide Mylan and alcohol
It is not recommended to drink alcohol while being treated with leflunomide. Drinking alcohol during treatment with Leflunomide Mylan may increase the risk of liver damage.

Pregnancy and breastfeeding
Pregnancy
Do not take leflunomide if you are pregnant or think you might be pregnant. If you are pregnant or become pregnant while taking leflunomide, the risk of having a baby with serious birth defects is increased. Women of childbearing potential must not take Leflunomide Mylan unless using a reliable method of contraception.
Inform your doctor if you are planning a pregnancy after stopping treatment with Leflunomide Mylan, because it is essential to ensure that any trace of leflunomide has been eliminated from your body before trying to conceive. This may take up to 2 years.
This period can be reduced to a few weeks by taking certain medicines that accelerate the removal of leflunomide from the body.
In either case, a blood test must confirm that leflunomide has been sufficiently eliminated from the body, and you must then wait at least one additional month before attempting to become pregnant.
For further information on laboratory tests, contact your doctor.
If you suspect you have become pregnant while taking Leflunomide Mylan or within two years after stopping it, you must contact your doctor immediately to confirm pregnancy. If pregnancy is confirmed, your doctor may recommend treatment with certain medicines to rapidly and sufficiently eliminate leflunomide from the body, thereby reducing the risk to the fetus.

Breastfeeding
Do not take Leflunomide Mylan if you are breastfeeding, as leflunomide passes into breast milk.

Driving and using machines
Leflunomide Mylan may cause dizziness, which may affect your ability to concentrate and react. If this occurs, you must not drive or operate machinery.

Leflunomide Mylan contains lactose.
If you have been diagnosed by your doctor with an intolerance to certain sugars, consult your doctor before taking this medicine.

3. How to take Leflunomide Mylan

Take this medicine exactly as your doctor or pharmacist has told you.
If you are unsure, consult your doctor or pharmacist.
The recommended starting dose of Leflunomide Mylan is 100 mg once daily for the first
3 days. Afterwards, most patients require a maintenance dose of:

For rheumatoid arthritis: 10 mg or 20 mg of Leflunomide Mylan once daily, depending on the severity of the disease.
For psoriatic arthritis: 20 mg of Leflunomide Mylan once daily.

Swallow the tablet whole with plenty of water. Leflunomide Mylan may be taken
with or without food. The score line is intended to facilitate tablet splitting for ease of
swallowing and is not intended for dividing the tablet into equal doses.
It may take about 4 weeks or longer before you start to feel an improvement in your condition.
Some patients may experience further improvement even after 4–6 months of treatment.
Leflunomide Mylan is usually taken for long periods of time.
If you take more Leflunomide Mylan than you should
If you take more Leflunomide Mylan than prescribed, contact your doctor or seek medical advice immediately.
If possible, take the tablets or the container with you to show the doctor.
You may experience one or more of the following symptoms: stomach pain, diarrhoea, itching, and skin rash.
If you forget to take Leflunomide Mylan
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 or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.
Contact your doctor immediately and stop taking Leflunomide Mylan:

if you experience weakness, feel faint or dizzy, or have difficulty breathing (with or without a rash including flushed, itchy skin, swelling of hands, feet, ankles, face, lips, mouth or throat with difficulty swallowing), as these may be signs of a severe allergic reaction
if you develop a skin rash or inflammation and ulceration in the mouth, as these may indicate serious, sometimes potentially 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 conditions such as inflammation (hepatitis) or liver failure, which can be fatal
any signs of infection such as fever, mouth ulcers (signs of agranulocytosis, marked decrease in certain white blood cells, very rare), sore throat or cough, as this medicine may increase the risk of serious infections, including sepsis (rare), which may be potentially fatal
inflammation of small blood vessels (vasculitis, including necrotizing cutaneous vasculitis)
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 these may indicate nerve problems (peripheral neuropathy)
loss of appetite; abdominal pain; abdominal tenderness; feeling unwell and general malaise, vomiting, fever; these may be signs of inflammation of the pancreas (pancreatitis)
sudden, sharp pain on one or both sides of the back, sudden stabbing pain – this usually starts in the back below the ribs and radiates to the abdomen, and sometimes to the groin and genitals; blood in the urine; feeling unwell or vomiting; frequent urge to urinate, or burning sensation during urination; fever; nausea, vomiting; rash; weight gain; these may be signs of kidney failure
cutaneous lupus (characterized by skin rash/erythema on areas of skin exposed to light)
colitis (causing persistent and unexplained diarrhoea).

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

moderate allergic reactions
loss of appetite or weight (usually not significant)
fatigue (asthenia)
headache, dizziness
abnormal skin sensations such as tingling (paraesthesia)
moderate increase in blood pressure
diarrhoea
nausea, vomiting
abdominal pain
increased levels in liver function tests
increased hair loss
eczema, dry skin, rash, itching
tendinitis (pain caused by inflammation of the membranes surrounding tendons, usually in the feet or hands)
increased levels of certain enzymes in the blood (creatine phosphokinase).

Uncommon (may affect up to 1 in 100 people):

decreased potassium levels in the blood
anxiety
altered sense of taste
urticaria
tendon rupture
increased levels of fats in the blood (cholesterol and triglycerides)
decreased phosphate levels in the blood.

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

increase in blood cells called eosinophils (eosinophilia)
severe increase in blood pressure
increased levels of certain blood enzymes (lactate dehydrogenase).

Not known (frequency cannot be estimated from the available data)
Other side effects may occur, including decreased levels of uric acid in the blood, pulmonary
hypertension, male infertility (which is reversible after discontinuation of treatment with this
medicine), and psoriasis (new onset or worsening).
Medicines such as leflunomide have been associated with an increased risk of developing
tumours.
Reporting of side effects
If you experience any side effects, 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 at
www.agenziafarmaco.gov.it/content/come-segnalare-una-sospetta-reazione-avversa. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Leflunomide Mylan

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister/ bottle and outer packaging,
following the wording “Exp.”. The expiry date refers to the last day of that month.
This medicine does not require any special storage conditions.
Do not dispose of medicines via wastewater or household waste. Ask your pharmacist
how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What Leflunomide Mylan contains
The active substance is leflunomide. One film-coated tablet contains 10, 20 or 100 mg of
leflunomide.
The tablet core contains microcrystalline cellulose, pregelatinized corn starch,
povidone K30 (E1201), crospovidone (E1202), anhydrous colloidal silica, magnesium stearate
(E470b), lactose monohydrate.
The film coating additionally contains titanium dioxide (E171), hypromellose (E464) and macrogol.
The 20 mg tablet also contains talc and yellow iron oxide (E172).
Description of the appearance of Leflunomide Mylan and package contents
Leflunomide Mylan 10 mg film-coated tablets: white, round, biconvex tablets with a diameter of approximately 6.1 mm. The product is packaged in cardboard boxes containing blisters or a bottle with an integrated desiccant (white silica gel) or a desiccant sachet.
The desiccant must not be ingested.
Pack sizes of 30 and 100 film-coated tablets.
Leflunomide Mylan 20 mg film-coated tablets: yellow, round, biconvex tablets with a score line on one side, with a diameter of approximately 8.1 mm. The product is packaged in cardboard boxes containing blisters or a bottle with an integrated desiccant (white silica gel) or a desiccant sachet. The desiccant must not be ingested.
Pack sizes of: 30, 100 and 500 (bottle HDPE only) film-coated tablets.
Leflunomide Mylan 100 mg film-coated tablets: white, oblong, biconvex tablets with a score line on one side, measuring approximately 19.4 mm x 7.8 mm. The product is packaged in cardboard boxes containing blisters. Pack sizes of 3 film-coated tablets.
The score line is provided only to facilitate breaking the tablet if there is difficulty swallowing it whole and is not intended for dividing the tablet into equal doses.
Not all pack sizes may be marketed.
Marketing Authorization Holder:
Mylan S.p.A., Via Vittor Pisani 20, 20124 Milano
Manufacturers:
Pharmathen S.A., 6, Dervenakion str., Pallini Attiki, Hellas, Greece
Pharmathen International S.A., Industrial Park Sapes, Rodopi Prefecture, Block No 5, Rodopi
69300, Hellas, Greece
McDermott Laboratories Limited trading as Gerard Laboratories, 35/36 Baldoyle Industrial
Estate, Grange Road, Dublin 13, Ireland
This medicinal product is authorized in the Member States of the European Economic Area under the following names:
Czech Republic Leflugen 20 mg, potahované tablety
France LEFLUNOMIDE MYLAN 10 mg, comprimé pelliculé
LEFLUNOMIDE MYLAN 20 mg, comprimé pelliculé
Germany Leflunomid Mylan 10 mg Filmtabletten
Leflunomid Mylan 20 mg Filmtabletten
Leflunomid Mylan 100 mg Filmtabletten
Italy LEFLUNOMIDE MYLAN
Spain Leflunomida MYLAN 10 mg comprimidos recubiertos con película
EFG
Leflunomida MYLAN 20 mg comprimidos recubiertos con película
EFG
Netherlands Leflunomide Mylan 10 mg, filmomhulde tabletten
Leflunomide Mylan 20 mg, filmomhulde tabletten
Leflunomide Mylan 100 mg, filmomhulde tabletten
United Kingdom Leflunomide Mylan 10 mg film-coated tablets
Leflunomide Mylan 20 mg film-coated tablets