LEFLUNOMIDE AUROBINDO

Package leaflet: Information for the user

Leflunomide Aurobindo 20 mg film-coated tablets

Equivalent medicine
Please read this leaflet carefully before you start taking this medicine, as 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 others, even if they have the same symptoms as you, because it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, talk to your doctor or pharmacist. See section 4.

Contents of this leaflet:

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

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

Leflunomide Aurobindo belongs to a group of medicines called disease-modifying antirheumatic drugs (DMARDs). It contains the
active substance leflunomide.
Leflunomide Aurobindo 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 Aurobindo

Do not take Leflunomide Aurobindo:

• 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 to severe kidney problems;
• if you have extremely low levels of protein in the blood (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 Aurobindo:

• if you have ever suffered from 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 male and wish to father a child. Since it cannot be ruled out that leflunomide passes into semen, you must use a reliable contraceptive method during treatment with Leflunomide Aurobindo. Men who intend to father a child should contact their doctor, who may advise stopping treatment with Leflunomide Aurobindo and taking certain medications to rapidly and sufficiently eliminate leflunomide from the body. Afterwards, a blood test must be performed to confirm that Leflunomide Aurobindo has been sufficiently eliminated from your body, and you must then wait at least another 3 months before attempting conception;
• 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 Aurobindo may impair wound healing.

Rarely, leflunomide may cause blood, liver, lung, or nerve problems (in arms or legs). Leflunomide Aurobindo 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 skin 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 Aurobindo, your doctor will prescribe regular blood tests to monitor blood cells and liver function. Your doctor will also monitor your blood pressure regularly, as leflunomide 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 Aurobindo (see also section 4).

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

Other medicines and Leflunomide Aurobindo
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 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 Aurobindo 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 Aurobindo.

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

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

Pregnancy, breastfeeding and fertility
Do not take Leflunomide Aurobindo if you are pregnant or think you might be pregnant. If you become pregnant while being treated with Leflunomide Aurobindo, the risk of having a baby with serious birth defects is increased. Women of childbearing potential must not take Leflunomide Aurobindo without using reliable contraceptive measures.
If you plan to become pregnant after stopping treatment with Leflunomide Aurobindo, it is important to inform your doctor in advance, as you must ensure that all traces of Leflunomide Aurobindo have been eliminated from your body before attempting to conceive. Elimination of Leflunomide Aurobindo 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 Aurobindo from the body.
In either case, blood tests must confirm that Leflunomide Aurobindo has been sufficiently eliminated from your body before you become pregnant, and you must then wait at least one additional month.
For further information on laboratory tests, contact your doctor.
If you suspect you are pregnant during treatment with Leflunomide Aurobindo 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 Aurobindo from your body, thereby reducing the risk to your baby.

Do not take Leflunomide Aurobindo during breastfeeding, as leflunomide passes into breast milk.

Driving and using machines
Leflunomide may cause dizziness, which may affect your concentration and reaction ability. If this occurs, do not drive or operate machinery.

Leflunomide Aurobindo contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, i.e. it is essentially ‘sodium-free’.

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

3. How to take Leflunomide Aurobindo

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 Aurobindo 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 Aurobindo, depending on the severity of the disease.
• For psoriatic arthritis: a daily dose of 20 mg of Leflunomide Aurobindo.

Swallow the tablet whole with plenty of water.
It may take about 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 Aurobindo is taken for long periods of time.
If you take more Leflunomide Aurobindo than you should
If you take more Leflunomide Aurobindo than prescribed, contact your doctor or seek medical advice immediately. If possible, bring the tablets or the packaging with you to show your doctor.
If you forget to take Leflunomide Aurobindo
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 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 everyone will experience them.
Stop treatment with Leflunomide Aurobindo and contact your doctor immediately if:

• you feel weak, lightheaded or dizzy, or have difficulty breathing, as these signs may indicate a severe allergic reaction;
• you 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 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 (pulmonary interstitial disease, pulmonary hypertension or lung nodule);
• tingling, unusual weakness or 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 (paraesthesiae);
• 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 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)

• increased number of blood cells called eosinophils (eosinophilia); mild decrease in white blood cells (leucopenia); reduction in all blood cell types (pancytopenia);
• increased blood pressure;
• lung inflammation (pulmonary interstitial 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 blood enzymes (lactate dehydrogenase).

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

• marked decrease in certain white blood cells (agranulocytosis);
• severe, 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;
• severe, sometimes fatal reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other side effects with unknown frequency may also occur, such as 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 ulcers (a round, open lesion in the skin through which underlying tissues are visible).

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 at www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you help provide more information on the safety of this medicine.

5. How to store Leflunomide Aurobindo

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the pack and blister after EXP.
The expiry date refers to the last day of that month.
For Al-Al blister packs: Store below 30°C.
For PVC/PVdC-Al blister packs: Store below 25°C.
For HDPE bottle packs: This medicine does not require any special storage precautions.
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 Aurobindo contains

• The active substance is leflunomide. Each tablet contains 20 mg of leflunomide.
• The other components are: Tablet core: Lactose monohydrate, pregelatinized starch (maize starch), povidone (K-30), anhydrous colloidal silica, crospovidone (Type B), magnesium stearate. Tablet coating: Polyvinyl alcohol, talc (E553b), titanium dioxide (E171), glyceryl monocaprylocaprate, sodium lauryl sulfate.

Description of the appearance of Leflunomide Aurobindo and package contents
Film-coated tablets.
Leflunomide Aurobindo 20 mg film-coated tablets: [Size: approximately 7.2 mm]
Film-coated tablet, pale yellow to yellow, round, biconvex, marked ‘LF’ on one side and ‘20’ on the other side.
Leflunomide Aurobindo film-coated tablets are available in blister packs and HDPE bottles.
Pack sizes:
Blister packs: 10, 15, 30, 60, 90 and 100 film-coated tablets.
HDPE bottles: 30 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorization Holder
Aurobindo Pharma (Italia) S.r.l.
via San Giuseppe, 102
21047 - Saronno (VA)
Italy

Manufacturer
APL Swift Services (Malta) Limited
HF26, Hal Far Industrial Estate,
Hal Far, Birzebbugia, BBG 3000
Malta
Generis Farmacêutica, S.A.
Rua Joao De Deus, no 19,
Venda Nova, 2700-487 Amadora
Portugal
Arrow Génériques,
26 Avenue Tony Garnier,
Lyon, 69007
France

This medicinal product is authorised in the European Economic Area countries under the following names:
Belgium: Leflunomide AB 10 mg/20 mg filmomhulde tabletten/comprimés pelliculés/Filmtabletten
France: Leflunomide Arrow 10 mg/20 mg, comprimé pelliculé
Germany: Leflunomid Puren 10 mg/15 mg/20 mg Filmtabletten
Italy: Leflunomide Aurobindo
Netherlands: Leflunomide Aurobindo 10 mg/20 mg, filmomhulde tabletten
Poland: Leflunomide Aurovitas
Portugal: Leflunomida Generis
Spain: Leflunomida Aurovitas 10 mg/20 mg comprimidos recubiertos con película EFG