LEFLUNOMIDE PHARMATHEN 10 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Leflunomide Pharmathen 10 mg film-coated tablets EFG

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 further questions, 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 signs of illness are the same as yours.

• If you experience any side effects, talk to your doctor, pharmacist, or nurse, even if it is not listed in this leaflet. See section 4.

Contents of the pack

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

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

Leflunomide Pharmathen belongs to a group of medicines called antirheumatic medicines. It contains leflunomide as the active substance.

Leflunomide is used to treat adult patients with active rheumatoid arthritis or active psoriatic arthritis.

The symptoms of rheumatoid arthritis include joint inflammation, swelling, difficulty moving, and pain. Other symptoms that affect the whole body include loss of appetite, fever, lack of energy, and anemia (reduction in the number of red blood cells in the blood).

The symptoms of active psoriatic arthritis include joint inflammation, swelling, difficulty moving, pain, red-colored plaques, and scaly skin (skin lesions).

2. What you need to know before you take Leflunomide Pharmathen

Do not take Leflunomide Pharmathen

• if you have ever had an allergic reactionto leflunomide (especially a severe skin reaction, often accompanied by fever, joint pain, red spots on the skin, or blisters, e.g., 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 kidney problemsof moderate to severe degree,
• if you have a severe decrease in blood protein levels(hypoproteinemia),
• if you have any immune system problems(e.g., AIDS),
• if you have any bone marrow problemsor if you have a reduced number of red or white blood cells or platelets in your blood,
• if you have a severe infection,
• if you are pregnant, think you may be pregnant, or are breast-feeding.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start taking Leflunomide Pharmathen

• if you have ever had lung inflammation(interstitial lung disease)
• if you have ever had tuberculosisor if you have been in close contact with someone who has or has had tuberculosis. Your doctor may perform tests to see if you have tuberculosis.
• if you are maleand want to have children. As it cannot be excluded that leflunomide passes into semen, reliable contraceptive methods must be used during treatment with Leflunomide Pharmathen.

Male patients who want to have children should contact their doctor, who may advise them to stop treatment with Leflunomide Pharmathen and take certain medications to quickly and sufficiently eliminate leflunomide from their body. In this case, a blood test will be necessary to ensure that leflunomide has been sufficiently eliminated from their body, and then they should wait at least 3 months before trying to have children.

• if you are scheduled to have a specific blood test (calcium level). A false decrease in calcium levels may be detected.
• if you are going to undergo or have recently undergone major surgery, or if you still have an unhealed wound after surgery. Leflunomide Pharmathen may interfere with wound healing.

Occasionally, Leflunomide Pharmathen may cause some blood, liver, lung, or nerve problems in the arms or legs. It may also cause some severe allergic reactions (including drug rash with eosinophilia and systemic symptoms [DRESS]), or increase the risk of serious infections. For more information on these side effects, see section 4 (Possible side effects).

DRESS initially appears with symptoms similar to those of the flu and a skin rash on the face, followed by a widespread skin rash with fever, elevated liver enzyme levels in the blood, and an increase in a type of white blood cell (eosinophilia) and enlarged lymph nodes.

Your doctor will perform blood testsat regular intervals, before and during treatment with Leflunomide Pharmathen, to monitor blood cells and liver function. Your doctor should also check your blood pressure regularly, as leflunomide may cause an increase in blood pressure.

Talk to your doctor if you experience chronic diarrhea of unknown origin. You may need to undergo additional tests to establish a differential diagnosis.

Tell your doctor if you develop a skin ulcer during treatment with Leflunomide Pharmathen (see section 4).

Children and adolescents

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

Other medicines and Leflunomide Pharmathen

Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. This includes medicines obtained without a prescription.

This is especially important if you are taking:

• other medicines for rheumatoid arthritis, such as antimalarials (e.g., chloroquine and hydroxychloroquine), gold salts by intramuscular or oral route, D-penicillamine, azathioprine, and other immunosuppressive medicines (e.g., methotrexate), as these combinations are not recommended,
• warfarin and other oral medicines used as blood anticoagulants, as monitoring is required to reduce the risk of adverse effects of this medicine
• teriflunomide for multiple sclerosis
• repaglinide, pioglitazone, nateglinide, or rosiglitazone for diabetes
• daunorubicin, doxorubicin, paclitaxel, or topotecan for cancer
• duloxetine for depression, urinary incontinence, or renal insufficiency in diabetics
• alosetron for severe diarrhea
• theophylline for asthma
• tizanidine, a muscle relaxant
• 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 pills)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or rheumatoid arthritis

a medicine called cholestyramine (used to reduce high cholesterol) or activated charcoal, as these medicines may reduce the amount of leflunomide absorbed by the body.

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

Vaccinations

Talk to your doctor if you need to be vaccinated. Some vaccines should not be given while you are being treated with Leflunomide Pharmathen or for a certain period after stopping treatment.

Taking Leflunomide Pharmathen with food, drinks, and alcohol

Leflunomide Pharmathen can be taken with or without food.

It is not recommended to drink alcohol during treatment with leflunomide. Drinking alcohol during treatment with Leflunomide Pharmathen may increase the risk of liver damage.

Pregnancy and breast-feeding

Do nottake Leflunomide Pharmathen if you are or think you may be pregnant. If you are pregnant or become pregnant while taking leflunomide, there is an increased risk of having a child with serious birth defects. Women of childbearing age must not take Leflunomide Pharmathen without using reliable contraceptive methods.

Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomide Pharmathen, as it is necessary to ensure that there are no remaining levels of leflunomide in your body before becoming pregnant. The elimination of the medicine from the body may take up to 2 years. This time period can be reduced to a few weeks by taking certain medicines that accelerate the elimination of leflunomide from the body.

In any case, before becoming pregnant, a blood test must be performed to confirm that leflunomide has been sufficiently eliminated from your body, and once this test has been performed, you should wait at least 1 month before becoming pregnant.

For more information on laboratory tests, contact your doctor.

If you suspect that you may be pregnant during treatment with leflunomide or in the 2 years after treatment, you must immediatelycontact your doctor for a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest that you start treatment with certain medicines to quickly and sufficiently eliminate leflunomide from your body, thereby reducing the risk to your child.

Do nottake Leflunomide Pharmathen while breast-feeding, as leflunomide passes into breast milk.

Driving and using machines

Leflunomide Pharmathen may make you feel dizzy, which may affect your ability to concentrate and react. If this happens, do not drive or use machines.

Leflunomide Pharmathen contains lactose

If your doctor has told you that you have an intolerance to some sugars, contact them before taking this medicine.

3. How to take Leflunomide Pharmathen

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. If you are unsure, talk to your doctor or pharmacist again.

The recommended initial dose of Leflunomide Pharmathen is 100 mg of leflunomide once daily for the first three days. After this, most patients need a dose of:

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

Swallowthe tablet wholeand with plenty of water.

The score line is only for breaking the tablet if you have difficulty swallowing it whole.

It may take about 4 weeks or even longer before you start to feel better. Some patients may even notice improvement after 4 or 6 months of treatment.

Leflunomide Pharmathen is usually taken for long periods of time.

If you take more Leflunomide Pharmathen than you should

If you take more Leflunomide Pharmathen than you should, talk to your doctor or any other healthcare service. If possible, take the tablets or the box with you to show the doctor.

In case of overdose or accidental ingestion, contact your doctor or pharmacist immediately or call the Toxicology Information Service, phone: 91 562 04 20, indicating the medicine and the amount taken.

If you forget to take Leflunomide Pharmathen

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 forgotten doses.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Tell your doctor immediatelyand stop taking Leflunomide Pharmathen:

• if you feel weak, dizzy, or faint, or have difficulty breathing, as these may be symptoms of a severe allergic reaction,
• if you develop skin rashes or mouth ulcers, as these may indicate severe reactions that can be life-threatening (e.g., Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic symptoms [DRESS]), see section 2.

Tell your doctor immediatelyif you experience:

• pale skin, tiredness, or bruising, as these may indicate blood problems caused by an imbalance in the different types of cells that make up the blood,
• tiredness, abdominal pain, or yellowing of the eyes or skin (jaundice), as these may indicate serious problems such as liver failure, which can be life-threatening,
• any symptoms of infection, such as fever, sore throat, or cough, as this medicine may increase the risk of serious infections, which can be life-threatening,
• cough or respiratory problems, as these may indicate lung problems (interstitial lung disease or pulmonary hypertension),
• numbness, 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 the number of white blood cells in the blood (leucopenia),
• mild allergic reactions,
• loss of appetite, weight loss (usually insignificant),
• fatigue (asthenia),
• headache, dizziness,
• abnormal sensations in the skin, such as tingling (paresthesia),
• mild increase in blood pressure,
• colitis,
• diarrhea,
• nausea, vomiting,
• mouth inflammation or mouth ulcers,
• abdominal pain,
• increase in liver test results,
• increase in hair loss,
• eczema, dry skin, skin rash, and itching (pruritus),
• tendinitis (pain caused by inflammation of the membrane surrounding the tendons, usually in the feet or hands),
• increase in certain enzyme levels in the blood (creatine phosphokinase),
• nerve problems in the arms or legs (peripheral neuropathy)

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

• decrease in the number of red blood cells in the blood (anemia) and platelets (thrombocytopenia),
• decrease in potassium levels in the blood,
• anxiety,
• taste disturbances,
• skin rash (urticaria),
• tendon rupture,
• increase in blood fat levels (cholesterol and triglycerides),
• decrease in phosphate levels in the blood.

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

• increase in the number of blood cells called eosinophils (eosinophilia); mild decrease in the number of white blood cells in the blood (leucopenia); and decrease in the number of all blood cells (pancytopenia),

• severe increase in blood pressure,
• lung inflammation (interstitial lung disease),
• increase in liver test values, which can lead to serious conditions such as hepatitis and jaundice,
• serious infections, known as sepsis, which can be life-threatening,
• increase in certain enzyme levels in the blood (lactate dehydrogenase).

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

• significant decrease in the number of certain white blood cells in the blood (agranulocytosis),
• severe allergic reactions and potentially severe allergic reactions,
• inflammation of blood vessels (vasculitis, including cutaneous necrotizing vasculitis),
• inflammation of the pancreas (pancreatitis),
• severe liver damage, such as liver failure or necrosis, which can be life-threatening,
• severe reactions that can be life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)

Other side effects may also occur, with a frequency not known, such as kidney failure, decrease in uric acid levels in the blood, pulmonary hypertension, male infertility (this effect is reversible once treatment with this medicine is stopped), cutaneous lupus (characterized by skin rash/erythema in sun-exposed areas), psoriasis (new or worsening), DRESS, and skin ulcers (open sores in the skin through which underlying tissues can be seen), may occur with a frequency not known.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist, even if it is not listed in this leaflet. You can also report side effects directly to the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting side effects, you can help provide more information on the safety of this medicine.

5. Storage of Leflunomida Pharmathen

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister/pack and on the outer packaging after "EXP". The expiry date is the last day of the month indicated.

Blister: this medicine does not require any special storage conditions.

HDPE bottles: this medicine does not require any special storage conditions.

Medicines should not be disposed of via wastewater or household waste. Deposit the packaging and any unused medicines in the SIGRE collection point at your pharmacy. If you are unsure, ask your pharmacist how to dispose of the packaging and any unused medicines. This will help protect the environment.

6. Package Contents and Additional Information

What Leflunomida Pharmathen contains

• The active ingredient is leflunomida. Each film-coated tablet contains 10 mg of leflunomida.

• The other ingredients are:

Tablet core:

Microcrystalline cellulose M102D+

Pregelatinized corn starch

Povidone K 30 (E1201)

Crospovidone (E1202)

Anhydrous colloidal silica

Magnesium stearate (E470b)

Lactose monohydrate

Film coating:Opadry II White OY-LS-28908

[Which consists of:

Titanium dioxide (E171)

Lactose monohydrate

Hypromellose 15cP (E464)

Hypromellose 3cP (E464)

Hypromellose 50cP (E464)

Macrogol 4000]

Appearance of the Product and Package Contents

• Leflunomida Pharmathen 10 mg film-coated tablets EFG are white, biconvex, round tablets with a diameter of approximately 6.1 mm. The product is presented in a cardboard box containing OPA/ALU/PVC - Aluminum (Alu/Alu) blister packs or a white opaque high-density polyethylene bottle with a tamper-evident closure and a desiccant sachet.

Package sizes: 30, 50, 60, 90, 100 film-coated tablets

Not all package sizes may be marketed.

Marketing Authorization Holder

Pharmathen S.A.

6, Dervenakion str.

Pallini, Attiki

153 51

Greece

Manufacturer

Pharmathen S.A.

Dervenakion 6

Pallini 15351

Attiki,

Greece

Or

Pharmathen International S.A.

Industrial Park Sapes,

Rodopi Prefecture,

Block No 5,

Rodopi 69300,

Greece

Date of the Last Revision of this Leaflet:September 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/