LEFLUNOMIDE PHARMATHEN 20 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Leflunomida Pharmathen 20 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. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

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

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

Leflunomida 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 Leflunomida Pharmathen

Do not take Leflunomida Pharmathen

• if you have ever had an allergic reactionto leflunomida (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 starting Leflunomida 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 leflunomida passes into semen, reliable contraceptive methods should be used during treatment with Leflunomida Pharmathen.

Males who want to have children should contact their doctor, who may advise stopping treatment with Leflunomida Pharmathen and taking certain medications to quickly and sufficiently eliminate leflunomida from the body. In this case, a blood test will be necessary to ensure that leflunomida has been sufficiently eliminated from the body, and then you 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. Leflunomida Pharmathen may interfere with wound healing.

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

DRESS syndrome 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 Leflunomida Pharmathen, to monitor blood cells and liver function. Your doctor should also check your blood pressure regularly, as leflunomida 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 Leflunomida Pharmathen (see section 4).

Children and adolescents

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

Other medicines and Leflunomida 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 colestyramine (used to reduce high cholesterol) or activated charcoal, as these medicines may reduce the amount of leflunomida 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 Leflunomida Pharmathen.

Vaccinations

Talk to your doctor if you need to be vaccinated. Some vaccines cannot be administered while you are being treated with Leflunomida Pharmathen or for a certain period after stopping treatment.

Taking Leflunomida Pharmathen with food, drinks, and alcohol

Leflunomida Pharmathen can be taken with or without food.

It is not recommended to consume alcohol during treatment with leflunomida. Alcohol consumption during treatment with Leflunomida Pharmathen may increase the risk of liver damage.

Pregnancy and breast-feeding

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

Tell your doctor if you plan to become pregnant after stopping treatment with Leflunomida Pharmathen, as it is necessary to ensure that there are no remaining amounts of leflunomida 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 leflunomida from the body.

In any case, before becoming pregnant, a blood test must be performed to confirm that leflunomida has been sufficiently eliminated from the 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 leflunomida or in the 2 years after treatment, you should immediatelycontact your doctor for a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest starting treatment with certain medicines to quickly and sufficiently eliminate leflunomida from your body, thereby reducing the risk to your child.

Do nottake Leflunomida Pharmathen while breast-feeding, as leflunomida passes into breast milk.

Driving and using machines

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

Leflunomida 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 Leflunomida Pharmathen

Follow exactly the administration instructions of this medicine given by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

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

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

Swallowthe tablet wholeand with plenty of water.

The score line is only to facilitate 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 further improvement after 4 or 6 months of treatment.

Leflunomida Pharmathen is usually taken for long periods of time.

If you take more Leflunomida Pharmathen than you should

If you take more Leflunomida Pharmathen than you should, talk to your doctor or go to the nearest hospital. If possible, take the tablets or the package 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 Leflunomida 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 Leflunomida Pharmathen:

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

Tell your doctor immediatelyif you experience:

• pale skin, tiredness, or bruising, as these can 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 can 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 can increase the risk of serious infections, which can be life-threatening,
• cough or respiratory problems, as these can indicate lung problems (interstitial lung disease or pulmonary hypertension),
• numbness, weakness, or pain in the hands or feet, as these can 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 (anemia) and platelets (thrombocytopenia) in the blood,
• decrease in potassium levels in the blood,
• anxiety,
• taste disturbances,
• skin rash (urticaria),
• tendon rupture,
• increase in fat levels in the blood (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 eosinophils (a type of white blood cell) in the blood; 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 necrotizing cutaneous vasculitis),
• inflammation of the pancreas (pancreatitis),
• severe liver damage, such as liver failure or necrosis, which can be life-threatening,
• severe reactions that can sometimes be life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme)

Other side effects can also occur, with an unknown frequency, such as kidney failure, decrease in uric acid levels in the blood, pulmonary hypertension, male infertility (this effect is reversible after stopping treatment with this medicine), cutaneous lupus (characterized by skin rash/erythema in sun-exposed areas), psoriasis (new or worsening), DRESS syndrome, and skin ulcers (open sores in the skin through which underlying tissues can be seen), may occur with an unknown frequency.

Reporting of side effects

If you experience any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly to the Spanish Medicines Monitoring System for Human Use: 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 containers and medicines you no longer need at the SIGRE point in your pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

What Leflunomida Pharmathen contains

• The active substance is leflunomida. Each film-coated tablet contains 20 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 OY-SR-6497

[Which consists of:

Titanium dioxide (E171)

Talc

Hypromellose 15cP (E464)

Macrogol 6000

Yellow iron oxide (E172)]

Appearance of the product and package contents

Leflunomida Pharmathen 20 mg film-coated tablets EFG are yellow, round, biconvex tablets with a score line on one side, with a diameter of approximately 8.1 mm. The product is presented in a cardboard box containing OPA/ALU/PVC-Aluminum (Alu/Alu) blister packs or a high-density polyethylene opaque white 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 last revision of this leaflet:September 2024

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