LEFLUARTIL 20 mg FILM-COATED TABLETS

Introduction

Package Leaflet: Information for the User

Lefluartil 20 mg film-coated tablets EFG

Leflunomide

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 or pharmacist.
• 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 get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the pack

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

1. What is Lefluartil 20 mg and what is it used for

Lefluartil belongs to a group of medicines called antirheumatic medicines.

Lefluartil 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 Lefluartil

Do not take Lefluartil

• if you have ever had an allergic reactionto leflunomide (especially a severe skin reaction, these severe reactions are 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 Lefluartil,
• if you have any liver problems,
• if you have kidney problemsof moderate to severe degree,
• if you have a severe decrease in the concentration of proteins in the blood(hypoproteinemia), if you have any problem that affects your immune system(e.g. AIDS),
• if you have any problem in your bone marrowor 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 pregnantor breastfeeding.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting treatment with Lefluartil:

• 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 wish to have children. As it cannot be excluded that Lefluartil passes into semen, reliable contraceptive methods should be used during treatment with Lefluartil.

Men who wish to have children should contact their doctor, who may advise them to stop treatment with Lefluartil and take certain medications to quickly and sufficiently eliminate Lefluartil from their body. In this case, a blood test will be necessary to ensure that Lefluartil has been sufficiently eliminated from the body and then they should wait at least another 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. Lefluartil may impair wound healing.

Occasionally, Lefluartil can cause some problems in the blood, liver, lungs, or nerves of the arms or legs. It can also cause some severe allergic reactions (including drug rash with eosinophilia and systemic symptoms [DRESS syndrome]), or increase the possibility of suffering a severe infection. 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 and then 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 Lefluartil, to monitor blood cells and liver function. Your doctor should also regularly check your blood pressure, as Lefluartil may cause an increase in blood pressure.

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

Inform your doctor if you develop a skin ulcer during treatment with Lefluartil (see section 4).

Use in children:

The use of Lefluartil is not recommended in children and adolescents under 18 years of age.

Use of other medicines

Inform your doctor or pharmacist if you are using or have recently used other medicines, including those 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 the use of these combinations is not recommended.
• warfarin (used as a blood anticoagulant), as monitoring is necessary 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 Lefluartil absorbed by the body.

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

Vaccinations

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

Taking Lefluartil with food and drinks

Lefluartil can be taken with or without food.

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

Pregnancy and breastfeeding

Do not takeLefluartil if you are or think you may be pregnant. Women of childbearing age should not take Lefluartil without using effective contraceptive measures.

Inform your doctor if you plan to become pregnant after stopping treatment with Lefluartil, as it is necessary to ensure that there are no remaining amounts of Lefluartil 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 medications that accelerate the elimination of Lefluartil from the body. In any case, before becoming pregnant, a blood test must be performed to confirm that Lefluartil 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 Lefluartil or in the 2 years following treatment, you should immediatelycontact your doctor to have a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest that you start treatment with certain medications to accelerate the elimination of Lefluartil from your body, and thus reduce the risk to your child.

Do not takeLefluartil while breastfeeding, as leflunomide passes into breast milk.

Driving and using machines

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

Important information about some of the ingredients of Lefluartil

Lefluartil contains . If your doctor has told you that you have an intolerance to certain sugars, consult them before taking this medicine.

3. How to take Lefluartil 20 mg

Always take Lefluartil exactly as your doctor has told you. Consult your doctor or pharmacist if you have any doubts.

The usual initial dose of Lefluartil is 100 mg once a day for the first three days. After this, most people need a dose of:

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

Swallow the tablet whole and with plenty of water.

• For psoriatic arthritis: 20 mg of Lefluartil once a day.

It may take about 4 weeks or even longer to start noticing an improvement in your condition. Some patients may even notice a new improvement after 4 or 6 months of treatment. In general, Lefluartil should be taken for prolonged periods of time.

If you take more Lefluartil than you should

If you take more Lefluartil than you should, consult your doctor or any other healthcare service. If possible, take the tablets or the box to show the doctor.

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

If you forget to take Lefluartil

If you forget to take a dose, take it as soon as you remember, unless it is almost time to take the next dose. Do not take a double dose to make up for the forgotten dose.

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

4. Possible side effects

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

Tell your doctor immediatelyand stop taking Lefluartil:

• if you feel weak, dizzy or lightheaded, or have difficulty breathing, as these can be symptoms of a severe allergic reaction,

• if you get skin rashesor mouth ulcers, as they may indicate serious reactions that can be life-threatening (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Tell your doctor immediatelyif you experience:

• pale skin, tiredness, or increased tendency to bruise, as they may indicate blood problems caused by an imbalance in the different types of cells that make up the blood,
• tiredness, abdominal pain, or jaundice(yellowing of the eyes or skin), as they may indicate serious problems such as liver failure, which can be life-threatening,

• any symptoms of infectionsuch as fever, sore throat, or cough, as Lefluartil may increase the risk of suffering from severe infections that can be life-threatening,

• coughor respiratory problemsas they may indicate lung inflammation (interstitial lung disease) or pulmonary hypertension.

Common side effects (affecting between 1 and 10 in every 100 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,
• diarrhea,
• nausea, vomiting,
• mouth inflammation, mouth ulcers,
• abdominal pain,
• increase in the results of some liver tests,
• increase in hair loss,
• eczema, dry skin, skin rash, and itching (pruritus),
• tendinitis (pain caused by inflammation of the membrane that surrounds the tendons, usually in the feet or hands),

• increase in the levels of certain enzymes in the blood (creatine phosphokinase).
• colitis

Uncommon side effects (affecting between 1 and 10 in every 1,000 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 disorders,
• skin rash (urticaria),
• tendon rupture,
• increase in blood fat levels (cholesterol and triglycerides),
• decrease in phosphorus levels in the blood.

Rare side effects (affecting between 1 and 10 in every 10,000 people)

• increase in the number of blood cells called red blood cells or 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 that can be symptoms of serious conditions such as hepatitis and jaundice,
• severe infections known as sepsis, which can be life-threatening,
• increase in the levels of certain enzymes in the blood (lactate dehydrogenase).

Very rare side effects (affecting less than 1 in every 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 small blood vessels (vasculitis, including necrotizing cutaneous vasculitis),
• problems in the nerves of the arms and legs (peripheral neuropathies),
• inflammation of the pancreas (pancreatitis),
• severe liver damage such as liver failure or necrosis, which can be life-threatening,
• severe skin reactions that can be life-threatening (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other side effects such as kidney failure, decrease in uric acid levels in the blood, pulmonary hypertension, male infertility (this effect is reversible once treatment with Lefluartil is stopped) may occur with an unknown frequency.

If you think any of the side effects you are experiencing is serious, or if you notice any side effects not listed in this leaflet, tell your doctor or pharmacist.

5. Storage of Lefluartil 20 mg film-coated tablets EFG

Keep out of the reach and sight of children.

Do not use Lefluartil tablets after the expiry date stated on the carton. The expiry date refers to the last day of the month shown.

Store in the original package.

Medicines should not be disposed of via wastewater or household waste. Return any unused medicine to a pharmacy for proper disposal. By doing so, you will help protect the environment.

6. Packaging Content and Additional Information

Composition of Lefluartil 20 mg film-coated tablets EFG

• The active ingredient is leflunomide. Each film-coated tablet contains 20 mg of

leflunomida.

• The other components are: microcrystalline cellulose, lactose monohydrate, pregelatinized starch

(corn starch 1500), povidone (E1201), crospovidone (E1202), anhydrous colloidal silica, magnesium stearate

(E470b) in the tablet core, as well as titanium dioxide (E171), lactose monohydrate, hypromellose 15cP (E464),

macrogol 4000, hypromellose 3cP (E464) and hypromellose 50 cP (E464) in the coating.

Product Appearance and Packaging Content

Lefluartil is presented in the form of yellow, round, and biconvex film-coated tablets.

The tablets are packaged in blisters of 30 and 100 tablets.

Only some package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

ARAFARMA GROUP, S.A.

C/ Fray Gabriel de San Antonio, 6-10

Pol.Ind. del Henares

19180 Marchamalo (Guadalajara). Spain

Date of the Last Revision of this Prospectus:

July 2024

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