Leaflet: information for the user

Lefluartil 20 mg film-coated tablets EFG

Leflunomide

Read this leaflet carefully before you start taking this medicine, because it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you must not give it to others even if they have the same symptoms as you, as it may harm them.
• If you experience any side effects, consult your doctor or pharmacist, even if they are not listed in this leaflet. See section 4.

1. What Lefluartil is and what it is used for

2. What you need to know before you start taking Lefluartil

3. How to take Lefluartil

4. Possible side effects

5. Storage of Lefluartil

6. Contents of the pack and additional information

Lefluartil belongs to a group of medicines called anti-rheumatic 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 affecting the whole body include loss of appetite, fever, lack of energy, and anemia (reduction in the number of red blood cells).

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

Do not take Lefluartil

• if you have ever experienced an allergic reaction to leflunomide (especially a severe skin reaction, these severe reactions are usually accompanied by fever, joint pain, red skin patches, or blisters, for example, Stevens-Johnson syndrome) or to any of the other components of Lefluartil,
• if you have any liver problems,
• if you have moderate to severe kidney problems,
• if you have a severe decrease in the concentration of proteins in your blood (hypoproteinemia), if you have any condition that affects your immune system (for example, HIV),
• if you have any problems with your bone marrow or if you have a reduced number of red or white blood cells in your blood or a reduced number of platelets,

• if you have a severe infection,
• if you are pregnant or breastfeeding.

Warnings and precautions

Consult your doctor, pharmacist, or nurse before starting to take Lefluartil:

• if you have ever experienced inflammation of the lungs (interstitial lung disease)
• if you have ever had tuberculosis or 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 a male and wish to have children.As Lefluartil may pass into the semen, reliable contraceptive methods should be used during treatment with Lefluartil.

Males who wish to have children should contact their doctor, who may advise them to interrupt 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 eliminated sufficiently from their body, and then they should wait at least 3 months before trying to have children.

• if a specific blood test (calcium level) is planned. A false decrease in calcium levels may be detected.
• if you are scheduled to undergo or have recently undergone a major surgical procedure, or if you still have an open wound after a surgical procedure. Lefluartil may impair wound healing.

Lefluartil may occasionally cause some problems in the blood, liver, lungs, or nerves in the arms or legs. It may also cause some severe allergic reactions (including drug eruption with eosinophilia and systemic symptoms [DRESS syndrome]), or increase the risk of a severe infection. For more information on these adverse effects, see section 4 (Possible adverse effects).

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

Your doctor will perform blood tests at regular intervals, before and during treatment with Lefluartil, to monitor blood cells and the liver. 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. Additional tests may be performed to establish a differential diagnosis.

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

Use in children:

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

Use of other medications

Inform your doctor or pharmacist if you are using or have recently used other medications, including those purchased without a prescription.

This is especially important if you are taking:

• other medications for rheumatoid arthritis, such as antimalarials (for example: chloroquine and hydroxychloroquine), gold salts administered intramuscularly or orally, D-penicillamine, azathioprine, and other immunosuppressive medications (for example: methotrexate), as the use of these combinations is not recommended.
• warfarin (used as an anticoagulant), as a control is necessary to reduce the risk of adverse effects of this medication
• 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 control
• theophylline for asthma
• tizanidine, a muscle relaxant
• oral contraceptives (containing ethinylestradiol and levonorgestrel)
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin for infections
• indometacin, ketoprofen for pain or inflammation
• furosemide for heart disease (diuretic, diuretic pills)
• zidovudine for HIV infection
• rosuvastatin, simvastatin, atorvastatin, pravastatin for hypercholesterolemia (high cholesterol)
• sulfasalazine for inflammatory bowel disease or for rheumatoid arthritis
• a medication called cholestyramine (used to reduce high cholesterol) or activated charcoal, as these medications may reduce the amount of Lefluartil absorbed by the body.

If you are taking a nonsteroidal anti-inflammatory drug (NSAID) and/or corticosteroids, you may continue to take 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 treatment is completed.

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. Drinking alcohol during treatment with Lefluartil may increase the risk of liver damage.

Pregnancy and breastfeeding

Do not takeLefluartil if you are or think you may bepregnant.Women of childbearing age should not take

Lefluartil without using effective contraceptive methods.

Inform your doctor if you plan to become pregnant after interrupting treatment with Lefluartil, as it is necessary to ensure that there are no remaining traces of Lefluartil in your body before becoming pregnant. The elimination of the medication from the body may take up to 2 years. This time interval may be reduced to a few weeks by taking certain medications that accelerate the elimination of Lefluartil from the body. In any case, a blood test should be performed before becoming pregnant to confirm that Lefluartil has been eliminated sufficiently 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 Lefluartil or in the 2 years after treatment, you should contact your doctor immediately for a pregnancy test. If the test confirms that you are pregnant, your doctor may suggest that you start taking 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 operating machinery

Lefluartil may cause dizziness, which may affect your ability to concentrate and react. If this happens, do not drive or operate machinery.

Important information about some of the components of Lefluartil

Lefluartil containslactose.If your doctor has told you that you have an intolerance to certain sugars, consult with him before taking this medication.

Always take Lefluartil exactly as your doctor has told you. Consult with 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.

You may take up to 4 weeks or even longer to notice an improvement in your condition. Some patients may even notice a new improvement after 4 or 6 months of treatment. Lefluartil is usually taken for prolonged periods of time.

If you take more Lefluartil than you should

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

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

If you forgot to take Lefluartil

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

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

Like all medications, Lefluartil may cause side effects, although not everyone will experience them.

Inform your doctor immediately and stop taking Lefluartil:

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

symptoms of a severe allergic reaction,

• if you develop skin rashes or mouth ulcers, because it may indicate severe reactions that in some cases can be fatal (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme).

Inform your doctor immediately if you experience:

• paleness, fatigue, or a greater tendency to bruise, because they may indicate blood disorders caused by an imbalance in the different types of cells that make up the blood,
• fatigue, abdominal pain, or jaundice (yellowing of the eyes or skin), because they may indicate severe problems such as liver failure, which could be fatal,

may indicate severe problems such as liver failure, which could be fatal,

• any symptom of infection such as fever, sore throat, or cough, because Lefluartil may increase the risk of severe infections, which could be fatal,

may increase the risk of severe infections, which could be fatal,

• cough or respiratory problems, because they may indicate inflammation of the lungs (interstitial lung disease) or pulmonary hypertension,

may indicate inflammation of the lungs (interstitial lung disease) or pulmonary hypertension,

Frequent side effects (affecting between 1 and 10 in 100 people)

• slight 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),
• slight increase in blood pressure,
• diarrhea,
• nausea, vomiting,
• inflammation of the mouth, mouth ulcers,
• abdominal pain,
• increase in liver function test results that may be symptoms of severe situations such as hepatitis and jaundice,
• hair loss,
• eczema, dry skin, skin rash, and itching (pruritus),
• tendinitis (pain caused by inflammation of the membrane surrounding the tendons of, usually, the feet or hands),

usually, the feet or hands),

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

Rare side effects (affecting between 1 and 10 in 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,
• alterations in taste,
• skin rash (urticaria),
• tendon rupture,
• increase in levels of fat in the blood (cholesterol and triglycerides),
• decrease in levels of phosphorus in the blood.

Very rare side effects (affecting between 1 and 10 in 10,000 people)

• increase in the number of blood cells called red blood cells or eosinophils (eosinophilia), slight 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,
• inflammation of the lungs (interstitial lung disease),
• increase in values of some liver function tests that may be symptoms of severe situations such as hepatitis and jaundice,
• severe infections to which they are called sepsis, which can be fatal,
• increase in levels of certain enzymes in the blood (lactate dehydrogenase).

Very rare side effects (affecting fewer than 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 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 that can be fatal,
• severe skin reactions that can be fatal (Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme).

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

If you consider that any of the side effects you are experiencing are severe or if you notice any side effect not mentioned in this prospectus, inform your doctor or pharmacist.

Keep out of reach and sight of children.

Do not use the Lefluartil tablets after the expiration date shown on the packaging. The expiration date is the last day of the month indicated.

Store in the original packaging.

Medicines should not be disposed of through drains or in the trash. Dispose of the packaging and unused medicines at the SIGRE collection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of unused packaging and medicines.This will help protect the environment.

Composition of Lefluartil 20 mg film-coated tablets

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

leflunomide.

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

starch (cornstarch 1500), povidone (E1201), crospovidone (E1202), colloidal anhydrous

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.

Appearance of the product and contents of the packaging

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

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

Only some package sizes may be commercially marketed.

Holder of the marketing authorization and responsible manufacturer

ARAFARMA GROUP, S.A.

C/ Fray Gabriel de San Antonio, 6-10

Pol.Ind. del Henares

19180 Marchamalo (Guadalajara). Spain

Last review date of this leaflet:

July 2024

Detailed and updated information on this medication is available on the website of the

Spanish Agency for Medicines and Medical Devices (AEMPS)http://www.aemps.es/