Leflunomide bluefish

Patient Information Leaflet

Leflunomid Bluefish, 10 mg, film-coated tablets
leflunomide
Please read all of this leaflet carefully before 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 personally. Do not pass it on to others. It may harm someone else, even if their symptoms are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist, or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Leaflet contents:

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

1. What Leflunomid Bluefish is and what it is used for

Leflunomid Bluefish belongs to a group of medicines called disease-modifying antirheumatic drugs (DMARDs). It contains the active substance leflunomide.
Leflunomid Bluefish is used in adult patients for the treatment of active rheumatoid arthritis or active psoriatic arthritis.
Symptoms of rheumatoid arthritis include joint inflammation, swelling, difficulty in moving, and pain. Other symptoms affecting the whole body include loss of appetite, fever, loss of energy, and anaemia (lack of red blood cells).
Symptoms of psoriatic arthritis include joint inflammation, swelling, difficulty in moving, pain, as well as redness and flaking of the skin (skin changes).

2. Important information before using Leflunomid Bluefish

When not to use Leflunomid Bluefish

• if the patient has ever had an allergic reaction to leflunomide (especially severe skin reactions, often accompanied by fever, joint pain, red spots or blisters on the skin, e.g. Stevens-Johnson syndrome), to peanuts or soy, or to any of the other ingredients of this medicine (listed in section 6), or if allergic to teriflunomide (used in the treatment of multiple sclerosis),
• if the patient has impaired liver function,
• if the patient has moderate to severe impairment of kidney function,
• if the patient has a significant decrease in blood protein levels (hypoproteinaemia),
• if the patient has any disease that reduces the body's immunity (e.g. AIDS),
• if the patient has bone marrow disorders or a significantly reduced number of red blood cells, white blood cells or platelets,
• if the patient has a serious infection,
• if the patient is pregnant, suspects she may be pregnant, or is breastfeeding.

Warnings and precautions
Before starting treatment with Leflunomid Bluefish, consult your doctor,
pharmacist or nurse

• if the patient has ever had interstitial lung disease,
• if the patient has ever had tuberculosis or has had contact with someone who has or had tuberculosis in the past. The doctor may recommend screening tests to check whether the patient has tuberculosis,
• if the patient is a man planning to father a child. Since it cannot be ruled out that Leflunomid Bluefish passes into semen and may affect the foetus, patients taking Leflunomid Bluefish should use effective contraception. A man planning to father a child should contact his doctor, who may advise discontinuing Leflunomid Bluefish and recommend medications to accelerate elimination of Leflunomid Bluefish from the body. Effective elimination of the drug must be confirmed by appropriate blood tests, and a decision about fatherhood should not be made earlier than 3 months after this point,
• if the patient is to undergo a specific blood test (calcium level measurement). The results of calcium level tests may be falsely low.
• if the patient is undergoing or has recently undergone major surgery, or if the patient still has an unhealed surgical wound. Leflunomid Bluefish may impair wound healing.

Leflunomid Bluefish may occasionally cause blood count abnormalities, liver or lung function disorders,
or problems with the nerves in the hands or feet. It may also cause serious allergic reactions (including
drug rash with eosinophilia and systemic symptoms - DRESS) or increase the risk of serious infections.
For more information on this, see section 4 (Possible side effects).
DRESS initially presents as flu-like symptoms and a rash on the face,
followed by a rash spreading to other parts of the body and high fever, elevated
liver enzymes (detectable in blood tests), increased levels of certain white blood cells
(eosinophilia), and enlarged lymph nodes.
Before starting treatment with Leflunomid Bluefish and during its use, the treating physician
should order regular blood tests to monitor blood counts and liver function. Blood pressure
should also be monitored regularly, as Leflunomid Bluefish may increase it.
Inform your doctor if you experience unexplained chronic diarrhoea. The doctor may
perform additional tests for differential diagnosis.
Inform your doctor if skin ulceration occurs during treatment with Leflunomid Bluefish (see section 4).
Children and adolescents
Leflunomid Bluefish is not recommended for use in children and adolescents under 18 years of age.
Leflunomid Bluefish and other medicines
Tell your doctor or pharmacist about all medicines you are currently taking or have recently taken,
as well as any medicines you plan to take. This includes medicines available without a prescription.
This is particularly important if the patient is taking:

• other medicines used for rheumatoid arthritis, such as antimalarials (e.g. chloroquine and hydroxychloroquine), intramuscular or oral gold preparations,
  D-penicillamine, azathioprine, and other immunosuppressive medicines (e.g. methotrexate), as such
  combinations are not recommended,

• warfarin and other oral medicines used to reduce blood clotting, as patient monitoring is required to reduce the risk of adverse effects of this medicine,

• teriflunomide, used in the treatment of multiple sclerosis,

• repaglinide, pioglitazone, nateglinide, or rosiglitazone used in the treatment of diabetes,

• daunorubicin, doxorubicin, paclitaxel, or topotecan used in cancer treatment,

• duloxetine used in the treatment of depression, urinary incontinence, or kidney disease in diabetic patients,

• alosetron used in the treatment of acute diarrhoea,

• theophylline used in the treatment of asthma,

• tizanidine, a muscle relaxant,

• oral contraceptives (containing ethinylestradiol and levonorgestrel),

• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin used in the treatment of infections,

• indomethacin, ketoprofen used in the treatment of pain or inflammation,

• furosemide used in the treatment of heart disease (a diuretic),

• zidovudine used in the treatment of HIV infections,

• rosuvastatin, simvastatin, atorvastatin, pravastatin used in the treatment of hypercholesterolaemia (high cholesterol levels),

• sulfasalazine used in the treatment of inflammatory bowel disease and rheumatoid arthritis,

• cholestyramine (used in the treatment of increased serum lipid levels) and activated charcoal, which may reduce the binding of Leflunomid Bluefish to proteins and thereby reduce its effectiveness.

A patient using non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids may
continue treatment with these medicines after starting Leflunomid Bluefish.
Vaccinations
If planning vaccinations, consult your doctor. While taking Leflunomid Bluefish and for some time
after stopping treatment with this medicine, vaccinations should not be administered.
Leflunomid Bluefish with food, drink and alcohol
Leflunomid Bluefish may be taken with food or independently of meals.
Consumption of alcoholic beverages is not recommended during treatment with Leflunomid Bluefish. Drinking
alcohol during therapy with Leflunomid Bluefish may increase the risk of liver damage.
Pregnancy and breastfeeding
Do not use Leflunomid Bluefish if the patient is pregnant or suspects she may be pregnant. If Leflunomid Bluefish is taken during pregnancy or if pregnancy is planned while taking this medicine, there is an increased risk of severe congenital malformations in the child. Leflunomid Bluefish must not be used in women of childbearing potential unless they are using effective contraception.
Inform your treating doctor if a woman plans to become pregnant after completing treatment with Leflunomid Bluefish, to ensure that Leflunomid Bluefish has been completely eliminated from the body before conception. The elimination period may take up to 2 years. However, this time can be shortened to several weeks by taking medicines that accelerate the elimination of Leflunomid Bluefish from the body.
In all cases, appropriate blood tests should be performed to confirm that elimination of the drug has been sufficiently effective. After obtaining a normal result, wait at least one month before attempting conception.
For more information about the laboratory test, consult your treating doctor.
If a patient suspects she may be pregnant while taking Leflunomid Bluefish or if less than 2 years have passed since stopping treatment, she should immediately contact her doctor
to perform pregnancy tests. If test results confirm pregnancy, the doctor may recommend
treatment with medicines that rapidly and effectively eliminate Leflunomid Bluefish from the body, which may
reduce the risk to the foetus.
Do not use Leflunomid Bluefish during breastfeeding, as leflunomide passes into breast milk.
Driving and operating machinery
Leflunomid Bluefish may cause dizziness, which may impair concentration and reaction speed.
Patients must not drive or operate machinery if such effects occur.
Leflunomid Bluefish contains lactose
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should
consult a doctor before taking this medicine.
Leflunomid Bluefish contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per 10 mg tablet, meaning the medicine is considered "sodium-free".
Leflunomid Bluefish contains soy lecithin
Do not use if hypersensitivity to peanuts or soy has been diagnosed.

3. How to use Leflunomid Bluefish
This medicine should always be used exactly as prescribed by the doctor or pharmacist. In case of
doubt, consult the doctor or pharmacist.
The usual initial dose of Leflunomid Bluefish is 100 mg of leflunomide once daily for the first three days. From the fourth day onwards, effective doses for most patients are:

• for the treatment of rheumatoid arthritis: 10 or 20 mg of Leflunomid Bluefish once daily, depending on disease severity.
• for the treatment of active psoriatic arthritis: 20 mg of Leflunomid Bluefish once daily.

The tablet should be swallowed whole, taken with a large amount of water.
Noticeable improvement in health may occur 4 weeks after starting treatment. Some
patients experience further improvement after 4 to 6 months of treatment.
Leflunomid Bluefish is usually taken for a long period.
Taking more than the recommended dose of Leflunomid Bluefish
If more than the recommended dose of Leflunomid Bluefish is taken, contact a doctor or seek medical advice. If possible, bring the tablets or packaging to show the doctor.
Missing a dose of Leflunomid Bluefish
If a dose is missed, take it as soon as remembered, provided the next dose is not due soon. Do not take a double dose to make up for a missed dose.
If you have any further questions about the use of this medicine, consult your
doctor, pharmacist or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
You must immediately inform your doctor and stop using Leflunomid Bluefish if:

• you experience weakness, mild dizziness or breathing difficulties, as these may be symptoms of a serious allergic reaction,
• you develop a skin rash or mouth ulcers, which may indicate serious, sometimes life-threatening reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug rash with eosinophilia and systemic symptoms - DRESS), see section 2.

You must immediately inform your doctor if you experience:

• pallor, feeling of fatigue, increased tendency to infections or bruising, which may indicate blood disorders caused by imbalance in different types of blood cells,
• feeling of fatigue, abdominal pain or jaundice (yellowing of eyes or skin), which may indicate serious liver disease that may lead to death,
• signs of infection, such as fever, sore throat or cough, because this medicine may increase the risk of serious, potentially life-threatening infections,
• cough or breathing difficulties, which may indicate lung disease (interstitial lung disease or pulmonary hypertension),
• unusual tingling, weakness or pain in hands or feet, which may indicate nerve problems (peripheral neuropathy).

Common (may affect up to 1 in 10 patients)

• slight decrease in white blood cell count (leukopenia),
• mild allergic reactions,
• loss of appetite, weight loss (usually mild),
• weakness (asthenia),
• headache, dizziness,
• unusual sensory sensations such as tingling (paresthesia),
• mild increase in blood pressure,
• colitis,
• diarrhea,
• nausea, vomiting,
• inflammation of the mouth or mouth ulcers,
• abdominal pain,
• increased levels of certain liver function parameters,
• increased hair loss,
• rash, dry skin, redness and itching of the skin,
• tendonitis (pain due to inflammation of the membrane surrounding tendons, usually in the hands and feet),
• increased activity of certain enzymes in blood (creatine kinase),
• nerve problems in arms or legs (peripheral neuropathy).

Uncommon (may affect up to 1 in 100 patients)

• decreased number of red blood cells (anemia) and decreased number of platelets (thrombocytopenia),
• decreased potassium levels in blood,
• anxiety,
• taste disturbances,
• urticaria (hives),
• tendon rupture,
• increased blood lipid levels (cholesterol and triglycerides),
• decreased phosphate levels in blood.

Rare (may affect up to 1 in 1,000 patients)

• increased number of eosinophils in blood, called eosinophilia, mild decrease in white blood cell count (leukopenia), decrease in all types of blood cells (pancytopenia),
• severe increase in blood pressure,
• lung inflammation (interstitial lung disease),
• severe increase in certain liver function parameters, potentially leading to serious disorders such as hepatitis and jaundice,
• severe infections called sepsis, which may lead to death,
• increased activity of certain enzymes in blood (lactate dehydrogenase).

Very rare (may affect up to 1 in 10,000 patients)

• significant decrease in certain white blood cells (agranulocytosis),
• severe and potentially severe allergic reactions,
• blood vessel inflammation (vasculitis, including cutaneous necrotizing vasculitis),
• pancreatitis,
• severe liver damage, such as liver failure or necrosis, which may lead to death,
• severe, sometimes life-threatening skin reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).

Other adverse reactions, such as kidney failure, decreased uric acid levels in blood, pulmonary hypertension, male infertility (transient after discontinuation of treatment with this medicine), cutaneous lupus erythematosus (characterized by rash/redness on skin areas exposed to light), psoriasis (new onset or worsening of symptoms), DRESS and skin ulceration (a round, open wound in the skin through which subcutaneous tissues are visible), may also occur with unknown frequency.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181 C, PL-02 222 Warsaw, Tel.: +48 22 49 21 301, Fax: +48 22 49 21 309, Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps provide more information on the safety of this medicine.

5. How to store Leflunomid Bluefish
Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the bottle and carton after "Expiry date (EXP)". The expiry date refers to the last day of the stated month.
Keep the bottle tightly closed to protect from moisture.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help protect the environment.

6. Contents of the pack and other information

What Leflunomid Bluefish contains

• The active substance is leflunomide. One film-coated tablet contains 10 mg of leflunomide.
• The other ingredients are:
  Tablet core: monohydrate lactose, hydroxypropylcellulose (low substituted), tartaric acid, sodium lauryl sulfate, magnesium stearate.
  Tablet coating: lecithin (soy), polyvinyl alcohol, talc, titanium dioxide (E 171) and xanthan gum.

What Leflunomid Bluefish looks like and contents of the pack
Leflunomid Bluefish 10 mg film-coated tablets are white or almost white, round, with a diameter of approximately 6 mm.
The film-coated tablets are packed in bottles.
Pack sizes: 30 film-coated tablets.

Marketing Authorisation Holder:
Bluefish Pharmaceuticals AB
P.O. Box 49013
100 28 Stockholm
Sweden

Manufacturer:
Bluefish Pharmaceuticals AB
Gävlegatan 22
113 30 Stockholm
Sweden

Haupt Pharma Münster GmbH
Schleebrüggenkamp 15
48159 Münster
Germany

This medicinal product is authorised in the European Economic Area countries under the following names: