Package leaflet: Information for the patient

Leflunomide Orion, 20 mg, film-coated tablets
leflunomide
Please read this leaflet carefully before taking the medicine, as it contains
important information for the patient.

Keep this leaflet so that you can read it again if necessary.
If you have any questions, please consult your doctor or pharmacist.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If you experience any adverse reactions, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Table of contents of the leaflet

What Leflunomide Orion is and what it is used for
Important information before taking Leflunomide Orion
How to take Leflunomide Orion
Possible side effects
How to store Leflunomide Orion
Contents of the pack and other information

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

Leflunomide Orion belongs to a group of medicines called disease-modifying antirheumatic drugs (DMARDs). It contains the active substance leflunomide.
Leflunomide Orion 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 movement, and pain. Other systemic symptoms include loss of appetite, fever, fatigue, and anaemia (deficiency of red blood cells).
Symptoms of psoriatic arthritis include joint inflammation, swelling, difficulty in movement, pain, as well as redness and scaling of the skin (pathological skin changes).

2. Important information before taking Leflunomide Orion

When not to take Leflunomide Orion

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]) or to any of the other ingredients of this medicine (listed in section 6)
if the patient is 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 (hypoproteinemia)
if the patient has any disease that reduces the body's immunity (e.g. AIDS)
if the patient has bone marrow disorders or significantly reduced numbers of red blood cells, white blood cells, or platelets
if the patient has a severe infection
if the patient is pregnant, suspects she may be pregnant, or is breastfeeding.

Warnings and precautions
Before starting treatment with Leflunomide Orion, discuss this with your doctor or
pharmacist if:

the patient has ever had lung inflammation (interstitial lung disease).
the patient has ever had tuberculosis or has had close contact with someone who has or has previously had tuberculosis. The doctor may order tests to determine whether the patient has tuberculosis.
the patient is a man and is planning to father a child. It cannot be ruled out that Leflunomide Orion passes into semen; therefore, effective contraception should be used during treatment. Men planning fatherhood should consult their doctor, who may advise discontinuing Leflunomide Orion and recommend appropriate treatment to rapidly and effectively eliminate the drug from the body. Effective elimination of the drug must be confirmed by appropriate blood tests. The decision to father a child should not be made earlier than 3 months after this point.
the patient is due to have or has had a specific blood test (calcium level measurement). Results of calcium level tests may be falsely low.
if the patient is undergoing or has undergone major surgery, or still has an unhealed surgical wound. Leflunomide Orion may impair wound healing.

Leflunomide Orion may rarely cause blood disorders, liver or lung dysfunction, or neuropathy in the hands or feet. It may also cause severe allergic reactions (including drug rash with eosinophilia and systemic symptoms - DRESS) or increase the risk of serious infections. More information on this can be found in section 4 "Possible side effects".
The DRESS syndrome initially presents with flu-like symptoms and facial rash, followed by spreading rash, high fever, increased liver enzyme activity and elevated levels of certain white blood cells (eosinophilia) in blood tests, as well as enlarged lymph nodes.
Before starting treatment with Leflunomide Orion and regularly during treatment, the doctor will recommend blood tests to monitor blood counts and liver function. The doctor will also recommend regular monitoring of blood pressure, as Leflunomide Orion may cause an increase in blood pressure.
If the patient develops chronic diarrhoea of unknown cause, medical advice should be sought. The doctor may order additional tests to establish a diagnosis.
Inform the doctor if skin ulceration occurs during treatment with Leflunomide Orion (see also section 4).
Children and adolescents
Leflunomide Orion is not recommended for use in children and adolescents under 18 years of age.
Leflunomide Orion and other medicines
Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, as well as any medicines the patient plans to take.
This is particularly important if the patient is taking:

other medicines used to treat rheumatoid arthritis, such as antimalarial drugs (e.g. chloroquine and hydroxychloroquine), gold-containing products administered intramuscularly or orally, D-penicillamine, azathioprine, and other immunosuppressive drugs (e.g. methotrexate), as such combinations are not recommended
warfarin and other oral anticoagulants, as monitoring is required to reduce the risk of adverse effects
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 severe 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
indometacin, ketoprofen, used in the treatment of pain or inflammation
furosemide, used in the treatment of heart disease (a diuretic, water tablet)
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 to reduce high cholesterol levels) and activated charcoal, as they may reduce the absorption of Leflunomide Orion.

If the patient is taking non-steroidal anti-inflammatory drugs (NSAIDs) and/or corticosteroids, treatment with these medicines may be continued after starting Leflunomide Orion.
Vaccinations
If the patient plans to be vaccinated, they should consult their doctor. Certain vaccines should not be administered during or for some time after treatment with Leflunomide Orion.
Leflunomide Orion with food, drink and alcohol
Leflunomide Orion may be taken with food or independently of meals.
Alcohol
Consumption of alcoholic beverages is not recommended during treatment with Leflunomide Orion. Drinking alcohol during treatment with Leflunomide Orion may increase the risk of liver damage.
Pregnancy, breastfeeding and fertility
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult her doctor or pharmacist before using this medicine.
Do not take Leflunomide Orion if the patient is pregnant or suspects she may be pregnant. If a woman is pregnant or becomes pregnant while taking Leflunomide Orion, there is an increased risk of severe congenital malformations in the child. Women of childbearing potential must not use Leflunomide Orion unless they are using effective contraception.
Women planning pregnancy after discontinuation of Leflunomide Orion should inform their doctor, as it is necessary to ensure in advance that Leflunomide Orion has been completely eliminated from the body. This may take up to 2 years. However, this period can be shortened to several weeks by taking medications that accelerate the elimination of Leflunomide Orion from the body. In each case, appropriate blood tests must be performed to confirm that Leflunomide Orion has been effectively eliminated from the body. After obtaining normal test results, at least one month should be waited before attempting pregnancy.
For more information about the laboratory test, consult the treating physician.
If the patient suspects she has become pregnant during treatment with Leflunomide Orion or within 2 years after its discontinuation, she should immediately contact her doctor to perform a pregnancy test. If the test confirms pregnancy, the doctor may recommend specific medications to rapidly and effectively eliminate Leflunomide Orion from the body, which may reduce the risk to the child.
Do not take Leflunomide Orion during breastfeeding, as leflunomide passes into breast milk.
Driving and operating machinery
Leflunomide Orion may cause dizziness, which may impair concentration and reaction speed. If this occurs, driving or operating machinery should not be undertaken.
Leflunomide Orion contains lactose
This medicine contains 36 mg of lactose (as monohydrate). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult their doctor before taking this medicine.
3. How to take Leflunomide Orion
This medicine should always be taken exactly as prescribed by the doctor or pharmacist. If in doubt, consult the doctor or pharmacist.
The usual initial dose is 100 mg of leflunomide (five tablets of Leflunomide Orion) once daily for the first three days. After this period, most patients are given:

For the treatment of rheumatoid arthritis: 10 or 20 mg of Leflunomide Orion once daily, depending on the severity of the disease. For a 10 mg dose, the doctor may prescribe another medicine containing leflunomide to achieve the appropriate dose for the patient.
For the treatment of active psoriatic arthritis: 20 mg of Leflunomide Orion once daily.

The tablet should be swallowed whole with a large amount of water.
The break line on the tablet is intended only to facilitate breaking the tablet for easier swallowing.
Noticeable improvement in health may occur after 4 weeks or longer from the start of treatment. Some patients experience further improvement after 4 to 6 months of treatment. Leflunomide Orion is usually taken for a long duration.
Taking more than the recommended dose of Leflunomide Orion
If more than the recommended dose of Leflunomide Orion is taken, contact a doctor or seek medical advice immediately. If possible, bring the tablets or packaging to show the doctor.
Missing a dose of Leflunomide Orion
If a dose is missed, take it as soon as remembered, unless it is almost time for the next dose. Do not take a double dose to make up for a missed dose.
If there are any further doubts regarding the use of this medicine, consult the doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
You should immediately inform your doctor and stop taking Leflunomide Orion if:

you experience weakness, mild dizziness or vertigo, or difficulty breathing, as these may be symptoms of a severe allergic reaction
you develop a skin rash or mouth ulcers, as these may indicate serious, sometimes life-threatening reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, drug reaction with eosinophilia and systemic symptoms [DRESS]). See section 2 "Warnings and precautions".

You should promptly inform your doctor if the patient experiences:

pale skin, feeling tired, or tendency to bruise easily, as these may be symptoms of blood disorders caused by imbalance between different types of blood cells
feeling tired, abdominal pain, or jaundice (yellowing of the eyes or skin), as these may indicate serious conditions such as liver failure, sometimes leading to death
symptoms of infection, such as fever, sore throat, or cough, as this medicine may increase the risk of severe, potentially life-threatening infections
cough or difficulty breathing, as these may indicate lung disease (interstitial lung disease or pulmonary hypertension or lung nodule)
unusual tingling, weakness, or pain in the hands or feet, as these symptoms may indicate nerve disorders (peripheral neuropathy).

Frequent (may affect up to 1 in 10 people):

slight decrease in white blood cell count (leukopenia)
mild allergic reactions
loss of appetite, weight loss (usually slight)
weakness (asthenia)
headache and dizziness
unusual sensory sensations such as tingling (paresthesia)
slight increase in blood pressure
colitis
diarrhea
nausea, vomiting
inflammation or ulceration of the mouth
abdominal pain
increased values in certain liver function tests
increased hair loss
rash, dry skin, skin rash and itching
tendonitis (pain caused by inflammation of the membrane surrounding tendons, usually in the area of feet and hands)
increased activity of certain enzymes in blood (creatine kinase)
nerve disorders in hands or legs (peripheral neuropathy)

Uncommon (may affect up to 1 in 100 people):

decrease in red blood cells (anemia) and decrease in 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 people):

increased number of eosinophils in blood (eosinophilia), slight decrease in white blood cells (leukopenia), decrease in all types of blood cells (pancytopenia)
significant increase in blood pressure
lung inflammation (interstitial lung disease)
increased values of certain liver function parameters, which may indicate development of serious disorders such as hepatitis and jaundice
severe infections called sepsis, which may result in death
increased activity of certain enzymes in blood (lactate dehydrogenase)

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

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

Frequency not known (frequency cannot be estimated from available data):

kidney failure
decreased uric acid levels in blood
pulmonary hypertension
male infertility (reversible after discontinuation of this medicine)
cutaneous lupus erythematosus (characterized by rash and/or redness in areas of skin exposed to light), psoriasis (new onset or worsening of existing disease), DRESS syndrome and skin ulcers (round, open wound in the skin through which subcutaneous tissues are visible)

Reporting of side effects
If any adverse reactions occur, including any adverse reactions not listed
in this leaflet, you should 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 to provide more information on the safety of the medicine.

5. How to store Leflunomide Orion
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and carton. The expiry date refers to the last day of the stated month.
No special storage conditions are required for this medicine.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help protect the environment.

6. Contents of the pack and other information

What Leflunomide Orion contains

The active substance is leflunomide. Each tablet contains 20 mg of leflunomide.
Other components of the medicine are:
Tablet core: Microcrystalline cellulose, lactose monohydrate (type 102), pregelatinized corn starch, crospovidone, povidone (K 30), colloidal anhydrous silica, magnesium stearate.
Tablet coating Opadry Yellow OY-SR-6497: Hypromellose 2910 (15 cP), titanium dioxide (E 171), macrogol 6000, talc, iron oxide yellow (E 172).

What Leflunomide Orion looks like and contents of the pack
Yellow, round, biconvex coated tablets with a break line on one side, approximately 8 mm in diameter.
Coated tablets are packed in blisters and placed in cardboard boxes.
Pack sizes: 30 tablets.

Marketing Authorisation Holder
Orion Corporation
Orionintie 1
02200 Espoo
Finland

Manufacturer
Orion Corporation Orion Pharma
Orionintie 1
02200 Espoo
Finland
Pharmathen S.A.
Dervenakion 6
15351 Pallini
Attiki
Greece
Pharmathen International S.A.
Industrial Park Sapes
Rodopi Prefecture, Block No 5
69300 Rodopi
Greece

For further information about this medicine, please contact the local representative of the Marketing Authorisation Holder:
Orion Pharma Poland Sp. z o.o.
[email protected]