Teriflunomide zentiva

Package leaflet: Information for the patient

Teriflunomide Zentiva, 14 mg, film-coated tablets
Teriflunomidum
Please read carefully the entire leaflet before taking this medicine, as it contains
important information for the patient.

• Keep this leaflet, as you may need to read it again.
• If you have any further 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 someone else, 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

1. What Teriflunomide Zentiva is and what it is used for
2. Important information before taking Teriflunomide Zentiva
3. How to take Teriflunomide Zentiva
4. Possible side effects
5. How to store Teriflunomide Zentiva
6. Contents of the pack and other information

1. What Teriflunomide Zentiva is and what it is used for

What Teriflunomide Zentiva is
Teriflunomide Zentiva contains the active substance teriflunomide, which is an immunomodulatory and disease-modifying agent that helps reduce the immune system's attack on the nervous system.
What Teriflunomide Zentiva is used for
Teriflunomide Zentiva is used to treat adults, children, and adolescents (aged 10 years and older) with relapsing-remitting multiple sclerosis.
What is multiple sclerosis
Multiple sclerosis is a chronic disease that affects the central nervous system. The central nervous system consists of the brain and spinal cord. In multiple sclerosis, inflammatory processes destroy the protective covering (called myelin) around the nerves in the central nervous system. This process is known as demyelination. As a result, nerves are unable to function properly.
In relapsing-remitting multiple sclerosis, patients experience repeated attacks (relapses) of physical symptoms caused by impaired nerve function. Symptoms vary between individuals but usually include:

• difficulty walking
• vision problems
• balance difficulties.

These symptoms may completely disappear after a relapse ends, but over time some symptoms may persist between relapses. This may lead to physical disability, making it difficult to perform daily activities.
How Teriflunomide Zentiva works
Teriflunomide Zentiva helps protect the central nervous system from immune system activity by reducing the increase in certain white blood cells (lymphocytes). This reduces the inflammation that leads to nerve damage in patients with multiple sclerosis.

2. Important information before taking Teriflunomide Zentiva

When not to take Teriflunomide Zentiva:

• if the patient is allergic to teriflunomide or to any of the other ingredients of this medicine (listed in section 6),
• if the patient has ever experienced severe skin rash, skin peeling, blisters and/or mouth ulcers after taking teriflunomide or leflunomide,
• if the patient has severe liver disease,
• if the patient is pregnant, suspects she may be pregnant, or is breastfeeding,
• if the patient has any severe diseases affecting the immune system, e.g. acquired immunodeficiency syndrome (AIDS),
• if the patient has any severe bone marrow disorders or has low numbers of red or white blood cells or reduced platelet count,
• if the patient has a severe infection,
• if the patient has severe kidney disease requiring dialysis,
• if the patient has very low levels of proteins in the blood (hypoproteinemia).
  If in doubt, consult a doctor or pharmacist before taking this medicine.

Warnings and precautions
Before starting treatment with Teriflunomide Zentiva, discuss with your doctor or
pharmacist if:

• the patient has liver function disorders and/or drinks large amounts of alcohol. The doctor will perform blood tests before and during treatment to check whether liver function is normal. If test results indicate liver function abnormalities, the doctor may discontinue treatment with Teriflunomide Zentiva. Please refer to section 4.
• the patient has high blood pressure (hypertension), regardless of whether it is controlled with medication or not. Teriflunomide Zentiva may increase blood pressure. The doctor will check the patient’s blood pressure before starting treatment and regularly thereafter. Please refer to section 4.
• the patient has an infection. Before the patient takes Teriflunomide Zentiva, the doctor will ensure that the patient has sufficient levels of white blood cells and platelets in the blood. Since Teriflunomide Zentiva reduces the number of white blood cells, it may affect the ability to fight infections. The doctor may perform blood tests to check white blood cell count if the patient suspects any infection. Viral infections such as herpes virus infections, including cold sores or shingles, may occur during treatment with teriflunomide. In some cases, serious complications have occurred. Inform the doctor immediately if any symptoms suggestive of herpes virus infection develop. Please refer to section 4.
• the patient has severe skin reactions.
• the patient has respiratory symptoms.
• the patient experiences weakness, numbness, or pain in hands and feet.
• the patient intends to receive vaccination.
• the patient is taking leflunomide together with Teriflunomide Zentiva.
• the patient is switching from another medication to Teriflunomide Zentiva or from Teriflunomide Zentiva to another medicine.
• the patient is scheduled for a specific blood test (calcium level measurement). Test results for calcium levels may be falsely low.

Discuss with the doctor or pharmacist:

• if the patient develops skin ulcers or impaired wound healing during treatment with Teriflunomide Zentiva.
• if the patient has planned or recently undergone surgery or if a surgical wound has not yet healed, as Teriflunomide Zentiva may impair wound healing.

Respiratory system reactions
Inform the doctor if the patient develops unexplained cough or shortness of breath (difficulty breathing). The doctor may perform additional tests.
Children and adolescents
Teriflunomide Zentiva is not intended for use in children under 10 years of age,
as it has not been studied in patients with multiple sclerosis in this age group.
The warnings and precautions listed above also apply to children. The following
information is important for children and their caregivers:

• Cases of pancreatitis have been observed in patients receiving teriflunomide. The child’s doctor may perform blood tests if pancreatitis is suspected.
  Teriflunomide Zentiva and other medicines
  Tell your doctor or pharmacist about all medicines the patient is currently taking or has recently taken, including medicines obtained without a prescription, as well as any medicines the patient plans to take. In particular, inform the doctor or pharmacist if the patient is taking any of the following medicines:
• leflunomide, methotrexate, and other medicines affecting the immune system (often called immunosuppressive or immunomodulatory medicines),
• rifampicin (a medicine used to treat tuberculosis and other infections),
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy,
• St. John’s wort (a herbal medicine for depression),
• repaglinide, pioglitazone, nateglinide, or rosiglitazone used to treat diabetes,
• daunorubicin, doxorubicin, paclitaxel, or topotecan, used to treat cancer,
• duloxetine used to treat depression, urinary incontinence, or kidney disease in patients with diabetes,
• alosetron used to treat severe diarrhoea,
• theophylline used to treat asthma,
• tizanidine, a muscle relaxant,
• warfarin, an anticoagulant medicine used to thin the blood (i.e. make it more fluid) to prevent blood clots,
• oral contraceptives (containing ethinylestradiol and levonorgestrel),
• cefaclor, benzylpenicillin (penicillin G), ciprofloxacin, used to treat infections,
• indometacin, ketoprofen, used to treat inflammation or pain,
• furosemide used to treat heart conditions,
• cimetidine, used to reduce gastric acid secretion,
• zidovudine, used to treat HIV infection,
• rosuvastatin, simvastatin, atorvastatin, pravastatin, used to treat hypercholesterolemia (elevated cholesterol levels in the blood),
• sulfasalazine, used for inflammatory bowel disease or rheumatoid arthritis,
• cholestyramine, used for elevated cholesterol levels or itching in liver disease,
• activated charcoal, used to reduce absorption of medicines or other substances.

Pregnancy and breastfeeding
Do not take Teriflunomide Zentiva if the patient is pregnant or suspects she may be pregnant.
For patients who are pregnant or become pregnant while taking Teriflunomide Zentiva, there is an increased risk of congenital malformations in the unborn child. Women of childbearing potential must not take this medicine without using effective contraceptive methods.
If a girl starts menstruating while taking Teriflunomide Zentiva, inform the doctor, who will provide specialist advice regarding contraception and potential risks in case of pregnancy.
If a woman plans to become pregnant after stopping Teriflunomide Zentiva, she should inform her doctor, as it is essential to confirm that the medicine is no longer present in the body before attempting pregnancy. Elimination of the active substance may take up to 2 years. This period can be shortened to several weeks by taking specific medicines that accelerate the removal of Teriflunomide Zentiva from the body.
In both cases, blood testing must confirm that the active substance has been sufficiently eliminated from the body, and the doctor must confirm that the blood concentration of Teriflunomide Zentiva is low enough to allow pregnancy.
Further information about laboratory tests can be obtained from the treating doctor.
If a woman suspects she has become pregnant while taking Teriflunomide Zentiva or within two years after stopping treatment, she must stop taking Teriflunomide Zentiva and immediately contact her doctor to perform a pregnancy test. If the test confirms pregnancy, the doctor may recommend appropriate treatment to rapidly and adequately eliminate Teriflunomide Zentiva from the body to reduce the risk to the unborn child.
Contraception
During treatment with Teriflunomide Zentiva and after stopping it, the woman should use an effective method of contraception. Teriflunomide remains in the blood for a long time after stopping treatment. An effective contraceptive method should be continued after stopping treatment.

• This method should be used until blood levels of Teriflunomide Zentiva are sufficiently low – this will be confirmed by the doctor.
• Discuss with the doctor the best contraceptive method and any potential need to change contraceptive methods.

Do not take Teriflunomide Zentiva while breastfeeding, as teriflunomide passes into human milk.
Driving and using machines
Teriflunomide Zentiva may cause dizziness, which may impair the ability to concentrate and react. Patients experiencing such symptoms should not drive or operate machinery.
Teriflunomide Zentiva contains lactose
Teriflunomide Zentiva contains lactose (a type of sugar). If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking this medicine.
Teriflunomide Zentiva contains sodium
This medicine contains less than 1 mmol (23 mg) of sodium per tablet, which means the medicine is considered "sodium-free".

3. How to take Teriflunomide Zentiva

This medicine should always be taken as directed by the doctor. If in doubt,
consult the doctor.
The use of Teriflunomide Zentiva will be supervised by a physician experienced
in the treatment of multiple sclerosis.
Adults
The recommended dose is one 14 mg tablet per day.
Children and adolescents (aged 10 years and older)
The dose depends on body weight:

• Children with body weight greater than 40 kg: one 14 mg tablet per day.
• Children with body weight less than or equal to 40 kg: one 7 mg tablet per day.

Teriflunomide Zentiva 14 mg film-coated tablets are not suitable for children and adolescents
with body weight ≤ 40 kg.
Other medicinal products containing teriflunomide are available in a lower strength (as 7 mg
film-coated tablets).
Children and adolescents who achieve a stable body weight above 40 kg will be informed by
the doctor to change the dose to one 14 mg tablet per day.
Route/method of administration
Teriflunomide Zentiva is intended for oral use.
Teriflunomide Zentiva should be taken daily as a single dose at any time of the day.
Tablets should be swallowed whole with water.
Teriflunomide Zentiva may be taken with food or independently of meals.
Taking more Teriflunomide Zentiva than prescribed
If more Teriflunomide Zentiva than prescribed has been taken, contact the doctor immediately.
Adverse effects similar to those described in section 4 below may occur.
Missing a dose of Teriflunomide Zentiva
Do not take a double dose to make up for a missed tablet. Take the next dose according to the
prescribed dosing schedule.
Stopping Teriflunomide Zentiva
Do not stop taking Teriflunomide Zentiva or change the dose without first consulting the doctor.
If there are any further questions about the use of this medicine, consult the doctor or pharmacist.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
The following adverse reactions may occur during treatment with this medicine.
Serious adverse reactions
Some adverse reactions may be or may become serious. If any of the following symptoms occur, you should immediately contact your doctor.
Common (may occur in up to 1 in 10 people)

• Pancreatitis, which may cause symptoms such as abdominal pain, nausea or vomiting (frequency: common in children and adolescents and uncommon in adult patients)

Uncommon (may occur in up to 1 in 100 people)

• Allergic reactions, which may include symptoms such as rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties
• Severe skin reactions, which may cause symptoms such as skin rash, blisters on the skin, fever or mouth ulcers
• Severe infections or sepsis (a type of infection potentially life-threatening), which may cause symptoms such as high fever, seizures, chills, reduced urine output or confusion
• Lung inflammation, which may cause symptoms such as shortness of breath or persistent cough

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

• Severe liver disease, which may cause symptoms such as yellowing of the skin or whites of the eyes, dark urine, unexplained nausea and vomiting, or abdominal pain

Other adverse reactions may occur with the following frequency:
Very common (may occur in more than 1 in 10 people)

• Headache
• Diarrhoea, nausea
• Increased AlAT activity (increased activity of certain liver enzymes in blood tests)
• Hair thinning

Common (may occur in up to 1 in 10 people)

• Influenza, upper respiratory tract infection, urinary tract infection, bronchitis, sinusitis, sore throat and discomfort when swallowing, cystitis, viral gastroenteritis, tooth infection, laryngitis, fungal foot infection
• Herpes virus infections, including cold sores and shingles, with symptoms such as blisters, burning, itching, numbness or pain of the skin, usually on one side of the upper body or face, and other symptoms such as fever and fatigue
• Laboratory findings: decreased number of red blood cells (anaemia), changes in liver and white blood cell test results (see section 2), increased activity of muscle enzymes (creatine phosphokinase) has also been observed
• Mild allergic reactions
• Feeling anxious
• Tingling sensation, feeling of weakness, numbness, tingling or pain in the lower back or leg (sciatica), numbness, burning, tingling or pain in hands and fingers (carpal tunnel syndrome)
• Palpitations
• Increased blood pressure
• Vomiting, toothache, upper abdominal pain
• Rash, acne
• Tendon, joint, bone pain, muscle pain (musculoskeletal pain)
• Need to urinate more often than usual
• Heavy menstrual bleeding
• Pain
• Lack of energy or feeling of weakness (asthenia)
• Weight loss

Uncommon (may occur in up to 1 in 100 people)

• Decreased number of platelets (mild thrombocytopenia)
• Increased sensitivity (especially of the skin), stabbing or pulsating pain along one or more nerves, nerve disorders of arms or legs (peripheral neuropathy)
• Changes in nails, severe skin reactions
• Traumatic pain
• Psoriasis
• Inflammation of the mucous membrane of the mouth/lips
• Abnormal levels of fats (lipids) in the blood
• Inflammation of the large intestine

Rare (may occur in up to 1 in 1000 people)

• Liver inflammation or damage

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

• Pulmonary hypertension

Children (aged 10 years and older) and adolescents
The adverse reactions listed above also apply to children and adolescents. The following additional information is important for children, adolescents and their caregivers:
Common (may occur in up to 1 in 10 people)

• Pancreatitis

Reporting of adverse reactions
If any adverse reactions occur, including any adverse reactions not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products, Al. Jerozolimskie 181C, 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 authorisation holder or representative of the marketing authorisation holder. Reporting adverse reactions helps to provide more information on the safety of this medicine.

5. How to store Teriflunomide Zentiva

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the cardboard packaging after 'EXP'. The expiry date refers to the last day of the specified month.
No special storage instructions 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. Such measures will help protect the environment.

6. Contents of the pack and other information

What Teriflunomide Zentiva contains
The active substance is teriflunomide. Each tablet contains 14 mg of teriflunomide.
The other ingredients are: monohydrate lactose, microcrystalline cellulose (type PH-102), corn starch,
sodium carboxymethyl starch (type A), hydroxypropylcellulose (300 - 600 mPas), magnesium stearate,
hypromellose (15 mPas), calcium carbonate, triacetin, Indigo Carmine, aluminium lake (E132).

What Teriflunomide Zentiva looks like and contents of the pack
Teriflunomide Zentiva 14 mg, film-coated tablets (tablets) are round, blue, 7 mm in diameter,
and marked with "C14" on one side.
Blister packs made of OPA/Aluminium/PVC/Aluminium foil containing 14, 28, 84 or 98 film-coated tablets in a cardboard carton.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Zentiva, k.s.
U kabelovny 130,
Dolní Měcholupy,
102 37 Prague 10, Czech Republic

Manufacturer
Coripharma ehf.
Reykjavikurvegur 78
Hafnarfjörður
IS-220, Iceland

This medicinal product is authorised in the European Economic Area under the following names:
Austria, Bulgaria, Croatia, Denmark, Iceland, Germany, Norway, Czech Republic, Sweden:
Teriflunomid Zentiva
Spain, Portugal, Romania: Teriflunomida Zentiva
Estonia, France, Lithuania, Latvia, Poland, Slovakia, Hungary, Italy: Teriflunomide Zentiva

For further information, please contact the local representative of the Marketing Authorisation Holder in Poland:
Zentiva Polska Sp. z o.o.,
ul. Bonifraterska 17
00-203 Warsaw, Poland
tel.: +48 22 375 92 00