TERIFLUNOMIDE VIPHARM

Patient Information Leaflet

Teriflunomide Vipharm, 14 mg, film-coated tablets
Teriflunomide
Please read this leaflet carefully before taking this medicine, as it contains
important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, tell your doctor or pharmacist. See section 4.

Leaflet Contents

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

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

Teriflunomide Vipharm 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 Vipharm is used for
Teriflunomide Vipharm is used to treat adults, children, and adolescents (aged 10 years and older) with relapsing-remitting multiple sclerosis (MS).
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, inflammation damages the protective covering (called myelin) surrounding the nerves in the central nervous system. This process is known as demyelination. As a result, nerves are unable to function properly.
In people with relapsing-remitting multiple sclerosis, there are recurring episodes (relapses) of physical symptoms caused by impaired nerve function. Symptoms vary between individuals but typically include:

• difficulty walking,
• vision problems,
• problems with balance.

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

2. Important information before using Teriflunomide Vipharm

When not to take Teriflunomide Vipharm

• if the patient is allergic to teriflunomide or 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 oral ulceration 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 disease 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 protein in the blood (hypoproteinemia). If in doubt, consult a doctor or pharmacist before taking this medicine.

Warnings and precautions
Before starting treatment with Teriflunomide Vipharm, discuss with the doctor or
pharmacist if:

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

Respiratory 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 Vipharm 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:

• pancreatitis has been observed in patients receiving teriflunomide. The child's doctor may perform blood tests if pancreatitis is suspected.

Teriflunomide Vipharm and other medicines
Tell the 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, including over-the-counter medicines.
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 (used to treat tuberculosis and other infections);
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy;
• St John's wort (herbal remedy 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 diabetic patients;
• alosetron, used to treat severe diarrhoea;
• theophylline, used to treat asthma;
• tizanidine (a muscle relaxant);
• warfarin (an anticoagulant) used to thin the blood (i.e. make it more fluid) to prevent 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, medicines used to treat hypercholesterolaemia (high blood cholesterol);
• sulfasalazine, used for inflammatory bowel disease or rheumatoid arthritis;
• cholestyramine, used for high blood cholesterol or to relieve itching in liver disease;
• activated charcoal, used to reduce absorption of medicines or other substances.

Pregnancy and breastfeeding
Do not take Teriflunomide Vipharm if the patient is pregnant or suspects she may be pregnant. If the patient is pregnant or becomes pregnant while taking Teriflunomide Vipharm, there is an increased risk of birth defects in the unborn child. Women of childbearing potential who do not use effective contraception must not take this medicine. If a girl starts menstruating while taking Teriflunomide Vipharm, inform the doctor, who will provide specialist advice regarding contraception and potential risks in case of pregnancy.
If the patient plans to become pregnant after stopping Teriflunomide Vipharm, she should inform her doctor, as it is essential to confirm that the medicine has been eliminated from 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 Vipharm from the body.
In both cases, blood testing must confirm that the active substance has been sufficiently eliminated from the body. The doctor should confirm that the blood concentration of Teriflunomide Vipharm is low enough to allow pregnancy.
For additional information regarding laboratory tests, contact the doctor.
If pregnancy is suspected during treatment with Teriflunomide Vipharm or within two years after stopping treatment, immediately contact the doctor to perform a pregnancy test and, if necessary, discontinue Teriflunomide Vipharm. If the test confirms pregnancy, the doctor may prescribe appropriate medicines to rapidly and adequately eliminate Teriflunomide Vipharm from the body to reduce risk to the unborn child.

Contraception
During treatment with Teriflunomide Vipharm and after stopping treatment, the patient should use an effective method of contraception. Teriflunomide remains in the blood for a long time after stopping treatment. Therefore, effective contraception should continue after stopping treatment.

• This method should be used until the blood concentration of Teriflunomide Vipharm is sufficiently low – this will be verified by the doctor.
• Discuss with the doctor the most suitable method of contraception for the patient, and also in case of any need to change the method of contraception.

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

3. How to use Teriflunomide Vipharm

Treatment with Teriflunomide Vipharm will be supervised by a physician experienced
in the treatment of multiple sclerosis.
This medicine should always be taken exactly as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
Adults
The recommended dose is one 14 mg tablet per day.
Children and adolescents (aged 10 years and above)
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 Vipharm 7 mg is not available; therefore, other medicinal products containing teriflunomide 7 mg should be used.

Children and adolescents who reach a stable body weight above 40 kg will be informed by the
physician about changing the dose to one 14 mg tablet per day.
Route and method of administration
Teriflunomide Vipharm is administered orally. Teriflunomide Vipharm is taken
daily at any time of the day as a single daily dose.
Tablets should be swallowed whole with water.
Teriflunomide Vipharm may be taken with food or independently of meals.
Use of a higher than recommended dose of Teriflunomide Vipharm
If a higher than recommended dose of Teriflunomide Vipharm is taken, contact your doctor immediately.
Adverse effects similar to those described below in section 4 may occur.
Missed dose of Teriflunomide Vipharm
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 Vipharm
Do not stop taking Teriflunomide Vipharm or change the dose without prior consultation with your doctor.
If you have any further questions about the use of this medicine, consult your
doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will get them.
The following side effects may occur after taking this medicine.
Serious side effects
Some side effects may be or may become serious. If any of the following symptoms occur, seek immediate medical advice from a doctor.
Common (may occur in up to 1 in 10 people)

• inflammation of the pancreas, which may include symptoms such as abdominal pain, nausea or vomiting (frequency is 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 include 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 include symptoms such as high fever, seizures, chills, reduced urine output or confusion;
• inflammation of the lungs, which may include symptoms such as shortness of breath or persistent cough.

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

• severe liver disease, which may include symptoms such as yellowing of the skin or whites of the eyes, darker than normal urine, unexplained nausea and vomiting, or abdominal pain.

Other side effects 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) observed in 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, dental infection, laryngitis, fungal foot infection;
• herpes virus infections, including cold sores and shingles, with symptoms such as blisters, burning, itching, tingling or pain in the skin, usually on one side of the upper body or face, and other symptoms such as fever and fatigue;
• laboratory test results: decreased number of red blood cells (anaemia), changes in the liver and in white blood cell counts (see section 2.), increased activity of muscle enzymes (creatine kinase) has also been observed;
• mild allergic reactions;
• feeling anxious;
• tingling and prickling sensations, feeling of weakness, numbness, tingling or pain in the lower back or leg (sciatica), numbness, burning, tingling or pain in the hands and fingers (carpal tunnel syndrome);
• sensation of "heart beating";
• increased blood pressure;
• vomiting, toothache, epigastric pain;
• rash, acne;
• tendon, joint, bone pain, muscle pain (musculoskeletal pain);
• need to urinate more often than usual;
• heavy menstrual periods;
• pain;
• lack of energy or feeling weak (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, disorders of the nerves in arms or legs (peripheral neuropathy);
• changes in nails, severe skin reactions;
• post-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)

• inflammation or damage to the liver.

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

• pulmonary hypertension.

Children and adolescents (aged 10 years and above)
The side effects 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)

• inflammation of the pancreas.

Reporting of side effects
If any side effects occur, including any side effects not listed in this leaflet, tell your doctor, pharmacist or nurse.
Side effects can be reported directly to the Department of Monitoring of Adverse Drug Reactions of the 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
Side effects can also be reported to the marketing authorisation holder.
Reporting side effects helps provide more information on the safety of this medicine.

5. How to store Teriflunomide Vipharm

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging after "EXP".
The expiry date refers to the last day of the stated month.
No special storage instructions are required for this medicine.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Contents of the pack and other information

What Teriflunomide Vipharm contains
The active substance is teriflunomide.
Teriflunomide Vipharm 14 mg, film-coated tablets

• Each film-coated tablet contains 14 mg of teriflunomide.
• The other ingredients are: microcrystalline cellulose (PH 101), lactose monohydrate, sodium carboxymethyl starch (type A), hydroxypropyl cellulose (353 mPas - 658 mPas), colloidal anhydrous silica, magnesium stearate, hypromellose 2910 (6 mPas), titanium dioxide (E 171), macrogol 400, polysorbate 80 (see section 2. "Teriflunomide Vipharm contains lactose").

What Teriflunomide Vipharm looks like and contents of the pack
Teriflunomide Vipharm 14 mg film-coated tablets
White, pentagon-shaped, biconvex film-coated tablets, smooth on both sides.
Teriflunomide Vipharm 14 mg film-coated tablets are packed in blisters made of
OPA/Aluminium/PVC/Aluminium. The blisters are placed in a cardboard box containing 14, 28,
84 or 98 film-coated tablets.
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder
Vipharm S.A.
ul. Artura i Franciszka Radziwiłłów 9
05-850 Ożarów Mazowiecki
e-mail: [email protected]

Manufacturer
Pharmacare Premium Ltd.
HHF003, Hal Far Industrial Estate
Birzebbugia, BBG3000
Malta

This medicinal product is authorised in the European Economic Area under the following names:
Czech Republic Teriflunomide Vipharm
Malta Teriflunomide Vipharm 14 mg film-coated tablets
Poland Teriflunomide Vipharm
Slovakia Teriflunomide Vipharm 14 mg obalené tablety
Hungary Teriflunomide Vipharm 14 mg filmatabletta