Terebio

Package leaflet: Information for the patient

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

• Keep this leaflet for future reference.
• If you have any questions, please consult your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not share it with others. This medicine may harm others, even if their symptoms are similar.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Contents of the leaflet

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

1. What Terebyo is and what it is used for

What Terebyo is
Terebyo contains the active substance teriflunomide, which is an immunomodulatory agent that regulates the immune system to reduce its attack on the nervous system.

What Terebyo is used for
Terebyo is used in the treatment of adults and 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, inflammation damages the protective covering (called myelin) around the nerves in the central nervous system. This process is known as demyelination. This damage prevents nerves from functioning properly.

In people with relapsing forms of multiple sclerosis, there are repeated attacks (relapses) of physical symptoms caused by abnormal nerve function. Symptoms vary among patients but usually include:

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

These symptoms may completely disappear after a relapse ends, but over time, some problems may persist between relapses. This may lead to physical disability that makes it difficult to perform daily activities.

How Terebyo works
Terebyo helps protect the central nervous system from the immune system by reducing the increase in number of certain white blood cells (lymphocytes). This reduces the inflammation that, in patients with multiple sclerosis, leads to nerve damage.

2. Important information before taking Terebyo

When not to take Terebyo:

• 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 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 a reduced number of platelets;
• 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 Terebyo, discuss with your doctor or pharmacist if:

• the patient has liver function disorders and/or drinks large amounts of alcohol; the doctor may perform blood tests to check whether liver function is normal before and during treatment. If test results indicate liver function abnormalities, the doctor may discontinue treatment with Terebyo. Please refer to section 4.
• the patient has high blood pressure (hypertension), regardless of whether it is controlled with medication or not. Terebyo 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 Terebyo, the doctor will ensure that the patient has adequate levels of white blood cells and platelets in the blood. Since Terebyo 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 any infection. 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 are suspected. Please refer to section 4.
• the patient experiences severe skin reactions.
• the patient has respiratory symptoms.
• the patient has weakness, numbness, or pain in the hands or feet.
• the patient plans to receive a vaccination.
• the patient is taking leflunomide together with Terebyo.
• the patient is switching from another medicine to Terebyo or from Terebyo to another medicine.
• the patient is scheduled for a specific blood test (calcium level measurement). Calcium test results may be falsely low. 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
Terebyo 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 treating physician may perform blood tests if pancreatitis is suspected.

Terebyo 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 immunosuppressants or immunomodulators);
• rifampicin (used to treat tuberculosis and other infections);
• carbamazepine, phenobarbital, phenytoin, used to treat epilepsy;
• St John’s wort (a 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 patients with diabetes;
• 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 hypercholesterolemia (elevated blood cholesterol levels);
• sulfasalazine, used for intestinal inflammation and rheumatoid arthritis;
• cholestyramine, used in cases of elevated blood cholesterol or itching in liver disease;
• activated charcoal, used to reduce absorption of medicines or other substances.

Pregnancy and breastfeeding
Do not take Terebyo if the patient is pregnant or suspects she may be pregnant. In women who are pregnant or who become pregnant while taking Terebyo, there is an increased risk of congenital malformations in the child. Women of childbearing potential who are not using effective contraception must not take this medicine.
If a girl starts menstruating while taking Terebyo, 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 Terebyo, she should inform her doctor, as it is essential to ensure that the medicine is no longer present in the body before attempting pregnancy. Elimination of the active substance may take up to two years. This period can be shortened to several weeks by taking appropriate medicines that accelerate the removal of Terebyo from the body.
In both cases, adequate elimination of the active substance from the body must be confirmed by a blood test. The doctor should confirm that the blood concentration of Terebyo is sufficiently low for the woman to become pregnant.
More information about laboratory tests can be obtained from the doctor.
If pregnancy is suspected during treatment with Terebyo or within two years after stopping treatment, discontinue Terebyo and immediately contact the doctor to perform a pregnancy test. If the test confirms pregnancy, the doctor may recommend appropriate medicines to rapidly and adequately eliminate Terebyo from the body to reduce the risk to the child.

Contraception
During treatment with Terebyo 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. For this reason, effective contraception should continue after stopping treatment.

• This method should be used until the teriflunomide blood concentration is sufficiently low (as confirmed by the doctor).
• Discuss with the doctor the most suitable contraceptive method for the patient, as well as any need to change the contraceptive method.

Do not take Terebyo while breastfeeding, as teriflunomide passes into human milk.

Driving and operating machinery
Terebyo may cause dizziness, which may impair concentration and reaction ability. Patients experiencing such symptoms should not drive or operate machinery.

Terebyo contains lactose
Terebyo 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.

Terebyo contains Allura Red AC (E 129)
Allura Red AC (E 129) may cause allergic reactions.

Terebyo contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium per coated tablet, meaning the medicine is considered “sodium-free”.

3. How to take Terebyo

Treatment with Terebyo 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. In case of doubt, consult your doctor.

Adults
The recommended dose is one 14 mg coated tablet per day.

Children and adolescents (aged 10 years and older)
The dose depends on body weight:

• Children with body weight > 40 kg: one 14 mg tablet per day.
• Children with body weight ≤ 40 kg: one 7 mg tablet per day. Terebyo is available only as 14 mg coated tablets; therefore, for this group of patients, the physician will recommend another available medicine. 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
Terebyo is administered orally. Terebyo should be taken every day at any time as a single daily dose.
Tablets should be swallowed whole with water.
Terebyo may be taken with food or independently of meals.

Taking more Terebyo than recommended
If more Terebyo than recommended has been taken, contact your doctor immediately. Adverse effects may occur similar to those described in section 4 below.

Missing a dose of Terebyo
Do not take a double dose to make up for a missed tablet. Take the next dose according to the prescribed dosing schedule.

Stopping Terebyo treatment
Do not stop taking Terebyo or change the dose without first consulting your doctor.

If you have any further questions about the use of this medicine, consult your doctor or pharmacist.

4. Possible adverse effects

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

• pancreatitis, which may cause 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 cause symptoms including rash, hives, swelling of the lips, tongue or face, or sudden breathing difficulties;
• severe skin reactions, which may cause symptoms including skin rash, blisters, fever or mouth ulcers;
• severe infections or sepsis (a type of infection potentially life-threatening), which may cause symptoms including high fever, seizures, chills, reduced urine output or confusion;
• pneumonia, which may cause symptoms including shortness of breath or persistent cough.

Frequency unknown (frequency cannot be estimated from available data)

• severe liver disease, which may cause symptoms including yellowing of the skin or whites of the eyes, darker than usual urine, unexplained nausea and vomiting, or abdominal pain.

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

• headache;
• diarrhoea, nausea;
• increased AlAT activity (elevated activity of certain liver enzymes in blood) observed in laboratory 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 during 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 weakness;
• laboratory findings: decreased number of red blood cells (anaemia), changes in the liver and white blood cell test results (see section 2), increased activity of muscle enzymes (creatine kinase) has also been observed;
• mild allergic reactions;
• feeling of anxiety;
• tingling sensation, 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 "pounding heartbeat";
• increased blood pressure;
• vomiting, toothache, upper abdominal pain;
• rash, acne;
• tendon, joint or bone pain, muscle pain (musculoskeletal pain);
• need to pass urine more often than usual;
• heavy menstrual periods;
• 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 in arms or legs (peripheral neuropathy);
• nail changes, severe skin reactions;
• traumatic pain;
• psoriasis;
• inflammation 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 unknown (frequency cannot be estimated from available data)

• pulmonary hypertension.

Children (aged 10 years and older) and adolescents
The adverse 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)

• pancreatitis.

Reporting of adverse effects
If any adverse effects occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse effects 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 181C, 02-222 Warsaw, tel.: + 48 22 49 21 301, fax: + 48 22 49 21 309, website: https://smz.ezdrowie.gov.pl.
Adverse effects can also be reported to the marketing authorisation holder.
Reporting adverse effects helps to provide more information on the safety of this medicine.

5. How to store Terebyo

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the blister and the carton after "EXP". The expiry date refers to the last day of the stated month.
No special storage instructions apply.
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 Terebyo contains
The active substance is teriflunomide. Each coated tablet contains 14 mg of teriflunomide.
The other ingredients are:
Tablet core: monohydrate lactose, corn starch, microcrystalline cellulose, type 101D+,
hydroxypropylcellulose, sodium carboxymethyl starch (type A), colloidal anhydrous silica,
magnesium stearate.
Tablet coating: hypromellose 2910 (6 mPas), titanium dioxide (E 171), indigo carmine, aluminium lake (E 132), glycerol, talc, brilliant blue FCF, aluminium lake (E 133), and Allura red AC, aluminium lake (E 129).

What Terebyo looks like and contents of the pack
Blue, biconvex, round coated tablet (approximately 7 mm in diameter) with the imprint “14” on one side.
The tablets are packed in blisters made of OPA/Aluminium/PVC/Aluminium foil, placed in cardboard folding cartons.
Blisters containing 28 coated tablets per carton (1 carton containing 28 tablets).

Marketing Authorisation Holder
Sandoz GmbH
Biochemiestrasse 10
6250 Kundl
Austria

Manufacturer/Importer
Combino Pharm (Malta) Limited
HF60, Hal Far Industrial Estate
BBG3000 Birzebbuga, Malta
Salutas Pharma GmbH
Otto-Von-Guericke-Allee 1
39179 Barleben, Germany
HBM Pharma s.r.o.
Sklabinská 30
SK-036 80 Martin, Slovakia

This medicinal product is authorised in the European Economic Area under the following names:
Austria Terebyo 14 mg Filmtabletten
Belgium Terebyo 14 mg filmomhulde tabletten
Bulgaria TEREBYO 14 mg film-coated tablet
Czech Republic TEREBYO
Estonia Terebyo
Germany TEREBYO
Greece TEREBYO ΕΠΙΚΑΛΥΜΜΕΝΟ ΜΕ ΛΕΠΤΟ ΥΜΕΝΙΟ ΔΙΣΚΙΟ 14 MG/TAB
France TEREBYO 14 mg, comprimé pelliculé
Italy Terebyo
Latvia Terebyo 14 mg apvalkotās tabletes
Lithuania Terebyo 14 mg plėvele dengtos tabletės
Poland TEREBYO
Romania TEREBYO 14 mg Comprimate filmate
Slovakia TEREBYO 14 mg filmom obalené tablety
Slovenia TEREBYO 14 mg filmsko obložene tablete

For more detailed information about this medicinal product, please contact the local representative of the Marketing Authorisation Holder:
Sandoz Polska Sp. z o.o.
ul. Domaniewska 50C
02-672 Warszawa
tel. +48 22 209 70 00

Other sources of information
Detailed and up-to-date information on this medicinal product is available by scanning the QR code located in the patient leaflet with a smartphone or other device. The same information is also available at the following URL: www.sandoz-teriflunomide.com
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